Synthesis, characterization and first application of keggin-type heteropoly acids supported on silica coated NiFe2O4as novel magnetically catalysts for the synthesis of tetrahydropyridines

Article abstract of DOI:10.1039/c4ra05133e

In this study, two heteroploly acids with Keggin structures (phosphotungestic acid (PWA) and phosphomolybdic acid (PMA)) have been supported on silica coated nickel ferrite nanoparticles (NiFe₂O₄@SiO₂). The synthesized catalysts were characterized by several methods (FT-IR, SEM, TEM, VSM, XRD, BET and ICP-AES), and the catalytic activities of these new and magnetic catalysts in synthesis of tetrahydropyridine derivatives have been investigated. These new catalysts showed that they can carry out reactions at room temperature in a short time and under solvent-free conditions. Moreover, the obtained results indicated that PWA supported NiFe₂O₄@SiO₂is a stronger acid than PMA to run these reactions. More importantly, the catalysts were easily isolated from the reaction mixture by a magnetic bar and reused at least five times without significant degradation in their activities. This journal is

Full text of DOI:10.1039/c4ra05133e

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Synthesis, characterization and first application of
keggin-type heteropoly acids supported on silica
coated NiFe2O4 as novel magnetically catalysts for
the synthesis of tetrahydropyridines†
Cite this: RSC Adv., 2014, 4, 39782
a
b
c
Hossein Eshghi, Amir Khojastehnezhad, Farid Moeinpour, Mehdi Bakavoli,a
*
*
Seyed Mohammad Seyedia and Mohsen Abbasia
In this study, two heteroploly acids with Keggin structures (phosphotungestic acid (PWA) and
phosphomolybdic acid (PMA)) have been supported on silica coated nickel ferrite nanoparticles
(NiFe2O4@SiO2). The synthesized catalysts were characterized by several methods (FT-IR, SEM, TEM,
VSM, XRD, BET and ICP-AES), and the catalytic activities of these new and magnetic catalysts in synthesis
of tetrahydropyridine derivatives have been investigated. These new catalysts showed that they can carry
out reactions at room temperature in a short time and under solvent-free conditions. Moreover, the
obtained results indicated that PWA supported NiFe2O4@SiO2 is a stronger acid than PMA to run these
reactions. More importantly, the catalysts were easily isolated from the reaction mixture by a magnetic
bar and reused at least five times without significant degradation in their activities.
Received 30th May 2014
Accepted 21st August 2014
DOI: 10.1039/c4ra05133e
www.rsc.org/advances
process. Magnetic separation of super MNPs is simple,
economic and promising for industrial applications.6,7
Introduction
Recently, Heydari and et al. reported synthesis of Fe3O4
MNPs for immobilizing HPAs catalyst, their synthesized catalyst
showed that can act as a magnetic separable catalyst and aer
completing the reaction can be isolated by using an external
magnet easily.8 Raee and et al. reported another MNPs with the
formula Fe2O3 for supporting PWA HPA, they obtained good
results in catalytic activity of these catalysts.9,10 In addition to
Fe3O4 and Fe2O3, there are iron oxides with ferrite structure and
general formula (AFe2O4), where A can be Mn, Co, Ni, Cu and
Zn.11–13 Ni ferrites (NiFe2O4) are one of the most versatile
magnetic materials, which have high saturation magnetization,
high Curie temperature, chemical stability and relatively high
permeability.14 Due to the sensitivity of the MNPs and strong
surface affinity toward silica, these NPs can be directly coated
with amorphous silica and give silica coated nickel ferrite
(NiFe2O4@SiO2 (designated as NFS)).
Development of new methods for preparation of recyclable
catalysts is of great economic and environmental importance in
the chemical and pharmaceutical industries. Immobilization of
homogeneous catalysts on various insoluble supports can lead
to simplied catalyst recycling via ltration or centrifugation.1
At present, nanoparticles (NPs) are attractive candidates as solid
supports for the immobilization of well dened homogeneous
catalysts.2 Because of the large surface area, which can carry a
high amount of catalytically active species, these supported
catalysts exhibit very high activity under mild conditions.
Among these NPs, much attention has been directed toward the
production of magnetic nanoparticles (MNPs),3–5 because these
NPs can be well dispersed in the reaction mixtures without
magnetic eld providing large surface for readily access of
substrate molecules. More importantly, aer completing the
reactions, the MNP catalysts can be isolated efficiently from the
Heteropoly acids (HPAs) are an important class of catalysts
having both redox and acid properties.15–17 Among them; HPAs
with Keggin structures such as PWA (H3PW12O40) and PMA
(H3PMo12O40) have received the most attention due to their
unique structure and strong acidity.18,19 Several advantages to be
highlighted of using supported HPAs compared to homoge-
neous examples include easier recovery and recycling aer
carrying out reactions, and simpler product separation.20
However, separation and recovery of the immobilized HPAs are
usually performed by ltration or centrifugation, which are not
eco-friendly processes. The immobilization of PWA and PMA on
product solution through
a simple magnetic separation
aDepartment of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad,
Mashhad, Iran
bDepartment of Chemistry, College of Science, Mashhad Branch, Islamic Azad
University, Mashhad, Iran. E-mail: akhojastehnezhad@yahoo.com; Fax: +98-511-
8435115; Tel: +98-511-8435000
cDepartment of Chemistry, College of Science, Bandar Abbas Branch, Islamic Azad
University, Bandar Abbas, 7915893144, Iran. E-mail: f.moeinpour@gmail.com;
fmoeinpour52@iauba.ac.ir; Fax: +98 761 6670242; Tel: +98 761 6670242
† Dedicated to memory of Prof. Dr Mohammad Rahimizadeh.
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silica-coated NiFe2O4 NPs (designated as NFS-PWA and NFS- surface area of the material was measured by nitrogen adsorp-
PMA) can be employed to derive a novel heterogeneous cata- tion isotherm method with (BET; NOVA 1200 Quanta Chro-
lyst system that possesses both a high separation efficiency and meinstrument). IR spectra were recorded on a Thermo Nicolet
a relatively high surface area to maximize catalyst loading and AVATAR-370 FT-IR spectrophotometer and 1H NMR spectra
activity.
Based on our earlier success in the preparation of MNPs as
were recorded on a Bruker DRX400 spectrometer.
catalysts21–23 and in continuation our achievements in synthesis
of novel catalysts,24–28 in this report, we synthesized NFS-PWA
and NFS-PMA as novel nanomagnetically-recoverable catalysts
and assessed their catalytic activities in synthesis of tetrahy-
dropyridine derivatives in room temperature and solvent-free
conditions. To the best of our knowledge, there are no exam-
ples of the use of nano magnetic catalysts, especially NiFe2O4
and HPAs for the synthesis of tetrahydropyridine derivatives
from condensation of aromatic aldehydes, substituted anilines
and ethyl acetoacetate. Therefore, we wish to report a simple,
green and an efficient synthetic method for synthesis of tetra-
hydropyridine derivatives using NFS-PWA and NFS-PMA as
heterogeneous and reusable catalysts under room temperature
and solvent-free conditions (Scheme 1).
Preparation of NFS-PWA and NFS-PMA
The silica coated MNPs (NFS, Fig. 1) were synthesized according
to our previous reports21–23 and then for immobilization of
different HPAs on the NFS, 0.75 g of PWA or 0.5 g of PMA was
dissolved in 5 mL of methanol. This solution was added drop
wise to a suspension of 1.0 NFS in methanol (50 mL) and then
ꢀ
the mixture was heated at 70 C for 48 h under vacuum while
being mechanically stirred and give supported magnetic nano
catalyst. The catalyst was collected by a permanent magnet and
dried in a vacuum overnight and aer rst drying, the
supported nano catalyst was calcined at 250 ꢀC temperature for
2 h.8–10
Synthesis of tetrahydropyridine derivatives (4a–u)
A mixture of primary amines (2.0 mmol), ethyl acetoacetate (1.0
mmol) and catalyst (0.03 g) was stirred for 5–10 min. Aer that
Experimental
All reagents were purchased from Merck and Aldrich and used aromatic aldehydes (2.0 mmol) were added to the reaction
without further purication. Melting points were determined mixture and stirred for 20–45 min at room temperature under
on an Electrothermal type 9100 melting point apparatus. The solvent-free conditions. Upon completion, the chloroform was
particle size and morphology of synthesized catalyst were added to the reaction mixture to dissolve the product and then
characterized with a transmission electron microscope (TEM) the catalyst could be placed on the side wall of the reaction
(Philips CM-200 and Titan Krios) and scanning electron vessel with the aid of an external magnet, and the reaction
microscope (SEM) (Philips XL 30 and S-4160) with gold coating. mixture was decanted to another vessel and the separated
The size dispersion of the samples was obtained using a laser catalyst was washed and dried to be reused in the next run. To
particle size analyzer (CORDOUAN, Vasco3). X-ray diffraction another vessel, the solvent was evaporated and the resulting
(XRD) measurements were performed using a Bruker axs crude product was recrystallized from ethanol and was collected
Company, D8 ADVANCE diffractometer (Germany). The BET and gave compounds (4a–u) in high yields.
Scheme 1 Synthesis of tetrahydropyridine derivatives in presence of NFS-PWA and NFS-PMA as nano acidic catalyst.
Fig. 1 Preparation of NFS-PWA and NFS-PMA.
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The known products (4a–p), were reported previously in the
Ethyl-(3-iodophenyl)-4-(3-iodophenylamino)-2,6-bis(4-
nitrophneyl)-1,2,5,6 tetrahydropyridine-3-carboxylate (4u).
Light yellow solid; IR (KBr): 3246, 3058, 2979, 2872,1652, 1593,
1448, 1372, 1253, 1070,cmꢁ1; 1HNMR (400 MHz, CDCl3) d ppm:
1.54 (t, J ¼ 7.5 Hz, 3H), 2.8 (d, J ¼ 15.2 Hz, 2H), 4.34–4.47 (m,
2H), 5.25 (m, 1H), 6.42–6.5 (m, 2H), 6.75–6.8 (m, 1H), 7.17 (m,
2H), 7.19 (m, 2H), 7.48–7.63 (m, 4H), 8.07–8.35 (m, 10H), 8.52 (d,
J ¼ 8.5, 2H), 10.28 (s, 1H, NH). Elemental analysis for:
1
literatures29–33 and the analytical and spectral data IR, H, and
13C NMR spectroscopy, mass spectrometry, and elemental
analysis for new products (4q–u) are described next.
Ethyl-(4-bromophenyl)-4-(4-bromophenylamino)-2,6-bis(4-
methoxyphenyl)-1,2,5,6 tetrahydropyridine-3-carboxylate (4q).
White solid: IR (KBr): 3239, 3064, 2979, 2834,1647, 1603, 1462,
1
1370, 1248, 1068,cmꢁ1; HNMR (400 MHz, CDCl3) d ppm: 1.47
(t, J ¼ 8.0 Hz, 3H), 2.70 (dd, J ¼ 15.4, 2.7 Hz, 1H), 2.83 (dd, J ¼
15.4, 5.6Hz, 1H), 3.79 (s, 6H), 4.27–4.35 (m, 1H), 4.42–4.49 (m,
1H), 5.04 (s, 1H), 6.20 (d, J ¼ 6.0, 2H), 6.29 (s, 1H),6.39 (d, J ¼
6.80 Hz, 2H), 6.76–6.88 (m, 5H), 7.04–7.24 (m, 7H), 10.26 (br s,
1H); 13C NMR (400 MHz, CDCl3) d ppm: 15.93, 34.73, 55.83,
56.4, 56.48, 58.75, 61.06, 100.17, 109.47, 114.84, 115.29, 115.78,
120.3, 128.3, 128.52, 128.69, 132.7, 133.14, 135.11, 136.21,
138.2, 147.12, 156.45, 159.39, 160.06, 169.32; MS m/z: 692;
Elemental analysis for: C34H32Br2N2O4: C, 58.97; H, 4.66; N,
4.05. Found: C, 59.16; H, 4.43; N, 3.89%.
Ethyl-(3-iodophenyl)-4-(3-iodophenylamino)-2,6-bis(phenyl)-
1,2,5,6tetrahydropyridine-3-carboxylate (4r). White solid: IR
(KBr): 3252, 3051, 2986, 2872, 1652, 1592, 1448, 1373, 1253,
1070,cmꢁ1; 1HNMR (400 MHz, CDCl3) d ppm: 1.53 (t, J ¼ 7.2 Hz,
3H), 2.72 (dd, J ¼ 14.4, 2.2 Hz, 1H), 2.84 (dd, J ¼ 14.4, 5.4Hz,
1H), 4.30–4.33 (m, 1H), 4.40–4.48 (m, 1H),5.08–5.18 (m, 1H),
6.26–6.33 (m, 1H), 6.37 (s, 1H), 6.49 (m, 1H),6.63 (t, J ¼ 7.0 Hz,
2H), 6.76 (t, J ¼ 7.5 Hz, 1H), 6.85 (d, J ¼ 7.2 Hz, 2H), 6.94 (d, J ¼
6.0 Hz, 1H), 7.15–7.29 (m, 9H), 7.43 (d, J ¼ 6.8 Hz, 1H), 10.29 (br
s, 1H); 13C NMR (400 MHz, CDCl3) d ppm: 16.02, 34.55, 56.29,
59.29, 61.16, 95.14, 96.58, 99.88, 113.48, 122.74, 126.27, 126.53,
127.3, 127.3, 127.64, 127.8, 128.76, 129.6, 130.2, 131.46, 135.51,
136.07, 140.21, 142.91, 144.18, 149.28, 156.37, 169.24; MS m/z:
726; Elemental analysis for: C32H28I2N2O2: C, 52.91; H, 3.89; N,
3.86. Found: C, 53.40; H, 3.63; N, 3.85%.
C
32H26I2N4O2: C, 47.08; H, 3.21; N, 6.86. Found: C, 47.45; H,
3.35; N, 6.52%.
Result and discussion
In order to determine the properties of these new acidic sup-
ported nanomagnetic catalysts, they were characterized by
various techniques, such as FT-IR (Fig. 2), SEM and TEM
(Fig. 3), particle size dispersion (Fig. 4), VSM (Fig. 5), XRD
(Fig. 6), BET (Table 1), and ICP/AES. The FT-IR spectra of NFS,
PWA, PMA, NFS-PWA and NFS-PMA are compared in Fig. 2. The
FT-IR spectrum of NFS (Fig. 2a) exhibits high intense absorp-
tion bands at 1200 cmꢁ1 and 1100 cmꢁ1 and these bands are
assigned to the longitudinal and transverse stretching vibration
modes of the Si–O–Si asymmetric bond respectively. Additional
bands at 812 cmꢁ1 and 470 cmꢁ1 are also identied as the
characteristic bands of Si–O–Si bond respectivelꢁy.2 The other
band observed at 950 cmꢁ1 assigned to the SiO3 vibrations
indicates the existence of non bridging oxygen ions.11 The
Ethyl-(3-bromophenyl)-4-(3-bromophenylamino)-2,6-bis(4-
chlorophenyl)-1,2,5,6 tetrahydropyridine-3-carboxylate (4s).
White solid: IR (KBr): 3237, 3056, 2966, 2855,1647, 1604, 1451,
1
1372, 1252, 1071 cmꢁ1; HNMR (400 MHz, CDCl3) d ppm: 1.50
(t, J ¼ 7.5 Hz, 3H), 2.71 (dd, J ¼ 14.6, 2.7 Hz, 1H), 2.79 (dd, J ¼
14.6, 5.4Hz, 1H), 4.32–4.37 (m, 1H), 4.44–4.50 (m, 1H), 5.09 (m,
1H), 6.30 (s, 1H), 6.37–6.43 (m, 4H), 6.61 (s, 1H), 6.78 (d, J ¼ 7.6
Hz, 2H), 6.90–7.30 (m, 9H), 10.30 (br s, 1H); 13C NMR (400 MHz,
CDCl3) d ppm: 15.97, 34.58, 55.89, 58.59, 61.36, 99.61, 112.8,
116.75, 120.98, 123.64, 124.51, 125.42, 128.68, 128.99, 128.18,
129.46, 129.95, 130.31, 131.25, 131.79, 133.64, 134.51, 140.1,
142.22, 142.53, 148.88, 156.05, 168.4; MS m/z: 700; Elemental
analysis for: C32H26Br2Cl2N2O2: C, 54.81; H, 3.74; N, 3.99.
Found: C, 54.65; H, 4.15; N, 4.05%.
Ethyl-(3-iodophenyl)-4-(3-iodophenylamino)-2,6-di(4-tolyl)-
1,2,5,6 tetrahydropyridine-3-carboxylate (4t). White solid; IR
(KBr): 3239, 3080, 2978, 2859,1647, 1603, 1454, 1371, 1255,
1068,cmꢁ1; 1HNMR (400 MHz, CDCl3) d ppm: 1.52 (t, J ¼ 7.6 Hz,
3H), 2.28 (s, 3H), 2.37 (s, 3H), 2.68 (dd, J ¼ 15.5, 2.2 Hz), 2.81
(dd, J ¼ 15.5, 5.6Hz), 4.34 (m, 1H), 4.47 (m, 1H), 5.05 (d, J ¼ 2.5,
1H), 6.23–6.83 (m, 2H), 6.4 (s, 1H), 6.47–6.51 (m, 2H), 6.75–6.93
(m, 4H), 7.03–7.44 (m, 8H), 10.28 (br s, 1H). Elemental analysis
for: C34H32I2N2O2: C, 54.13; H, 4.28; N, 3.71. Found: C, 54.19; H,
4.35; N, 3.52%.
Fig. 2 The FT-IR spectrum of (a) NFS (b) PWA (c) PMA (d) NFS-PWA
and (e) NFS-PMA.
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The morphological features and distribution of the NFS
MNPs were investigated by TEM and SEM techniques (Fig. 3a
and b). The TEM and SEM photographs demonstrate that the
NFS MNPs are almost spherical with regular in shape. Also, the
particle size dispersion diagram (Fig. 4) from the NFS NPs
shows that these MNPs have a size between 25 to 97 nm and
mean diameter is 53 nm.
It is of great importance that the core/shell material should
possess sufficient magnetic and superparamagnetic properties
for its practical applications. Magnetic hysteresis measure-
ments for the NiFe2O4 were done in an applied magnetic eld at
r.t., with the eld sweeping from ꢁ10 000 to +10 000 Oersted. As
shown in Fig. 5, the M (H) hysteresis loop for the samples was
completely reversible, showing that the nanoparticles exhibit
superparamagnetic characteristics. The hysteresis loops of
them reached saturation up to the maximum applied magnetic
eld. The magnetic saturation values of the NiFe2O4 are 16.71
emugꢁ1 at r.t. These MNPs showed high permeability in
magnetization and their magnetization was sufficient for
magnetic separation with a conventional magnet.
Fig. 3 (a) TEM and (b) SEM images of NFS.
The XRD diffraction patterns of prepared NiFe2O4, NFS-PWA
and standard pattern of NiFe2O4 are shown in Fig. 6. The
diffraction peaks in NiFe2O4 and NFS-PWA (Fig. 6a and b)
indicates that these MNPs have the spinel structure, with all the
major peaks matching the standard pattern of bulk NiFe2O4
(Fig. 6c) (JCPDS 10-325).11 In addition, it should be pointed out
that no separate crystal phase characteristic of bulk PWA existed
in the NFS-PWA, which conrms the high dispersion of PWA on
the support NFS.
Fig. 4 Particle size dispersion of NFS.
The surface area (BET) was determined by the nitrogen
adsorption–desorption isotherms of previously degassed solids,
at 120 ꢀC. Measurements were carried out at liquid nitrogen
boiling point, in a volumetric apparatus, using nitrogen as the
probe. The NFS, NFS-PWA and NFS-PMA have surface area 58,
37 and 41 m2 gꢁ1 respectively (Table 1). It is worth noting that
reducing surface area is a consequence of successful immobi-
lizing PWA and PMA onto the surface of silica coated Ni ferrite
NPs and this result is in agreement with FT-IR result.
According to inductively coupled plasma/atomic electron
microscopy (ICP/AEM), the content of PWA in the sample was
conrmed. The weight percentage of PWA in the fresh catalyst
was 32.1 wt%. For checking leaching stability of this supported
catalyst, aer completion the reaction, the catalyst was sepa-
rated by using of an external magnet and washed with excess
methanol and again; its PWA content was analyzed by ICP-AEM
technique. The weight percentage of PWA in the recovered
Fig. 5 Magnetization curve of NiFe2O4 at room temperature.
spectrum of PWA (Fig. 2b) shows typical bands for absorptions catalyst was 31.3 wt%. Based on these results, we can conclude
at 1080 (P–O), 982 (W]O), 890 and 802 (W–O–W) cmꢁ1
that there is no substantial difference in weight percentage of
,
also the spectrum of PMA (Fig. 2c) shows determined bands PWA in the recovered and fresh catalyst. Furthermore, in order
for absorptions at 1064 (P–O), 962 (Mo]O), 882 and 767 to further verify the stability of NFS-PWA during the reaction
(Mo–O–Mo) cmꢁ1 10 In the FT-IR spectrum of NFS-PWA (Fig. 2d) process, a control experiment was also carried out. Synthesis of
.
the appeared bands in the regions about 984, 888 and 807 cmꢁ1 tetrahydropyridines was rst carried out at room temperature
conrm the successful immobilizing of the PWA on the surface under solvent-free condition in the presence of NFS-PWA for 15
of silica coated nickel ferrite NPs. In the last FT-IR spectrum min and then the catalyst was removed from the reaction
corresponds to NFS-PMA (Fig. 2e), the characteristic bands at mixture. The reaction mixture (without NFS-PWA) was
963, 880 and 765 cmꢁ1 conrm that the PMA was supported well continued to be stirred under previous conditions for 15 min
on the surface of NFS.
any more. As shown in Fig. 7, the yield of the reaction was stable
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Fig. 6 XRD patterns of (a) prepared NiFe2O4 MNPs, (b) NFS-PWA and (c) standard pattern of bulk NiFe2O4 (JCPDS 10-325).
Table 1 BET surface area of NFS, NFS-PWA and NFS-PMA
mixture from the NFS-PWA and PWA was strongly adsorbed on
the surface of NFS NPs.
To investigate of the optimum amount of catalyst and
solvent effect, the model reaction, including of benzaldehyde,
aniline and ethyl acetoacetate was chosen. The efficiency of the
Compound
BET m2 gꢁ1
NFS
NFS-PWA
NFS-PMA
58
37
41
Table 2 Comparison of the amount of NFS-PWA and yields for
synthesis of tetrahydropyridine derivative (4p)
Entry
Catalyst amount (g)
Time (min)
Yield (%)
1
2
3
4
5
6
None
0.01
0.02
0.03
0.05
0.10
120
45
30
30
30
30
None
54
79
96
96
97
Table 3 Comparison of different solvents and solvent-free conditions
for synthesis of tetrahydropyridine derivatives (4p) using NFS-PWA and
NFS-PMA
Fig. 7 The results of the control experiments for the synthesis of
tetrahydropyridines, (green diagram) without catalyst filtration and
(blue diagram) catalyst filtration after 15 min.
Entry Catalyst Solvent
Time (min) Temperature Yield (%)
1
2
3
4
5
6
7
8
None
NFS-PWA H2O
solvent-free 120
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
No reaction
60
60
60
60
31
54
59
76
96
87
92
aer the removal of NFS-PWA. These results once again veried
that NFS-PWA was stable under our reaction conditions. The
reaction mixture was subjected to the elemental analysis by ICP-
AEM technology and no W was detected, which also indicated
that the supported PWA was not released into the reaction
NFS-PWA C2H5OH
NFS-PWA CH3OH
NFS-PWA CH3CN
NFS-PWA solvent-free 30
NFS-PMA solvent-free 30
NFS-PMA solvent-free 60
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Table 4 Synthesis of tetrahydropyridine derivatives (4a–u) using of NFS-PWA and NFS-PMA as a catalysta
Entry
R1
R2
Productb
Time (min)
Yieldc (%)
Mp (ꢀC)
Lit. Mp (ꢀC) ref.
1
2
3
4
5
6
7
8
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-NO2C6H4
4-CH3OC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
4-CH3C6H4
Ph
4-BrC6H4
4-NO2C6H4
4-CH3OC6H4
Ph
4-ClC6H4
4-BrC6H4
4-CH3C6H4
Ph
4-CH3OC6H4
4-BrC6H4
4-ClC6H4
4-CH3C6H4
4-CH3OC6H4
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
22/25
35/41
45/40
36/40
33/39
32/40
25/30
32/35
20/30
30/30
28/35
43/45
32/30
25/32
45/45
30/40
35/40
43/45
39/42
41/45
38/45
94/90
82/80
83/80
90/86
92/82
89/88
93/88
94/90
95/89
91/82
95/92
96/94
95/88
92/87
89/80
96/90
96/92
90/85
91/84
92/92
90/88
172–174
230–231
237–238
213–215
217–219
249–251
178–179
200–201
240–241
228–229
186–188
194–196
202–204
190–192
172–174
174–175
184–186
170–172
183–185
205–207
140–142
169–171 (32)
230–231 (33)
237–239 (30)
216–217 (32)
219–222 (32)
247–250 (33)
180–181 (30)
200–202 (31)
236–238 (31)
228–230 (31)
184–184 (29)
197–198 (32)
201–202 (33)
194–196 (32)
172–173 (33)
175–176 (33)
This work
9
10
11
12
13
14
15
16
17
18
19
20
21
Ph
Ph
Ph
Ph
4-CH3OC6H4
Ph
4-ClC6H4
4-CH3C6H5
4-NO2C6H5
4-BrC6H4
3-IC6H4
3-BrC6H4
3-IC6H5
This work
This work
This work
This work
4s
4t
4u
3-IC6H5
a
Benzaldehyde 1 (2.0 mmol), aniline 2 (2.0 mmol), ethyl acetoacetate 3 (1.0 mmol) and NFS-PWA and NFS-PMA (0.03 g) at room temperature under
solvent-free conditions. b The known products were identied by comparing of their melting points and new products were characterized by (FT-IR
and 1H NMR). c Isolated yields.
reaction is affected mainly by the amount of catalyst (NFS-PWA) the product 4p (entries 2, 3). The optimum amount of NFS-PWA
(Table 2). No product was obtained in the absence of the catalyst was 0.03 g (entry 4); increasing the amount of the catalyst
(entry 1) indicating that the catalyst is necessary for the reac- beyond this value did not increase the yield noticeably (entries
tion. Raising the amount of the catalyst increased the yield of 5, 6).
Scheme 2 Proposed mechanism for reactions between substituted benzaldehydes 1, aniline derivatives 2 and ethyl acetoacetate 3 for
generation of tetrahydropyridine derivatives 9.
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The same model reaction in the presence of 0.03 g of the show that, PWA is a stronger acid than PMA in catalyzed this
NFS-PWA was carried out in solvent-free conditions and also in reaction.
different solvents to assess the effect of solvent on the reaction
Aer optimization of the reaction conditions, the catalytic
yield. As shown in Table 3, for the reason of anionic structure activities of these new catalysts were tested by different
generation and hydrogen bonding formation in the polar aromatic amines, number of aromatic aldehydes, and ethyl
solvents such as H2O, MeOH, EtOH and MeCN, by the HPAs, the acetoacetate. The corresponding compounds (4a–t) were
reaction could be carried out in moderate yields (entries 2–5), synthesized by the reaction of aldehydes, amines, and ethyl
but the yields of the reaction under solvent-free conditions were acetoacetate using 0.03 g NFS-PWA and NFS-PMA at room
greater and the reaction times were generally shorter than the temperature and under solvent-free conditions. The results are
conventional methods. The best result was obtained at room shown in Table 4. As shown in Table 4, it was found that this
temperature for 30 min under solvent-free conditions (entry 6). method works well with a wide variety of substrates. The yields
Increasing the reaction time did not improve the yield. Subse- of the reactions in the presence of rst catalyst (NFS-PWA) were
quently, therefore, all reactions were carried out at room good to excellent. However, in some cases, yield of the reactions
temperature in the presence of 0.03 g NFS-PWA under solvent- in the presence of second catalyst (NFS-PMA) was not good
free conditions (entry 7). Moreover, the model reaction in the (entry 2, 3). The reaction of methyl, methoxy, chloro, bromo,
presence of 0.03 g NFS-PMA was carried out, we observed that and iodo substituted aromatic amines reacted in higher yield
the yield of the reaction in the same time and presence of a compared with nitroaniline (entry 4). Similarly, the reaction of
second catalyst (NFS-PMA) was lower than rst catalyst (NFS- chloro, methyl, and methoxy benzaldehyde proceeds smoothly
PWA) (entry 7), however, increasing the time reaction moder- compared to nitrobenzaldehyde (entry 6), in which, the yields
ately increased the yield of the reaction (entry 8). These results were low due to steric factors as well as the electron-
withdrawing effect of the nitro group.
Based on the proposed mechanism in the literature,34,35 it is
reasonable to assume that tetrahydropyridine derivatives 9 were
formed from the initial condensation of aromatic aldehyde 1
and b-ketoester 2 with aniline 3 that their carbonyl groups were
activated with HPAs supported nano catalysts (NFS-PWA and
NFS-PMA) to give enamine 4 and imine 5 (Scheme 2). Next,
enamine 4 reacts with imine 5 to produce intermediate 6
through an intermolecular Mannich-type reaction. The reaction
between intermediate 6 and aldehyde gives intermediate 7 by
the elimination of H2O. Then, tautomerization of 7 generates
intermediate 8, which immediately undergoes an intra-
molecular Mannich-type reaction to give desired tetrahy-
dropyridine derivatives 9.
To determine the applicability of catalyst recovery, at the end
Fig. 8 Reusability of NFS-PWA (blue columns) and NFS-PMA (brown
of the reaction, with the aid of an external magnet, the catalyst
columns) for model reaction.
Fig. 9 FT-IR spectrum of (a) fresh and recovered (after five times) NFS-PWA and (b) fresh and recovered (after five times) NFS-PMA.
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RSC Advances
was held on the side wall of the reaction vessel, while the 10 E. Raee and S. Eavani, J. Mol. Catal. A: Chem., 2013, 373, 30.
solution was decanted. The catalyst was washed with methanol 11 A. Chaudhuri, M. Mandal and K. Mandal, J. Alloys Compd.,
and chloroform to remove the residual product, dried at 100 ꢀC
2009, 487, 698.
¨
˘
¨
¨
under vacuum and reused in a subsequent reaction in excellent 12 Y. Koseoglua, A. Baykalb, M. S. Toprakc, F. Gozuaka,
yields. It showed the same activity as the fresh catalyst without
A. C. Ba¸sarand and B. Akta¸sd, J. Alloys Compd., 2008, 462,
any signicant loss of its activity (Fig. 8).
209.
The FT-IR spectra of NFS-PWA and NFS-PMA catalysts before 13 X. Hou, J. Feng, X. Xu and M. Zhang, J. Alloys Compd., 2010,
use (fresh) and aer reuse ve times (recovered) were studied. 491, 258.
As shown in Fig. 9, the FT-IR spectrum of the recovered NFS- 14 A. Goldman, Modern Ferrite Technology, Van Nostrand
PWA and NFS-PMA showed that the structure of catalysts Reinhold, New York, 1990.
remained almost the same aer ve-run reuse. In addition, the 15 M. T. Pope, Heteropoly and Isopoly Oxometallates, Springer-
weight of the recovered catalyst is the same as the amount of the
Verlag, Berlin, 1993.
fresh catalyst that was used the rst time in the reaction.
16 N. Mizuno and M. Misono, Chem. Rev., 1998, 98, 199.
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2014, DOI: 10.1016/j.arabjc.2014.02.009.
Conclusion
In summary, we prepared novel catalysts, including two types of
Keggin structures supported on the silica nickel ferrite NPs. The
prepared samples were characterized by FT-IR, SEM, TEM, XRD,
VSM, and BET. The content of the W in catalysts was measured
by inductively coupled plasma atomic emission spectroscopy
(ICP-AEM). The synthesis of tetrahydropyridine derivatives was
carried out using these nano acidic catalysts at room tempera-
ture in low time and under solvent-free conditions. Moreover,
the catalyst could be readily separated by use of a magnetic
force and reused at least ve runs without any signicant loss of
its catalytic activity.
24 M. Ghiaci, M. Zarghani, A. Khojastehnezhad and
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Acknowledgements
The authors are grateful to Ferdowsi University of Mashhad and
Islamic Azad University, Bandar Abbas and Mashhad Branches
for nancial support.
28 A. Davoodnia, A. Khojastehnezhad and N. Tavakoli-Hoseini,
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29 M. Lashkari, M. T. Maghsoodlou, N. Hazeri, S. M. Habibi-
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This journal is © The Royal Society of Chemistry 2014
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