Functionalization of superparamagnetic Fe3O4@SiO2 nanoparticles with a Cu(II) binuclear Schiff base complex as an efficient and reusable nanomagnetic catalyst for N-arylation of α-amino acids and nitrogen-containing heterocycles with aryl halides

Article abstract of DOI:10.1002/aoc.6051

Fe₃O₄@SiO₂ nanoparticles was functionalized with a binuclear Schiff base Cu(II)-complex (Fe₃O₄@SiO₂/Schiff base-Cu(II) NPs) and used as an effective magnetic hetereogeneous nanocatalyst for the N-arylation of α-amino acids and nitrogen-containig heterocycles. The catalyst, Fe₃O₄@SiO₂/Schiff base-Cu(II) NPs, was characterized by Fourier transform infrared (FTIR) and ultraviolet-visible (UV-vis) analyses step by step. Size, morphology, and size distribution of the nanocatalyst were studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scatterings (DLS) analyses, respectively. The structure of Fe₃O₄ nanoparticles was checked by X-ray diffraction (XRD) technique. Furthermore, the magnetic properties of the nanocatalyst were investigated by vibrating sample magnetometer (VSM) analysis. Loading content as well as leaching amounts of copper supported by the catalyst was measured by inductive coupled plasma (ICP) analysis. Also, thermal studies of the nanocatalyst was studied by thermal gravimetric analysis (TGA) instrument. X-ray photoelectron spectroscopy (XPS) analysis of the catalyst revealed that the copper sites are in +2 oxidation state. The Fe₃O₄@SiO₂/Schiff base-Cu(II) complex was found to be an effective catalyst for C–N cross-coupling reactions, which high to excellent yields were achieved for α-amino acids as well as N-hetereocyclic compounds. Easy recoverability of the catalyst by an external magnet, reusability up to eight runs without significant loss of activity, and its well stability during the reaction are among the other highlights of this catalyst.

Full text of DOI:10.1002/aoc.6051

Received: 1 June 2020
DOI: 10.1002/aoc.6051
Revised: 26 August 2020
Accepted: 19 September 2020
F U L L P A P E R
Functionalization of superparamagnetic Fe O @SiO
3
4
2
nanoparticles with a Cu(II) binuclear Schiff base complex
as an efficient and reusable nanomagnetic catalyst for
N-arylation of α-amino acids and nitrogen-containing
heterocycles with aryl halides
A. R. Sardarian
| M. Kazemnejadi
| M. Esmaeilpour
Chemistry Department, College of
Fe O @SiO nanoparticles was functionalized with a binuclear Schiff base
Sciences, Shiraz University, Shiraz, 71946
3
4
2
84795, Iran
Cu(II)-complex (Fe O @SiO /Schiff base-Cu(II) NPs) and used as an effective
3
4
2
magnetic hetereogeneous nanocatalyst for the N-arylation of α-amino acids
and nitrogen-containig heterocycles. The catalyst, Fe @SiO /Schiff base-Cu
II) NPs, was characterized by Fourier transform infrared (FTIR) and
Correspondence
A. R. Sardarian, Chemistry Department,
College of Sciences, Shiraz University,
Shiraz 71946 84795, Iran.
3
O
4
2
(
ultraviolet-visible (UV-vis) analyses step by step. Size, morphology, and size
distribution of the nanocatalyst were studied by transmission electron micros-
copy (TEM), scanning electron microscopy (SEM), and dynamic light scatter-
Email: sardarian@shirazu.ac.ir
Funding information
Shiraz University; Iran National Science
Foundation; Research Council of Shiraz
University
ings (DLS) analyses, respectively. The structure of Fe O nanoparticles was
3
4
checked by X-ray diffraction (XRD) technique. Furthermore, the magnetic
properties of the nanocatalyst were investigated by vibrating sample magne-
tometer (VSM) analysis. Loading content as well as leaching amounts of cop-
per supported by the catalyst was measured by inductive coupled plasma (ICP)
analysis. Also, thermal studies of the nanocatalyst was studied by thermal
gravimetric analysis (TGA) instrument. X-ray photoelectron spectroscopy
(XPS) analysis of the catalyst revealed that the copper sites are in +2 oxidation
state. The Fe O @SiO /Schiff base-Cu(II) complex was found to be an effective
3
4
2
catalyst for C–N cross-coupling reactions, which high to excellent yields were
achieved for α-amino acids as well as N-hetereocyclic compounds. Easy recov-
erability of the catalyst by an external magnet, reusability up to eight runs
without significant loss of activity, and its well stability during the reaction are
among the other highlights of this catalyst.
K E Y W O R D S
magnetic heterogeneous catalyst, N-arylation, nitrogen-containing heterocycles, Schiff base
copper(II) complex, α-amino acids
Appl Organomet Chem. 2020;e6051.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
1 of 20
https://doi.org/10.1002/aoc.6051

2
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SARDARIAN ET AL.
1
| INTRODUCTION
Fe O NPs, but also they possess the both advantages of
3
4
Fe O nanoparticle core (High aspect ratio, unique cata-
3
4
In the last decades, copper complexes (Cu(0), (I), or
II)) along with various ligands have been used for the
lytic, magnetic and electrical properties) and ability to
[50]
(
preparation of shells with different structures.
The
[
51]
[52]
C–N cross-coupling reactions (known as amination or
N-arylation) of aryl halides with different type of
Fe O NPs, whether alone
or supported,
lytic activity in order to coupling reactions. Tang et al.
supported ionic liquids on the magnetic Fe O @SiO as
have cata-
3
4
[53]
[1–6]
amines,
because of the lower cost of copper salts and
3
4
2
its application in the cross-coupling reactions as similar as
an efficient catalyst of the C–N cross-coupling reactions
[7,8]
Pd.
The first copper catalyzed C–N bond formation
along with using CuCl. Also, supporting of EDTA-Cu(II)
[9,10]
was developed by Ullman and Goldberg.
Various
complex on Fe O4 nanoparticles was used for the
3
[
54]
types of N-arylation have been reported in the literature
that some examples come as follows: N-arylation of
N-arylation of amines.
N-arylation of chiral α-amino
acids is one of the useful and applicable C–N coupling
[11–16]
[17]
imidazoles,
Cu(I)-catalyzed N-arylation of indoles,
reactions which leads to core structures for a number of
[
55]
C–N coupling of aniline with terminal alkynes (synthesis
biologically important molecules. Cu(I)-catalyzed was a
[
18]
of α-ketoamides),
tion of azido compounds and aryl halides,
of aryl halides with alkyl amine using CuBr catalyst
copper-mediated C–N coupling reac-
general method for the N-arylation of α-amino acids with
[19]
[55]
N-arylation
various aryl halides previously reported by Ma et al.
Also, the N-arylation of α-amino acids has been reported
[
20]
[56]
which benefits from phosphoramidite as a ligand,
Cu(I)-catalyzed N-arylation of pyrazoles,
by the assistance of microwave irradiation.
Sharma et al.
Previously,
[21]
[25]
N-arylation of
used Cu(I) as a catalyst and β-diketone-
aryl iodide with hypervalent aryl siloxanes by Cu (OAc)
type ligand 2-isobutyrylcyclohexanone for coupling reac-
2
[22]
along with a ligand,
N-arylation of α-amino acids
tions of amino acids, amino acid esters, and peptides with
[23–25]
[57]
catalyzed by Cu(I),
cross-coupling reaction of aryl
aryl iodides. Han et al.
reported the synthesis of PI3K
halides to aryl amines catalyzed by Cu O in solution of
inhibitor GDC-0077 via a stereocontrolled N-arylation of
2
[26]
ammonia,
N-alkynylation of amides catalyzed by
α-amino acids by Cu O. Very recently, we have developed
2
[27]
[28–30]
Cu(I),
Ullmann-type N-arylation of anilines,
intramolecular adjacent C–N coupling (asymmetric
Cu(I)-amidation catalyzed of aryl halides,
two polyvinyl alcohol (PVA)-based resins for the Cu-
[31]
Cu-catalyzed
catalyzed N-arylation of α-amino acids using solid-phase
[
58]
organic synthesis (SPOS) approach.
The most reported
[32]
0
synthesis of atropisomeric compounds),
Cu/N,N -
methods for the C–N coupling reactions endure from high
reaction times and temperatures, which also needs stabil-
ity of catalyst. Moreover, reusability of a heterogeneous
catalyst is one of the significant issues in coupling reac-
tions that was a serious problem in previously reported
methods. So finding an efficient method for C–N cross-
coupling reaction which covers the above-mentioned
impediments is in demand. Therefore, herein, we report
synthesis and full characterization of a reusable binuclear
bis-salophen Cu(II) complex-functionalized super-
paramagnetic Fe O @SiO nanoparticles which would be
dibenzyloxalamide-catalyzed N-arylation of hetero-
[33]
[34]
anilines,
Cu-catalyzed N-arylation of sulfoximines,
Cu-catalyzed decarboxylative N-arylation of indole-2-car-
[35]
boxylic acids, and Cu-catalyzed intramolecular benzylic
[
36]
C–H amination for the synthesis of isoindolinones.
Magnetic nanoparticles (MNs) are class of
nanoparticles which include magnetic elements (com-
a
[37,38]
monly Fe, Ni, or Co or their combinations),
but they
suffer from agglomeration phenomena due to large inter-
action between nanoparticles arising from their nano-size
and high aspect ratio. So, to overcome this impediment,
they are coated with silica shell, which minimizes the
3
4
2
susceptible for efficient catalysis of N-arylation reactions
and can be easily removed from the reaction media by an
external magnet. Also, N-arylation of α-amino acid, which
can generate new valuable α-amino acid derivatives was
examined in the present study. Moreover, the yield of the
products was comparable to the previously reported
[
39–41]
mentioned interactions and makes them stabilize.
Also, this strategy provides an excellent opportunity for
functionalization of the surface of silica shell and conse-
quently immobilization of variety of organic compounds,
transition metal complexes, and homogeneous catalysts
[
23,56–61]
homogeneous systems.
[42,43]
on their surface.
In recent years, magnetic iron oxide core-shell
nanocomposites prepared from Fe O and silica shell have
2 | EXPERIMENTAL
3
4
been highly regarded due to their widespread applications
[
44]
[45–58]
in various fields such as biomedicine
and environ-
2.1 | Chemicals and instrumentation
[49]
mental remediation data storage,
which all of these
applications were not only thank to unique magnetic
properties, biocompatibility and easy manipulation of
All chemicals were purchased as the reagent grade
from commercial suppliers and used without further

SARDARIAN ET AL.
3 of 20
purification. Analytical thin-layer chromatography
were dissolved in 30-ml deionized water with mechani-
cal stirring for 0.5 h in 80 C. Then, hexamethylenetet-
ꢀ
(TLC) was performed on glass plates precoated with
silica gel impregnated with a fluorescent indicator, and
the plates were visualized by an exposure to ultraviolet
light. NMR spectra for characterization of coupling
products were recorded on a Bruker Avance DPX-250
ramine (HMTA; 1.0 M) was added dropwise with
vigorous stirring to provide a black solid product when
basicity of the mixture reaches pH = 10. The resultant
ꢀ
mixture was heated on a water bath for 2 h at 60 C,
1
13
spectrometer operating for H at 250 MHz and for
C
and the obtained Fe O4 nanoparticles were removed
3
at 62.9 MHz in CDCl . Fourier transform infrared
by an external magnet, washed with deionized water
(2 × 10 ml), and dried under vacuum at 50 C
3
ꢀ
(FTIR) spectra were run on a Shimadzu FTIR 8300
spectrometer using a KBr pellet method. GC analyses
were done using a Shimadzu-14B gas chromatography
for 10 h.
equipped with HP-1 capillary column and N as carrier
2
gas. Anisole was used as an internal standard. The
X-ray diffraction (XRD) analysis of the powder samples
was performed on a Bruker AXS D8-advance X-ray dif-
fractometer using CuKα radiation. Transmission elec-
tron microscopy (TEM) was taken on a Philips EM208
microscope and was run at 100 kV. X-ray photoelec-
tron spectroscopy (XPS) analysis of the nanomagnetic
catalyst was performed on a XR3E2 (VG Microtech)
twin anode X-ray source with AlKα = 1486.6 eV. Field
emission scanning electron microscopy (FE-SEM)
images were performed on a Philips XL-30ESEM.
Dynamic light scatterings (DLS) were recorded on a
HORIBA-LB550. Ultraviolet-visible (UV-vis) spectra
were obtained on a PerkinElmer Lambda 25 UV-vis
spectrometer. The elements in samples were deter-
mined by energy-dispersive X-ray (EDX) spectroscopy
accessory to the Philips scanning electron microscopy
2.3 | Preparation of Fe O @SiO NPs
3
4
2
In a general procedure, 0.5-g Fe O powder was first dis-
3
4
persed in 5-ml deionized water. An absolute ethanol solu-
tion (50 ml) containing 5.0 ml of NaOH (10 wt%) was
then added to the magnetite suspension with stirring at
room temperature. Then, 0.2 ml of tetraethyl orthosilicate
(TEOS) was slowly poured into the solution, and the mix-
ture was stirred for 30 min. Finally, Fe O @SiO
2
3
4
nanospheres were magnetically removed, washed in turn
with ethanol and deionized water three times, and dried
ꢀ
[59,62]
at 80 C for 10 h.
2.4 | Preparation of Fe O @SiO -Cl
3
4
2
Fe O @SiO -Cl was prepared using
a
previously
3
4
2
[
63]
(SEM). The thermal gravimetric analysis (TGA) data
described procedure.
Fe O @SiO (1 g) was dispersed
3
4
2
were obtained by a PerkinElmer device manufactured
by Thermal Sciences. Vibrating sample magnetometer
in 20 ml of ethanol through ultrasonication, followed by
an addition of 3-chlorotriethoxypropylsilane (6 mmol),
and the resultant mixture was stirred under reflux for
12 h. The silica-coated magnetic NPs grafted with
3-chlorotriethoxypropylsilane (Fe O @SiO -Cl) were sep-
(VSM) measurements were performed using a BHV-55
VSM. The elemental analyses (C, H, and N) for the
coupling products were obtained from a Thermo Fin-
nigan Flash EA-1112 CHNSO rapid elemental analyzer.
The loading amount of Cu was determined by induc-
tively coupled plasma (ICP, Varian, Vista-pro). Melting
points were measured in open capillaries using an
Electrothermal 9100 apparatus. The products were
3
4
2
arated from the reaction media using a magnet and
washed several times with ethanol and deionized water
ꢀ
to remove unreacted species and dried at 60 C.
1
identified by their melting points and H NMR and
13
C NMR spectra, which have been displayed in the
2.5 | Synthesis of p-bis
(3,4-diaminobenzophenimine)
phenylenediamine (1)
Supporting Information, and comparison with the
values were reported in literature.
PDBP was prepared according to the previously described
[
64]
2
.2 | General procedure for synthesis of
procedure.
in ethanol (15 ml) at room temperature. Then
,4-diaminobenzophenone (2 mmol, 0.43 g) was added,
p-PDBP (1 mmol, 0.11 g) was dissolved
Fe O nanoparticles
3
4
3
Fe O NPs were obtained by chemical coprecipitation
and the mixture was stirred for 4 h. The purple solid
crude product was filtered and then recrystallized
from methanol to give pure PDBP (0.46 g, yield: 92%,
3
4
[59,60]
method according to our previous research.
tially, 1.3 g FeCl .6H O (4.8 mmol), 0.9 g FeCl
2
Ini-
3
2
ꢀ
ꢀ
(4.5 mmol), and PVA (15,000; 1.0 g) as a surfactant
mp. 229 C–231 C).

4
of 20
SARDARIAN ET AL.
2
.6 | Synthesis of p-bis[(3,4-salicylicimino)
was removed under reduced pressure to get the coupling
product. The resulting crude product was purified by
flash chromatography to give the desired products.
benzophenimine] PDBP (Schiff base
ligand, PSBP) (2)
PDBP (0.25 g,0.5 mmol) and salicylaldehyde (0.25 g,
2
mmol) were added to 15 ml of water as a solvent, and
2.10 | General procedure for the N-
arylation of α-amino acids with aryl
halides
the mixture was stirred at room temperature for 8 h. The
dark yellow solid product (2, PSBP) was filtered and puri-
fied by recrystallization from methanol (0.43 g, yield:
ꢀ
ꢀ
[64]
8
5%, mp. 195 C–197 C).
N-Arylation of α-amino acids catalyzed by Fe O @SiO /
3
4
2
Schiff base-Cu(II) (5) was taken place as follows: A mix-
ture of α-amino acid (1 mmol), aryl halide (1 mmol),
K CO (2.0 mmol), and catalyst (0.015 g, 0.75 mol%) was
2
.7 | Preparation of Schiff base complex of
2
3
Cu(II) 3
dissolved in DMF (3 ml) in a 10-ml round-bottom flask.
ꢀ
This mixture was stirred at 80 C. Termination of the
PSBP (0.15 g, 0.16 mmol) was solved in 10 ml of ethanol,
reaction was detected by TLC. At the end of the reaction,
the catalyst was separated from the reaction mixture by
an external magnetic field. The residual solution was
cooled to room temperature and diluted with water and
ethyl acetate (1:1, 20 ml). Then, the mixture was acidified
(pH = 2–3) by HCl (37%), and the two phases were sepa-
rated. The aqueous layer was extracted with ethyl acetate
then Cu (OAc) (0.06 g, 0.32 mmol) was added gradually
2
during 20 min and the mixture stirred at room tempera-
ture for 12 h. The resulting product was filtered and
washed with ethanol and dried in vacuum to give the
Schiff base complex of Cu(II) 3 as a green solid.
(
3 × 20 ml), and the combined organic layers was dried
2
.8 | Immobilization of Schiff base
over Na SO and then filtered. Ethyl acetate was evapo-
2
4
complex of Cu(II) on Fe O @SiO NPs
rated with rotary evaporator, and the coupling product
was isolated as a solid powder. Recrystallization in etha-
nol was utilized for further purification.
3
4
2
The Fe O @SiO -Cl NPs 4 (1.5 g) produced from the pre-
3
4
2
vious step were ultrasonically dispersed in a solution con-
taining K CO3 (0.53 g, 4 mmol), catalytic amount of
2
tetrabutylammonium bromide (TBAB, 0.02 g, 0.06 mmol),
the Schiff base complex of Cu(II) 3 (1.0 mmol), and
MeCN (15 ml). Then, the mixture was refluxed under
constant stirring for 12 h. Finally, the Fe O @SiO /Schiff
3 | RESULTS AND DISCUSSION
The nanocatalyst was initially produced through the com-
plexation of Cu(II) with a bis-salophen ligand followed by
immobilization on Fe O @SiO nanoparticles (Schemes 1
3
4
2
base-Cu(II) complex NPs 5 were separated with a magnet
3
4
2
and washed with ethanol and water for three times to
remove unreacted reagents and dried at 60 C overnight.
and 2) and then characterized by various analytical
methods.
ꢀ
FTIR spectra of the samples have been shown in
Figure 1a–f. Stretching vibration related to Fe–O bond at
−
1
2
.9 | General procedure for the
Fe O was found at 572 cm . Moreover, two peaks at
3 4
1
N-arylation of nitrogen-containing
heterocycles with aryl halides
3,407 and 1,622 cm− show the vibration of the adsorbed
[
65]
water on Fe O nanoparticles framework.
The pres-
3
4
ence of the three main peaks in the spectrum of
In a 10-ml round-bottom flask, a mixture of aryl halide
Fe O @SiO at regions of 575 (Fe–O stretching vibra-
3
4
2
(1 mmol), nitrogen-containing heterocycles (1.2 mmol),
tion), 1,090 (Si–O–Si asymmetric stretching), and
3,407 cm− (–OH stretching vibration) confirm the suc-
cessful coating of the Fe O surface nanoparticles by SiO
1
Cs CO (2 mmol), Fe O @SiO /Schiff base-Cu(II) NPs
2
3
3
4
2
(
0.012 g, 0.6 mol%), and DMF (3 ml) was stirred under
3
4
2
ꢀ
nitrogen atmosphere at 110 C, whereas the completion of
reaction was monitored by TLC. The catalyst was
removed from the reaction mixture by an external mag-
net. Then, the reaction mixture was diluted with 20 ml of
water, and the product was extracted with 20-ml ethyl
acetate three times. The organic phases were combined
and dried over anhydrous Na SO (5 g), then the solvent
shell (Figure 1b). Figure 1c shows the vibration of C–H
(stretching), –CH – (bending), and C–Cl (stretching) at
2
−
1
2,955, 1,443, and 702 cm , respectively for 4, which
formed through the treatment of Fe O @SiO with
3
4
2
3-chloromethoxypropylsilane. Stretching vibration of
imine bond (C N) at 1,651 cm− is an evidence for the
synthesis of PSBP (2) (Figure 1d). The chelation of
1
2
4

SARDARIAN ET AL.
5 of 20
SCHEME 1 Preparation
process of Schiff base complex
of Cu(П) (3)
3 4 2
SCHEME 2 Preparation process of Schiff base complex of Cu(П) supported on superparamagnetic Fe O @SiO nanoparticles (5)
1
copper to PSBP causes a red shift of imine bond vibration
vibrations at 702 cm− in FTIR of 5 in addition to the
presence of vibrations allocated to the bis-salophen cop-
per complex (3) is enough evidence for immobilization of
the copper complex (5) on Fe O @SiO nanoparticles
−
1
from 1,651 to 1,635 cm as shown in Figure 1e, which is
an evidence for the complex formation of copper by
the Schiff base ligand. The presence of peaks of
Cu(II) binuclear Schiff base complex and Fe O @SiO
2
3
4
2
(Figure 1f). More importantly, advent of the new strong
absorption at 1,126 cm− that was assigned to C–O–C
stretching bond (bridging bond) strongly confirms the
formation of ether bond between the nanoparticles and
the ligand. Given that there is no other place in the
Cu-Schiff base complex to bridging to nanoparticles,
therefore, the structure drawn for the catalyst in Scheme 2
3
4
1
core-shell in FTIR spectrum of 5 confirms well immobili-
zation of 3 on the surface of Fe O @SiO nanoparticles
3
4
2
(Figure 1f). Moreover, the evidence for ligands bridging
between nanoparticles provide with comparing FTIR
spectrum of the Cu-Schiff base complex 3 with
Fe O @SiO NPs. The elimination of C–Cl stretching
3
4
2

6
of 20
SARDARIAN ET AL.
base-Cu(II) NPs, which confirm the successful func-
tionalization of Fe O NPs. It was found that the diffrac-
3
4
tion peaks of the functionalized MNs (Figure 2a(B,C))
decreased in intensity in comparison with those of bare
magnetic particles, probably due to the amorphous silica
and Schiff base complex coating. This result indicates
that the core-shell nanoparticles have been successfully
synthesized without damaging the crystal structure of
Fe O core during the silica coating and surface func-
3
4
tionalization. Besides the peaks related to iron oxide, the
XRD patterns of Fe O @SiO and Fe O @SiO /Schiff
3
4
2
3
4
2
base-Cu(II) NPs present a broad XRD peak at low diffrac-
ꢀ
tion angle (2θ = 5–25 ), which is allocated to the amor-
phous state SiO2 and Schiff base complex shells
(
(
Figure 2a(B,C)). For Fe O @SiO /Schiff base-Cu
3 4 2
II) nanoparticles, this broad peak is shifted to the lower
angles because of the synergetic effect of amorphous sil-
[
67,68]
ica and Cu(II) binuclear Schiff base complex.
More-
over, using XRD analysis, the size of the nanoparticles
was calculated using the Scherrer's equation: D = Kλ/β
cosθ, where K is a constant (K = 0.9 for Cu–Kα), D is the
ꢀ
average diameter in A , β is the broadening of the diffrac-
tion line measured at half of its maximum intensity in
radians, λ is the wavelength of the X-rays, and θ is the
Bragg diffraction angle. The sizes measured by this
method were 11, 20, and 29 nm that correspond to Fe O ,
3
4
Fe O @SiO , and Fe O @SiO /Schiff base-Cu(II),
3
4
2
3
4
2
respectively.
The oxidation state of the copper species present in
the catalyst was studied by 2p-high resolution (energy
corrected) XPS analysis. As shown in Figure 2b, the two
peaks appearing in 934.5 and 954.2 eV are related to the
bonding energies 2p3/2 and 2p1/2, respectively. The peak
positions appearing in the spectrum are in agreement
2
+ [69,70]
with the oxidation state of Cu .
The absence of
+
2
other peaks in this area also indicates that only Cu spe-
cies are present in the catalyst.
FIGURE 1 FTIR spectra of (a) Fe
c) Fe @SiO –Cl, (d) PSBP, (e) Cu(II) binuclear Schiff base
complex, and (f) Fe @SiO /Schiff base-Cu(II)
3 4 3 4 2
O , (b) Fe O @SiO ,
(
3
O
4
2
FE-SEM, TEM, and DLS analyses of the synthesized
nanoparticles have been shown in Figure 3. The synthe-
sized Fe O nanoparticles have a well-size distribution;
3
O
4
2
3
4
however, in some areas, bigger structures with non-
spherical morphology are also could be seen (Figure 3a).
The Fe O particles have an average diameter of 10 nm
appears to be the most likely structure, and it is suggested
that the connection between the ligand and the
nanoparticles is carried out through oxygen groups.
The crystalline structures of Fe O , Fe O @SiO , and
3
4
(Figure 3d). The FE-SEM and TEM images of the
Fe O @SiO NPs are shown in Figure 3b,e. It is apparent
3
4
3
4
2
3
4
2
Fe O @SiO /Schiff base-Cu(II) NPs were studied by XRD
that the synthesized Fe O @SiO nanoparticles are well
3 4 2
3
4
2
measurement (Figure 2a). The characteristic peaks at
dispersed, are nearly spherical in shape (Figure 3b), and
have an average diameter of 20 nm (Figure 3e). From the
TEM results, the thickness of silica shell in spherical-
magnetite composites is inferred to be around 5 nm
(Figure 3e). Figure 3c depicts typical FE-SEM image of
the core-shell structured Fe O @SiO /Schiff base-Cu(II)
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
ϴ = 30.1 , 35.4 , 43.1 , 53.4 , 57.0 , and 62. 6 , which
are marked respectively by their indices (220), (311),
400), (422), (511), and (440), have a good matching with
Fe O nanoparticles cubic spinel crystal structure (refer-
(
3
4
[66,67]
ence JCPDS card no. 19–629).
These patterns are
3
4
2
also observed for Fe O @SiO and Fe O @SiO /Schiff
nanoparticles with near-spherical morphology. More
3
4
2
3
4
2

SARDARIAN ET AL.
7 of 20
3 4 3 4 2 3 4 2
FIGURE 2 (a) XRD patterns of (A) Fe O and (B) Fe O @SiO and Fe O @SiO /Schiff base-Cu(II) NPs. (b) High resolution (energy
corrected) XPS spectrum of Fe3O4@SiO2/Schiff base-Cu(II) NPs
detailed information is obtained from the TEM image.
After successive coating with the Schiff base complex,
these composites still maintain their spherical shape with
an average diameter of approximate 30 nm (Figure 3f).
To investigate the size distribution of these nanoparticles,
particle size histograms were prepared by DLS analysis
show only one peak around at 285 nm, which is masked
after immobilization of Schiff base copper complex by
*
π ! π absorptions. UV-vis spectrum of Schiff base-Cu
(II) shows that the copper valence state is +2 in the com-
plex, in accordance with Cu (OAc) adsorption at 307 nm
2
*
and in agreement with the XPS results. Also, n ! π tran-
(
Figure 3g–i). This size distribution is centered at a value
sition for C N bonds in the Schiff base complex appears
at 360 nm. The electronic spectrum of the catalyst shows
two characteristic peaks at 300 and 363 nm related to the
transitions for benzene rings and imine bonds respec-
of 12, 20, and 33 nm for Fe O , Fe O @SiO , and
3
4
3
4
2
Fe O @SiO /Schiff base-Cu(II) nanoparticles, respec-
3
4
2
tively (Figure 3g–i). The results were completely in agree-
ment with the results from FE-SEM and TEM images as
well as XRD analysis.
tively. Also, in comparison with Cu (OAc) UV-vis spec-
2
trum, it could be concluded that the valence of copper
has not changed and remains +2 after immobilization on
The components of the composite particles were con-
firmed by EDX analysis given in Figure 4a,b. The EDX
results of Fe O @SiO /Schiff base-Cu(II) demonstrated
[
71]
the Fe O @SiO NPs.
3
4
2
Thermogravimetric analysis of Fe O @SiO /Schiff base-
3
4
2
3
4
2
that Cu(II) binuclear Schiff base complex has been
immobilized onto the Fe O @-SiO NPs. The weight per-
Cu(II) along with its precursors was performed, and their
spectra were exhibited in Figure 5a. Fe O @SiO shows
3
4
2
3
4
2
centage of the elements was shown as an inset table in
Figure 4a,b. The results showed that 3.3%wt copper was
present in the catalyst. The absence of Cl element in the
catalyst indicates the covalent bonding of the
Cu(II) complex 3 to the substrate via its hydroxyl groups
good thermal stability, and only ꢁ12% weight loss is
ꢀ
occurred until 800 C. The same phenomenon is taken place
in the thermal analysis of Fe O @SiO -Cl NPs. Small weight
3
4
2
loss in the beginning of thermal analysis of Fe O @SiO –Cl
3
4
2
ꢀ
(50–200 C) shows scape of humidity and solvent from the
(completely in agreement with the FTIR spectrum), as
structure of core-shell. A weight loss at higher temperatures
ꢀ
illustrated in Scheme 2.
around 390 C supports the effective functionalization of
Electronic spectra for Cu (OAc) , Fe O @SiO , Schiff
Fe O @SiO NPs with 3-chlorotrimethoxypropylsilane.
2
3
4
2
3
4
2
base-Cu(II) complex 3, and Fe O @SiO /Schiff base-Cu
Thermal behavior of Fe O @SiO /Schiff base-Cu(II)
3 4 2
3
4
2
(
II) complex 5 were scrolled at region of 250–750 nm,
complex is occurred in one step corresponded to 37.8%
weight loss that shows the decomposition of Schiff base
which are shown in Figure 4c. Fe O @SiO nanoparticles
3
4
2

8
of 20
SARDARIAN ET AL.
FIGURE 3 FE-SEM images of (a) Fe
e) Fe @SiO , and (f) Fe @SiO /Schiff base-Cu(II); and the size distributions of (g) Fe
base-Cu(II) NPs, respectively
3
O
4
, (b) Fe
3
O
4
@SiO
2
, and (c) Fe
3
O
4
@SiO
2
/Schiff base-Cu(II); TEM images of (d) Fe
3 4
O ,
(
3
O
4
2
3
O
4
2
3
O
4
, (h) Fe @SiO , and (h) Fe O @SiO /Schiff
3
O
4
2
3 4 2
complex moiety as well as immobilized organic compounds
particles do not have permanent magnetic moments in
the absence of an external field but can respond to an
external magnetic field. The saturation magnetization
for Fe O , Fe O @SiO , and Fe O @SiO /Schiff base-Cu
ꢀ
on Fe O @SiO in the temperature span 200–680 C. This
3
4
2
main degradation strongly confirms the immobilization of
Schiff base complex on the Fe O @SiO core shell, which is
3
4
2
3
4
3
4
2
3
4
2
not observed in the thermal behavior of Fe O @SiO or
(II) NPs was found to be 64.8, 40.3, and 29.1 emu/g,
respectively. Although the saturation magnetization
decreases after coating of the surface of the Fe O
3 4
3
4
2
Fe O @SiO –Cl NPs.
3
4
2
The magnetic properties of Fe O , Fe O @SiO , and
3
4
3
4
2
[
72]
Fe O @SiO /Schiff base-Cu(II) NPs were examined by
core,
the complete magnetic separation of
3
4
2
VSM analysis at room temperature (Figure 5b). This
figure shows almost zero coercivity and remanence,
which proves the superparamagnetic properties of the
synthesized MNs. Although these superparamagnetic
Fe O @SiO /Schiff base-Cu(II) complex samples is
3
4
2
achieved in 0.5 min by placing a magnet near the vessels
containing the aqueous dispersion of the nanoparticles
(Figure 4d).

SARDARIAN ET AL.
9 of 20
FIGURE 4 EDX spectra of (a) Fe
3
O
4
@SiO
2
and (b) Fe
3
O
4
@SiO
2
/Schiff base-Cu(II); (c) UV-vis spectra of Cu (OAc)
2 3 4 2
, Fe O @SiO ,
Schiff base-Cu(II), and Fe
3
O
4
@SiO
2
/Schiff base-Cu(II); (d) photo images of magnetic field-responsive of Fe
3
O
4
@SiO /Schiff base-Cu
2
(
II) nanoparticles before magnetic field and under magnetic field
FIGURE 5 (a) Thermogravimetric analysis of (A) Fe
3
O
4
@SiO
and Fe
2
, (B) Fe @SiO
3
O
4
2
3 4 2
–Cl, and (C) Fe O @SiO /Schiff base–Cu(II);
(
b) magnetization curves for (A) Fe and (B) Fe @SiO
3
O
4
3
O
4
2
3
O
4
@SiO /Schiff base-Cu(II) NPs
2

10 of 20
SARDARIAN ET AL.
The amount of copper content of the Schiff base com-
plex copper immobilized on the surface of Fe O @SiO
2
NPs was determined by ICP analysis. The obtained
results revealed the presence of 0.52 mmol of copper per
with 93% and 90% yields, respectively (Table 1, entries
6 and 11), and water and ethanol provide the lowest
yields (Table 1, entries 8 and 9). Another effective param-
eter is temperature which was explored (Table 1, entries
6 and 19–22). This study discloses the highest catalyst
3
4
1
g of Fe O @SiO /Schiff base copper complex.
3 4 2
ꢀ
To show the merit of application of this magnetic
efficiency at 110 C (Table 1, entry 6) and raising the reac-
ꢀ
nanocatalyst in organic synthesis, we planned to employ
it as the catalyst in the N-arylation of nitrogen-containing
heterocycles and α-amino acids (Scheme 3). Therefore, in
order to determine optimum conditions, the reaction of
imidazole with iodobenzene was picked up as a model
reaction, and the effect of the involved parameters such
as solvent, catalyst amount, base, and temperature was
investigated on the its efficiency. The obtained data are
tabulated in Table 1. There is no progress for the model
reaction in absence of the catalyst, which indicates vital
role of the catalyst in this reaction (Table 1, entry 1).
tion temperature to higher than 110 C does not show any
increasing in its efficiency (Table 1, entry 22). Moreover,
the reaction does not show any progress at room temper-
ature (Table 1, entry 19). Finally, on the basis of the data
summarized in Table 1, it is clarified that the model reac-
tion gives the highest yield of the desired product when
0.6 mol% catalyst is used along with Cs CO (2 mmol) as
2
3
ꢀ
a base in DMF (3 ml) at 110 C for 3.5 h (Table 1,
entry 6).
The above-mentioned optimum conditions were
served for a wide variety of N-arylation of nitrogen-
containing heterocycles, and their data are registered in
Table 2. As shown in Table 2, high to excellent yields
were obtained for all substrates with different electronic
type of substitution, electron-rich, or electron-deficient.
The existence of electron withdrawing substitutions on
aryl halides leads to higher efficiency than electron
donating groups. The highest efficiencies were achieved
in the coupling of 4-nitroiodobenzene with imidazole
and 2-iodopyridine with indole with 95% and 94% yields
respectively (Table 2, entries 3 and 6). Aryl bromides
undergo the N-arylation reaction efficiently but in lower
yield than iodide counterpart even after longer reaction
time (Table 2, entries 13–20). Piperazine as an aliphatic
amino substrate carries out the reaction and results in
high yield of 1,4-diphenylpipirazine when it reacts with
Also, bare Fe O4 did not show any catalytic activity
3
(Table 1, entry 2). Moreover, the efficiency of the reaction
depends on the amount of the catalyst. So that 0.6 mol%
of the catalyst is sufficient for completion of the model
reaction and production of the desired product in 93%
yield (Table 1, entry 6) and using higher and lower
amounts than 0.6 mol% of the catalyst are led to reduc-
tion in the reaction efficiency (Table 1, entries 3–5 and
7
). Among the used bases, Cs CO shows the best perfor-
2 3
mance for the coupling reaction. The other bases do not
provide suitable yields except t-BuONa, which give the
ꢀ
related product with 81% yield in DMF at 110 C after
1
2 h (Table 1, entry 17). The efficiency of the catalyst was
also checked in various solvents, and according to the
results, high efficiencies are observed in DMF and DMSO
SCHEME 3 N-arylation of N-heterocyclic
compounds and α-amino acids catalyzed by
Fe O @SiO /Schiff base-Cu(II) nanoparticles
3 4 2

SARDARIAN ET AL.
11 of 20
3 4 2
TABLE 1 Influence of the reaction parameters in the catalyzed N-arylation of imidazole by Fe O @SiO /Schiff base-Cu(II) NPs
ꢀ
b
Entry
Catalyst amount (mol%)
Base
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Temp ( C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
None
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
Cs
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
140
110
110
110
110
110
110
Reflux
Reflux
Reflux
110
110
110
110
110
110
110
110
r.t
12
3.5
12
8
0
Bare Fe
0.2
0.3
0.4
0.6
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
3
O
4
Trace
41
53
75
93
89
7
5
3.5
3.5
12
10
10
4
2
H O
EtOH
CH CN
17
46
90
78
54
21
28
73
81
63
Trace
51
87
92
10
11
12
13
14
15
16
17
18
19
20
21
22
3
DMSO
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
12
12
12
12
12
12
12
12
12
5
NaOH
Et
NaOAc
CO
t-BuONa
PO
3
N
K
2
3
K
3
4
Cs
2
Cs
2
Cs
2
Cs
2
CO
CO
CO
CO
3
3
3
3
80
100
120
4
a
3 4 2
Reaction conditions: Iodobenzene (1 mmol), imidazole (1.2 mmol), base (2 mmol), Fe O @SiO /Schiff base-Cu(II) catalyst, and sol-
vent (3 ml).
b
Isolated yield.
two equivalent of iodobenzene (Table 2, entry 11). Also,
N-phenylpiperazin gives 1-phenyl-4-(pyridine-2-yl) piper-
azine in excellent yield (Table 2, entry 20).
95% of the desired product at ambient temperature and
ꢀ
80 C, respectively (Table 3, entries 7 and 10). No more
ꢀ
efficiency is achieved at higher temperature than 80 C
Due to the ability of Fe O @SiO /Schiff base-Cu(II)
(Table 3, entry 11). The experiments show 0.75 mol% of
the catalyst is sufficient in order to get the highest
efficiency (Table 3, entry 10). Using higher amount of the
catalyst does not create impressive change in efficiency of
the reaction (Table 3, entry 12). To evaluate the base
effect, the model reaction was also tested toward the
N-arylation reaction in the presence of various kinds of
3
4
2
complex as an efficient catalyst in arylation of amines
and nitrogen-containing heterocycles, it was decided to
apply this catalyst for N-arylation of α-amino acids
(
Scheme 3). First of all, the reaction of L-leucine with
iodobenzene was chosen as a model reaction for optimi-
zation of effective parameters in N-arylation of α-amino
acids. The effect of solvent, temperature, and catalyst
amount was examined, which the corresponding col-
lected data have been presented in Table 3. These results
show that all of the parameters are effective on the effi-
ciency of the reaction. Among the solvents employed,
DMSO and DMF show the highest performance with 90%
and 95% yields, respectively (Table 3, entries 4 and 10).
ꢀ
bases and 0.75 mol% catalyst in DMF at 80 C (Table 3,
entries 10, 13–18). The results indicated using the bases
such as K PO , NaOAc, Et N, and NaOH result in low to
3
4
3
moderate yield of the N-arylated product (Table 3, entries
14–17) and although the reaction shows good reactivity
in the presence of t-BuONa (Table 3, entry 13) but excel-
lent results are obtained when K CO and Cs CO are
2
3
2
3
The reaction in protic solvents such as H O and EtOH
does not happen (Table 3, entries 5 and 6). The reaction
was also temperature dependence and yields 27% and
applied (Table 3, entries 10 and 18). Due to accessibility
and lower price of K CO relative to Cs CO , we choose
2
2
3
2
3
K CO for the rest of study. The control experiments, that
2
3

12 of 20
SARDARIAN ET AL.
a
TABLE 2 Catalyzed N-arylation of nitrogen-containing heterocycles by Fe
3
O
4
@SiO
2
/Schiff base-Cu(II) NPs
c
Entry
Aryl halide
N(H)-heterocycle
Product
Time (h)
Yield (%)
1
C
6
H
5
I
Imidazole
3.5
93
89
95
94
2
3
4
4-Me–C
6
H
4
I
Imidazole
Imidazole
Indole
7
3
5
4-NO
2
6 4
–C H I
6 5
C H I
5
6
7
4-Me–C
6
H
4
I
Indole
5.5
90
94
83
2-Iodopyridine
Indole
4
C
C
6
H
5
I
I
2-Me-Indole
6
8
9
6
H
5
Benzimidazole
Benzimidazole
4
6
92
86
6 4
4-MeO-C H I
(
Continues)

SARDARIAN ET AL.
13 of 20
TABLE 2 (Continued)
c
Entry
Aryl halide
N(H)-heterocycle
Product
Time (h)
Yield (%)
10
11
12
13
14
15
16
C
C
C
C
6
6
6
6
H
H
H
H
5
5
5
5
I
Pyrrole
4
91
84
87
89
7
b
I
Piperazine
1-Phenylpiperazine
Imidazole
6
5
I
Br
9
4-Me–C
6
H
4
Br
Imidazole
10
5
4-NO
2
–C
6
H
4
Br
Imidazole
92
93
2-Bromopyridine
Imidazole
6
17
18
19
C
6
H
5
Br
Indole
10
86
93
86
2-Bromopyridine
2-Bromopyridine
Indole
7
Benzimidazole
7
(
Continues)

14 of 20
SARDARIAN ET AL.
TABLE 2 (Continued)
c
Entry
Aryl halide
N(H)-heterocycle
Product
Time (h)
Yield (%)
2
0
2-Bromopyridine
Phenylpiperazine
6
91
a
Reaction conditions: Aryl halide (1 mmol), amine (1.2 mmol), Cs
3 mL), 110 C.
2
CO
3
(2 mmol), Fe
3
O
4
@SiO
2
/Schiff base-Cu(II) catalyst (0.6 mol%), DMF
ꢀ
(
b
Reaction conditions: Aryl halide (2 mmol), amine (1.2 mmol), Cs
2
CO
3
(4 mmol), Fe
3
O
4
@SiO
2
/Schiff base-Cu(II) catalyst (1 mol%), DMF
ꢀ
(
5 mL), 110 C.
c
Isolated yield.
is, the model reaction in the absence of the catalyst or in
the presence of bare Fe O (Table 3, entries 24 and 25),
did not proceed at all, which reveals the vital role of the
catalyst in the reaction. The premium amount for DMF
as a solvent was found to be 3.0 ml (Table 3,
entries 19–23).
3
4
When these optimized conditions (i.e., aryl halide
[1 mmol], α-amino acid [1 mmol], K CO [2.0 mmol],
2
3
a
TABLE 3 Summary of optimization results in N-arylation of L-leucine
ꢀ
b
Entry
Catalyst amount (mol% Cu)
Base
Solvent
THF
Temp ( C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.5
K
K
K
K
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
80
80
80
80
80
80
RT
50
80
80
90
80
80
80
80
80
80
80
80
80
80
80
80
80
80
8
8
5
5
8
8
5
5
3
2
2
2
8
8
8
8
8
2
2
2
2
2
2
2
2
75
Toluene
55
CH
3
CN
88
DMSO
90
H
2
O
N. R.
10
EtOH
DMF
27
DMF
55
DMF
77
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
0.75
0.75
0.90
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
-
DMF
95
DMF
93
DMF
92
t-BuONa
PO
NaOAc
Et
NaOH
Cs CO
DMF
88
K
3
4
DMF
68
DMF
35
3
N
DMF
22
DMF
18
2
3
DMF
94
K
K
K
K
K
K
K
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
DMF (1.0 ml)
DMF (2.0 ml)
DMF (3.0 ml)
DMF (4.0 ml)
DMF (6.0 ml)
DMF
90
92
95
95
92
Trace
Trace
Bare Fe
3
O
4
DMF
a
Reaction conditions: Iodobenzene (1 mmol), L-leucine (1 mmol), base (2.0 mmol), Fe
0–24, 3 ml), temperature.
3 4 2
O @SiO /Schiff base-Cu(II), solvent (except entries
2
b
Isolated yield.

SARDARIAN ET AL.
15 of 20
TABLE 4 Catalyzed N-arylation of
α-amino acids with various aryl halides
a
3 4 2
by Fe O @SiO /Schiff base-Cu(II) NPs
α-Amino acid
Aryl halide
b
Entry
(R)
X
Y
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
L-leucine (–CH
2
CH(CH
3
)
2
)
4-Cl
4-Br
I
CH
3
14
9
78
98
88
95
67
87
75
98
87
96
80
65
80
2
CO H
2-Br
H
8
I
7
Cl
Br
4-Cl
4-Br
I
H
14
12
14
8
H
L-cysteine (–CH
2
SH)
CH
3
CO
2-Br
H
2
H
6
10
11
12
13
I
6
Br
Cl
Br
H
10
11
10
H
H
a
Reaction conditions: Aryl halide (1 mmol), α-amino acid (1 mmol), K
2
CO
3
(2.0 mmol),
ꢀ
Fe
3
O
4
@SiO
2
/Schiff base-Cu(II) (0.75 mol%), DMF (3 ml), 80 C.
b
Isolated yield.
Fe O @SiO /Schiff base-Cu(II) complex as catalyst
acids of L-leucine and L-cysteine (Table 4, entries 5 and
11). Furthermore, iodobenzene shows higher efficiency
than bromobenzene and chlorobenzene (Table 4, entries
4–6 and 10–12), which is in agreement with the C–N cou-
3
4
2
ꢀ
[
0.75 mol%], DMF [3 ml], and 80 C) were utilized toward
N-arylation of α-amino acids with a variety of aryl
halides, it is found that aryl halides with electron-
releasing and electron-withdrawing substitutions
undergo this reaction (Table 4). Lower efficiency was
belonged to chlorobenzene toward both of the α-amino
[
66]
pling reactions reported in literature.
This finding will
be felt better when 1-bromo-2-iodobenzene is applied in
the reaction (Table 4, entries 3 and 9). Also, L-cysteine,
FIGURE 6 The results obtained from (a) recoverability and (b) leaching experiments of the catalyst for several runs. Reaction
conditions: iodobenzene (1 mmol), L-leucine (1 mmol), K CO (2.0 mmol), Fe @SiO /Schiff base–Cu(II) (0.75 mol%), DMF (5 ml), 80 C.
(2 mmol), Fe @SiO /Schiff base-Cu(II) (0.6 mol%), DMF
ꢀ
2
3
3
O
4
2
Reaction conditions: iodobenzene (1 mmol), imidazole (1.2 mmol), Cs
2
CO
3
3
O
4
2
ꢀ
(
3 ml), 110 C

16 of 20
SARDARIAN ET AL.
FIGURE 7 (a) FTIR spectra of (A) the fresh and (B) recovered catalyst after eighth run. (b) FE-SEM, (c) VSM, and (d) TEM of the
recovered catalyst after eighth run
which bears –SH in addition to –NH functional group,
Figure 6a, without any considerable change in reactivity.
Copper leaching from the surface of catalyst was mea-
sured by ICP analyzer, which the related data can be seen
in Figure 6b. These analyses showed that 4.68% and
4.10% copper leaching after six and eight runs in
N-arylation of imidazole and L-leucine with iodobenzene,
respectively. These findings were confirmed when the
chemical structure, morphology, size, and magnetic
behavior of the recovered catalyst, after eighth run the
N-arylation of L-leucine, were examined by FTIR, VSM,
FE-SEM, and TEM analyses (Figure 7). The FTIR spec-
trum of the recovered catalyst does not show any signifi-
cant change in comparing to the fresh catalyst, which is
an evidence for remaining of the chemical structure of
2
undergoes the high selective N-arylation when it is
treated with iodobenzenes and bromobenzenes (Table 4,
entries 8–11).
Recoverability and reusability of the catalyst, which
are
chemistry,
two
important
aspects
in
the
green
[40,41,73,74]
were checked in N-arylation of
nitrogen-containing heterocycles as well as α-amino
acids. For this goal, the reaction of iodobenzene with
imidazole and L-leucine was chosen respectively, as the
model reactions. The nanocatalyst was successfully
retrieved from two reaction mixtures by an external mag-
net and reused for six and eight runs in N-arylation of
imidazole and L-leucine respectively, as shown in

SARDARIAN ET AL.
17 of 20
SCHEME 4 Presentation of a
plausible reaction mechanism for
N-arylation of α-amino acids and
nitrogen heterocycles catalyzed by
3 4 2
Fe O @SiO /Schiff base-Cu(II)
3 4 2
TABLE 5 Comparison among efficiency of Fe O @SiO /Schiff base-Cu(II) with the reported catalysts for preparation of 1-phenyl-1H-
imidazole from iodobenzene with imidazole
Entry
Catalyst
Cu O (10 mol%)
Conditions
Time (h)
Yield (%)
Reference
ꢀ
[79]
[80]
[81]
[82]
[83]
[84]
[85]
[86]
[5]
1
2
3
2
DMSO, KOH, 110 C
24
10
24
24
24
24
9
99
98
91
99
98
99
87
85
92
78
94
93
ꢀ
Metformin (10 mol %)/Cu(I) (5 mol %)
Nano-CuO (2.5 mol%)
DMF, Cs
2
CO
3
, 110 C
ꢀ
DMSO, KOH, 110 C
a
ꢀ
4
Cu (OAc)
2
.H
2
O (15 mol%)/8-HQ
DMF, K
DMF, Cs
DMF, K
2
CO
CO
CO
3
, 130 C, Ar Atm.
ꢀ
5
6
Cu(I)/MNP-3 (10 mol%)
Cu-Y zeolite (10.8 mol%)
2
3
, 110 C
ꢀ
2
3
, 120 C
b
ꢀ
7
Fe
CuFe
CoFe
Cu
3
O
4
@TiO
2
/Cu
2
O composite (0.01 g)
DMSO, KOH, 100 C
ꢀ
8
2
O
4
K
3
PO
CH OH, R.T.
EtOH/H
4
, PEG-400, 100 C
12
5
c
9
2
O
4
@SiO
2
-NH
2
-Furfural-Cu (5 Wt%)
3
c
ꢀ
[87]
[59]
2
O (0.05 mol%)/Ligand (20 mol%)
2
O, TBAB, NaOH, 120 C
12
5
ꢀ
Fe
3
O
4
@SiO
@SiO
2
2
-PVA_Cu(II) catalyst (0.6 mol%)
/Schiff base-Cu(II) (0.6 mol%)
DMF/t-BuONa/100 C
ꢀ
1
0
Fe
3
O
4
DMF, Cs
2
CO
3
, 110 C
3.5
Present work
Abbreviation: HQ, hydroxylquinoline.
a
Aryl halide is bromobenzene.
Phenylboronic acid is used instead aryl halide.
-(2-Me-hydrazine-1-carbonyl)-isoquinoline 2-oxide.
b
c
1
fresh catalyst during eight runs reaction (Figure 7a) and
VSM analysis reveals its supermagnetization behavior with
saturation magnetization of ꢁ30 emu.g (Figure 7c). and
The FE-SEM and TEM images of the recovered catalyst
appear the spherical shape nanoparticles with slightly
bigger size in compare to the fresh catalyst (Figure 7b,d).
−1

18 of 20
SARDARIAN ET AL.
In order to determine the responsible active copper
4 | CONCLUSIONS
species in catalyzing the coupling reaction and the extent
of Cu leaching into the reaction mixture, we have utilized
Herein, we have introduced a novel approach to func-
tionalization of superparamagnetic Fe O @SiO core-
[75]
the hot filtration test.
model reaction, that is, iodobenzene (1 mmol), imidazole
1.2 mmol), Cs CO (2 mmol), catalyst (0.6 mol%), and
This test was performed over the
3
4
2
shell nanoparticles with a binuclear Cu(II) Schiff base
complex to synthesize a novel, efficient heterogeneous,
and magnetic catalyst which is able to catalysis effi-
ciently the N-arylation of aliphatic amines, nitrogen-
containing heterocycles, and α-amino acids. The catalyst
was thoroughly characterized with FTIR, XRD, FE-SEM,
TEM, DLS, UV-vis, TGA, VSM, EDX, XPS, and ICP
analyses. The special features of the present catalyst
are (a) heterogeneity, (b) easy recoverability by an exter-
nal magnet, (c) reusability, (d) stability against heating
and moisture, (e) easy handling, and (f) production
N-arylated products in high to excellent yields. Conse-
quently, we have provided suitable opportunity for
highly efficient, cost-effective, and relatively benign
route for N-arylation of aliphatic amines, N-heterocycles,
and α-amino acids.
(
2
3
ꢀ
DMF (3 ml), 110 C. The heterogeneous nanomagnetic
copper complex catalyst was removed magnetically from
the reaction mixture after 40% conversion (GC analysis)
and was allowed to the residual reaction mixture to be
ꢀ
stirred at 110 C for 4 h. The GC analysis of the mixture
showed only 3% raising in conversion. This result dis-
closed the heterogeneous nature of responsible catalyst
and also negligible leaching of copper into the reaction
mixture.
3.1.1 | Mechanism study
[
76]
According to the mechanism described by Kong et al.,
[77]
[54]
Kianmehr et al.,
and Mostafalu et al.,
for Cu-
catalyzed N-arylation of nitrogen-containing heterocy-
cles, we proposed a plausible mechanism based on our
observations that were in agreement with the literature
ACKNOWLEDGEMENTS
This work was supported by the Research Council of
Shiraz University and Iran National Science Foundation
from the Iran Society for the Promotion of Science.
(
Scheme 4). The proposed mechanism involves a nucleo-
II
philic coordination between Cu in the catalyst I, and
the amine group in α-amino acid in the first stage which
II
I[[78]]
is resulted in the reduction of Cu to Cu
metal car-
AUTHOR CONTRIBUTIONS
bonate (M CO , M K, or Cs) as a base abstract hydrogen
Ali sardarian: Conceptualization; funding acquisition;
methodology; supervision. Milad Kazemnejadi: Data
curation; formal analysis. mohsen esmaeilpour: Data
curation; formal analysis.
2
3
atom from the intermediate ΙΙ to make III. Then electro-
philic coordination through the amino group at α-amino
acid forms the intermediate IV which undergoes the
oxidative addition with aryl iodide to produce the Cu(III)
species V. The reductive elimination on V is led to the
desired N-arylated α-amino acid and regeneration of the
DATA AVAILABILITY STATEMENT
The data that support findings of this study are available
in the Supplementary Information.
II
I
catalyst (Cu L ) through the oxidation of Cu L (VI) with
2
2
air oxygen. As a support for proofing of the vital role of
oxygen, the model reaction was run under an inert
ORCID
atmosphere (N or Ar) but no indication of the expected
product production was observed after 4 h.
A. R. Sardarian https://orcid.org/0000-0003-4407-2527
M. Kazemnejadi https://orcid.org/0000-0002-5424-9640
M. Esmaeilpour https://orcid.org/0000-0003-1085-8599
2
In order to demonstrate the superiority of the present
method over previous ones, the present catalytic system
was compared with some other catalysts in the literature
for N-arylation of imidazole (Table 5). As shown in
Table 5, Fe O @SiO /Schiff base-Cu(II) as a magnetic
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