Bis(4-pyridylamino)triazine-stabilized magnetite nanoparticles: preparation, characterization and application as a retrievable catalyst for the green synthesis of 4H-pyran, 4H-thiopyran and 1,4-dihydropyridine derivatives

Article abstract of DOI:10.1002/aoc.3557

Synthesis of bis(4-pyridylamino)triazine stabilized on silica-coated nano-Fe₃O₄ particles, and their feasibility as a reusable heterogeneous basic catalyst are reported. The catalytic performance of this novel material was studied fo

Full text of DOI:10.1002/aoc.3557

Full paper
Received: 16 May 2016
Revised: 7 June 2016
Accepted: 12 June 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3557
Bis(4-pyridylamino)triazine-stabilized
magnetite nanoparticles: preparation,
characterization and application as a
retrievable catalyst for the green synthesis of
4H-pyran, 4H-thiopyran and 1,4-
dihydropyridine derivatives
M. A. Bodaghifard*, A. Mobinikhaledi and S. Asadbegi
Synthesis of bis(4-pyridylamino)triazine stabilized on silica-coated nano-Fe3O4 particles, and their feasibility as a reusable hetero-
geneous basic catalyst are reported. The catalytic performance of this novel material was studied for the green synthesis of highly
functionalized 4H-pyran, 4H-thiopyran and 1,4-dihydropyridine derivatives via one-pot multicomponent reactions. Eco-friendly
method, high yield and purity of desired products, short reaction time along with ease of workup procedure outline the advan-
tages of these new methodologies over earlier ones. Surface and magnetic properties of the core–shell hybrid nanoparticles were
characterized via transmission and scanning electron microscopies, X-ray diffraction, energy-dispersive X-ray and Fourier trans-
form infrared spectroscopies and vibrating sample magnetometry. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: magnetic nanoparticles; green chemistry; 4H-pyrans; 4H-thiopyrans; 1,4-dihydropyridines
structure of natural product analogues with numerous activities
Introduction
such as anti-bacterial,[14] anticancer,[15] anti-psychiatric,[16] anti-
hyperplasia[17] analgesic and anti-inflammatory[18] activities. Most
One of the most important carbon–carbon bond formations
in organic synthesis is the Knoevenagel condensation
reaction.[1] Specifically, the resulting α,β-unsaturated products
are beneficial intermediates in combination with Michael
addition, Diels–Alder reaction, Robinson annulations and
ene reaction for the production of highly functionalized
compounds.[2]
of the reported procedures for the synthesis of these compounds
are multiple-step reactions, which are accompanied with low
isolated yields, long reaction times and costly reagents.
2-Cyanothioacetamide[19] and carbon disulfide with primary
amines[20] have been used as the sulfur source for the synthesis
of thiopyrans.
4H-Pyran compounds represent a distinct structural motif[3] with
a broad range of biological and pharmacological properties such as
anticancer,[4] anti-HIV,[5] anti-inflammatory,[6] anti-microbial,[7]
anti-malarial,[8] anti-hyperglycaemic and anti-dyslipidemic[9]
properties. Moreover, 4H-pyrans are used for the treatment of
neurodegenerative diseases including Huntington’s, Parkinson’s
and Alzheimer’s diseases.[10] Traditional processes for 4H-pyran
synthesis were reported as the reaction of active methylene
compounds with an aldehyde or ketone in the presence of an
organic base such as piperidine or triethylamine under reflux and
multiple-step conditions.[11]
1,4-Dihydropyridines (1,4-DHPs) are a significant group of
heterocyclic compounds in the field of pharmaceuticals and
drugs.[21] 1,4-DHPs possess
a wide range of biological
activities such as anti-atherosclerotic,[22] vasodilator[23]
anti-diabetic,[24] geroprotective and hepatoprotective[25]
activities and
a group of calcium modulators for the
treatment of cardiovascular diseases.[26] For that reason,
increasing interest in 1,4-DHPs as synthetic targets is not
unexpected. The Hantzsch reaction is commonly used for
the preparation of 1,4-DHPs.[27] This method includes the
Thiopyran derivatives have been less studied than pyran
analogues. These compounds are used as multipurpose building
blocks in organic molecule synthesis and as key units in biological
and medicinal chemistry.[12] A broad range of biological activities
have been reported for sulfur-containing heterocyclic
compounds.[13] For instance, thiopyrans are broadly found in the
*
Correspondence to: Mohammad Ali Bodaghifard, Department of Chemistry,
Faculty of Science, Arak University, 38156-88349 Arak, Iran. E-mail:
mbodaghi2007@yahoo.com; m-bodaghifard@araku.ac.ir
Department of Chemistry, Faculty of Science, Arak University, 38156-88349, Arak,
Iran
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

M. A. Bodaghifard et al.
reaction of aldehydes, dicarbonyls and ammonium acetate
(primary amine/ammonia) in one-pot reflux with alcohol or
acetic acid.[28] In recent years, various modified methods have
been developed.[29]
Results and discussion
Characterization of novel MNPs-BPAT catalyst
Bis(4-pyridylamino)triazine-stabilized silica-coated magnetite nano-
particles were prepared via the procedure illustrated in Scheme 2.
Fourier transform infrared (FT-IR) spectroscopy, field emission scan-
ning electron microscopy (FE-SEM), transmission electron micros-
copy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray
diffraction (XRD), thermogravimetric analysis (TGA) and vibrating
sample magnetometry (VSM) were used to identify and character-
ize the prepared catalyst.
The FT-IR spectra of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2-NH2,
Fe3O4@SiO2-TCl2 and MNPs-BPAT are shown in Fig. 1. The FT-IR
spectrum of magnetic Fe3O4 MNPs shows the characteristic Fe O
absorption around 576 cmÀ1 (Fig. 1a). Fe3O4@SiO2 shows character-
istic FT-IR bands at around 1091 cmÀ1 (asymmetric stretching),
954 cmÀ1 (symmetric stretching), 815 cmÀ1 (in plane bending)
and 459 cmÀ1 (rocking mode) for the Si O Si group and confirm
the formation of SiO2 shell. A weak peak at 1616 cmÀ1 (twisting
vibration mode of H O H adsorbed in the silica shell) and broad
peaks in the range 3200–3500 cmÀ1 (stretching vibration mode of
Si OH) are apparent in the spectrum. The presence of the attached
alkyl groups is confirmed by the weak bands at 2931 and
2958 cmÀ1 related to C H symmetric and asymmetric stretching
modes (Fig 1c–e). Also, peaks appear at 1490–1620 cmÀ1 (C N in
heterocyclic rings) and 1430 cmÀ1 (C C in heterocyclic rings) indi-
cating the bond formation of bis(4-pyridylamino)triazine (Fig. 1e).
Therefore the obtained results prove that the functional groups
were successfully grafted onto the surface of the MNPs.
Organic–inorganic hybrid materials are of great interest as
heterogeneous catalysts in organic synthesis, since these
materials feature the functional diversity and flexibility of
organic structures merged with thermal and mechanical
stability of inorganic solids.[30] Their large surface area per
unit volume, a consequence of their small diameter, makes
them interesting in the area of heterogeneous catalysis;
Heterogeneous catalysis at the nanoscale takes advantage
of a high exposure of the active species leading to a higher
efficiency of the catalyst.[31] Nevertheless, the applications
of heterogeneous nanocatalysts are usually limited by the
inevitable loss of catalyst during the tedious separation
processes, i.e. filtration or centrifugation. In this vein, easily
separable magnetic nanoparticles (MNPs), e.g. Fe3O4, have
demonstrated
high
stability,
easy
synthesis
and
functionalization along with high surface area, low toxicity
and low cost. These superb properties make MNPs a target
for extensive investigation as inorganic supports in the
synthesis of semi-heterogeneous catalysts.[32] These metallic
nanoparticles can be coated with a silica shell to introduce
numerous surface Si OH groups for further modification and
higher chemical and colloidal stability since magnetic
agglomeration will be diminished.[33]
For the above reasons, we describe the synthesis and
characterization of a pyridine-based magnetic nanocatalyst,
namely bis(4-pyridylamino)triazine (MNPs-BPAT), to give
access to 4H-pyrans, 4H-thiopyrans and 1,4-dihydropyridines
as a new eco-friendly method (Scheme 1). This newly
designed catalyst fulfilled our endeavour towards a heteroge-
neous system with green synthetic aspects by avoiding the
use of hazardous basic conditions for accessing target hetero-
cyclic compounds.
FE-SEM was used to determine the size and morphology of the
MNPs-BPAT catalyst particles (Fig. 2a). MNPs-BPAT particles, as can
be seen from Fig. 2(a), have a mean diameter of about 15–30 nm
Scheme 1. Synthesis of 4H-pyran, 4H-thiopyran and 1,4-dihydropyridine
Scheme 2. Preparation of bis(4-pyridylamino)triazine-stabilized silica-
derivatives using novel MNPs-BPAT as catalyst.
coated nano-Fe3O4 particles (MNPs-BPAT).
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Appl. Organometal. Chem. (2016)

Synthesis of six-membered heterocycles by a novel MNPs catalyst
Figure 3. EDS spectrum of MNPs-BPAT nanoparticles.
Figure 1. Comparison of FT-IR spectra for (a) Fe3O4, (b) Fe3O4@SiO2, (c)
Fe3O4@SiO2-NH2, (d) MNPs-TCl2 and (e) MNPs-BPAT.
(533) planes of Fe3O4, respectively. These results match well with
the standard Fe3O4 sample (JCPDS card no. 85–1436) and showing
that the Fe3O4 nanoparticles are pure and have a cubic spinel struc-
ture. The broad peak from 2θ = 20° to 27° is consistent with an
amorphous silica phase of MNPs-BPAT (Fig. 4b).[34] The average
crystallite size of the MNPs by Scherrer’s formula (D = 0.9λ/β cos θ)
was estimated from the (311) XRD peak.[35] The crystallite size of
the MNPs as calculated from the width of the peak at 2θ = 35.7°
(311) is 19.11 nm, which is in the range determined using FE-SEM
and TEM analysis (Fig. 2).
TGA and DTG were used to determine the stability of the MNPs-
BPAT catalyst (Fig. 5). The magnetic catalyst shows two stages of
weight loss over the temperature range of the TGA (Fig. 5). The first
stage, including a low amount of weight loss at T < 250 °C, is due to
the removal of physically adsorbed solvent and surface hydroxyl
groups; the second stage at about 250 to nearly 580 °C is attributed
to the decomposition of the coating organic moiety in the nano-
composite. Therefore, the weight loss between 250 and 580 °C
gives the organic grafting ratios of the magnetic catalyst. The
and a nearly spherical shape. TEM analysis displays a grey silica shell
about 5–10 nm thick on a dark Fe3O4 core and the average size of
the synthesized nanoparticles is 15–30 nm (Fig. 2b). EDS analysis
clearly indicates the presence of N and C in the MNPs-BPAT catalyst
nanoparticles (Fig. 3). Additionally, the presence of Si, O and Fe sig-
nals shows that the iron oxide particles are loaded into silica, and
the higher intensity of the Si peak than the Fe peak demonstrates
that the Fe3O4 nanoparticles are trapped by the SiO2 layer.
The degree of crystallinity as well as the presence of MNPs-BPAT
catalyst and magnetic Fe3O4 was investigated using XRD measure-
ments (Fig. 4). In the XRD patterns of both MNPs-BPAT and MNPs
the same peaks are observed, demonstrating the retention of the
crystalline spinel ferrite core structure through the silica-coating
procedure.
The XRD patterns of the synthesized MNPs show diffraction
peaks at 2θ = 30.3°, 35.7°, 43.3°, 53.7°, 57.3°, 62.9° and 74.5° which
can be assigned to the (220), (311), (400), (422), (511), (440) and
Figure 2. (a) FE-SEM image and (b) TEM image of MNPs-BPAT nanoparticles.
Appl. Organometal. Chem. (2016)
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M. A. Bodaghifard et al.
Figure 4. XRD patterns of (a) Fe3O4 MNPs and (b) MNPs-BPAT.
Figure 6. Magnetic hysteresis loops of (a) Fe3O4 MNPs and (b) MNPs-BPAT.
Left-hand inset: magnified view from À20 to 20 Oe. Right-hand inset:
catalyst dispersed in liquid and attracted to an external magnet.
organic moiety grafted on the Fe3O4@SiO2 MNPs was approximately
16 wt.%. In accordance with this mass loss, it was calculated that
0.40 mmol of BPAT was loaded on 1 g of MNPs-BPAT catalyst. The
organic layer decomposition shows three weight loss steps at
250–420 °C (8 wt.%), 420–500 °C (3 wt.%) and 500–580 °C (5 wt.
%). Based on the weights of organic groups grafted onto the
surface of Fe3O4@SiO2 nanoparticles, these steps correspond to
4-aminopyridine, triazine and 3-aminopropylsilane, respectively.
Therefore, the MNPs-BPAT is stable around or below 250 °C.
The agreement between the organic content of MNPs-BPAT
measured by elemental analysis (0.38 mmol gÀ1) and the organic
group loading determined by TGA (0.40 mmol gÀ1) is clear
evidence that the organic BPAT groups are located on the surface
of Fe3O4@SiO2 nanoparticles.
VSM was used to characterize the magnetic properties of the
nanoparticles (Fig. 6). The hysteresis curve allows determination
of the saturation magnetization (Ms), remanent magnetization
(Mr) and coercivity (Hc). The magnetization of samples could be
completely saturated at high fields of up to 8000.0 Oe and, due
to the formation of a silica shell around the Fe3O4 core, Ms. of sam-
ples changes from 57.8 to 33.4 emu gÀ1. The hysteresis loops show
the superparamagnetic behaviour of the Fe3O4 and MNPs-BPAT
particles in which Mr. and Hc are close to zero (Mr = 0.80 and
1.15 emu gÀ1 and Hc = 4.80 and 15.35 Oe, respectively).[36] The
strong magnetization of the MNPs-BPAT particles is apparent by
virtue of their attraction to an external magnet (Fig. 6).
an external magnet, thereby removing the necessity for filtration
or centrifugation.
Synthesis of 4H-pyrans catalysed by MNPs-BPAT
For optimization of the reaction conditions, benzaldehyde,
malononitrile and ethyl acetoacetate were selected as model
substrates for the preparation of 4H-pyran compounds. First,
with MNPs-BPAT as the catalyst and using the mentioned
substrates, solvents with various polarity were used
(Table 1). Ethanol serves as the best solvent with respect to
green nature, polarity and clean workup procedure for this
synthesis. For the reaction completion, various amounts of
MNPs-BPAT were: 30 mg of the catalyst is sufficient. The
Table 1. Optimization of reaction conditions for preparation of 4H-
pyrans
After the characterization of the MNPs-BPAT catalyst, its role as a
heterogeneous catalyst was evaluated for synthesis of 4H-pyran,
4H-thiopyran and 1,4-dihydropyridine derivatives (Scheme 1). An
important feature of this nanocatalyst is simple separation using
Entry
Catalyst (mg)
Solvent Temp. (°C) Time (min) Yield (%)a
1
MNPs-BPAT (10) CH3CN
MNPs-BPAT (10) CH2Cl2
MNPs-BPAT (10) THF
MNPs-BPAT (10) H2O
MNPs-BPAT (10) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (50) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
r.t.
r.t.
15
25
25
15
20
20
20
15
15
15
25
45
20
20
20
20
90
65
87
85
70
93
90
90
90
88
73
45
58
60
65
45
2
3
r.t.
4
r.t.
5
r.t.
6
r.t.
7
r.t.
8
40
9
60
10
11
12
13
14
15
16
Reflux
0
—
EtOH
EtOH
r.t.
Fe3O4 (30)
r.t.
Fe3O4@SiO2 (30) EtOH
MNPs-NH2 (30) EtOH
MNPs-TCl2 (30) EtOH
r.t.
r.t.
r.t.
aIsolated yield.
Figure 5. TGA and DTG curves for MNPs-BPAT nanoparticles.
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Appl. Organometal. Chem. (2016)

Synthesis of six-membered heterocycles by a novel MNPs catalyst
model reaction using MNPs-BPAT as the catalyst was carried
out at various temperatures and the results are given in
Table 1. The best results are obtained at room temperature.
To define the role of MNPs-BPAT as a catalyst for the prepara-
tion of 4H-pyran, the model reaction was performed under
the same conditions with Fe3O4, Fe3O4@SiO2 and MNPs-BPAT
and without the catalyst. With respect to reaction time and
yield of product, the best results are achieved using MNPs-
BPAT as the catalyst (Table 1).
Arylaldehydes with either electron-withdrawing or electron-
donating groups as well as heteroaromatic aldehydes were exam-
ined using the optimized conditions to produce desired products.
It is found that the reactions for all of the various substrates proceed
efficiently to corresponding 4H-pyran products in excellent yields
(Table 2).
Scheme 3. Proposed mechanism for synthesis of 4H-pyrans using MNPs-
BPAT as catalyst.
A possible mechanism for the synthesis of 4H-pyrans is shown in
Scheme 3. Firstly, in the presence of MNPs-BPAT, standard
Knoevenagel condensation of aldehyde and malononitrile takes
place to form arylidene malononitrile as an intermediate. Then
ethyl acetoacetate anion attacks arylidene malononitrile via a
Michael addition and the process continues to the obtained target
product.
A possible mechanism for the formation of 4H-thiopyrans has
been considered previously.[20] The arylidene malononitrile
obtained from Knoevenagel condensation is attacked by a
second malononitrile anion and then by in situ formed
propylcarbamodithioic acid with propylamine and carbon disulfide
(Scheme 4).
Synthesis of 4H-Thiopyrans catalysed by MNPs-BPAT
Synthesis of 1,4-dihydropyridines catalysed by MNPs-BPAT
The best reaction conditions were investigated using the
reaction of benzaldehyde (1 mmol), malononitrile (2 mmol),
carbon disulfide (1.2 mmol) and propylamine (1 mmol) as a
model reaction (Table 3). The best result is achieved using
10 mg of MNPs-BPAT at room temperature in ethanol as a
solvent with respect to green nature, reaction time and yield
of the desired 4H-thiopyran (Table 3, entry 5). Arylaldehydes
with either electron-withdrawing or electron-donating groups
and heteroaromatic aldehydes can lead to the desired prod-
ucts in good to excellent yields (Table 4).
In order to optimize the method, the reaction of benzaldehyde
(1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol)
and ammonium acetate (1.2 mmol) was examined. This model
reaction for various solvents, temperatures and catalyst amounts
was studied to find the best conditions (Table 5). With respect to
yield of products and reaction time, the best result is achieved
using 30 mg of MNPs-BPAT as a catalyst in ethanol as a solvent
under reflux condition (Table 5, entry 6).
Table 3. Optimization of reaction conditions for preparation of 4H-
thiopyran derivatives
Table 2. Multicomponent one-pot synthesis of 4H-pyran derivatives
using MNPs-BPAT as catalyst
Entry
Aldehyde
Time Yield
(min) (%)a
M.p. (°C)b
Found Reported
Entry
Catalyst (mg)
Solvent Temp. (°C) Time (min) Yield (%)a
1
2
3
4
5
6
7
8
9
Benzaldehyde
20 93 191–193 194–195[37]
15 95 179–181 178–180[38]
15 90 157–160 154–157[39]
15 96 170–172 170–171[40]
20 94 180–182 179–180[41]
4-Nitrobenzaldehyde
4-Fluorobenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
1
MNPs-BPAT (10) CH3CN
MNPs-BPAT (10) CH2Cl2
MNPs-BPAT (10) THF
MNPs-BPAT (10) H2O
MNPs-BPAT (10) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (50) EtOH
MNPs-BPAT (10) EtOH
MNPs-BPAT (10) EtOH
MNPs-BPAT (10) EtOH
MNPs-BPAT (10) EtOH
r.t.
r.t.
20
15
20
30
15
15
15
10
10
20
25
30
30
30
30
30
72
81
73
0
2
3
r.t.
4
r.t.
4-(Dimethylamino)benzaldehyde 25 89 160–163 163–165[38]
5
r.t.
88
81
75
76
65
57
74
25
35
42
38
32
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
3-Nitrobenzaldehyde
25 86 139–142 143–145[37]
25 90 177–180 179–181[40]
15 92 184–186 184–186[42]
25 82 165–167 164–165[43]
15 85 156–158 152–154[42]
15 86 177–180 178–180[44]
15 85 190–192 189–191[40]
25 81 177–179 176–178[38]
15 91 158–160 175–177[45]
25 85 141–143 180–183[46]
6
r.t.
7
r.t.
8
40
10 3-Hydroxybenzaldehyde
11 3-Chlorobenzaldehyde
12 2-Nitrobenzaldehyde
13 2-Chlorobenzaldehyde
14 2-Bromobenzaldehyde
15 Thiophene-2-carbaldehyde
16 Nicotinaldehyde
9
60
10
11
12
13
14
15
16
Reflux
0
—
EtOH
EtOH
r.t.
Fe3O4 (10)
r.t.
Fe3O4@SiO2 (10) EtOH
MNPs-NH2 (10) EtOH
MNPs-TCl2 (10) EtOH
r.t.
r.t.
r.t.
aIsolated yield.
bMelting points were not corrected.
aIsolated yield.
Appl. Organometal. Chem. (2016)
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M. A. Bodaghifard et al.
Table 4. Multicomponent one-pot synthesis of 4H-thiopyran
Table 5. Optimization of reaction conditions for preparation of 1,4-
derivatives
dihydropyridine derivatives
Entry
Aldehyde
Time Yield
(min) (%)a
M.p. (°C)b
Reported
Found
1
2
3
4
5
6
Benzaldehyde
15 88 186–188 183–185[47]
10 88 197–199 202–204[48]
10 76 172–174 172–172.5[19]
10 85 188–190 189–190[19]
15 80 185–187 187–188[19]
15 82 171–173163[19]
4-Nitrobenzaldehyde
4-Fluorobenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-(Dimethylamino)
Entry
Catalyst (mg)
Solvent Temp. (°C) Time (min) Yield (%)a
1
MNPs-BPAT (10) CH3CN
MNPs-BPAT (10) CH2Cl2
MNPs-BPAT (10) THF
MNPs-BPAT (10) H2O
MNPs-BPAT (10) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (50) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
MNPs-BPAT (30) EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
60
45
45
30
45
25
20
20
25
25
25
25
45
30
30
30
30
61
48
74
33
81
95
92
68
59
35
16
12
37
48
41
29
2
3
4
benzaldehyde
15 78 182–184189[19]
5
7
8
9
4-Methylbenzaldehyde
3-Nitrobenzaldehyde
3-Bromoobenzaldehyde
10 88 211–213 210–211[19]
10 83 180–182 189–191[19]
15 79 172–174 173–175[19]
15 75 181–183 187–189[19]
10 81 166–168 164–165[19]
10 75 172–174 171–172[19]
10 85 212–214 212–214[20]
15 81 162–165 162–165[49]
15 78 202–204 198–201[19]
6
7
8
10 3-Metoxybenzaldehyde
11 2-Hydroxybenzaldehyde
12 2-Nitrobenzaldehyde
13 2-Chlorobenzaldehyde
14 2,4-Dichlorobenzaldehyde
15 Thiophene-2-carbaldehyde
16 Nicotinaldehyde
9
40
10
11
12
13
14
15
16
r.t.
0
—
EtOH
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
Fe3O4 (30)
Fe3O4@SiO2 (30) EtOH
MNPs-NH2 (30) EtOH
MNPs-TCl2 (30) EtOH
aIsolated yield.
bMelting points were not corrected.
aIsolated yield.
Likewise, arylaldehydes with either electron-withdrawing or
electron-donating groups and heteroaromatic aldehydes were
tested using the optimized conditions. For all of the various
substrates, the reactions proceed efficiently to corresponding
1,4-dihydropyridine products in good to excellent yields (Table 6).
A plausible mechanism for the formation of 1,4-dihydropyridine
derivatives is shown in Scheme 5. In the presence of MNPs-BPAT,
the arylidene malononitrile obtained from Knoevenagel condensa-
tion is attacked by ethyl acetoacetate anion. This intermediate
reacts with ammonium acetate to form the corresponding
1,4-dihydropyridine.
Catalyst recovery and reusability
Catalyst recovery and reusability are very important for industrial
and commercial uses as well as in green chemistry. Therefore, the
recovery and reusability of MNPs-BPAT (10 mg) were investigated
Table 6. Multicomponent one-pot synthesis of 1,4-dihydropyridine
derivatives
Entry
Aldehyde
Time Yield
(min) (%)a
M.p. (°C)b
Found Reported
1
2
3
4
5
6
7
8
9
Benzaldehyde
20
20
20
20
20
25
30
30
95 191–193 188–190[50]
96 170–172 173–175[50]
90 227–229 223–225[51]
93 221–222 221–223[50]
89 203–205 197–199[52]
91 185–187 188–190[51]
93 219–221 221–223[50]
86 188–191 192–194[52]
88 161–163 166–168[53]
85 177–179 176–177[54]
91 163–166 158–159[55]
89 213–215 209–211[51]
90 126–128 123–125[51]
86 208–210 204–205[54]
86 211–213 208–209[50]
89 220–222 226–228[53]
4-Nitrobenzaldehyde
4-Fluorobenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
3-Methoxybenzaldehyde
3,4-Dimethoxybenzaldehyde 30
10 3-Methylbenzaldehyde
25
20
30
20
25
25
25
11 3-Nitrobenzaldehyde
12 2-Methoxybenzaldehyde
13 2-Nitrobenzaldehyde
15 Furan-2-carbaldehyde
14 Thiophene-2-carbaldehyde
16 Nicotinaldehyde
aIsolated yield.
bMelting points were not corrected.
Scheme 4. Proposed mechanism for formation of 4H-thiopyrans using
MNPs-BPAT as catalyst.
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Appl. Organometal. Chem. (2016)

Synthesis of six-membered heterocycles by a novel MNPs catalyst
Conclusions
We have developed a facile, versatile, multicomponent, one-pot
and green methodology to access 4H-pyran, 4H-thiopyran and
1,4-dihydropyridine derivatives in the presence of MNPs-BPAT as
a new, efficient, magnetically separable and reusable heteroge-
neous catalyst. The MNPs-BPAT nanocatalyst was characterized
using FT-IR spectroscopy, XRD, TEM, FE-SEM, EDS, VSM and
TGA–DTG. Due to its magnetic property, the catalyst can be easily
separated using a magnet and is stable under reaction conditions.
The method offers several advantages, including green solvent
system, mild reaction conditions, high yields, short reaction times,
high atom economy and easy workup procedure.
Scheme 5. Proposed mechanism for synthesis of 1,4-dihydropyridines
using MNPs-BPAT as catalyst.
Experimental
General procedure for preparation of MNPs-BPAT
Fe3O4 MNPs were prepared by chemical co-precipitation of Fe3+
and Fe2+ ions as described in the literature.[56] The silica-coated
Fe3O4@SiO2 core–shell nanoparticles were prepared using
the Stöber method.[57] Aminopropyl-modified silica-coated
MNPs were prepared according to a reported procedure.[58]
N-Ethyldiisopropylamine as a base (0.7 ml) was added to a mixture
of oven-dried Fe3O4@SiO2-NH2 MNPs (1 g) and dry tetrahydrofuran
(THF; 10 ml) in a 50 ml round-bottomed flask. The reaction mixture
was stirred in an ice bath at 5 °C for 15 min and triazine trichloride
(1 g) was then added to the reaction mixture and stirred for 24 h at
this temperature. Upon completion, the triazine chloride-grafted
silica-coated MNPs (MNPs-TCl2) were collected and the resulting
solid washed thoroughly with hot toluene to remove unreacted
triazine trichloride.
Figure 7. Recyclability of MNPs-BPAT in the synthesis of 4H-thiopyran
MNPs-TCl2 (1 g) was added to a solution of 4-aminopyridine (1 g)
and N-ethyldiisopropylamine (1.3 ml) in dry toluene (10 ml) and
stirred at 80 °C for 16 h. Upon completion, the resulting solid was
separated using a magnet, and then washed with water and
ethanol and dried at 50 °C under vacuum to afford MNPs-BPAT
(analysis (%): C, 9.03; H, 0.80; N, 5.14).
derivatives.
General procedure for synthesis of 4H-Pyran derivatives
At room temperature, MNPs-BPAT (20 mg) was added to a mixture
of an aldehyde (1 mmol), malononitrile (1 mmol) and ethyl
acetoacetate (1 mmol) dissolved in ethanol (5 ml). The mixture
was stirred for the time given in Table 2. After completion of the
reaction, as confirmed by TLC, the catalyst was removed from the
reaction mixture using an external magnet and the product
solidified by the addition of water to the mixture. The solid product
was filtrated and then washed with ethanol, and dried in an oven at
70 °C. All of the desired products were characterized by comparison
of their physical data with those of known compounds in the
literature.
Figure 8. FT-IR spectra of fresh catalyst and that reused six times.
in the reaction of carbon disulfide (1.2 mmol), propylamine
(1 mmol), benzaldehyde (1 mmol) and malononitrile (2 mmol)
in 5 ml of ethanol at room temperature. After completion of the
reaction, the catalyst was easily separated using an external
magnet, washed with ethanol, dried under vacuum and reused
in a subsequent reaction. Nearly quantitative recovery of the
catalyst (up to 98%) could be achieved from each run. The
recycled nanocatalyst could be reused six times without an
appreciable reduction in catalytic activity or any additional treat-
ment (Fig. 7). After six runs, the recovered catalyst had no distinct
change in structure, as evident from a comparison of its FT-IR
spectrum with that of fresh catalyst (Fig. 8).
General procedure for synthesis of 4H-thiopyran derivatives
Propylamine (1 mmol) and carbon disulfide (1.2 mmol) were added
to a magnetically stirred mixture of 5 ml of ethanol as solvent,
aldehyde (1 mmol), malononitrile (2 mmol) and MNPs-BPAT
(0.01 g). At room temperature, the reaction mixture was stirred
and the progress of the reaction was checked by TLC. After comple-
tion of the reaction, the catalyst was easily separated using an
external magnet. With the addition of water to the mixture, the
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

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General procedure for synthesis of 1,4-dihydropyridine
derivatives
Aldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate
(1 mmol), ammonium acetate (1.2 mmol) and MNPs-BPAT (3 mg)
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We gratefully acknowledge the financial support of this work (grant
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