N-heterocyclic carbene-Pd(II) complex based on theophylline supported on Fe3O4@SiO2 nanoparticles: Highly active, durable and magnetically separable catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara coupling reactions

Article abstract of DOI:10.1016/j.jorganchem.2018.08.002

In this paper, a novel heterogeneous palladium catalyst was synthesized by anchoring N-heterocyclic carbene-Pd(II) complex based on theophylline on magnetic Fe₃O₄@SiO₂ nanoparticles. The synthesized magnetic composite was characterized by fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray analysis (EDX), thermogravimetric analysis (TGA), vibration sample magnetometry (VSM), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), N₂ adsorption-desorption isotherm analysis (BET), UV–vis spectroscopy and elemental analysis. Also, loading content of palladium on the catalyst was measured by inductive coupled plasma (ICP) analysis. The synthesized catalyst was used successfully for the Suzuki cross-coupling reactions of various aryl halides (I, Br, Cl) with phenylboronic acids. This reaction was best performed in water as a green solvent in the presence of just 0.37–0.5 mol% of the catalyst at 60 °C. Also, we have reported this recyclable catalytic system as a stable phosphine-free Pd catalyst for the Sonogashira cross-coupling of aryl halides (I, Br, Cl) with terminal aromatic and aliphatic alkynes under solvent-free conditions. All coupling reactions proceeded with good to excellent yields. The catalyst showed good stability and was recovered and reused for eight reaction cycles without a significant loss in its catalytic activity. Also, the leaching of the catalyst has been examined by a hot filtration test and ICP-AES analysis.

Full text of DOI:10.1016/j.jorganchem.2018.08.002

Accepted Manuscript
N-heterocyclic carbene-Pd(II) complex based on theophylline supported on
Fe O @SiO nanoparticles: Highly active, durable and magnetically separable
3 4
2
catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara coupling reactions
Mohsen Esmaeilpour, Ali Reza Sardarian, Habib Firouzabadi
PII:
S0022-328X(18)30392-9
10.1016/j.jorganchem.2018.08.002
JOM 20529
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 21 May 2018
Revised Date: 15 July 2018
Accepted Date: 2 August 2018
Please cite this article as: M. Esmaeilpour, A.R. Sardarian, H. Firouzabadi, N-heterocyclic carbene-Pd(II)
complex based on theophylline supported on Fe O @SiO nanoparticles: Highly active, durable and
3 4
2
magnetically separable catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara coupling reactions,
Journal of Organometallic Chemistry (2018), doi: 10.1016/j.jorganchem.2018.08.002.
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ACCEPTED MANUSCRIPT
Graphical abstract
N-Heterocyclic carbene-Pd(II) complex based on theophylline supported on Fe3O4@SiO2 NPs as
a catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara coupling reactions.

ACCEPTED MANUSCRIPT
N-Heterocyclic carbene-Pd(II) complex based on theophylline supported on
Fe3O4@SiO2 nanoparticles: Highly active, durable and magnetically separable
catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara coupling
reactions
Mohsen Esmaeilpour, Ali Reza Sardarian* Habib Firouzabadi*
,
Chemistry Department, College of Sciences, Shiraz University, Shiraz71946 84795, Iran
*Corresponding author. Tel.: +98 7136137107, fax: +98 7136460724.
E-mail addresses: sardarian@shirazu.ac.ir (A.R. Sardarian);firouzabadi@chem.susc.ac.ir (H.
Firouzabadi)
Abstract
In this paper, a novel heterogeneous palladium catalyst was synthesized by anchoring N-
heterocyclic carbene-Pd(II) complex based on theophylline on magnetic Fe3O4@SiO2
nanoparticles. The synthesized magnetic composite was characterized by fourier transform
infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy
(XPS), energy dispersive X-ray analysis (EDX), thermogravimetric analysis (TGA), vibration
sample magnetometry (VSM), transmission electron microscopy (TEM), field emission scanning
electron microscopy (FE-SEM), dynamic light scattering (DLS), N2 adsorption-desorption
isotherm analysis (BET), UV-vis spectroscopy and elemental analysis. Also, loading content of
palladium on the catalyst was measured by inductive coupled plasma (ICP) analysis. The
synthesized catalyst was used successfully for the Suzuki cross-coupling reactions of various aryl
halides (I, Br, Cl) with phenylboronic acids. This reaction was best performed in water as a green
solvent in the presence of just 0.37-0.5 mol% of the catalyst at 60 oC. Also, we have reported this
recyclable catalytic system as a stable phosphine-free Pd catalyst for the Sonogashira cross-
coupling of aryl halides (I, Br, Cl) with terminal aromatic and aliphatic alkynes under solvent-
free conditions. All coupling reactions proceeded with good to excellent yields. The catalyst
showed good stability and was recovered and reused for eight reaction cycles without a
significant loss in its catalytic activity. Also, the leaching of the catalyst has been examined by a
hot filtration test and ICP-AES analysis.
Keywords
Magnetic palladium nanocatalyst; N-heterocyclic carbenes complex; Theophylline; Suzuki-
Miyaura reaction; Sonogashira-Hagihara reaction; Green synthesis
1. Introduction
In recent years, more attentions have been paid to fabrication and characterization of the
magnetic nanoparticles particularly Fe3O4 nanoparticles due to their unique magnetic
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properties and feasibility of preparation [1, 2]. These nanoparticles have been widely
used as magnetic materials in biomedicine, magnetically targeted drug and gene delivery,
magnetic hyperthermia, enzyme immobilization, magnetic resonance imaging (MRI),
data storage, catalysis, and environmental remediation due to their excellent properties
such as superparamagnetic, low toxicity, biocompatibility, high magnetic susceptibility
and high saturation magnetization [3-8]. However, bar magnetic particles due to magnetic
dipolar attractions are liable to aggregation, alteration of magnetic properties, and rapid
biodegradation when they are directly exposed to the biological system [9]. Therefore, a
protection layer is required as the stabilizer, which prevents direct contact between the
nanoparticles [10].
Among different kinds of coating materials like noble metals, polymer material and metal
oxide, silica is extensively used as such a protective layer [11, 12]. Silica is stable under
acidic conditions and inert to redox reactions and possesses numerous favorable
properties, including large pore volume, high surface area, excellent biocompatibility,
tunable pore size and low cytotoxicity [13]. In addition, its silanol surfaces is easily
modified, which can be used to graft various desirable functional groups [14, 15].
Owing to the above mentioned properties of Fe3O4and silica , recently, magnetic
nanoparticles consisting of an iron oxide core and silica shell have aroused great interest
in current researches because of their unique chemical and physical properties, such as
chemically modifiable surface, low cytotoxicity, unique magnetic responsivity [16-19]
and easily removal from reaction mixtures by an external magnetic field [20]. Therefore,
these magnetic NPs have been employed not only as an effective material for water
treatment but also as a good support for preparation of novel magnetic heterogeneous
catalysts [21-23].
Palladium catalyzed carbon-carbon bond formation via the cross coupling reactions have
occupied special place in synthetic organic chemistry due to their wide application scope,
their compatibility with various functional groups and the mildness of the conditions
required [24-29]. Carbon-carbon bond-forming reactions, such as the Suzuki-Miyaura
and Sonogashira coupling processes, play key roles in the synthesis of many natural
products and bioactive compounds [30-32]. The Sonogashira coupling reaction of
terminal alkynes with aryl or vinyl halides usually proceeds in an aprotic, polar solvent
such as benzene, THF or DMF in the presence of different palladium catalysts involving
ligands such as amines, phosphines and dibenzylidineacetone and a copper salt as a co-
catalyst [33, 34]. Despite their importance, the most of these palladium catalyzed
reactions suffer from inherent problems related to the separation, instability of the
homogeneous catalysts at high temperatures, Pd metal aggregation and precipitation,
recovery, using expensive ligands and toxic organic solvents, and Glaser-type
homocoupling reaction of the terminal alkynes in the presence of oxidative agents or air
[35-37]. Also, the palladium-catalyzed coupling of an aryl halide with aryl boronic acid
(Suzuki coupling) is recognized as the most successful method for versatile
transformations in biaryl synthesis from both academic and industrial points of view [38,
39]. These compounds have considerable application for the synthesis of biologically
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active substances such as herbicides and pharmaceuticals [40]. In the past two decades,
advances have been made to develop even more efficient catalytic systems for the
Suzuki-Miyaura coupling reaction [41-46]. Unfortunately, most of these well-known
systems, in addition to moderate yields and poor substrate generality have serious
disadvantages such as using high reaction temperatures, harmful organic solvents and
excess stoichiometric amounts of palladium promoter. Consequently, the development of
economical, accessible phosphine-free catalytic systems to overcome these difficulties is
still of desirable goal.
Regarding to the improvements reported in the literature for increasing stability and
reactivity of the metal catalysts in these catalytic coupling reactions by application of
efficacious supporting ligands such as N-heterocyclic carbenes [47-51] and importance of
environmental and economic aspects in organic synthesis [52], herein and in
continuation of our ongoing research program on employment of novel magnetically
recoverable catalysts for ecofriendly preparation of different class of organic compounds
[53-57], we wish to report the synthesis of N-heterocyclic carbene-Pd(II) complex based
on theophylline supported on Fe3O4@SiO2 nanoparticles according to scheme 1 and its
application in the Suzuki-Miyaura and Sonogashira-Hagihara cross coupling reactions
under green conditions.
2. Experimental
2.1. Materials and physical measurements
Chemical reagents were purchased from the Merck and Aldrich Chemical Company and
were used without further purification. 1H NMR and 13C NMR spectra were monitored on
a Bruker Avance DPX 250 MHz spectrometer using CDCl3 and DMSO-d6 as the solvents
and tetramethylsilane as an internal standard. FT-IR spectra were obtained with
potassium bromide pellets in the range 500-3800 cm-1 with a Shimadzu FT-IR 8300
spectrometer. The crystalline structures of the nanoparticles were evaluated by X-ray
diffraction (XRD) analysis on a Bruker AXS D8-advance X-ray diffractometer with
CuKα radiation at 40 kV (λ= 1.5418). Transmission electron microscopy (TEM) images
were obtained with a Philips EM208 transmission electron microscopy operating at 100
kV accelerating voltage. Micrographs of nanoparticles were taken through field emission
scanning electron microscopy (FE-SEM) of Hitachi S-4160 instrument. Dynamic light
scattering (DLS) were recorded on a HORIBALB550. Energy dispersive X-ray analysis
(EDX) results were obtained using Philips (Model XL-30) instrument. X-ray
photoelectron spectroscopy (XPS) measurements were performed using an XR3E2 (VG
Microtech) twin anode X-ray source with AlKα= 1486.6 eV. UV/vis diffuse reflectance
spectra were recorded on a PerkinElmer (Lambda 25). The magnetization curve was
measured at room temperature under a varying magnetic field from -8000 to 8000 Oe
using a vibrating sample magnetometer (BHV-55). The thermogravimetric curves were
obtained using a Perkin Elmer instrument. Nanoparticles were heated from room
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temperature up to 700 °C under airflow using alumina sample holders. BET surface areas
of the nanoparticles were tested by nitrogen physisorption on Micromeritics ASAP 2000
apparatus. The amount of palladium present in the composite materials was estimated by
inductively coupled plasma (ICP) analysis (Varian, Vista-pro). Elemental analyses for C,
H and N were performed using a Thermofinigan Flash EA-1112 CHNSO rapid Rapid
analyzer. The purity determination of the substrates and reaction monitoring were
accomplished by TLC on silica-gel polygram SILG/UV 254 plates. Melting points were
determined on a Buchi 510 instrument by open capillary method and were uncorrected.
2.2. General procedure
2.2.1. Preparation of silica coated magnetic nanoparticles (Fe3O4@SiO2 NPs)
Firstly, magnetite nanoparticles (Fe3O4) were prepared according to a previous report by
a chemical co-precipitation method [58]. As a typical procedure, FeCl3·6H2O (1.3 g, 4.8
mmol), FeCl2·4H2O (0.9 g, 4.5 mmol) and polyvinyl alcohol (PVA 15000) (1 g) as a
surfactant were dissolved in 30 mL of deionized water and stirred at 80 °C for 30 min.
Then, hexamethylenetetramine (HMTA) (1.0 mol/L) was slowly added over a period of
15 min with vigorous stirring when reaction media reaches pH 10. The resultant mixture
was stirred vigorously for 2 h at 60 °C and finally, the Fe3O4 was collected using a
magnet, washed with absolute ethanol several times, dried at 80 ◦C for 10 h and then kept
under vacuum for further use. Secondly, the Fe3O4@SiO2 nanoparticles were prepared by
the hydrolysis of tetraethyl orthosilicate (TEOS) on the surface of Fe3O4 nanoparticles by
a modified Stober method [59]. Briefly, the above Fe3O4 nanoparticles (0.5 g) suspended
in 50 mL ethanol were supplemented by 5 mL deionized water and 0.2 mL tetraethyl
orthosilicate (TEOS) as silica source, followed by the addition of 5.0 mL of NaOH (10
wt%). Subsequently, the suspension was stirred for 30 min at room temperature and
successively magnetically collected was washed with ethanol and water, and then dried at
80 ◦C for 10 h.
2.2.2. Preparation of Fe3O4@SiO2-NH2 NPs
To a solution of (3-aminopropyl) triethoxysilane (1 mmol, 0.25 mL) in ethanol (10 mL)
was added Fe3O4@SiO2 nanoparticles (1.0 g) and the mixture was stirred under reflux
conditions for 12 h. The modified Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2-NH2) were
separated by magnetic decantation and washed with water and ethanol successively to
remove the unattached substrates and dried in vacuum at 80 °C for 6 h.
2.2.3. Preparation of Fe3O4@SiO2-TCT NPs
Fe3O4@SiO2-NH2 (1.0 g) was added to a solution of cyanuric chloride (TCT, 1.0 mmol,
0.185 g) and diisopropylethylamine (DIPEA) (1 mmol, 0.17 mL) in THF (10 mL) and the
mixture was stirred for 16 h at room temperature. The resultant Fe3O4@SiO2-TCT
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nanoparticles were magnetically separated and washed with hot ethanol and deionized
water repeatedly and dried at 60 oC for 8 h.
2.2.4. Preparation of Fe3O4@SiO2-TCT-NH2 NPs
To a mixture of bis(3-aminopropyl) amine (2 mmol, 0.25 mL) and DIPEA (2 mmol, 0.35
mL) in DMF (5 mL) was added Fe3O4@SiO2-TCT (1.0 g) and the mixture was stirred at
80 oC for 12 h. Then the solid material (Fe3O4@SiO2-TCT-NH2) was magnetically
separated, washed repeatedly with deionized water and hot ethanol to remove any
unanchored species and then dried at 70 oC for 4 h.
2.2.5. Preparation of theophylline derivative (4)
A mixture of theophylline (1.0 mmol), 1,3-dibromopropane (2.0 mmol), K2CO3 (2
mmol), and DMF (5 mL) was stirred at room temperature for 24 h. After completion of
the reaction, water (20 mL) was added and the resulting precipitate was filtrated. The
crude precipitate (N-(3-bromopropyl)-theophylline) was purified by rinsing with ethyl
acetate (10 mL) to give the desired pure product (Yield: 91%). Then, a mixture of N-(3-
bromopropyl)-theophylline (1.0 mmol), ethyl iodide (1.5 mmol) and CH3CN (5.0 mL)
was stirred under reflux conditions for 5 h in an oil bath. The progress of the reaction was
monitored by TLC. After completion of the reaction, the solvent was removed under
reduced pressure and the residue was washed with hot ethyl acetate (15mL) to give the
pure product (Yield: 93%).
2.2.6. Preparation of Fe3O4@SiO2-NHC-Pd(II) MNPs
1 g of Fe3O4@SiO2-TCT-NH2 nanoparticles were dispersed in 5 mL of DMF in a single-
necked flask. Then, a mixture of theophylline derivative (4, 3 mmol) and DIPEA (3
mmol, 0.5 mL) were added to the flask. The reaction mixture was then stirred for 12 h at
80 oC. The theophylline derivative functionalized Fe3O4@SiO2 NPs (Fe3O4@SiO2-
Theophylline) was then isolated by an external magnet, washed several times with water
and ethanol, and then dried at 60 oC for 3 h. In order to prepare Fe3O4@SiO2-NHC-Pd(II)
MNPs, 1 g of Fe3O4@SiO2-Theophylline MNPs were dispersed in 10 mL of THF using
an ultrasonic bath to produce a uniform suspension and then 0.18 g of palladium acetate
(0.8 mmol) was added. The resulting mixture was stirred for 8 h at 50 oC. The solid
catalyst was collected by an external magnetic force, rinsed with ethanol, and then dried
at 60 oC for 5 h.
2.3. General procedure for the Suzuki-Miyaura coupling reaction
A mixture of Fe3O4@SiO2-NHC-Pd(II) (0.006 g, 0.37 mol%), aryl boronic acid (1.1
mmol), aryl halide (1.0 mmol), and K2CO3 (2 mmol) in H2O (3 mL) was stirred at 60 oC
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for the appropriate time as indicated in Table 3. The completion of the reaction was
monitored by TLC. After completion of the reaction, the catalyst was removed by an
external magnetic field and was then washed with H2O (5 mL) and ethyl acetate (10 mL).
The organic layer was separated, dried over anhydrous Na2SO4, and filtered. Then, the
solvent was evaporated under reduced pressure. The pure product was obtained via silica
gel column chromatography with an eluent of n-hexane and ethylacetate.
2.4. General procedure for Sonogashira cross coupling reactions
Aryl halide (1 mmol), alkyne (1.1 mmol), piperidine (2 mmol) and the Fe3O4@SiO2-
NHC-Pd(П) catalyst (0.007 g, 0.43 mol%) was stirred at 90 °C for the appropriate time as
indicated in Table 5 and reaction progress was confirmed by TLC. After completion of
the reaction, the reaction mixture was diluted with ethyl acetate (10 mL) and the catalyst
was separated with an external magnet. Solvent was evaporated under reduced pressure
and the crude residue was then purified by column chromatography using ethyl
acetate/hexane as an eluent to give the desired Sonogashira product (5a-5ak; Table 5).
3. Results and discussion
3.1. Catalyst characterization
The successful fabrication of silica coat and functionalization with N-heterocyclic
carbene-Pd(II) complex groups were confirmed by the IR spectra of the naked Fe3O4,
Fe3O4@SiO2, Fe3O4@SiO2-NH2, Fe3O4@SiO2-TCT, Fe3O4@SiO2-TCT-NH2,
Fe3O4@SiO2-Theophylline, and Fe3O4@SiO2-NHC-Pd(II) MNPs (Fig. 1a-h). Fig. 1a
shows FTIR spectrum of Fe3O4 nanoparticles, in which, in addition to the characteristic
peak appears at 570 cm-1 which is allocated to the Fe-O stretching vibration [58], the
another peak is also occurred at around 3400 cm-1 which was attributed to the stretching
of O-H groups of water [60]. In the case of Fe3O4@SiO2 nanoparticles, there are some
new bands around 1100 cm-1 corresponding to the asymmetric stretching vibration of Si-
O-Si and around 800 cm-1 for symmetric vibration of Si-O-Si, confirming the formation
of silica layers (Fig.1 b). In the FT-IR spectrum of Fe3O4@SiO2-NH2, the obvious bands
at 2810-2986 cm-1 were assigned to the asymmetric and symmetrical C-H stretching from
the successful immobilization of (3-aminopropyl) triethoxysilane on the surface of the
Fe3O4@SiO2 NPs. Also, the FT-IR spectrum of Fe3O4@SiO2-NH2 emerged absorption
peaks at 3050-3250, 1123, 1000-1150 and 576 cm-1 are attributed to N-H (stretching
vibration), C-N (stretching vibration), Si-O-Si (asymmetric stretching) and Fe-O
(stretching vibration), respectively (Fig. 1c). The FT-IR spectra of Fe3O4@SiO2-NH2 NPs
modified by cyanuric chloride groups were characterized by the following absorption
bands: 2866-2992 cm-1 (C-H stretching vibration), 1511, 1564 and 1711 cm-1 (C=N
stretching vibration), 1226 cm-1 (C-N stretching vibration), 1091 cm-1 (Si-O-Si
asymmetric stretching) and 576 cm-1 (Fe-O stretching vibration). Due to the presence of
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strong Si-O-Si bond, the C-Cl bond of cyanuric chloride at 1100 cm-1 has been mashed
(Fig. 1d). According to Fig. 1e, the successful Fe3O4@SiO2-TCT surface modification
with bis(3-aminopropyl)-amine groups is verified. Also, it was not possible to assign the
N-H band in the FT-IR spectrum, due to interference from the core-shell O-H band. The
FT-IR spectrum of synthesized theophylline derivative 4 (Fig. 1f) shows two sharp band
at 1666 and 1697 cm-1 which corresponds to the stretching vibrations of C=O groups.
Peaks appearing at 2954 and 3101 cm-1 are characteristic of C-H stretching vibrations.
The band at 1474 cm-1 is assigned to CH2 bending vibration and that of 1373 cm-1 to CH3
bending of theophylline groups. Also, the band at 625 cm-1 displays the stretching
vibrations of the C-Br bond. In the FT-IR spectrum of Fe3O4@SiO2-Theophylline (Fig.
1g) the appeared bands in the regions about 1700 (C=O stretching), 1659 (overlap C=O
and C=N theophylline, stretching), 1476 (CH2 bending) and 1374 cm-1 (CH3 bending)
and also the absence of C-Br bond confirm the successful immobilizing of the
theophylline derivative 4 on the surface of Fe3O4@SiO2-TCT-NH2 NPs. In the last FT-IR
spectrum corresponds to Fe3O4@SiO2-NHC-Pd(II) (Fig. 1h), a new peak at 1479 cm-1
may be assigned to Pd-C-Nimidazol (stretching vibration)[61] in N-heterocyclic carbene-
Pd(II) complex supported on Fe3O4@SiO2 nanoparticles.
The crystalline structure and phase purity of the Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2-
NHC-Pd(Π) NPs were demonstrated by XRD as shown in Fig. 2. All the diffraction
peaks at 2ϴ= 30.1◦, 35.4◦, 43.1◦, 53.4◦, 57◦ and 62.6◦ for Fe3O4@SiO2 and Fe3O4@SiO2-
NHC-Pd(II) nanocomposites are observed, which are in agreement with the XRD peaks
of pure Fe3O4 NPs. These peaks correspond to (220), (311), (400), (422), (511) and (440)
Bragg reflection of magnetite, respectively, indicating the formation of iron oxide with a
cubic inverse spinel structure, which are consistent with the standard data for magnetite
(JCPDS card no.00-019-0629) [62]. The same position of characteristic peaks for
Fe3O4@SiO2 and Fe3O4@SiO2-NHC-Pd(II), indicated the stability of the crystalline
phase of Fe3O4 nanoparticles during silica coating and surface modification. The intensity
of all of Fe3O4 diffraction peaks in XRD spectra of Fe3O4@SiO2 and Fe3O4@SiO2-NHC-
Pd(II) NPs were weaker than those of Fe3O4, which indicates the presence of amorphous
materials on the surface of Fe3O4 [62]. Also, the presence of a broad peak at 2ϴ= 15-25o
in the XRD pattern of Fe3O4@SiO2 core-shell nanoparticles shows amorphous state of
SiO2 coated on Fe3O4 nanoparticles. For Fe3O4@SiO2-NHC-Pd(II) NPs, the broad peak
was slightly transferred to lower angles due to the synergetic effect of amorphous silica
and N-heterocyclic carbene-Pd(II) complex.
The average grain size (D) of the Fe3O4 particles was calculated using the Scherrer’s
equation (1) as follows [63]:
D= kλ/βCosϴ
Where D is the average crystal size of the Fe3O4 nanoparticles, k is the form factor (k=
0.9), λ is the X-ray wavelength (0.154 nm), β is the broadening of the diffraction line
measured at half of its maximum intensity in radians and ϴ is the Bragg diffraction angle.
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The particle sizes of the magnetite calculated using the Scherrer equation were 11.33,
12.64, and 15.51 nm for Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2-NHC Pd(II), respectively
(Table 1).
The TEM images of Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2-NHC-Pd(П) NPs are shown
in Fig. 3. According to these images, Fe3O4 nanoparticles were of spherical shape with a
diameter of 10 nm. After coating with silica, Fe3O4@SiO2 nanoparticles had the
diameters 15-25 nm with spherical shape as shown in Fig. 3b, in which a typical core-
shell structure was clearly observed with presence of the magnetite nanoparticles as core
and the lighter contrast silica as shell. Fig. 3c depicts the TEM image of Fe3O4@SiO2-
NHC-Pd(П). It is clear that the synthesized nanoparticles are well dispersed, but also in
some areas bigger structures with non-spherical morphology are observed. The average
size of these nanoparticles are about 35 nm.
The representative FE-SEM images of Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2-NHC-
Pd(П) NPs are shown in Fig. 3d-f, respectively. FE-SEM image of the Fe3O4 particles
confirm the uniform size and nearly spherical shape (Fig. 3d). Fig. 3e displayed typical
FE-SEM image of Fe3O4@SiO2 nanospheres, illustrating that the nanoparticles are all
well dispersed with approximately spherical morphology. Compared with the
Fe3O4@SiO2, the Fe3O4@SiO2-NHC-Pd(П) composite is slightly larger in diameter and
have relatively smooth surface, indicating the N-heterocyclic carbene-Pd(II) complex has
been deposited on the surface of Fe3O4@SiO2 nanoparticles (Fig. 3f).
DLS measurements were also carried out to measure the hydrodynamic diameter of the
magnetic nanoparticles. This size distribution was centered at a value of 12 and 20 nm for
Fe3O4 and Fe3O4@SiO2, respectively (Fig. 3g and h). The size of Fe3O4@SiO2-NHC-
Pd(II) became larger than Fe3O4@SiO2 because of the grafting of NHC-Pd(II) complex
based on theophylline on the surface of the Fe3O4@SiO2 NPs and was observed to be
around 36 nm (Fig. 3i).
N2 adsorption-desorption isotherms were conducted to investigate the porous structure
and surface area of the nanoparticles. The measured specific surface areas were 480,
430.3 and 373.1 m2/g for Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2-NHC-Pd(II) NPs,
respectively (Table 1).
The EDX characterization demonstrates that the Fe3O4@SiO2-NHC-Pd(П) nanoparticles
contains necessary and diagnostic elements of the precursors, C, N, O, Fe, Si, I and Pd
(Fig. 4a).
Diffuse reflectance UV-Vis measurement is a useful technique to obtain information
about the oxidation state of an incorporated metal species. The UV-Vis spectra of Fe3O4,
Fe3O4@SiO2-Theophylline and the supported Pd catalyst are given in Fig. 4. The UV
visible spectrum of the Fe3O4@SiO2-Theophylline shows characteristics band at 344 nm.
The band in this region are assigned to the π-π* transitions. For Fe3O4@SiO2-NHC-Pd(П)
nanocomposite, the band in the 361 nm region are assigned to the d-d transition of the
palladium, which strongly supports the Pd(II) oxidation state (Fig. 4b) [64]. Therefore,
the UV-Vis spectrum confirms the immobilization of NHC-Pd(II) complex on the
supports.
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Figure 4c shows the X-ray photoelectron spectroscopy (XPS) of fresh and recycled
catalyst. XPS is a powerful tool to investigate the electron properties of the species
formed on the surface, such as binding energy, and oxidation state of the core electron of
metal. The XPS spectra demonstrates that palladium oxidation state in the Fe3O4@SiO2-
NHC-Pd(П) is +2, corresponding to the binding energy of 338.86 eV (Pd 3d5/2) and
343.03 eV (Pd 3d3/2) [65].
The thermal stability of the nanoparticles was evaluated using thermogravimetric analysis
(TGA) between 50 and 700 °C at a rate of 10 °Cmin-1 (Fig. 5A). At temperatures up to
about 150 °C, weight loss could be attributed to the release of physically adsorbed water
on the surface of all samples [66]. The organic parts were decomposed completely in the
temperature range of 150-700 oC. According to the TGA, a significant weight loss of
53.4% was related to the decomposition of the theophylline derivative and organic
components on the surface of the MNPs (Fig. 5Ad). These results were in good
agreement with the elemental analysis data (C= 30.22%, H= 4.56% and N= 13.87%).
Fig. 5B displays the VSM magnetization curves of Fe3O4 MNPs, Fe3O4@SiO2 MNPs and
Fe3O4@SiO2-NHC-Pd(Π) magnetic composite at room temperature. The measured
saturation magnetization values (Ms) were 64.8, 40.3, and 24.6 emu/g for Fe3O4,
Fe3O4@SiO2, and Fe3O4@SiO2-NHC-Pd(Π), respectively (Fig. 5Ba-c) All the magnetic
.
nanoparticles show no hysteresis on the room temperature magnetization curves,
indicating the superparamagnetic character of these materials. Although the addition of
nonmagnetic portion leads to a decreased saturation magnetizations, the obtained
Fe3O4@SiO2-NHC-Pd(Π) have a high saturation magnetization. Therefore, these
nanoparticles with superparamagnetic characteristics and high magnetization values can
quickly respond to the external magnetic field and quickly redisperse once the external
magnetic field is removed.
As shown in Table 2, the elemental analysis matched well with TGA results and
proposed structures. According to the above-mentioned results, elemental analysis for
these nanoparticles confirmed successful grafting of organic groups on Fe3O4@SiO2
surface. Also, the Pd loading of catalyst was measured by Inductively Coupled Plasma
(ICP) analyzer and found to be 0.61mmol/g.
3.2. Catalytic activity
Suzuki-Miyaura and Sonogashira-Hagihara coupling reactions, which have been widely
used in organic synthesis and fine chemical industries were employed to evaluate the
performance of the prepared Fe3O4@SiO2-NHC-Pd(II) composite (Scheme 2).
Initially, we chose to study the reaction between 4-bromotoluene (1 mmol) and
phenylboronic acid (1.1 mmol) to optimize the reaction conditions (Table 3). The effect
of base, catalyst loading and temperature on the model Suzuki reaction was investigated.
Because of critical role of base in Suzuki reaction, the effectiveness of various inorganic
bases such as Na2CO3, K2CO3, K3PO4, KF, NaOH and NaOAc was studied on the model
reaction. Although all of bases applied showed good activity (Table 3, entries 1-6) but the
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most effective base was K2CO3 (Table 3, entry 2). Triethylamine, as an organic base, was
not effective as the inorganic bases used and resulted in only 43% yield of the desired
product (Table 3, entry 7). As expected, the model reaction did not show any progress in
the absence of catalyst and the starting material remained intact (Table 3, entry 8). When
the amount of catalyst was increased from 0.2 to 0.37 mol%, the model reaction exhibited
higher efficiency at 60oC in water and provided up to 96% of the desired product (3p)
(Table 3, entries 9, 10, 2). As it can be seen from the Table 3, using higher amount of the
catalyst was not resulted in further enhancement in the effectiveness of reaction (Table 3,
entries 11, 12). Having determined the optimum base and loading of catalyst for the
reaction, investigation pertaining to the choice of an appropriate temperature was
performed (Table 3, entries 2, 13-16). These data appeared when the temperature was
increased from room temperature (Table 3, entry 13) to 60 °C (Entry 2), the yield was
significantly raised up to 96% and was not observed any significant effect on the
reactivity of the catalyst at higher temperature than 60oC (Table 3, entries 15 and 16).
Therefore, the optimized reaction conditions were found to be 0.37 mol% of Fe3O4@
SiO2-NHC-Pd(II), K2CO3 (2 mmol) and H2O (3 mL) at 60 oC.
With having the optimized reaction parameters, generality and versatility of the catalyzed
Suzuki coupling reaction by Fe3O4@SiO2-NHC-Pd(II) were considered on the variety of
aryl halides (I, Br, Cl) and arylboronic acids. As shown in Table 4, aryl iodides with
electron-releasing or electron-withdrawing substitution exhibited similar activity and the
corresponding biaryls were produced in excellent yields in range of 45 min to 2.5 h
(Table 4, 3a-3o). No significant difference was observed in the reaction time or in yield
when the effect of various arylboronic acids was investigated (Table 4, entries 3a,3l, and
3o). Aryl bromides behaved similar but in longer reaction times (Table 4, 3p-3aa). From
3-bromo-thiophene and phenylboronic acid, the desired product was obtained in 94%
yield (Table 4, 3y), while 3-bromopyridine and 2-bromopyridine were converted to the
corresponding compounds in lower yields (Table 4, 3w, 3x), possibly as a result of the
coordination of the pyridine moiety to a catalyst center. In addition, ortho-substituted aryl
halides also provided the desired product in excellent yields (Table 4, 3d, 3e, 3r, 3ak).
Although the optimized reaction conditions used for aryl iodides and bromides were less
effective for Suzuki reaction of aryl chlorides but moderate to good yields of the desired
biaryls were obtained when higher amount of the catalyst (0.5 mol% Pd) was loaded in
the reaction mixture (Table 4, 3ab-3am).
Ability of the catalyst, Fe3O4@SiO2-NHC-Pd(П), in catalyzing of the Suzuki reaction
was a driving force for study of its catalytic activity in Sonogashira coupling reaction
between aryl halides (I, Br, Cl) and terminal acetylenes. Therefore, optimization of
reaction conditions was carried out on the reaction 1-bromo-4-nitrobenzene and
phenylacetylene, as a model in the presence of Fe3O4@SiO2-NHC-Pd(II) NPs and the
corresponding data were summarized in Table 5. These results revealed that the
optimized reaction conditions should be: 1 mmol of 1-bromo-4-nitrobenzene, 1.1 mmol
of phenylacetylene, 2 mmol of piperidine, 0.43 mol% of the catalyst under solvent-free
condition at 90 oC (Table 5, entry 1).
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To determine scope of reaction, Sonogashira reactions of various aryl halides (I, Br, Cl)
with alkynes were performed under the optimized conditions. Table 6 illustrates that the
reaction was effective in the presence of a wide variety of functional groups on the aryl
halides and gave the corresponding internal alkynes in high to excellent yields. The
Sonogashira reactions of electron-rich aryl iodides with phenylacetylene proceeded
smoothly to give the corresponding coupling products in excellent yields (Table 6, 5b-
5d).
Unsurprisingly, 4-iodoacetophenone, 1-chloro-4-iodobenzene and 4-nitroiodobenzene
were found to be the most reactive among the aryl iodides studied (Table 6, 5e-5g).
Similar results were obtained for the reaction of differently substituted aryl bromides with
phenylacetylene, as illustrated in Table 6 (5i-5t). This catalytic system was also applied
to heteroaromatic bromides, such as 5-bromopyrimidine, 3-bromopyridine and 3-
bromothiophene, and the expected internal alkynes were obtained efficiently within 5-6 h
(Table 6, 5r-5t). Also, the sterically hindered ortho-substituted aryl bromides such as 2-
bromotoluene, 2-bromoanisole and 2-bromobenzaldehyde were efficiently coupled in
yields of over 85% (89%, 86% and 87%, respectively, 5k, 5l and 5o). On the other hand,
the reaction of aryl chlorides with phenylacetylene was usually very slow with high
yields (Table 6, 5u-5ac).
Furthermore, the reaction of aryl halides (I, Br, Cl) with terminal alkynyl, such as
1‐octyne and 1-ethynyl-1-cyclohexanol, were led to the products in high to excellent
yields (Table 6, 5ad-5ak). In summary, we have established that N-heterocyclic carbene-
Pd(II) complex based on theophylline supported on Fe3O4@SiO2 NPs can catalyze
quantitatively the Sonogashira coupling reaction of aryl halides with terminal alkynes.
As a comparison, the results reported in the literature over palladium-based catalysts
were gathered in Table 7 along with the data achieved in this work. It shows that
Fe3O4@SiO2-NHC-Pd(II) NPs displayed good catalytic activity for the Suzuki and
Sonogashira reactions (Table 7, entries 12, 20). As can be seen, this catalytic system is
one of the most efficient and eco-friendly systems in the C-C bond forming via Suzuki
and Sonogashira coupling reactions with highest TOF. The other advantages of this
protocol are: a) using of thermal stable magnetically heterogeneous catalyst, b) avoidance
of using hazardous organic solvents, c) simple removal of the catalyst by an external
magnet, and d) need to low amount of the catalyst for performing of reaction.
The recyclability and reusability, which are environmentally and economically two
important aspects of utilization of catalysis systems, of Fe3O4@SiO2-NHC-Pd(II) catalyst
were checked on the both above-mentioned model reactions. In each case, after
completion of the reaction, the catalyst was separated by using an external permanent
magnet and washed respectively with hot ethanol (5 mL) and deionized water (5 mL) and
the catalyst was directly reused in the next run of the reaction. As shown in Fig. 6a, the
performance of the catalyst was retained during the reuse process, and it is possible to
recover and reuse it at least eight times without any significant loss in catalytic activity.
As illustrated in Fig. 6b, the catalyst shows the magnetic response towards an external
magnetic field and is attracted completely by the magnet but remains disperse in solution
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in the absence of magnetic field. FE-SEM and DLS images of the recovered catalyst after
eight runs are presented in Figure. 6c,d. The FE-SEM image of the recycled catalyst
shows uniformity and spherical-like morphology of nanoparticles and therefore confirms
preservation of structure of the catalyst during the reaction (Fig. 6c). Additionally, the
hydrodynamic diameter of the recovered catalyst is centered at a value of 41 nm which is
larger than the size of fresh prepared the catalyst and may be responsible factor for slight
decreasing in reactivity of the catalyst (Fig. 6d).
Leaching of Pd from the heterogeneous catalyst was checked by the hot filtration test
[26]. Accordingly, the Suzuki reaction mixture (model reaction) was filtered off to
separate the solid catalysts after 1.5 h in hot conditions and washed with ethyl acetate (5
mL). The filtrate was analyzed by GC (64% conversion). Then, after removal of ethyl
acetate, the reaction mixture was heated at 60 oC for another 5 h in the absence of any
added catalyst. The subsequent GC analysis did not show any further significant
conversion (66.4%). These results indicate the presence of little amount of the active
palladium species in the solution phase and confirm high recyclability of the catalyst.
Palladium leaching of the catalyst was further investigated by Inductively Coupled
Plasma Atomic Emission Spectroscopy (ICP-AES). It revealed that the leaching of
palladium from the catalyst into the solution was lower than 0.18 ppm after eight
consecutive runs, which suggests the heterogeneous nature of N-heterocyclic carbine
Pd(II) complex supported on superparamagnetic Fe3O4@SiO2 NPs.
4. Conclusions
In conclusion, we have successfully designed and synthesized magnetic core-shell Fe3O4@SiO2
nanoparticles functionalized by N-heterocyclic carbene-Pd(II) complex based on theophylline
which act as a novel recyclable catalyst for green Suzuki-Miyaura and Sonogashira-Hagihara
coupling reactions. Simple and environmentally benign procedures, short reaction times,
excellent yields, clean reaction profiles, easy product separations and purifications, low catalyst
loading, efficient magnetic separation and good chemical stability of catalyst are the
considerable features of this method. Furthermore, the Fe3O4@SiO2-NHC-Pd(II) NPs exhibited a
good magnetic property with high saturation magnetization and could be quickly separated by a
magnet and the recovered catalyst still shows high activity for the cross-coupling reactions after
being recycled eight times.
Acknowledgement
The authors are grateful to National Elite Foundation of Iran and Shiraz University
research council for financial support of this work.
References
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ACCEPTED MANUSCRIPT
[1] W. Gao, S. Sattayasamitsathit, K.M. Manesh, D. Weihs, J. Wang, J. Am. Chem. Soc. 132 (2010)
14403-14405.
[2] G. Leem, S. Sarangi, S. Zhang, I. Rusakova, A. Brazdeikis, D. Litvinov, T.R. Lee, Cryst. Growth
Des. 9 (2009) 32-34.
[3] Y. Chen, H. R. Chen, L. M. Guo, Q. J. He, F. Chen, J. Zhou, J. Feng, J. Shi, ACS Nano. 4 (2010)
529-539.
[4] D. Shi, H. S. Cho, Y. Chen, H. Xu, H. Gu, J. Lian, W. Wang, G. Liu, C. Huth, L. Wang, R. C.
Ewing, S. Budko, G. M. Pauletti, Z. Dong, Adv Mater. 21 (2009) 2170-2173.
[5] A. A. Jafari, H. Mahmoudi, H. Firouzabadi, RSC Adv. 5 (2015) 107474-107481.
[6] S. J. Zhang, X. H. Liu, L. P. Zhou, W. J. Peng, Mater Lett. 68 (2012) 243-246.
[7] H. Firouzabadi, N. Iranpoor, M. Gholinejad, J. Hoseini, Adv. Synth. Catal. 353 (2011) 125-132.
[8] M. Esmaeilpour, J. Javidi, J. Chin. Chem. Soc. 62 (2015) 614-626.
[9] H. Zhang, X. Zhong, J. J. Xu, H. Y. Chen, Langmuir. 24 (2008) 13748-13752.
[10] A. H. Lu, E. L. Salabas, F. Schuth, Angew. Chem. Int. Ed. 46 (2007) 1222-1244.
[11] Z. G. Xu, Y. Y. Feng, X. Y. Liu, M. Guan, C. D. Zhao, H. X. Zhang, Colloid. Surface. B. 81 (2010)
503-507.
[12] M. Esmaeilpour, J. Javidi, S. Zahmatkesh, N. Fahimi, Monatsh Chem. 148 (2017) 947-956.
[13] M. Esmaeilpour, J. Javidi, M. Divar, J. Magn. Magn. Mater. 423 (2017) 232-240.
[14] C. Hui, C. Shen, J. Tian, L. Bao, H. Ding, C. Li, Y. Tian, X. Shi, H. J. Gao, Nanoscale. 3 (2011) 701-
705.
[15] J. Javidi, M. Esmaeilpour, Mater. Res. Bull. 73 (2016) 409-422.
[16] N. Insin, J. B. Tracy, H. Lee, J. P. Zimmer, R. M. Westervelt, M. G. Bawendi. ACS Nano. 2 (2008)
197-202.
[17] M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji, H. Hassannezhad, J. Iran. Chem. Soc. 11 (2014)
1703-1715.
[18] A. Abou-Hassan, R. Bazzi, V. Cabuil. Angew. Chem., Int. Ed. 48 (2009) 7180-7183.
[19] M. Esmaeilpour, Jaber Javidi, J. Chin. Chem. Soc. 62 (2015) 328-334.
[20] G. Toskas, C. Cherif, R. D. Hund, E. Laourine, A. Fahmi, B. Mahltig, ACS. Appl. Mater. &
Interfaces. 3 (2011) 3673-3681.
[21] X. Q. Xu, C. H. Deng, M. X. Gao, W. J. Yu, P. Y. Yang, X. M. Zhang, Adv. Mater. 18 (2006) 3289-
3293.
[22] Y. H. Deng, D. W. Qi, C. H. Deng, X. M. Zhang, D. Y. Zhao, J. Am. Chem. Soc. 130 (2008) 28-29.
[23] M. Esmaeilpour, J. Javidi, M. Zandi, New. J. Chem. 39 (2015) 3388-3398.
[24] J. F. Hartwig, Nature. 455 (2008) 314-322.
[25] H. Firouzabadi, N. Iranpoor, A. Ghaderi, J. Mol. Catal A: Chem. 347 (2011) 38-45.
[26] M. Esmaeilpour, A. Sardarian, J. Javidi, Catal. Sci. Technol. 6 (2016) 4005-4019.
[27] A. R. Hajipour, N. S. Tadayoni, Z. Khorsandi, Appl. Organomet. Chem. 30 (2016) 590-595.
[28] V. Kandathil, B. D. Fahlman, B. S. Sasidhar, S. A. Patil, S. A. Patil, New J. Chem., 41 (2017)
9531-9545.
[29] M. Esmaeilpour, S. Zahmatkesh, N.Fahimi, M. Nosratabadi, Appl. Organomet. Chem. (2018)
Doi:10.1002/aoc.4302.
[30] H. Firouzabadi, N. Iranpoor, A. Ghaderi, Org. Biomol. Chem. 9 (2011) 865-871.
[31] Y. Koyama, M. J. Lear, F. Yoshimura, I. Ohashi, T. Mashimo, M. Hirama, Org. Lett. 7 (2005) 267-
270.
[32] Z. I. Dehimat, S. Yasar, D. Tebbani, I. Özdemir, Inorg. Chim. Acta. 469 (2018) 325-334.
[33] M. J. Climent, A. Corma, S. Iborra, M. Mifsud, Adv. Synth. Catal. 349 (2007) 1949-1954.
[34] M. N. Birkholz, Z. Freixa, P. W. N. M. van Leeuwen, Chem. Soc. Rev. 38 (2009) 1099-1118.
[35] M. Esmaeilpour, J. Javidi, M. Mokhtari Abarghoui, F. Nowroozi Dodeji, J. Iran. Chem. Soc. 11
(2014) 499-510.
[36] R. Chinchilla, C. Najera, Chem. Rev. 107 (2007) 874-922.
13

ACCEPTED MANUSCRIPT
[37] H. Firouzabadi, N. Iranpoor, F. Kazemi, M. Gholinejad, J. Mol. Catal A: Chem. 357 (2012) 154-161.
[38] N. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457-2483.
[39] L. Yin, J. Liebscher, Chem. Rev. 107 (2007) 133-173.
[40] S. Paul, J. H. Clark, Green Chem. 5 (2003) 635-638.
[41] T. Mino, Y. Shirae, M. Sakamoto, T. Fujita, J. Org. Chem. 70 (2005) 2191-2194.
[42] C. M. Crudden, D. P. Allen, Coord. Chem. Rev. 248 (2004) 2247-2273.
[43] N. Iranpoor, H. Firouzabadi, A. Safavi, S. Motevalli, M. M. Doroodmand, Appl Organomet. Chem.
26 (2012) 417-424.
[44] N. Iranpoor, H. Firouzabadi, S. Motevalli, M. Talebi, J. Organomet. Chem. 708-709 (2012) 118-124.
[45] S. Kim, H. J. Cho, D. S. Shin, S. M. Lee, Tetrahedron Lett. 58 (2017) 2421-2425.
[46] M. Khajehzadeh, M. Moghadam, J. Organomet. Chem. 863 (2018) 60-69.
[47] D. Kale, G. Rashinkar, A. Kumbhar, R. Salunkhe, React. Funct. Polym. 116 (2017) 9-16.
[48] T. Tu, Z. Sun, W. Fang, M. Xu, Y. Zhou, Org. Lett. 14 (2012) 4250-4253.
[49] Y. Takeda, Y. Ikeda, A. Kuroda, S. Tanaka, S. Minakata, J. Am. Chem. Soc. 136 (2014) 8544-8547.
[50] C. Gao, H. Zhou, S. Wei, Y. Zhao, J. You, G. Gao, Chem. Commun. 49 (2013) 1127-1129.
[51] M. Bahadori, S. Tangestaninejad, M. Moghadam, V. Mirkhani, A. Mechler, I. Mohammadpoor-
Baltork, F. Zadehahmadi, Micropor. Mesopor. Mat. 253 (2017) 102-111.
[52] C. J. Li, B. M. Trost, Proc. Natl. Acad. Sci. 105 (2008) 13197-13202.
[53] L. Chen, Chem. Soc. Rev. 35 (2006) 68-82.
[54] D. Dallinger, C. O. Kappe, Chem. Rev. 107 (2007) 2563-2591.
[55] M. Esmaeilpour, A. R. Sardarian, Green. Chem. Lett. Rev. 7 (2014) 301-308.
[56] M. Esmaeilpour, J. Javidi, F. Dehghani, S. Zahmatkesh, Res. Chem. Intermed. 43 (2017) 163-185.
[57] M. Esmaeilpour, A. R. Sardarian, Curr. Organocatal. 4 (2017) 75-82.
[58] S. Zahmatkesh, M. Esmaeilpour, J. Javidi, RSC Adv. 6 (2016) 90154-90164.
[59] J. Javidi, M. Esmaeilpour, M. Rajabnia Khansari, RSC Adv. 5 (2015) 73268-73278.
[60] M. Esmaeilpour, A. R. Sardarian, A. Jarrahpour, E. Ebrahimi, J. Javidi, RSC Adv. 6 (2016) 43376-
43387.
[61] E. Mohammadi, B. Movassagh, J. Mol. Catal A-Chem. 418-419 (2016) 158-167.
[62] M. Esmaeilpour, J. Javidi, S. Zahmatkesh, Appl. Organometal. Chem. 30 (2016) 897-904.
[63] M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji, M. Mokhtari Abarghoui, J. Mol. Catal A: Chem. 393
(2014) 18-29.
[64] D. S. Martin, R. M. Rush, G. A. Robin, Inorg. Chem. 19 (1980) 1705-1709.
[65] B. M. Choudary, K. R. Kumar, Z. Jarnil, G. Thyagarajan, Chem. Commun. (1985) 931-932.
[66] M. Esmaeilpour, J. Javidi, F. Dehghani, J. Iran. Chem. Soc. 13 (2016) 695-714.
[67] X. Jin, K. Zhang, J. Sun, J. Wang, Z. Dong, R. Li, Catal. Commun. 26 (2012) 199-203.
[68] L. Zhang, L. Wang, H. Li, P. Li, Synth. Commun. 38 (2008) 1498-1511.
[69] V. I. De Paula, C. A. Sato, R. Buffon, J. Braz. Chem. Soc. 23 (2012) 258-266.
[70] S. Sobhani, Z. Zeraatkar, F. Zarifi, New J. Chem. 39 (2015) 7076-7085.
[71] M. Zhu, G. Diao, J. Phys. Chem. C. 115 (2011) 24743-24749.
[72] A. S. Singh, U. B. Patil, J. M. Nagarkar, Catal. Commun. 35 (2013) 11-16.
[73] N. Salam, S. K. Kundu, A. S. Roy, P. Mondal, K. Ghosh, A. Bhaumik, S. M. Islam, Dalton Trans. 43
(2014) 7057-7068.
[74] M. Ghiaci, M. Zargani, F. Moeinpour, A. Khojastehnezhad, Appl. Organometal. Chem. 28 (2014)
589-594.
[75] S. Sobhani, F, Zarifi, Chin. J. Catal. 36 (2015) 555-563.
[76] F. R. Fortea-Pérez, I. Schlegel, M. Julve, D. Armentano, G. De Munno, S. E. Stiriba, J. Organomet.
Chem. 743 (2013) 102-108.
[77] B. Movassagh, A. Takallou, A. Mobaraki, J. Mol. Catal. A: Chem. 401 (2015) 55-65.
[78] B. N. Lin, S. H. Huang, W. Y. Wu, C. Y. Mou, F. Y. Tsai, Molecules. 15 (2010) 9157-9173.
[79] A. Cwik, Z. Hell, F. Figueras, Tetrahedron Lett. 47 (2006) 3023-3026.
14

ACCEPTED MANUSCRIPT
[80] L. Yang, Y. Li, Q. Chen, Y. Du, C. Cao, Y. Shi, G. Pang, Tetrahedron. 69 (2013) 5178-5184.
[81] F. Dehghani Firuzabadi, Z. Asadi, F. Panahi, RSC Adv. 6 (2016) 101061-101070.
[82] M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji, M. M. Abarghoui, Transition. Met. Chem. 39 (2014)
797-809.
[83] A. Modak, M. Pramanik, S. Inagaki, A. Bhaumik, J. Mater. Chem. A. 2 (2014) 11642-11650.
[84] H. Salemi, B. Kaboudin, F. Kazemi, T. Yokomatsu, RSC Adv. 6 (2016) 52656-52664.
Figure Captions:
Scheme 1. Synthetic process of N-Heterocyclic carbene-Pd(II) complex based on theophylline
supported on Fe3O4@SiO2 NPs (Fe3O4@SiO2-NHC-Pd(II) MNPs).
Scheme 2. Suzuki and Sonogashira coupling reactions in the presence of Fe3O4@SiO2-NHC-
Pd(II) MNPs.
Fig 1. FT-IR spectra: (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-NH2, (d )Fe3O4@SiO2-TCT,
(e) Fe3O4@SiO2-TCT-NH2, (f) Theophylline derivative 4, (g) Fe3O4@SiO2-Theophylline, and
(h) Fe3O4@SiO2-NHC-Pd(II) MNPs.
Fig 2. XRD patterns of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(II) NPs.
Fig 3. TEM images of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(П) NPs; FE-
SEM images of (d) Fe3O4, (e) Fe3O4@SiO2, and (f) Fe3O4@SiO2-NHC-Pd(П) NPs and the
histograms illustrate the size distribution of (g) Fe3O4, (h) Fe3O4@SiO2, and (i) Fe3O4@SiO2-
NHC-Pd(П) NPs, respectively.
Fig 4. (a) EDX spectra of Fe3O4@SiO2-NHC-Pd(II) NPs; (b) UV-Vis spectra of Fe3O4@SiO2,
Fe3O4@SiO2-Theophylline and Fe3O4@SiO2-NHC-Pd(II) NPs; (c) XPS spectra of fresh
Fe3O4@SiO2-NHC-Pd(II) catalyst and after the first run.
Fig 5. (A) thermogravimetric analysis of (a) Fe3O4@SiO2-NH2, (b) Fe3O4@SiO2-TCT, (c)
Fe3O4@SiO2-TCT-NH2 and (d) Fe3O4@SiO2-NHC-Pd(II) NPs; (B) Room temperature magnetic
hysteresis loops of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(II) NPs.
Fig 6. (a) Reusability test for Fe3O4@SiO2-NHC-Pd(II) in the synthesis of 3p and 5i under the
optimized conditions; (b) and (c) FE-SEM and DLS images of Fe3O4@SiO2-NHC-Pd(II)
nanoparticles after eight reaction cycles (phenylboronic acid with bromobenzene).
Table Captions:
Table 1. Selected properties of Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2-NHC-Pd(II) NPs.
Table 2. Elemental analysis (EA) and TGA results for the preparation of N-heterocyclic carbene-
Pd(II) complex based on theophylline supported on Fe3O4@SiO2 NPs.
Table 3 Suzuki reaction of benzeneboronic acid with 4-bromotoluene catalyzed by Fe3O4@SiO2-
NHC-Pd(П).
Table 4 Suzuki reaction of arylboronic acids with aryl halides (I, Br, Cl) catalyzed by
Fe3O4@SiO2-NHC-Pd(П) NPs under optimal conditions.
Table 5 The optimization of Sonogashira reaction using Fe3O4@SiO2-NHC-Pd(П) catalyst.
Table 5. The optimization of Sonogashira reaction using Fe3O4@SiO2-NHC-Pd(П) catalyst.
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Table 6. Sonogashira cross-coupling reaction of different aryl halides (I, Br, Cl) with terminal
alkynes in the presence of Fe3O4@SiO2-NHC-Pd(П) NPs.
Table 7. Catalytic activity of Fe3O4@SiO2-NHC-Pd(II) in comparison with some other
supported Pd catalysts used for Suzuki (phenylboronic acid with bromobenzene) and
Sonogashira- Hagihara (phenylacetylene with bromo benzene) coupling reactions.
Scheme 1. Synthetic process of N-Heterocyclic carbene-Pd(II) complex based on theophylline
supported on Fe3O4@SiO2 NPs (Fe3O4@SiO2-NHC-Pd(II) MNPs).
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Fig 1. FT-IR spectra: (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-NH2, (d )Fe3O4@SiO2-TCT,
(e) Fe3O4@SiO2-TCT-NH2, (f) Theophylline derivative 4, (g) Fe3O4@SiO2-Theophylline, and
(h) Fe3O4@SiO2-NHC-Pd(II) MNPs.
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Fig 2. XRD patterns of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(II) NPs.
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Fig 3. TEM images of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(П) NPs; FE-
SEM images of (d) Fe3O4, (e) Fe3O4@SiO2, and (f) Fe3O4@SiO2-NHC-Pd(П) NPs and the
histograms illustrate the size distribution of (g) Fe3O4, (h) Fe3O4@SiO2, and (i) Fe3O4@SiO2-
NHC-Pd(П) NPs, respectively.
Table 1. Selected properties of Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2-NHC-Pd(II) NPs.
Sample
Fe3O4 crystal structure Specific surface area Magnetite particle size
(m2/g)a (nm)b
Fe3O4
Cubic spinel
Cubic spinel
Cubic spinel
480
11.33
12.64
15.51
Fe3O4@SiO2
430.3
373.1
Fe3O4@SiO2-NHC-Pd(II)
a Calculated by the BJH method.
b Calculated by the Scherrer equation based on powder X-ray diffraction (XRD) patterns.
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Fig 4. (a) EDX spectra of Fe3O4@SiO2-NHC-Pd(II) NPs; (b) UV-Vis spectra of Fe3O4@SiO2,
Fe3O4@SiO2-Theophylline and Fe3O4@SiO2-NHC-Pd(II) NPs; (c) XPS spectra of fresh
Fe3O4@SiO2-NHC-Pd(II) catalyst and after the first run.
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Fig 5. (A) Thermogravimetric analysis of (a) Fe3O4@SiO2-NH2, (b) Fe3O4@SiO2-TCT, (c)
Fe3O4@SiO2-TCT-NH2 and (d) Fe3O4@SiO2-NHC-Pd(II) NPs; (B) Room temperature magnetic
hysteresis loops of (a) Fe3O4, (b) Fe3O4@SiO2 and (c) Fe3O4@SiO2-NHC-Pd(II) NPs.
Table 2. Elemental analysis (EA) and TGA results for the preparation of N-heterocyclic
carbene-Pd(II) complex based on theophylline supported on Fe3O4@SiO2 NPs.
Sample
Fe3O4@SiO2-NH2
C (%)
6.614
6.746
7.464
7.377
15.946
16.172
32.856
33.341
H (%)
1.475
1.501
0.752
0.717
2.871
2.918
4.301
4.336
N (%)
2.532
2.627
5.614
5.736
10.377
10.564
15.211
15.323
EA (wt%)
TGA (wt%)
EA (wt%)
TGA (wt%)
EA (wt%)
TGA (wt%)
EA (wt%)
TGA (wt%)
Fe3O4@SiO2-TCT
Fe3O4@SiO2-TCT-NH2
Fe3O4@SiO2-NHC-Pd(II)
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Scheme 2. Suzuki and Sonogashira coupling reactions in the presence of Fe3O4@SiO2-NHC-
Pd(II) MNPs.
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Table 3 Suzuki reaction of benzeneboronic acid with 4-bromotoluene catalyzed by Fe3O4@SiO2-
NHC-Pd(П).a
Entry
1
2
3
4
5
6
7
8
Base
Catalyst (mol% Pd)
Temp. (°C) Time (h)
Yieldb (%)
3
3
3
5
3
5
3
16
7
4
3
3
5
3
3
3
82
93
74
62
67
72
40
-
0.37
0.37
0.37
0.37
0.37
0.37
0.37
None
0.2
0.3
0.43
0.5
0.37
0.37
0.37
0.37
Na2CO3
K2CO3
K3PO4
KF
NaOH
NaOAc
Et3N
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
70
60
60
80
60
60
70
Reflux
60
60
60
60
r.t
73
85
92
88
46
9
10
11
12
13
14
15
16
78
87
92
50
70
80
aReaction conditions: 4-bromotoluene (1.0 mmol), phenylboronic acid (1.1 mmol), base (2.0 mmol), Fe3O4@
SiO2-NHC-Pd(П), H2O (3 mL).
bIsolated yield.
Table 4 Suzuki reaction of arylboronic acids with aryl halides (I, Br, Cl) catalyzed by Fe3O4@SiO2-
NHC-Pd(П) NPs under optimal conditions.a
X= I, 3c: 1h, 95%
X= I, 3f: 1h, 92%
X= I, 3a: 1h, 97%
X= I, 3b: 1h, 93%
CH3
X= I, 3d: 1.5h, 94%
X= I, 3e: 1.5h, 95%
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X= I, 3g: 0.75h, 97%
X= I, 3h: 2h, 91%
X= I, 3i: 1h, 91%
X= I, 3l: 1h, 95%
X= I, 3o: 1h, 93%
X= I, 3j: 2.5h, 90%
X= I, 3m: 1.5h, 93%
X= I, 3k: 2.5h, 92%
X= I, 3n: 2h, 92%
Me
X= Br, 3q: 3h, 95%
X= Br, 3t: 2.5h, 94%
X= Br, 3p: 3h, 96%
X= Br, 3s: 3h, 91%
X= Br, 3r: 4h, 91%
X= Br, 3u: 2.5h, 93%
X= Br, 3v: 2h, 95%
X= Br, 3y: 2.5h, 94%
X= Br, 3x: 3h, 88%
X= Br, 3aa: 2h, 93%
X= Br, 3w: 3.5h, 87%
X= Br, 3z: 3.5h, 87%
X= Cl, 3ac: 16h, 72%
X= Cl, 3ab: 16h, 77%
X= Cl, 3ae: 20h, 69%
X= Cl, 3ad: 16h, 75%
X= Cl, 3ag: 16h, 71%
X= Cl, 3af: 16h, 79%
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X= Cl, 3aj: 12h, 83%
X= Cl, 3am: 16h, 70%
X= Cl, 3ah: 16h, 80%
X= Cl, 3ak: 12h, 80%
X= Cl, 3ai: 16h,78%
X= Cl, 3al: 14h, 74%
aReactions were carried out under aerobic conditions in 3 ml of H2O, 1.0 mmol of aryl halide, 1.1 mmol of arylboronic
acid and 2 mmol of K2CO3 in the presence of Fe3O4@SiO2-NHC-Pd(П) catalyst (0.37 mol% Pd for X= I and Br; 0.5
mol% Pd for X=Cl) at 60°C.
bIsolated yield.
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Table 5. The optimization of Sonogashira reaction using Fe3O4@SiO2-NHC-Pd(П) catalyst.a
Fe3O4@SiO2-NHC-Pd(II)
Reaction conditions
O2N
Br
O2N
+
Entry
Catalyst
Solvent
Base
Temp. (°C) Time (h) Yieldb (%)
(mol% Pd)
0.43
0.43
0.43
0.43
0.43
0.43
0.43
0.43
None
0.25
0.3
90
90
90
90
90
90
90
90
130
90
90
90
90
2.5
3.5
5.5
3.5
6
5
5
7
94
73
68
81
52
76
87
40
-
58
79
89
92
90
94
79
52
77
73
28
35
33
71
83
93
1
2
3
4
5
6
7
8
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
DMF
DMSO
MeOH
EtOH
H2O
THF
Toluene
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Piperidine
K2CO3
Na2CO3
Cs2CO3
K3PO4
NaOAc
Et3N
NaOH
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
24
10
5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3
0.37
0.5
2.5
2.5
3
90
0.55
0.43
0.43
0.43
0.43
0.43
0.43
0.43
0.43
0.43
0.43
0.43
100
110
Reflux
Reflux
Reflux
Reflux
Reflux
r.t
5
10
10
8
10
12
24
8
70
80
100
5
4
aReaction conditions: 1-bromo-4-nitrobenzene (1.0 mmol), phenylacetylene (1.1 mmol), Fe3O4@SiO2-NHC-Pd(П)
catalyst, base (2 mmol) and solvent (3 mL).
bIsolated yield.
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Table 6. Sonogashira cross-coupling reaction of different aryl halides (I, Br, Cl) with terminal alkynes in
the presence of Fe3O4@SiO2-NHC-Pd(П) NPs.a,b
X= I, 5a: 1.5, 95%
X= I, 5d: 2.5h, 88%
X= I, 5b: 2h, 90%
X= I, 5e: 1h, 94%
X= I, 5c: 2.5h, 93%
X= I, 5f: 1.25h, 91%
X= Br, 5i: 4h, 95%
X= Br, 5l: 6h, 86%
X= Br, 5o: 5h, 87%
X= I, 5g: 1h, 96%
X= Br, 5j: 6h, 86%
X= I, 5h: 2.5h, 90%
X= Br, 5k: 7h, 89%
X= Br, 5m: 7h, 84%
X= Br, 5n: 5h, 92%
X= Br, 5q: 2.5h, 95%
X= Br, 5t: 6h, 87%
X= Br, 5p: 4h, 93%
X= Br, 5s: 6h, 90%
X= Br, 5r: 5h, 91%
X= Cl, 5u: 14h, 75%
X= Cl, 5x: 18h, 74%
X= Cl, 5aa: 14h, 81%
X= Cl, 5y: 20h, 77%
X= Cl, 5w: 18h, 68%
X= Cl, 5z: 14h, 79%
X= Cl, 5ac: 9h, 87%
X= Cl, 5ab: 12h, 85%
X= Br, 5ae: 6h, 90%
X= I, 5ad: 2.5h, 92%
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X= Br, 5af: 10h, 87%
C6H13
X= Br, 5ag: 8h, 85%
X= Cl, 5aj: 16h, 76%
X= Br, 5ah: 10h, 90%
X= Cl, 5ak: 20h, 84%
X= Cl, 5ai: 18h, 80%
aReaction conditions: aryl halide (1 mmol), alkyne (1.1 mmol), piperidene (2 mmol), Fe3O4@SiO2-NHC-Pd(П) catalyst
(0.43 mol%), solvent-free, 90°C.
bIsolated yield.
Table 7. Catalytic activity of Fe3O4@SiO2-NHC-Pd(II) in comparison with some other
supported Pd catalysts used for Suzuki (phenylboronic acid with bromobenzene) and Sonogashira-
Hagihara (phenylacetylene with bromo benzene) coupling reactions.
Reaction
Catalyst
Conditions
Time Yield TOF Ref.
(h)
(%)
(h-1)
66.7
(SMNPs-Salen Pd (II)
(0.5 mol%)
Silica-APTS-Pd (1 mol%)
Pd3(dba) (1 mol%)
Pd-BIP-γ-Fe2O3@SiO2
(0.5 mol%)
DMF/H2O (1:1/v:v), K2CO3,
100 oC
1
Suzuki
3
100
[67]
2
3
Suzuki
Suzuki
DMA, K2CO3, 100 oC
4
24
95
78.5
23.6
3.27
[68]
[69]
THF, K3PO4, 80 oC
4
Suzuki
DMF, Et3N, 100 oC
3
92
61.3
[70]
5
6
7
Suzuki
Suzuki
Suzuki
Pd/MFC (0.308 mol %)
Pd–ZnFe2O4 (4.62 mol%)
EtOH, K2CO3,Reflux
EtOH, K2CO3, Reflux
1
9
6
98
85
89
16.33 [71]
2.04
[72]
[73]
Ru-MPTAT-1 (2.25 mol%) DMF, K2CO3, 80 oC
SiO2-Pa-Cyan-Cys-Pd
H2O, K2CO3, 100 oC
(0.5 mol%)
Pd(II)-isatin-ɣ-Fe2O3
Solvent-free, Et3N, 100 oC
(1.5 mol%)
Bis(oxamato)palladate(Π)
n-Bu4NBr, Et3N, 120 oC
(5 mol%)
Fe3O4@SiO2@C22–Pd(II)
DMF/H2O/75 oC
(0.5 mol%)
8
9
Suzuki
Suzuki
5
88
90
65
84
96
35.2
80
[74]
[75]
[76]
[77]
0.75
10 Suzuki
11 Suzuki
12 Suzuki
2
6
3
6.5
28
Fe3O4@SiO2-NHC-Pd(II)
K2CO3, H2O, 60 oC
(0.37 mol%)
This
work
[78]
[79]
86.5
13 Sonogashira MCM-41-Pd (0.1 mol%)
14 Sonogashira Pd/MgLa (1.5 mol% Pd)
Toluene/Bu3N, 100 oC
DMF/Et3N/80 °C
24
24
56
64
23.3
1.8
NHC-palladium complex
(1 mol%)
CPS-MNPs-NNN-Pd
(0.5 mol%)
15 Sonogashira
DMSO/K3PO4/100 °C
1
73
76
73
[80]
[81]
H2O/DMF (2:1/v:v), K2CO3,
90 °C
16 Sonogashira
24
6.3
Fe3O4@SiO2/Schiff
base/Pd(II) (0.5 mol%)
18 Sonogashira Pd-TPOP-1 (5 mol%)
17 Sonogashira
DMF/K2CO3/90 °C
6
85
52
75
28.3
0.87
55
[82]
[83]
[84]
DMF, Hexamine, 100 oC
H2O/DMF (3:1/v:v), K2CO3,
100 oC
12
9
19 Sonogashira MNP-CD-Pd (0.15 mol%)
Fe3O4@SiO2-NHC-Pd(II)
20 Sonogashira
This
work
Solvent-free, Piperidine, 90 oC
4
95
55.2
(0.43 mol%)
28