Dendrimer-encapsulated Cu(Π) nanoparticles immobilized on superparamagnetic Fe3O4@SiO2 nanoparticles as a novel recyclable catalyst for N-arylation of nitrogen heterocycles and green synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1002/aoc.4300

In this study, dendrimer-encapsulated Cu(Π) nanoparticles immobilized on superparamagnetic Fe₃O₄@SiO₂ nanoparticles were prepared via a multistep-synthesis. Then, the synthesized composite was fully characterized by various techniques such as fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), UV-vis spectroscopy, energy dispersive X-ray analysis (EDX), thermogravimetric analysis (TGA) and vibration sample magnetometer (VSM). From the information gained by. FE-SEM and TEM studies it can be inferred that the particles are mostly spherical in shape and have an average size of 50?nm. Also, the amount of Cu is determined to be 0.51?mmol/g in the catalyst by inductively coupled plasma (ICP) analyzer. This magnetic nano-compound has been successfully applied as a highly efficient, magnetically recoverable and stable catalyst for N-arylation of nitrogen heterocycles with aryl halides (I, Br) and arylboronic acids without using external ligands or additives. The catalyst was also employed in a one-pot, three-component reaction for the efficient and green synthesis of 5-substituted 1H-tetrazoles using various aldehydes, hydroxylamine hydrochloride and sodium azide in water. The magnetic catalyst can be easily separated by an external magnet bar and is recycled seven times without significant loss of its activity.

Full text of DOI:10.1002/aoc.4300

Received: 10 September 2017
DOI: 10.1002/aoc.4300
Revised: 30 December 2017
Accepted: 2 January 2018
F U L L P A P E R
Dendrimer‐encapsulated Cu(Π) nanoparticles immobilized
on superparamagnetic Fe O @SiO nanoparticles as a novel
3
4
2
recyclable catalyst for N‐arylation of nitrogen heterocycles
and green synthesis of 5‐substituted 1H‐tetrazoles
Mohsen Esmaeilpour | Ali Reza Sardarian
| Habib Firouzabadi
Chemistry Department, College of
In this study, dendrimer‐encapsulated Cu(Π) nanoparticles immobilized on
superparamagnetic Fe O @SiO nanoparticles were prepared via a multistep‐
Sciences, Shiraz University, Shiraz 71946
4795, Iran
8
3
4
2
synthesis. Then, the synthesized composite was fully characterized by various
techniques such as fourier transform infrared (FT‐IR) spectroscopy, X‐ray
diffraction (XRD), dynamic light scattering (DLS), UV‐vis spectroscopy, energy
dispersive X‐ray analysis (EDX), thermogravimetric analysis (TGA) and
vibration sample magnetometer (VSM). From the information gained by
FE‐SEM and TEM studies it can be inferred that the particles are mostly
spherical in shape and have an average size of 50 nm. Also, the amount of Cu
is determined to be 0.51 mmol/g in the catalyst by inductively coupled plasma
Correspondence
Ali Reza Sardarian and Habib
Firouzabadi, Chemistry Department,
College of Sciences, Shiraz University,
Shiraz 71946 84795, Iran.
Email: sardarian@shirazu.ac.ir;
firouzabadi@chem.susc.ac.ir
(ICP) analyzer. This magnetic nano‐compound has been successfully applied as
a highly efficient, magnetically recoverable and stable catalyst for N‐arylation of
nitrogen heterocycles with aryl halides (I, Br) and arylboronic acids without
using external ligands or additives. The catalyst was also employed in a
one‐pot, three‐component reaction for the efficient and green synthesis of
5
‐substituted 1H‐tetrazoles using various aldehydes, hydroxylamine hydrochlo-
ride and sodium azide in water. The magnetic catalyst can be easily separated
by an external magnet bar and is recycled seven times without significant loss
of its activity.
KEYWORDS
Dendrimer‐encapsulated Cu(Π), 5‐substituted 1H‐tetrazoles, green synthesis, magnetic nanoparticles,
N‐arylation
1
| INTRODUCTION
biomedical and diagnostic fields, enzyme encapsulation,
DNA detection, magnetic resonance imaging (MRI), drug
The preparation and the use of nanoparticles (NPs) in
organic synthesis has become a subject of intense investi-
delivery, immunoassay, and molecular interactions in live
[
4–6]
cells.
Along this line, the use of magnetite
[1–3]
gation.
Moreover, in recent years, there has been an
nanoparticles attracted a lot of attention in the field of
catalysis due to their unique properties including a large
surface‐to‐volume ratio, biocompatibility, low toxicity,
superparamagnetism, and also the vast application for
increasing attraction in the design and development
of novel magnetic nanoparticles, especially Fe O4 for
3
various applications including bioseparation, biosensors,
Appl Organometal Chem. 2018;e4300.
wileyonlinelibrary.com/journal/aoc
Copyright © 2018 John Wiley & Sons, Ltd.
1 of 16
https://doi.org/10.1002/aoc.4300

2
of 16
ESMAEILPOUR ET AL.
[20,25,26]
different purposes. 7–9] However, iron oxide particles are
[
vast abundance and consequently less expensive.
prone to aggregate, which affects their activity and as
However, the reported methodologies suffer from numer-
ous limitations such as long reaction times, high reaction
temperatures, stoichiometric amount of copper reagents,
the use of toxic and air‐sensitive ligands, and also using
excess amounts of aryl halides in order to achieve
reasonable product yields. Thus, development of new
methods for C‐N bond formation under relatively mild
reaction conditions is of great demand and has received
increasing interests.
[10]
the result, hampers their applications.
In addition,
naked magnetite nanoparticles have fewer activating
group and be easily oxidized or dissolved in an acid
[11]
medium.
One way for surmounting this problem is to
use silica as a coating material and also as a stabilizer.
This prevents direct contact between the nanoparticles
that promotes their coagulation and also modifies
[12]
inherently their surfaces.
The use of silica as a coating
layer to the magnetite nanoparticles not only helps in
enhancing the advantages of their high biocompatibility,
and stability against degradation, dielectric property and
hydrophobicity but also facilitates easy surface modifica-
tion due to the presence of abundant silanol groups on
Tetrazoles are important heterocycles with a wide
range of applications in special explosives, cis‐peptide
bond mimics, carboxylic acid surrogates, ion and peptide
chelating agents, pharmaceuticals as lipophilic spacers,
photography, information recording systems and also as
[13]
[27–31]
the surface of the material.
Also, the presence of mag-
catalysts in asymmetric synthesis.
They are potential
[
32]
netic Fe O NPs in the core‐shell NPs, a well‐designed
TNF alpha inhibitors, P2X7‐antagonists, and inhibitors
3
4
[
33]
composite enables us to separate the material with an
external magnetic field that is a great practical advantage
to eliminate the necessity of filtration in the process of
of anandamide cellular uptake.
The tetrazole‐based
drugs possess various biological activities such as
anti‐inflammatory, antiviral, antiallergic, antifungal,
antibacterial, antiulcer, anticonvulsant and antitubercular
[14]
work up of the reaction mixture.
[
34]
Dendrimers are highly branched macromolecules
available in nanometer dimensions with unique properties
such as good structural homogeneity, good biocompatibil-
ity, having vast number of active groups and internal
porosity. The aforementioned properties have attracted
much attention in biomedicine, biomaterial, drug delivery,
therapeutic treatment of cancer cells, also in catalysis and
activities,
and have shown promising results in treat-
[35]
ment of dreadful diseases, such as cancer and AIDS.
In addition, they have important roles in coordination
chemistry as a ligand for preparation of complex heterocy-
[
36]
clic structures.
Various methods have been reported
for the synthesis of 5‐substituted 1H‐tetrazoles, which
most of them are based on the addition of trimethylsilyl
azide or sodium azide to nitrile group. The reactions were
[15]
etc.
In recent years, dendrimers immobilized on
[
37]
magnetic nanoparticles, silica or polymers have been
investigated intensively and applied to several catalytic
carried out by using catalysts such as nano‐CuFe O ,
2
4
[
38]
COY zeolites,
AlPO‐5 microporous molecular
[16,17]
[39]
[40]
organic transformations.
Among the solid support
sieves,
hydrotalcite,
Fe O @SiO /Salen of Cu(II),
Zn/Al
and
3
41]
4
2
[
[42]
[43]
[44]
materials, magnetic nanoparticles are more interesting
for the immobilization of homogeneous catalysts, because
their magnetic response causes simple recovery and
γ‐Fe O ,
Zn(OTf)2,
AlCl3
2
3
[
45]
Brønsted acid catalyst.
Heravi and co‐workers have
reported a method for the synthesis of 5‐substituted
1H‐tetrazoles by reaction of aldehydes, hydroxylamine
[18]
reusability of the catalyst by an external magnet.
[
46]
Nitrogen‐containing heterocycles are one of the most
powerful and important structural motifs widely utilized
in medicinal, biological and N‐heterocyclic carbene
and [bmim]N in DMF at 120 °C.
Also, Patil and his
3
co‐workers applied Cu(OAc) to synthesize 5‐substituted
2
1H‐tetrazoles via the reaction of organic oximes with
[19]
[47]
chemistry.
N‐Arylation reaction has been recognized
sodium azide in DMF at 120 °C.
Although most of
as one of the most practical methods for the preparation
of arylated N‐heterocyclic compounds. For this purpose,
Copper‐catalyzed Ullmann reaction is the classical well
established method for generation of C‐N bond in these
these methods are worthwhile, some of submitted
methods suffer from disadvantages such as formation of
highly volatile and toxic hydrazoic acid as by product,
use of toxic solvents, expensive reagents, elevated temper-
atures, some moisture sensitive reaction conditions, elon-
gation of the reaction time, poor yields, tedious workup of
the reaction mixture and difficulty in separation and
recovery of the catalyst. Therefore, the design of safe
and environmentally friendly protocols for the synthesis
of 5‐substituted 1H‐tetrazoles from simpler and more
available precursors is still highly desirable.
[20]
[21]
[22]
compounds.
Buchwald
and Hartwig
established
methods catalyzed by palladium for the production of
arylated N‐heterocyclic compounds. Modified Ullmann
reactions using copper salts are also reported by
[
22]
Hartwig.
The high costs and toxicity of palladium
[
23]
catalysts put restrictions on their uses in industries.
Thus, in order to replace palladium, researchers have
turned their attention again to the traditionally used
Now, the preparation of a magnetic heterogeneous
nano‐composite system,dendrimer‐encapsulated Cu(Π)
[24]
copper which is less toxic, more economical metal with

ESMAEILPOUR ET AL.
3 of 16
‐
1
nanoparticles immobilized on Fe O @SiO NPs, is
broad wavelength ranging from 500 to 3800 cm . NMR
spectra were taken in CDCl3 using a Bruker Avance
3
4
2
reported which has been applied as a highly efficient
and magnetically separable catalyst (Scheme 1, 2) in C‐N
coupling of nitrogen heterocycles with aryl halides (I, Br)
and arylboronic acids, and also as a catalyst in one‐pot,
three‐component synthesis of 5‐substituted 1H‐tetrazoles
in water.
1
DPX 250 spectrometer operating for H at 250 MHz and
13
for C at 62.9 MHz. X‐ray diffraction (XRD) measure-
ment was performed on a Bruker AXS D8‐advance X‐ray
diffractometer using CuKα radiation (λ¼ 1.5418). The
morphology and size of the NPs were determined by field
emission scanning electron microscopy (FE‐SEM; Hitachi
S‐4160 instrument). Transmission electron microscopy
2
2
| EXPERIMENTAL
(
TEM) observation was performed on a Philips EM208
microscope operated at a 100 kV accelerating voltage.
The hydrodynamic size of the nanoparticles was
determined by dynamic light scattering (DLS) using a
HORIBA‐LB550. UV‐vis absorption spectra were recorded
using a UV‐vis spectrophotometer (PerkinElmer, Lambda
25). The elements in the samples were probed by energy‐
dispersive X‐ray (EDX) spectroscopy accessory to the
Philips scanning electron microscopy (SEM). Thermogra-
vimetric analysis (TGA) was performed on a PerkinElmer
device manufactured by Thermal Sciences. Magnetic
.1 | Materials and physical
measurements
All reagents and solvents were purchased as reagent grade
from commercial suppliers and used without further
purification. Thin layer chromatography (TLC) analysis
was performed on Merck silica gel 60 F254. The Fourier
transform infrared (Shimadzu FT‐IR 8300) spectra of the
nanoparticles was used to characterize all the synthesized
particles at room temperature using KBr pellets over a
3 4 2 2
SCHEME 1 Preparation process of Fe O @SiO ‐TCT‐NH nanoparticles

4
of 16
ESMAEILPOUR ET AL.
3 4 2
SCHEME 2 Preparation process of Fe O @SiO ‐Dendrimer‐encapsulated Cu(Π)
properties of the samples were measured using a vibration
sample magnetometer (BHV‐55). The amount of copper
loading in the support materials was determined by ICP
analyzer (Varian, Vista‐pro). Melting points were
determined in open capillaries using a BUCHI 510
melting point apparatus and are uncorrected. The C, H,
N and S elemental analyses were carried out using a
Thermofinigan Flash EA‐1112 CHNSO rapid elemental
analyzer. Therefore, all the products were characterized
30 min under vigorous mechanical stirring. Then a
certain amount of hexamethylenetetramine (HMTA)
(1.0 mol/l) were added dropwise to the above mixture
until the pH was raised to 10 at which a black suspension
was formed. Then, this suspension was heated at 60 °C for
2 h with vigorous stirring. The black precipitates were
separated by an external magnetic bar, and the solvent
was easily removed. The resulting Fe O nanoparticles
3
4
were rinsed several times with ethanol and dried at
80 °C for 10 h.
1
13
by FT‐IR, H NMR and C NMR (Supporting Informa-
tion), and also by comparison with authentic samples.
2
.2.2 | Preparation of silica coated mag-
netic nanoparticles (Fe O @SiO MNPs)
3
4
2
2
2
.2 | General procedure
[
48]
According to the literature,
Fe O nanoparticles (0.5 g)
3 4
.2.1 | Preparation of Fe O magnetic NPs
3
4
were dispersed in a mixture of ethanol (50 ml), water
(5 mL), and tetraethoxysilane (TEOS) (0.20 ml).
Afterward, 5 ml NaOH (10 wt%) was added dropwise
and the reaction was allowed to proceed under stirring.
After stirring at room temperature for 30 min, the
Fe O @SiO particles were separated by magnetic field
Magnetic Fe O particles were synthesized based on a
modified
FeCl ·6H O (1.3 g, 4.8 mmol), FeCl ·4H O (0.9 g,
3
4
[
48]
co‐precipitation
method.
Typically,
3
2
2
2
4
.5 mmol) and polyvinyl alcohol (PVA (15000), 1.0 g)
were dissolved in 60 ml deionized water at 80 °C for
3
4
2

ESMAEILPOUR ET AL.
5 of 16
and washed with ethanol and water three times and dried
under vacuum at 80 °C for 10 h.
with deionized water and hot ethanol successively, and
finally dried for 4 h at 70 °C.
2
.2.3 | Preparation of Fe O @SiO func-
2.2.7 | Preparation process of dendritic
3
4
2
tionalized with (3‐chloropropyl)
trimethoxysilane (Fe O @SiO ‐Cl)
polymer functionalized Fe O @SiO nano-
3
4
2
particles (Fe O @SiO ‐dendrimer)
3
4
2
3
4
2
A suspension of the prepared Fe O @SiO NPs (1 g) in
In a 50 ml flask with a magnetic stirring bar, the obtained
Fe O @SiO ‐TCT‐NH nanoparticles (1.5 g) was
3
4
2
1
0 ml of ethanol was sonicated for 5 min. Then
3
4
2
2
(
3‐chloropropyl)trimethoxysilane (4 mmol, 0.7 ml) was
dispersed into 20 ml of THF. Then, TCT (12 mmol,
2.2 g) and DIPEA (12 mmol, 2.1 ml) were added to the
aforementioned mixture. The resulting mixture was
stirred at room temperature for 16 h. The functionalized
Fe O @SiO (Fe O @SiO ‐TCT ) was separated from the
added to the sonoreactor. This suspension was sonicated
again for 10 min and followed by stirring for 12 h under
reflux conditions. The precipitates of Fe O @SiO ‐Cl were
separated by an external magnetic bar and then
successively were washed with ethanol. Finally, the
collected Fe O @SiO ‐Cl nanoparticles were dried
3
4
2
3
4
2
3
4
2
2
reaction by an external magnet and washed with hot
THF in a Soxhlet apparatus and dried at 60 °C for 8 h.
Then the obtained Fe O @SiO ‐TCT (1.5 g) was reacted
3
4
2
overnight at 60 °C.
3
4
2
2
with bis(3‐aminopropyl)amine (24 mmol, 3 mL) and
DIPEA (24 mmol, 4.2 ml) in DMF (25 ml) under sonica-
tion for 5 min. The resulting mixture was stirred at
2
NPs
.2.4 | Preparation of Fe O @SiO ‐NH
3
4
2
2
8
0 °C for 10 h and then Fe O @SiO ‐dendrimer NPs were
3
4
2
Fe O @SiO ‐Cl NPs (1 g) were dispersed by ultrasonication
isolated by a magnet bar and washed with hot ethanol in a
3
4
2
in a solution containing dimethylformamide (10 ml),
bis(3‐aminopropyl)amine (4 mmol, 0.5 ml) and
triethylamine (4 mmol, 0.55 ml). The mixture was stirred
at 100 °C with continuous stirring for 12 h. Then, the
product precipitates were separated by an external
permanent magnet and washed several times using hot
ethanol. It was subsequently dried at 70 °C to obtain
Fe O @SiO ‐NH NPs.
Soxhlet apparatus and dried at 60 °C.
2
.2.8 | Preparation of Fe O @SiO ‐dendri-
3
4
2
mer‐encapsulated Cu(II) NPs
Fe O @SiO ‐Dendrimer (2 g) was added to a solution of
3
4
2
copper acetate (1.5 mmol, 0.27 g) in dry THF (30 ml).
The reaction mixture was refluxed with stirring for 4 h.
The resulting solid was separated by a magnet bar,
washed thoroughly with acetone and ethanol and dried
under vacuum at 50 °C for 6 h.
3
4
2
2
2
.2.5 | Preparation of Fe O @SiO ‐TCT
3
4
2
NPs
To a dispersion of Fe O @SiO ‐NH NPs (1 g) in THF
3
4
2
2
2
.3 | General procedure for the N‐
(15 mL) were added cyanuric chloride (TCT) (1.47 g,
arylation of N‐H heterocycles with aryl
halides (I, Br) using Fe O @SiO ‐
8
1
mmol) and diisopropylethylamine (DIPEA) (8 mmol,
.4 ml). The reaction mixture was mechanically stirred
3
4
2
dendrimer‐encapsulated Cu(II) NPs as a
for 14 h at room temperature. Fe O @SiO ‐TCT NPs
3
4
2
catalyst
was collected by a magnetic bar and was repeatedly
washed with hot THF in a Soxhlet apparatus to remove
the unreacted starting materials and then dried at
A mixture of aryl halide (I, Br) (1 mmol), amine
(1.2 mmol), Cs CO (2 mmol), Fe O @SiO ‐dendrimer‐
2
3
3
4
2
7
0 °C for 6 h.
encapsulated Cu(II) (0.01 g, 0.5 mol%) in DMF (3 ml)
was heated at 110 °C with magnetic stirring and the
progress of the reaction was monitored by TLC. After
completion of the reaction and separation of the catalyst
by a magnetic bar, water (15 ml) was added to the mixture
and extracted with ethyl acetate (2×15 ml). The organic
layer was washed by H O, dried over Na SO and
evaporated under reduced pressure. The residue was
purified by short column chromatography on silica gel
to afford the corresponding coupling products in up to
95% yield.
2
.2.6 | Preparation of Fe O @SiO ‐TCT‐
3
4
2
NH NPs
2
Bis(3‐aminopropyl)amine (16 mmol, 2.0 mL) and DIPEA
16 mmol, 2.8 ml) were added into the dispersion of
Fe O @SiO ‐TCT NPs (1 g) in DMF (20 mL).Then, the
(
2
2
4
3
4
2
dispersed mixture was ultrasonicated for 10 min and
stirred at 80 °C for 12 h. The resulting Fe O @SiO ‐
TCT‐NH NPs was separated with a magnet and washed
3
4
2
2

6
of 16
ESMAEILPOUR ET AL.
2
.4 | General procedure for the N‐
arylation of N‐H heterocycles with
arylboronic acids catalyzed by Fe O @SiO ‐
3
4
2
dendrimer‐encapsulated Cu(II) NPs
In an oven dried 10 ml round‐bottom flask, Fe O @SiO ‐
3
4
2
dendrimer‐encapsulated Cu(II) catalyst (0.01 g, 0.5 mol%),
arylboronic acid (1.2 mmol), N‐H heterocycles (1 mmol),
and 4 ml methanol were stirred under reflux conditions.
After the completion of the reaction as monitored by
TLC, the catalyst was separated by a magnet and washed
with methanol. The solvent was evaporated under
reduced pressure and followed by a conventional work
up (as mentioned in the preceding section). The organic
layer was separated, dried over anhydrous Na SO and
2
4
concentrated to get the crude product. Then, the crude
product was purified by column chromatography on silica
gel using mixture of hexane and ethyl acetate (7:3) as
eluent to provide the desired product. Finally they were
1
13
characterized by H NMR,
Supporting information), and also by comparison of their
physical and spectral data.
C NMR and FT‐IR
(
2
.5 | General process for preparation of 5‐
substituted 1H‐tetrazoles catalyzed by
Fe O @SiO ‐dendrimer‐encapsulated
Cu(II) NPs
3
4
2
A mixture of aldehyde (1.0 mmol), sodium azide
1.5 mmol), hydroxylamine hydrochloride (1.5 mmol),
Fe O @SiO ‐dendrimer‐encapsulated Cu(II) (0.008 g,
(
3
4
2
0
.4 mol%) and water (3 ml) was taken in a round‐bottomed
flask and stirred at 70 °C. The progress of the reaction was
monitored by TLC. After completion of the reaction, the
reaction mixture was diluted with ethyl acetate (15 ml)
and the catalyst was separated by an external magnet.
The filtrate was washed with HCl (4 N, 10 ml), dried over
anhydrous Na SO , and concentrated to give the crude
FIGURE
1
FTIR spectra of (a) Fe
3
O
4
,
(b) Fe
@SiO
‐Dendrimer‐
3
O
4
@SiO
2
,
(
c) Fe
f) Fe
3
O
4
@SiO
@SiO
2
‐Cl, (d) Fe
‐TCT‐NH
3
O
4
@SiO
2
‐NH
2
, (e) Fe
3
O
4
2
‐TCT,
(
3
O
4
2
2
and (g) Fe
3
O
4
@SiO
2
2
4
encapsulated Cu(II)
solid product. The crude product was further purified by
silica gel column chromatography using appropriate
solvent mixtures (hexane‐EtOAc, 1:1) to obtain the pure
products. All of desirable products were characterized by
H NMR, CNMR and FT‐IR spectroscopy. Spectra data
for all compounds are provided in Supporting Information.
the O‐H stretching and deforming vibrations of adsorbed
[
49]
water, respectively.
absorption centered around 570 cm , corresponding to
the Fe‐O vibration, is related to the magnetite phase.
The analysis indicated that the
‐1
1
13
[48]
‐
1
The presence of peaks centered at 1110 and 809 cm are
most probably due to the asymmetric and symmetric
stretching vibration of framework and terminal Si‐O
groups. The presence of 3‐chloropropyl trimethoxysilane
on the nanoparticle surface was confirmed by the
absorbance peaks at 702 (C‐Cl stretching), 1444 (CH2
bending) and 2954 (C‐H stretching) (Figure 1c).
3
| RESULTS AND DISCUSSIONS
The FTIR spectra of (a) naked Fe O , (b) Fe O @SiO , (c)
Fe O @SiO ‐Cl, (d) Fe O @SiO ‐NH , (e) Fe O @SiO ‐
TCT, (f) Fe O @SiO ‐TCT‐NH and (g) Fe O @SiO ‐Den-
3
4
3
4
2
3
4
2
3
4
2
2
3
4
2
3
4
2
2
3
4
2
drimer‐Cu(II) MNPs are presented in Figure 1. The bands
centered around 3400 cm and 1620 cm are assigned to
Characteristic bands of the N‐H at 3247 and 3278
(stretching vibration) and 1554 cm (bending vibrations)
‐
1
‐1
‐1

ESMAEILPOUR ET AL.
7 of 16
and also the saturated C‐H stretching vibrations at 2777‐
‐1
2
985 cm demonstrate the successful modification of the
Fe O @SiO ‐Cl nanoparticles. In addition, the absorption
3
4
2
peak related to C‐Cl disappeared after Fe O @SiO ‐NH
3
4
2
2
formation (see Figure 1d). Comparison of the spectrum of
Fe O @SiO ‐NH with Fe O @SiO ‐TCT composite
3
4
2
2
3
4
2
nanoparticles shows characteristic absorption bands at
‐
1
5
74, 1103 and 2754‐2962 cm and also adsorption peaks
‐
1
of cyanuric chloride at 1513, 1543 and 1724 cm .This
indicates that cyanuric chloride moieties are supported
[50]
on Fe O @SiO ‐NH nanoparticles (Figure 1e).
From
3
4
2
2
the IR spectra presented in Figure 1f and g, the absorption
peaks at 570‐580 cm‐ related to the stretching vibration
mode of Fe‐O bonds in Fe O , the absorption peak
1
3
4
‐1
appeared at 1100 cm is due to stretching vibration of the
framework and the terminal Si‐O‐ groups. Also, the
presence of vibration bands in 1220‐1270 (C‐N stretching),
1
2
500‐1700 (skeletal vibration of the cyanuric ring moiety),
880‐3060 (C‐H stretching) and 3200‐3600 (O‐H
stretching) demonstrated the existence of Fe O @SiO ‐
3
4
2
TCT‐NH and Fe O @SiO ‐dendrimer‐Cu(II) nanoparti-
2
3
4
2
cles in the spectrum (Figure 1f and g). Also, it was not pos-
sible to assign the N‐H band in the FT‐IR spectrum which
is due to the interference from the core‐shell O‐H band.
The XRD patterns for Fe O , Fe O @SiO and
FIGURE
2
XRD patterns of Fe
3
O
4
,
Fe
3
O
4
@SiO
2
and
3
4
3
4
2
Fe O @SiO ‐dendrimer‐encapsulated Cu(II) nanoparticles
3
4
2
Fe O @SiO ‐dendrimer‐Cu(II) nanoparticles exhibited
3
4
2
the similar pattern with respect to MNPs as shown in
dispersed, nearly spherical in shape (Figure 3b) and had
an average diameter of 20 nm (Figure 3e). The dark area
in the core of individual particles is Fe O and the outer
Figure 2. All diffraction peaks at 2ϴ¼ 30.1°, 35.4°, 43.1°,
5
3.4°, 57.0° and 62.6° for Fe O @SiO and Fe O @SiO ‐
3
4
2
3
4
2
3 4
dendrimer‐Cu(II) nanoparticles were also observed,
grey area is SiO with 8 nm thickness (Figure 3e). After
2
which are in agreement with the XRD peaks of pure
successive coating with dendritic polymer, as it is evident
from SEM and TEM Figures 3 (c and f), these composites
still maintained their spherical shape with an average
diameter of approximate 45 nm. DLS analysis showed
the particle size distribution of Fe O , Fe O @SiO and
[51]
Fe O4 nanoparticles.
These peaks corresponded to
220), (311), (400), (422), (511) and (440) reflection of
Fe O , respectively, indicating that the Fe O @SiO and
3
(
3
4
3
4
2
Fe O @SiO ‐dendrimer‐Cu(II) nanoparticles did not
3
4
2
3
4
3
4
2
result in the crystallinity change of Fe O nanospheres
Fe O @SiO ‐dendrimer‐Cu(II) NPs is centered at 12, 20,
and 51 nm, respectively (Figure 3 g‐i).
3
4
3
4
2
[52]
(cubic spinel structure, JCPDS card no. 19‐0629).
The
relative intensity of the peaks, which reflecting the
magnetite phase, decreased with silica layers and then
dendrimer molecules. Furthermore, a broad band near
The UV‐vis spectra of Fe O , Cu(OAc)2 and
3
4
Fe O @SiO ‐dendrimer‐Cu(II) is shown in Figure 4A.
3
4
2
For Fe O @SiO ‐dendrimer‐Cu(II) nanoparticles two
3
4
2
1
0‐25° (2θ) was observed when the magnetite nanoparti-
bands are present at 286 nm and around 360 nm that is
2+
[53]
cles were coated with SiO , demonstrating the existence
assigned to the presence of Cu species.
Furthermore,
2
of amorphous silica shell (Figure 2b,c). For Fe O @SiO ‐
the UV‐vis spectra of the Fe O @SiO ‐dendrimer‐Cu(II)
3
4
2
3
4
2
dendrimer‐Cu(II) nanoparticles, the broad peak was
nanoparticles exhibited a band as a shoulder around
600 nm assigned to B → B transition.
1g 2g
2
2
[54]
transferred to lower angles due to the synergetic effect of
[
52]
the amorphous silica and the dendrimer polymer.
The elemental composition of the Fe O @SiO ‐den-
3
4
2
FE‐SEM, TEM and DLS of the synthesized nanoparti-
cles are presented in Figure 3. As it is clear from the
drimer‐Cu(II) nanoparticles was determined by EDX
analysis for C, N, O, Fe, Si and Cu as shown in Figure 4B.
Figure 4C shows the TGA result of the nanoparticles. The
weight loss at temperatures below 150 °C could be attrib-
uted to water desorption from the surface of the sam-
presented picture, the spherical nanoparticles of Fe O4
3
are well dispersed with an average diameter of 10 nm
(
Figure 3d). FE‐SEM and TEM images of the Fe O @SiO
3
4
2
[
55]
NPs are also shown in Figure 3b and e. It was apparent
ples.
The TGA curves of nanoparticles show a weight
that the synthesized Fe O @SiO nanoparticles were well
loss from 150 to 600 °C, resulting from the decomposition
3
4
2

8
of 16
ESMAEILPOUR ET AL.
FIGURE 3 FE‐SEM images of a) Fe
3
O
4
, b) Fe
3
O
4
@SiO
2
, and c) Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II); TEM images of d) Fe
, h) Fe @SiO and i) Fe @SiO ‐dendrimer‐
3 4
O , e)
Fe @SiO , f) Fe @SiO ‐dendrimer‐Cu(II) and the size distributions of g) Fe
3
O
4
2
3
O
4
2
3
O
4
3
O
4
2
3
O
4
2
encapsulated Cu(II), respectively
of organic compounds grafted to the Fe O @SiO surface.
Figure 4E shows photograph of the response of the
3
4
2
As shown in Figure 4Ce, the TGA curve of Fe O @SiO ‐
Fe O @SiO ‐dendrimer‐Cu(II) under an external
3
4
2
3
4
2
dendrimer‐Cu(II) shows an initial weight loss of 7.1 %
below 150 °C, which might be due to the loss of adsorbed
water. The mass loss of about 38.7 % in the range of 150‐
magnetic force. The dispersed magnetic nanoparticles
could go straight towards the magnet and adhere to the
side wall of vials when the external magnetic field is
applied. These imply that the magnetic nanoparticles
could be isolated from the matrix conveniently by using
an external magnet when necessary. The amount of Cu
in Fe O @SiO ‐dendrimer‐Cu(II) has been also
7
00 °C is attributed to decomposition of the dendritic
polymer and organic volatile compounds, and the
maximum weight loss is occurred at 670 °C. On the basis
of these results, grafting of the dendritic polymer onto the
Fe O @SiO is verified.
3
4
2
determined by inductively coupled plasma (ICP) which
3
4
2
The hysteresis loops are presented in Figure 4D.
is 0.51 mmol/g.
There is no hysteresis in the magnetization for the three
tested nanoparticles. Neither coercivity nor remanence is
observed, suggesting that the three nanoparticles are
superparamagnetic and pure Fe O , Fe O @SiO , and
To explore the catalytic properties of Fe O @SiO ‐
3
4
2
dendrimer‐Cu(II), the N‐arylation reaction of nitrogen
heterocycles with aryl halides (I, Br) was conducted in
the presence of this dendrimeric composite (Scheme 3).
For optimization of the reaction conditions, the
reaction of iodobenzene with imidazole in the presence
of the Fe O @SiO ‐dendrimer‐Cu(II) nanoparticles as
3
4
3
4
2
Fe O @SiO ‐dendrimer‐Cu(II)
nanoparticles,
magnetization saturation (Ms) values of 64.8, 40.3, and
7.2 emu/g, respectively. This can easily be explained
that Fe O nanoparticles are covered by SiO moieties
have
3
4
2
2
3
4
2
the model reaction was studied with respect to the effect
of solvents, the amount of the catalyst, bases and the
temperature. As it is evident from the data tabulated in
Table 1, the solvent played a very crucial role in the
N‐arylation reaction. Low yields of the coupled products
3
4
2
and dendrimeric species which affect the paramagnetic
[56]
properties Fe O4 nanoparticles.
Anyhow, the
3
Fe O @SiO ‐dendrimer‐Cu(II) particles could be
3
4
2
magnetically concentrated and readily picked up using
a small magnet.
were obtained in H O, EtOH and MeOH (Table 1,
2

ESMAEILPOUR ET AL.
9 of 16
FIGURE 4 (A) UV‐Vis spectra of Cu(OAc)
2
, Fe
3
O
4
and Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II); (B) EDX spectra of Fe
@SiO ‐Cl, (b) Fe @SiO ‐NH , (c) Fe @SiO ‐TCT, (d)
‐dendrimer; (D) Magnetization curves for (a) Fe , (b) Fe @SiO and (c) Fe @SiO ‐dendrimer‐
encapsulated Cu(II) nanoparticles; (E) Composite ability for effective recovery from a solution by an external magnetic field
3 4 2
O @SiO ‐
dendrimer‐encapsulated Cu(II); (C) Thermogravimetric analysis of (a) Fe
Fe @SiO ‐TCT‐NH and Fe @SiO
3
O
4
2
3
O
4
2
2
3
O
4
2
3
O
4
2
2
3
O
4
2
3
O
4
3
O
4
2
3
O
4
2
reaction (Table 1, entries 11 and 12) and employing
higher amounts of it did not show any substantial
improvement in the yield of reaction (Table 1, entries 12
and 13). The model reaction was also examined in the
absence of the catalyst in DMF at 140 °C and the reaction
did not proceed at all even after 840 min (Table 1, entry
1
0). It was found that the coupling reaction was highly
dependent on the nature of the base (Table 1, entries 1,
5‐18). Among the bases screened, Cs CO gave the best
1
2
3
SCHEME
3
3 4 2
Using the Fe O @SiO ‐dendrimer‐encapsulated
result and the corresponding coupled product, 1‐phenyl‐
H‐imidazole, was obtained in 93% yield (Table 1, entry 1).
Cu(II) nanoparticles in N‐arylation of nitrogen heterocycles with
aryl halides (I, Br) and arylboronic acids, and synthesis of 5‐
substituted 1H‐tetrazole derivatives
1
Also, the effect of temperature was studied by carrying out
the model reaction at different temperatures. The best
°
entries 5‐7), and moderate to good yields were obtained in
result was obtained at 110 C (Table 1, entry 1) and using
DMSO, DME, NMP, MeCN and toluene (Table 1, entries
higher temperature than that did not show any enhance-
ment in the efficiency of reaction (Table 1, entry 22).
Therefore, the optimum conditions were found to be
1.0 mmol of aryl halide, 1.2 mmol of nitrogen heterocy-
cles, 0.5 mol% of Fe O @SiO ‐dendrimer‐encapsulated
2‐4, 8,9). When DMF served as solvent, and cesium
carbonate as base, a quantitative yield of the product
was isolated (Table 1, entry 1). Then, the model reaction
was examined in the presence of various amounts of the
catalyst (Table 1, entries 1, 11‐14). As presented in
Table 1, the best result was obtained when the model
reaction was carried out in the presence of 0.5 mol% of
the catalyst (Table 1, entry 1). Using lower amounts of
3
4
2
Cu(II) nanoparticles and 2.0 mmol of Cs CO in DMF
2
3
(3 ml) at 110 °C.
Our method was successfully amenable to a wide range
of aryl halides, allowing preparation of N‐arylheterocycles
in high yields, and the results are shown in Table 2. It was
0
.5 mol% of the catalyst decreased the efficiency of the

10 of 16
ESMAEILPOUR ET AL.
a
TABLE 1 Optimization of reaction conditions for the N‐arylation of imidazole with iodobenzene
Entry
Catalyst amount (mol%)
Solvent
Base
Temp. (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
None
0.25
0.4
0.6
0.75
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
DMF
DMSO
DME
NMP
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
2
2
2
2
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
110
4
96
81
57
78
Trace
18
13
51
87
0
110
7
Reflux
110
10
6
H
2
O
Reflux
Reflux
Reflux
Reflux
Reflux
140
14
12
14
9
EtOH
MeOH
MeCN
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
6
1
1
1
1
1
1
1
1
1
1
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
14
8
130
52
84
91
90
41
55
37
82
16
52
86
92
110
5
110
4
110
4
NaOH
PO
NaOAc
CO
110
12
12
12
12
10
8
K
3
4
110
110
K
2
3
110
Cs
2
Cs
2
Cs
2
Cs
2
CO
CO
CO
CO
3
rt
3
80
3
100
5
3
120
4
a
Reaction conditions: iodobenzene (1 mmol), imidazole (1.2 mmol), base (2 mmol), Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II) catalyst and solvent (3 ml).
observed that aryl halides with electron‐withdrawing
groups (Table 2, 3c, 3f, 3j,3 l, 3q and 3r) reacted at a shorter
time and afforded higher yields than aryl halides with
electron‐donating groups (Table 2, entries 3b,3e,3i and
wide range of arylboronic acids, allowing preparation of
N‐arylimidazoles in methanol without using any base
under reflux conditions in excellent yield, and the results
are shown in Table 3. We found that arylboronic acids con-
taining electron releasing groups as well as electron‐
withdrawing groups reacted with imidazole to give the
corresponding N‐arylated imidazoles. It was observed that
arylboronic acids with electron‐donating substitutions
(Table 3, 5b‐e) reacted at short time and afforded better
yields than arylboronic acids with electron‐withdrawing
substitutions (Table 3, 5f‐5i). Although similar results were
obtained when benzimidazole and pyrrazole were used in
place of imidazole (Table 3, 5j‐l), but the reactions took
longer time in compare to the reactions of imidazoles.
In order to evaluate the efficiency of the Fe O @SiO ‐
3
p). As expected, aryl iodides provided good yields in a
shorter time than aryl bromides. The N‐arylation of
imidazole could be smoothly carried out using various
aryl iodides (Table 2, 3a‐c). To test the scope of this
catalyst, a variety of the other nitrogen containing hetero-
cycles, such as indole, 2‐methyl‐indole, benzimidazole,
1‐phenylpiperazine, piperazine and pyrrole were success-
fully coupled with aryl halides to give the corresponding
N‐arylated products in good yields (Table 2, 3d‐n). When
piperazine, as an alicyclic diamine, was employed to react
with 2 mmol of phenyl iodide, the reaction was completed
within 5 h and provided 84% yield of the N,N’‐diarylated of
piperazine (Table 2, 3 m). N‐Arylation of N(H)‐heterocy-
cles using arylboronic acids as an alternative of aryl halides
was occurred under mild reaction conditions in shorter
reaction times. The method was successfully applied to a
3
4
2
dendrimer‐Cu(II) catalyst, the present catalytic system
was compared with some other catalysts, which have
been reported previously in the literature for N‐arylation
of imidazole. The gathered data in Table 4 showed that
this new proposed catalyst performs in shorter reaction

ESMAEILPOUR ET AL.
11 of 16
a,c
3 4 2
TABLE 2 Fe O @SiO ‐dendrimer‐encapsulated Cu(II)‐catalyzed amination of N(H)‐heterocycles with various aryl halides
X=I, 3a: 4 h, 96%
X=I, 3e: 6 h,
X=I, 3b: 7 h,
X=I, 3f: 5 h,
X=I, 3c: 3 h,
X=I, 3d: 5 h, 92%
X=I, 3 h: 5 h, 94%
8
9%
94%
X=I, 3 g: 6 h, 87%
X=I, 3 k:
8
8%
2%
91%
X=I, 3 l:
X=I, 3i: 8 h,
X=I, 3j: 4 h,
6
h, 86%
4.5 h, 89%
9
93%
b
X=I, 3m :
X=I, 3n: 5.5 h,
X=Br, 3r:
X=Br, 3o: 9 h, 89%
X=Br, 3 s: 10 h,
X=Br, 3p: 10 h,
5
h, 84%
93%
85%
X=Br, 3q: 8 h, 91%
X=Br, 3 t: 10 h, 84%
7
h, 92%
87%
a
Reaction conditions: aryl halide (1 mmol), N‐H heterocycle (1.2 mmol), Cs
2
CO
3
(2 mmol), and Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II) (0.5 mol%) in DMF
b
(
3 ml), at 110 °C. Reaction conditions: aryl halide (2 mmol), N‐H heterocycle (1.2 mmol), Cs
2
CO
3
(3.5 mmol), and Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II)
c
(
0.75 mol%) in DMF (5 ml), at 110 °C. Isolated yield.
a
3 4 2
TABLE 3 Using Fe O @SiO ‐dendrimer‐encapsulated Cu(II) in N‐arylation of N(H)‐heterocycles with various arylboronic acids
5
a: 1.5 h, 95%
5b: 2 h, 93%
5f: 5 h, 86%
5d: 2 h, 92%
5
c: 3 h, 85%
5
g: 4 h, 84%
5 h: 6 h, 80%
5
e: 3 h, 88%
5
i: 4 h, 83%
5 l: 4 h, 86%
5j: 3 h, 92%
5 k: 3 h, 93%
a
3 4 2
Reaction conditions: N(H)‐heterocycle (1 mmol), arylboronic acid (1.2 mmol), Fe O @SiO ‐dendrimer‐encapsulated.
b
Cu(II) (0.5 mol%) MeOH (4 ml), reflux. Isolated yield.
time with using much lower amount of copper and
produces the desired product 6a in excellent yield. The
other features of this magnetic catalyst are its thermal
stability and easy separation, which can be happened by
an external magnetic field.
For this purpose, the effect of solvents, the amounts of the
catalyst and the temperature was studied. According to the
results tabulated in Table 5, the optimized reaction condi-
tion was revealed to be: 1 mmol of aldehyde, 1.5 mmol of
hydroxylamine hydrochloride, 1.5 mmol of sodium azide,
Fe O @SiO ‐Dendrimer‐Cu(II) has been also success-
0.4 mol% of the catalyst in 3 ml of H O at 70 °C (Table 5,
3
4
2
2
fully applied for a one‐pot three‐ component syntheses of
aryl‐1H‐tetrazoles. In order to find the optimized condi-
tions, the reaction of benzaldehyde, hydroxylamine hydro-
chloride and sodium azide was studied as a model reaction.
entry 5).
Then the optimized condition was applied for the
production of different aryl‐1H‐tetrazoles using different
aldehydes. Although, in all cases, aromatic aldehydes

12 of 16
ESMAEILPOUR ET AL.
TABLE 4 Comparison of catalytic activity of Fe
imidazole with iodobenzene
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II) with some reported catalysts for N‐arylation of
a
Entry
Catalyst
Conditions
Time (h)
Yield (%)
Ref
[
[
[
[
[
[
[
[
[
[
[
57]
58]
59]
60]
61]
62]
63]
64]
65]
66]
67]
1
2
3
4
5
6
7
8
9
CuFAP (12.5 mol%)
DMSO, K
Toluene, Cs
DMSO, K CO
CH CN, Cs CO
DMF, K CO , 120 °C
2
CO
CO
, 130 °C
, 80 °C
3
, 110 °C
6
92
92
95
92
99
90
91
98
95
99
98
96
Silica immobilized copper catalyst (5 mol%)
Cellulose supported copper(0) (1.84 mol%)
PANI‐Cu (2.5 mol%)
2
3
, 100 °C
8
2
3
12
12
24
24
24
10
5
3
2
3
Cu‐Y zeolite (10.8 mol%)
2
3
Cu
2
O (10 mol%)
DMSO, KOH, 110 °C,
DMSO, KOH, 110 °C
Nano‐CuO (2.5 mol%)
Metformin (10 mol %)/CuI (5 mol %)
DMF, Cs
DMSO, K
DMF, K CO
2
CO
CO
, 130 °C/Ar
3
, 110 °C
[Cu
Cu(OAc)
CuI/MNP‐3 (10 mol%)
Fe @SiO ‐dendrimer‐encapsulated Cu(II) (0.5 mol%)
2
I
2
((‐)‐sparteine)
2
] (5 mol%)
2
3
, 115 °C
1
1
1
0
1
2
2
2
.H O (15 mol%)/8‐hydroxyquinoline
2
3
24
24
4
DMF, Cs
DMF, Cs
2
2
CO
3
3
, 110 °C
, 110 °C
3
O
4
2
CO
This work
TABLE 5 Synthesis of 5‐phenyl‐1H‐tetrazole in the presence of different amounts of the catalyst in various solvents at different
a
temperatures
b
Entry
Catalyst amount (mol%)
Solvent
Temp. (°C)
Time(h)
Yield (%)
1
2
3
4
5
6
7
8
9
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
None
0.25
0.5
0.4
0.4
0.4
DMSO
DMF
100
3
74
92
42
37
95
24
45
81
Trace
77
94
62
87
94
100
1
EtOH
MeOH
Reflux
Reflux
70
3
3
H
2
O
0.75
12
12
5
THF
Reflux
Reflux
120
Toluene
Solvent‐free
H
2
H
2
H
2
H
2
H
2
H
2
O
O
O
O
O
O
Reflux
70
14
6
1
1
1
1
1
0
1
2
3
4
70
2
rt
2
50
1
80
1
a
3 3 4 2
Reaction conditions: benzaldehyde (1 mmol), NaN (1.5 mmol), hydroxylamine hydrochloride (1.5 mmol), Fe O @SiO ‐dendrimer‐encapsulated Cu(Π) catalyst
b
(
0.4mol%) and solvent (3 ml). Isolated yield.
bearing both electron withdrawing and electron donating
substituents underwent the reaction and gave the title
products in excellent isolated yields (Table 6, entries 2‐14)
but the aldehydes with electron donating substituents
required longer reaction time (Table 6, entries 10‐14, 20)
because of less electrophile character of their carbonyl
group. Time and yield of the reaction were also affected
by steric effect. For example, 2‐cyanobenzaldehyde
produced the corresponding tetrazole in lower yield after
longer time in compare to 4‐cyanobenzaldehyde (Table 6,
entries 4 and 5). Also 9‐anthracenecarboxaldehyde and
9‐phenanthrenecarboxaldehyde, which suffer from
sever steric hindrance, carried out the reaction and pro-
vided 81% and 86% yield of the related 5‐substituted

ESMAEILPOUR ET AL.
13 of 16
a
TABLE 6 Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II)‐catalyzed synthesis of 5‐substituted 1H‐tetrazoles
b
Entry
Ar
Product
Time (min)
Yield (%)
M.p. (lit.) (°C)
[
68]
1
2
3
4
5
6
7
8
9
C
6
H
5
9a
9b
9c
45
50
45
60
70
40
30
30
60
60
70
50
80
120
45
75
90
120
100
60
75
95
94
90
94
85
93
96
94
87
89
91
87
92
90
93
91
84
86
81
85
83
213‐214 (214‐216)
[
69]
4‐Br‐C
4‐Cl‐C
6
H
4
266‐267 (265)
[
[
[
[
[
[
[
[
[
[
[
40]
48]
70]
71]
52]
72]
52]
52]
48]
71]
48]
6
H
4
260‐262 (261‐263)
253‐255 (254‐256)
207‐208 (208‐210)
157‐158 (155‐157)
215‐216 (217‐218)
180‐181 (178‐179)
231‐233 (230‐231)
249‐251 (249‐250)
232‐233 (233‐234)
211‐212 (213‐215)
204‐206 (206‐207)
4‐CN‐C
2‐CN‐C
6
6
H
4
9d
9e
H
4
3‐NO
2
2
‐C
‐C
6
6
H
4
9f
4‐NO
H
4
9 g
9 h
9i
3,5‐(NO
4‐MeO‐C
4‐Me‐C
4‐HO‐C
3,4‐(OH)
3,5‐(MeO)
2
)
2
‐C
6 3
H
6
H
4
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
6
H
4
9j
6
H
4
9 k
9 l
9 m
9n
9o
9p
9q
9r
2
‐C
‐C
‐C
6
H
3
2
6
H
3
[
48]
3,4,5‐(MeO)
3
6
H
2
201‐203 (201)
[
[
[
40]
71]
71]
2‐Pyridyl
208‐210 (210‐211)
203‐204 (205‐207)
159‐160 (161‐163)
2‐Naphthalene
3‐indole
[
52]
9‐Phenanthrenyl
9‐Anthracene
214‐215 (216)
[
71]
9 s
9 t
9u
150‐152 (148‐150)
[
40]
C
6
H
5
CH
2
‐
122‐124 (123)
100‐101 (98‐100)
[
70]
3‐phenyl‐propion‐
a
Reaction conditions: aldehyde (1.0 mmol), NaN
3
(1.5 mmol), hydroxylamine hydrochloride (1.5 mmol) and Fe
3 4 2
O @SiO ‐dendrimer‐encapsulated Cu(II) (0.4
b
mol%) in H
2
O (3 ml) at 70°C. Yields of isolated products.
SCHEME 4 Plausible mechanism for
N‐arylation of nitrogen heterocycles and
synthesis of 5‐substituted 1H‐tetrazoles

14 of 16
ESMAEILPOUR ET AL.
FIGURE 5 (A) Recyclability of Fe
3
O
4
@SiO
2
‐dendrimer‐encapsulated Cu(II) in the synthesis of 5‐phenyl‐1H‐tetrazole (6a) and in the
synthesis of 1‐phenyl‐1H‐imidazole (3a); (B) SEM and (C) DLS images of Fe
cycles. (a) Reaction conditions: benzaldehyde (1.0 mmol), NaN (1.5 mmol), hydroxylamine hydrochloride (1.5 mmol) and Fe
dendrimer‐encapsulated Cu(II) (0.4 mol%) in H O (3 ml) at 70 °C(b) Reaction conditions: iodobenzene (1 mmol), imidazole (1.2 mmol),
Cs CO (2 mmol), and Fe @SiO ‐dendrimer‐encapsulated Cu(II) (0.5 mol%) in DMF (3 ml), at 110 °C.
3
O
4
@SiO
2
‐dendrimer‐Cu(II) nanoparticles after seven reaction
3
3
O
4
2
@SiO ‐
2
2
3
3
O
4
2
tetrazoles after 100 and 120 min, respectively (Table 6,
entries 18 and 19). This catalytic system worked
also well for heteroaromatic aldehydes, such as 2‐
by addition of the N‐heterocyclic compound leads to the
formation of the intermediate (B). Then, the C‐N bond
product is formed by reductive elimination from (C)
and the initial Cu(I) species are regenerated. Finally,
Cu(I) formed in the process is reoxidized to Cu(II) in
the presence of air, and this forms a comfortable catalytic
pyridinecarboxaldehye
and
3‐indolecarboxaldehyde
(Table 6, entries 15 and 17). Aliphatic aldehydes, such as
2‐phenylacetaldehyde and 3‐phenylpropanal, performed
[
75]
the tetrazole formation smoothly and produced the desired
product in high yields (Table 6, entries 20, 21). These
results demonstrated the superior properties of
Fe O @SiO ‐dendrimer‐Cu(II) as novel heterogeneous
cycle.
Moreover, the plausible mechanism for the
catalytic activity of dendrimer‐encapsulated Cu(Π)
immobilized on Fe O @SiO NPs for the formation of
3
4
2
5‐substituted 1H‐tetrazoles is proposed as shown in
Scheme 4(b). First, the activation of the carbonyl group
of the aldehyde and the nucleophilic attack of the nitro-
gen atom of hydroxylamine to it, oxime is formed. After-
ward, Cu(OAc)2 activates the C¼N bond by co‐
coordinating with oxygen atom of oxime. This may facil-
itate the [3+2] cycloaddition between the C¼N bond of
3
4
2
catalysts for the synthesis of tetrazoles by [3+2] cycloaddi-
tion from oximes and sodium azide.
We propose a mechanism of the copper catalyzed
Ullmann type C‐N coupling reaction as shown in
[73,74]
Scheme 4(a).
Firstly, Cu(I) was generated in situ
from Fe O @SiO ‐dendrimer‐encapsulated Cu(II) under
3
4
2
reaction conditions. Then, oxidative addition of the aryl
oxime and NaN , and finally water elimination gives
3
halide generates a transient Cu(III) species (A), followed
the 5‐substituted 1H‐tetrazole product.

ESMAEILPOUR ET AL.
15 of 16
Recycling of catalysts in reactions is an important issue
from green chemistry point of views. Therefore, we paid
attention to this issue and studied the recycling of
Fe O @SiO ‐dendrimer‐encapsulated Cu(II) nanoparti-
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3
4
2
cles in the preparation of 1‐phenyl‐1H‐imidazole (3a) and
‐phenyl‐1H‐tetrazole (9a) (Figure 5A). The catalyst was
2
5
separated from the both reaction mixtures by a magnetic
bar and washed with ethanol and ethyl acetate. After dry-
ing the catalyst at 70 °C, it was reused in the next run. The
recycling was performed for seven times in the both reac-
tions without appreciable loss of its activity (Figure 5).
SEM and DLS images of the catalyst after seven
recycling in the synthesis of compound 3a and 9a under
optimized conditions are presented in Figure 5B, C. The
SEM image of the catalyst did not show significant
changes in the morphology of the surface of the catalyst
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(Figure 5B), this morphology preservation may be the
cause of the catalytic activity after recycling. Addition-
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larger than the size of fresh prepared the catalyst and
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The leaching of the catalyst into the reaction mixture
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iodobenzene was studied by hot filtration technique.
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reaction conditions. Work up of the resulting mixture
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Fe O @SiO ‐dendrimer‐encapsulated Cu(II) nanoparti-
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ICP analysis of the reaction mixture after seventh runs
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Iran and Shiraz University research council for financial
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SUPPORTING INFORMATION
2
Additional Supporting Information may be found online
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How to cite this article: Esmaeilpour M,
Sardarian AR, Firouzabadi H. Dendrimer‐
encapsulated Cu(Π) nanoparticles immobilized on
superparamagnetic Fe O @SiO nanoparticles as a
novel recyclable catalyst for N‐arylation of nitrogen
heterocycles and green synthesis of 5‐substituted
51] M. Esmaeilpour, A. R. Sardarian, A. Jarrahpour, E. Ebrahimi, J.
Javidi, RSC Adv. 2016, 6, 43376.
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54] D. N. Sathyanarayana, Electronic Absorption Spectroscopy and
Related Techniques, Universities Press India Limited 2001.
https://doi.org/10.1002/aoc.4300