MgFe2O4/cellulose/SO3H nanocomposite: a new biopolymer-based nanocatalyst for one-pot multicomponent syntheses of polysubstituted tetrahydropyridines and dihydropyrimidinones

Article abstract of DOI:10.1007/s13738-017-1120-2

A new biopolymer cellulose-based magnetic heterogeneous catalyst, MgFe₂O₄/cellulose/SO₃H nanocomposite, was prepared. Fourier-transform infrared spectra, X-ray diffraction, energy-dispersive X-ray, field-emission scanning electron microscopy, thermal analysis (TG, DTG and DSC), dynamic light scattering and vibrating sample magnetometer measurements have been used to characterize the catalyst. Then, it was applied efficiently as an inexpensive and green catalyst in two multicomponent syntheses of polysubstituted tetrahydropyridines and dihydropyrimidinones under solvent-free conditions. The nanocatalyst can be recovered and reused several times without significant loss of catalytic activity.

Full text of DOI:10.1007/s13738-017-1120-2

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1120-2
ORIGINAL PAPER
MgFe2O4/cellulose/SO3H nanocomposite: a new biopolymer‑based
nanocatalyst for one‑pot multicomponent syntheses
of polysubstituted tetrahydropyridines and dihydropyrimidinones
Ali Maleki1 · Abbas Ali Jafari2 · Somayeh Yousef1,2
Received: 21 November 2016 / Accepted: 13 April 2017
© Iranian Chemical Society 2017
Abstract A new biopolymer cellulose-based magnetic het-
erogeneous catalyst, MgFe2O4/cellulose/SO3H nanocom-
posite, was prepared. Fourier-transform infrared spectra,
X-ray diffraction, energy-dispersive X-ray, feld-emission
scanning electron microscopy, thermal analysis (TG, DTG
and DSC), dynamic light scattering and vibrating sample
magnetometer measurements have been used to charac-
terize the catalyst. Then, it was applied effciently as an
inexpensive and green catalyst in two multicomponent
syntheses of polysubstituted tetrahydropyridines and dihy-
dropyrimidinones under solvent-free conditions. The nano-
catalyst can be recovered and reused several times without
signifcant loss of catalytic activity.
environmental considerations for the synthesis of organic
compounds [1, 2]. The stability of magnetic nanocatalysts
and their ease of recovery and reusability represent a key
issue regarding their potential applications in green syn-
thesis [1]. Ferrite materials with a general formula MFe2O4
are very important magnetic materials because of their vari-
ous applications. They are relatively inexpensive and show
attractive electrical properties as well as chemical and ther-
mal stabilities. Due to their effcient catalytic activity and
convenient separation, they have been used as catalysts for
a variety of industrially important reactions. In addition,
they can reduce waste production of chemical industries. It
is an important reason of using ferrites in industrial compa-
nies because of increasing demands for environmental con-
siderations that make the chemical industry to reduce the
chemical wastes [3, 4].
Keywords Nanocatalyst · Cellulose · Solid acid ·
MgFe2O4 magnetic nanoparticles · Tetrahydropyridine ·
Dihydropyrimidinone
Magnesium ferrite (MgFe2O4) has a cubic structure of
normal spinel type and is a soft magnetic n-type semicon-
ducting material [5]. It has been observed that the presence
of Mg in ferrite spinel lattices strongly modifes its envi-
ronmental stability. Indeed, the cation distribution can be
affected by various properties of ferrite materials like their
structural, magnetic and catalytic activity characteristics.
So, these features make MgFe2O4 as a most suitable can-
didate to be applied in different felds [6]. In fact, due to its
catalytic, electronic and magnetic properties, it is one of the
most important ferrites that are extensively investigated in
the feld of medicine, heterogeneous catalysis, adsorption,
gas sensors and many other magnetic technologies.5 In con-
trast to the spinel ferrites, the catalyst Fe2O3 loses its activ-
ity as it is reduced to FeO and metallic iron. These show
the necessity of incorporation of Mg in hybrid and com-
posite structures. In fact, the catalytic activity of MgFe2O4
is much higher than MgO and Fe2O3 due to the synergisti-
cally catalytic effect of Mg in coupling with Fe [7].
Introduction
In recent years, magnetic nanocatalysts have attracted con-
siderable attentions with regard to the growing need of
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1120-2) contains supplementary
material, which is available to authorized users.
* Ali Maleki
maleki@iust.ac.ir
1
Catalysts and Organic Synthesis Research Laboratory,
Department of Chemistry, Iran University of Science
and Technology, Tehran 1684613114, Iran
2
Department of Chemistry, Faculty of Science, Yazd
University, Yazd 89195.741, Iran
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J IRAN CHEM SOC
Nanoparticles (NPs) can form aggregates that lead to
decrease in their catalytic activity by decreasing the sur-
face area. Therefore, the dispersion of NPs in a polymeric
matrix is an approving way to enhance their catalytic activ-
ity [8, 9]. Cellulose is the most abundant organic polymer
in the Earth and is an attractive natural polysaccharide due
to its good chemical stability, mechanical strength, bio-
compatibility, hydrophilic and biodegradation properties.
In addition, cellulose is well known as an ideal biopoly-
mer for grafting and immobilization of various functional
groups such as acidic catalysts [10–12]. The combination
of MgFe2O4, cellulose and sulfonic acid properties makes
them as an attractive solid-supported acid catalyst for
chemical reactions such as organic heterocyclic syntheses
of tetrahydropyridine and dihydropyrimidine derivatives.
Multicomponent reactions (MCRs) are powerful tools
for green synthesis of organic compounds as well as they
are able to reach complex molecules by employing sim-
ple starting materials via one pot. Simplicity of operation,
smaller amounts of chemical wastes and short reaction
times are other features that lead them to be known as atom
economical reactions [2, 13, 14].
Tetrahydropyridine and dihydropyrimidine derivatives
exhibit signifcant biological properties. The tetrahydro-
pyridines were found to be potent antihypoxic [15], anti-
oxidant, antimicrobial [16] and anticancer agents [17].
They are also useful for treating Alzheimer diseases [18].
Dihydropyrimidines were known as calcium channel mod-
ulators, α1a adrenoceptor-selective antagonists, anti-HIV,
anticancer, anti-infammatory and antibacterial agents [19].
In continuation of our previous works on the preparation
and application of nanocatalysts in MCRs [20–29], in this
paper, we wish to report MgFe2O4/cellulose/SO3H nano-
catalyst as a new biopolymer cellulose-based sulfonic acid-
functionalized magnetic nanocomposite for two important
one-pot organic synthetic reactions including a fve-compo-
nent reaction of aryl-aldehydes, β-ketoesters and anilines to
yield polysubstituted 1,2,5,6-tetrahydropyridine derivatives
4a–l, and a three-component reaction of aryl-aldehydes,
β-ketoesters and urea to obtain 3,4-dihydropyrimidine-
2-(1H)-ones derivatives 6a–j (Scheme 1).
Scheme 1 One-pot synthesis of tetrahydropyridines 4a–l and dihy-
dropyrimidinones 6a–j via MCRs in the presence of the MgFe2O4/
cellulose/SO3H nanocatalyst
With regard to the importance of MgFe2O4 among fer-
rites (as mentioned earlier) and its good stability at high
temperatures, we decided to use MgFe2O4 instead of Fe3O4
for the synthesis of tetrahydropyridine and dihydropyrimi-
dine derivatives. High yields of the products were obtained
by applying both MgFe2O4 as a Lewis acid and SO3H as
a Brønsted acid. For example, regarding the synthesis of
tetrahydropyridines, only by using MgFe2O4/cellulose high
yields were found. In addition, when we used cellulose/
SO3H as a catalyst, the yield of the product was low. There-
fore, it can be concluded that they have synergistic effect to
increase the yield of the reaction.
Results and discussion
First, the MgFe2O4/cellulose nanocomposite was prepared
by in situ synthesis. Then, it was functionalized by ClSO3H
to yield sulfonic acid-supported nanocomposite. The con-
tent of acid sites of the nanocomposite was calculated by
using inverse titration method and was found to be in the
range of 3.5–3.7 mmol g−1
.
Literature survey discloses a few MCR methods for the
synthesis of tetrahydropyridines by using dicarbonyl com-
pounds, aldehydes and amines. But, most of them usually
require long reaction times [30, 31], harsh catalyst prepara-
tion procedure [32], use of hazardous solvents [30, 33, 34]
and/or operational complexity [35].
Characterization of MgFe2O4/cellulose/SO3H
nanocomposite
The magnetically separable sulfonic acid nanocomposite
was characterized by using Fourier-transform infrared spec-
tra (FT-IR), X-ray diffraction (XRD), energy-dispersive
X-ray (EDX), thermal analysis [thermogravimetry (TG),
derivative thermogravimetry (DTG) and differential scan-
ning calorimetry (DSC)], vibrating sample magnetometer
(VSM), dynamic light scattering (DLS) and feld-emission
To the best of our knowledge, this is the frst
report on design, preparation and characterization of
MgFe2O4/cellulose/SO3H
magnetic
nanocomposite
and also its application as a nanocatalyst in the synthe-
sis of highly substituted 1,2,5,6-tetrahydropyridines and
3,4-dihydropyrimidine-2-(1H)-ones.
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J IRAN CHEM SOC
scanning electron microscopy (FE-SEM) measurements
(see also supplementary information for FT-IR and DLS).
FT-IR spectra of MgFe2O4/cellulose/SO3H showed the
adsorptions marked with arrows at around of 3444, 2900
and 1377 cm−1 that are assigned to the OH and CH2 groups
of cellulose (Fig. S1). The absorptions of MgFe2O4 can be
seen around 450 and 590 cm−1. The higher-frequency band
at around 590 cm−1 is attributed to the vibration of bonds
between metal ions and oxygen ions in tetrahedral sites.
A low-frequency band at around 450 cm−1 ascribed to the
intrinsic vibration of the octahedral sites. To confrm the
catalyst stability, the FT-IR spectrum of the present nano-
catalyst after six times reusing was also provided (Fig. S2).
As can be seen, the nanocatalyst had almost good stability.
In addition, energy-dispersive X-ray (EDX) spectra of
the nanocomposite indicated the presence of C, H, O, S,
Mg and Fe elements in the nanocomposite (Fig. 1).
Fig. 2 XRD patterns of a MgFe2O4/cellulose/SO3H nanocomposite
and b calcined MgFe2O4/cellulose/SO3H nanocomposite at 600 °C
To clarify the crystalline or amorphous structure of
MgFe2O4/cellulose/SO3H nanocomposite, its XRD pattern
was provided (Fig. 2). XRD patterns exhibited that Fe2O3 is
crystallized in an orthorhombic phase (powder diffraction
fle, Ref. Code 00-024-0072) and cellulose in a monoclinic
phase (powder diffraction fle, Ref. Code 00-024-1977).
In order to show the crystalline phase of MgFe2O4 appro-
priately, the XRD patterns of the calcined nanocomposite
were also taken at 600 °C. The peak positions and relative
intensity of all diffracted peaks matched well with those
standard cubic spinel crystalline structures (powder diffrac-
tion fle, Ref. Code 01-071-1232). The diffraction peaks
at 2θ = 30.1, 35.5, 43.2, 53.5, 57.1 and 62.7 are related to
MgFe2O4. Peaks at 2θ = 24.7, 25.2, 28.6, 31.9, 33.6, 44.6
and 47.2 correspond to the characteristic peaks of cellulose.
The thermal behavior of the prepared nanocomposite
was investigated by TG, DTG and DSC analyses over the
temperature range of 20–1000 °C at air atmosphere (Fig. 3).
Thermal analysis identifed two sharp exothermic weight
losses on the TG curve. The frst weight loss observed at
297 °C may be due to decomposition and elimination
of sulfonic and organic groups of cellulose. The second
weight loss at 352 °C may be related to amorphous to crys-
talline phase transformation of MgFe2O4. This corresponds
to the migration of cation between the octahedral and tetra-
hedral sites. The mass decreased up to 600 °C indicates the
formation of crystalline nanoparticles of MgFe2O4. This is
confrmed by EDX spectra of the calcined nanocomposite
and also is consistent with XRD results (Figs. 2, 4).
The morphology of the nanocomposite is shown in
Fig. 5. The FE-SEM images showed that the nanoparti-
cles are well distributed within the microporous cellulose
matrix. As can be seen, the cellulose matrix has an impor-
tant role in stabilization of nanoparticles and prevents from
agglomeration.
As it is observed in Fig. 6, the MgFe2O4/cellulose and
MgFe2O4/cellulose/SO3H nanocomposites are paramag-
netic and their magnetization parameters were obtained at
1.15 and 1.3 emug−1 in 8 kOe applied feld, respectively.
By calcination of the nanocomposite at 600 °C, MgFe2O4
nanoparticles showed superparamagnetic behavior. This
difference can be attributed to the presence of magnetically
Fig. 3 TG, DTG and DSC curves of MgFe2O4/cellulose/SO3H nano-
composite
Fig. 1 EDX pattern of MgFe2O4/cellulose/SO3H nanocomposite
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J IRAN CHEM SOC
Fig. 4 EDX pattern of calcined MgFe2O4/cellulose/SO3H nanocom-
posite at 600 °C
Fig. 6 Magnetization curves of a MgFe2O4/cellulose, b MgFe2O4/
cellulose/SO3H and c MgFe2O4
dead surface layers of polymeric matrix around the mag-
netic nanoparticles and also the low crystallinity of the
nanocomposite.
DLS technique was applied for the investigation of the
size distribution of the MgFe2O4/cellulose/SO3H nanocom-
posite particles (Fig. S3). The mean diameter was measured
to be 1280 nm. This large value proves the existence of sul-
fonic groups and polymer layer on the surface of magnetic
nanoparticles.
Application of MgFe2O4/cellulose/SO3H nanocomposite
for the synthesis of tetrahydropyridine derivatives
In order to investigate the catalytic activity of the prepared
nanocomposite, it was applied in the synthesis of tetrahy-
dropyridine derivatives. To optimize the reaction condi-
tions, a model experiment was carried out with p-methyl
benzaldehyde (1 mmol), aniline (1 mmol) and ethyl ace-
toacetate (0.5 mmol) in the presence of a catalytic amount
of the nanocomposite (10 mg) under solvent-free condi-
tions to afford 4c in high yield (Table 1).
To illustrate the importance of the nanocatalyst in the
reaction, a model experiment was carried out in the pres-
ence of MgFe2O4 (obtained by calcination of the nanocom-
posite), cellulose, cellulose–sulfonic acid, MgFe2O4/cel-
lulose and MgFe2O4/cellulose/SO3H. The best amount of
the nanocomposite was 10 mg. As can be seen, when both
MgFe2O4 (as a Lewis acid) and SO3H (as a Brønsted acid)
were incorporated in the nanocomposite, better catalytic
activity was obtained. The increase in the amount of catalyst
does not improve the reaction yield. Lower amounts of the
catalyst resulted lower yields. In the absence of the catalyst,
Fig. 5 FE-SEM images of MgFe2O4/cellulose/SO3H nanocomposite
with different magnifcations
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J IRAN CHEM SOC
Table 1 Optimization of the reaction conditions
Entry
Catalyst
Catalyst amount (mg)
Solvent
Temperature (°C)
Time
Yield (%)
1
–
–
–
–
24 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
10 h
5 h
25
2
Cellulose
10
10
10
10
10
7
–
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
40
60
70
80
90
r.t.
r.t.
r.t.
r.t.
Trace
Nil
Nil
35
3
MgFe2O4
–
4
MgFe2O4/cellulose
–
5
cellulose/SO3H
–
6
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
–
90
7
–
84
8
15
10
10
10
10
10
10
10
10
10
–
80
9
–
89
10
11
12
13
14
15
16
17
–
89
–
2 h
90
–
25 min
1 h
95
–
95
EtOH
CH3CN
DMF
CHCl3
24 h
24 h
24 h
24 h
40
45
Trace
30
a trace amount of the product was observed. In addition,
various solvents such as CH3CN, DMF, CHCl3 and EtOH
were used to optimize the reaction media. The best results
were obtained under solvent-free conditions. It was also
found that the time of the reaction was temperature depend-
ent. As can be seen, by increasing the temperature up to
80 °C, time of the reaction was decreased. Therefore, tem-
perature does not have positive effect on the reaction.
The catalytic capability of the prepared nanocatalyst
is also shown in Table 2. Although the present nanocata-
lyst was prepared with regard to the synthesis of new
green catalyst for acid-catalyzed reactions, it has more
advantageous than previously reported catalysts such as
ceric ammonium nitrate (CAN) [30], silica-supported
boron trifouride (BF3.SiO2) [34], in situ generated ZnO
NPs [35], hybrid heteropolyacid (H14[NaP5W30O110])
and surface-modifed Fe3O4 magnetic nanoparticles
with guanidine-propyltrimethoxysilane linker (Fe@
Si-Gu-Prs) [32], Β-1-imidazole-2,3,4,6-tetrasulfonic-d-
glucopyranosyl bisulfate ([Bmim-G-(SO3H)4]+[HSO4]−)]
[37] and sodium dioctyl sulfosuccinate (SDOSS) [38] in
the synthesis of polysubstituted tetrahydropyridines (4c
and 4l). As indicated, by implying the present catalyst
there is no need for applying non-green solvents (acetoni-
trile, acetic acid, methanol, THF). Furthermore, the prepa-
ration of the magnetic nanocatalyst is easier, its separation
is simpler, the time of the reaction is shorter, and the yield
of the reaction is higher than the similar reported ones.
The results summarized in Table 3 clearly show the eff-
cient synthesis of highly substituted tetrahydropyridine
derivatives via 5-CR in the presence of the nanocatalyst
under solvent-free conditions at 80 °C.
Table 2 Comparison of the nano-MgFe2O4/cellulose/SO3H with other literature reports for the synthesis of 4c and 4l
Entry
Product
Catalyst
Solvent
Temperature
Time
Yield (%)
References
1
2
4c
4c
4c
4c
4c
4c
4c
4c
4l
CAN
MeCN
MeOH
H2O/THF
AcOH
–
r.t.
65
r.t.
r.t.
r.t.
r.t.
r.t.
80
40
80
23 h
8 h
78
71
89
94
91
91
73
95
53
96
[30]
BF3–SiO2
[34]
3
ZnO NPs
3 h
[35]
4
–
25 min
30 min
7 h
[33]
5
Fe@Si-Gu-Prs
[32]
6
ZrCl4
EtOH
H2O
[36]
7
SDOSS
4 h
[38]
8
MgFe2O4/cellulose/SO3H
[Bmim-G-(SO3H)4]+[HSO4]−
MgFe2O4/cellulose/SO3H
–
25 min
5 h
Present work
[37]
9
EtOH
–
10
4l
10 min
Present work
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J IRAN CHEM SOC
Table 3 Synthesis of highly substituted tetrahydropyridines via a 5-CR in the presence of the magnetic nanocatalyst under solvent-free condi-
tions at 80 °C
Entry
R1
R2
R3
Product
Time (min)
45
Yielda (%)
88
MP (°C)
Found
Reported
1
H
H
Et
174–176
175–176 [30]
NH
N
O
OEt
4a
2
H
H
Me
35
92
190–194
194–195 [30]
NH
N
O
OMe
4b
3
4
5
4-Me
H
H
H
Et
25
20
30
95
98
95
234–236
216–217
166–168
230–231 [30]
215–216 [30]
166–168 [36]
NH
O
OEt
N
4c
4-Me
Me
NH
N
O
OMe
4d
4-OMe
Et
NH
O
OEt
N
O
O
4e
6
7
4-OMe
4-NO2
H
H
Me
15
96
65
182–184
249–252
182–183 [30]
247–250 [30]
NH
N
O
OMe
O
O
4f
Et
120
NH
N
O
OEt
O2N
NO2
4g
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J IRAN CHEM SOC
Table 3 continued
Entry
R1
R2
R3
Product
Time (min)
70
Yielda (%)
80
MP (°C)
Found
Reported
8
4-NO2
H
Me
239–242
240–241 [30]
NH
N
O
OMe
O2N
NO2
4h
9
H
4-Me
4-Me
4-Me
Et
25
20
30
92
98
82
198–200
168–170
184–185
198–199 [37]
169–171 [37]
184–185 [37]
NH
N
O
OEt
4i
10
4-Me
Me
NH
O
OEt
N
4j
11
4-CN
Et
NH
O
OEt
N
NC
CN
4k
12
4-OH
4-Me
Et
10
96
220
218–220 [37]
NH
N
O
OEt
HO
OH
4l
a
Isolated yields
Application of MgFe2O4/cellulose/SO3H nanocomposite
for the synthesis of 3,4‑dihydropyrimidine‑2‑(1H)‑ones
derivatives
reactions, its catalytic activity was also investigated in
Biginelli reaction. In this regard, to optimize the reac-
tion conditions, the effects of solvents, temperatures and
the amounts of the nanocatalyst were investigated on
times and yields of the products (Table 4). The model
reaction was carried out between 4-methylbenzaldehyde
Due to success of the MgFe2O4/cellulose/SO3H nano-
composite as a novel magnetic acid catalyst for organic
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J IRAN CHEM SOC
Table 4 Optimization of the reaction conditions
Entry
Catalyst
Catalyst amount (mg)
Solvent
Temperature (°C)
Time
Yield (%)
1
–
–
–
–
24 h
Nil
Nil
Trace
30
2
Cellulose
20
20
20
20
20
20
20
20
20
15
25
20
20
20
20
20
–
90
20 min
20 min
20 min
20 min
24 h
3
MgFe2O4
–
90
4
MgFe2O4/cellulose
–
90
5
Cellulose/SO3H
–
90
45
6
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
MgFe2O4/cellulose/SO3H
–
r.t.
Nil
Nil
Nil
80
7
–
60
–
8
–
80
–
9
–
90
20 min
20 min
25 min
20 min
24 h
10
11
12
13
14
15
16
17
–
100
90
82
–
73
–
90
76
EtOH
EtOH
CH3CN
CHCl3
DMF
r.t.
Nil
60
Refux
Refux
Refux
90
7 h
8 h
40
10 h
25
8 h
45
(1 mmol), urea (1.5 mmol) and β-ketoester (1 mmol). The
high yield of the product was obtained by using 20 mg
of the nanocomposite at 90 °C under solvent-free con-
ditions. As can be seen, no reaction was observed in the
absence of the catalyst or in temperatures less than 90 °C.
The yield of the product does not improve by applying
more amounts of the catalyst. Lower amounts of the cata-
lyst were also led to lower yields. In addition, the solvent
effect was studied by applying CH3CN, DMF, CHCl3
and EtOH. To illustrate the importance of the nanocata-
lyst in the reaction, the model experiment was done in
the presence of MgFe2O4 (obtained from calcination of
the nanocomposite), cellulose, cellulose sulfonic acid and
MgFe2O4/cellulose.
Subsequently, a series of different 3,4-dihydropyrimi-
dine-2-(1H)-ones derivatives were prepared successfully
under optimized conditions (Table 5). As indicated, the
products were obtained in short times in a green media
with relatively high yields.
As can be seen in proposed reaction mechanism in
Scheme 2, the nanocatalyst activates ethyl acetoacetate and
aldehyde for nucleophilic attack and obtaining interme-
diates 7, 8, 9 and 10. Intermediate 10 tautomerized to 11
which is transformed to the product 4a by intramolecular
cyclization and then tautomerization.
To demonstrate the recyclability of the present compos-
ite nanocatalyst, it was recovered and reused several times
in the model reactions. After completion of the reactions,
the nanocatalyst was simply removed by using an external
magnet, washed with EtOH and reused in the subsequent
fresh reactions. The recycling of the nanocatalyst was
investigated in the reaction of 4-methylbenzaldehyde, urea
and a β-ketoester (Fig. 7). The recovered nanocatalyst was
reused at least six times. As can be seen, there was no sig-
nifcant loss of its catalytic activity after six runs.
Experimental
General
All solvents, chemicals and reagents were purchased from
Merck, Fluka and Aldrich chemical companies. Melting
points were measured on an Electrothermal 9100 appara-
tus and were uncorrected. All reactions and the purity of
the products were monitored by thin-layer chromatography
(TLC) using aluminum plates coated with silica gel F254
plates (Merck) using ethyl acetate and n-hexane as eluents.
The spots were detected under UV light. FT-IR spectra
were recorded on a Shimadzu IR-470 spectrometer. The 1H
NMR spectra were recorded on a Bruker NMR-500 MHz
spectrometer. EDX spectra were recorded on Sirius SD,
England. XRD diffractogram was collected on a Philips
PW 1800 diffractometer with CuK radiation and X’Pert
PRO MPD PW 3050/60 diffractometer with CuK radia-
tion. The magnetic property was measured on VSM-AGFM
Scheme 3 shows the generally accepted Biginelli reac-
tion mechanism. The acid-catalyzed addition of enolic form
ethyl acetoacetate (12) to the C=N bond that is formed via
the reaction of an aldehyde with urea (13) leads to the for-
mation of 14. After that, a cyclodehydration affords the
desired product 6a.
1 3

J IRAN CHEM SOC
Table 5 Synthesis of
Entry
1
R1
R2
Product
Time (min) Yielda (%) MP (°C)
Found
dihydropyrimidines via 3-CR in
the presence of the nanocatalyst
under solvent-free conditions
at 90 °C
Reported
H
Et
30
83
201–203 201–203 [39]
O
NH
EtO
N
H
O
6a
2
H
Me
25
85
209–210 208–210 [40]
O
NH
MeO
N
O
H
6b
3
4-Me
Et
20
80
175–176 169–171 [41]
O
NH
EtO
N
O
H
6c
4
4-Me
Me
20
82
205–207 204–206.4 [42]
O
NH
MeO
N
O
H
6d
5
4-OMe Et
25
85
200–202 199–201 [39]
O
O
NH
EtO
N
H
O
6e
6
4-OMe Me
20
83
190–193 191–1933 [39]
O
O
MeO
NH
N
H
O
6f
1 3

J IRAN CHEM SOC
Reported
Table 5 continued
Entry
7
R1
R2
Product
Time (min) Yielda (%) MP (°C)
Found
4-NO2
Et
35
65
200–203 201.1–202.7 [42]
NO2
O
NH
EtO
N
H
O
6g
8
4-NO2
Me
NO2
30
70
235–237 235–237 [39]
O
NH
MeO
N
H
O
6h
9
4-Cl
Et
Cl
25
77
212–213 212–214 [41]
O
EtO
NH
N
H
O
6i
10
4-Cl
Me
Cl
20
80
204–207 204.3–207.1 [42]
O
NH
MeO
N
H
O
6j
a
Isolated yields
Scheme 2 Proposed mechanism for the formation of 4a–l
1 3

J IRAN CHEM SOC
Scheme 3 Proposed mechanism for the formation of 6a–j
(Meghnatis Daghigh Kavir Co., Iran) vibrating sample
magnetometer at room temperature. Thermal analysis was
performed with TGA/DSC1 in atmosphere of air. FE-SEM
images were obtained on ZEISS SIGMA VP instrument.
The size distribution of nanocomposite was determined by
Malvern Zetasizer Nano-ZS DLS instrument.
Preparation of MgFe2O4/cellulose/SO3H nanocomposite
A mixture of MgFe2O4/cellulose (1 g) and dichlorometh-
ane (20 mL) was cooled to 0 °C. Then, chlorosulfonic
acid (1 mL) was added drop-wise, while the resulting
mixture was stirred vigorously. When the addition was
completed, the mixture was stirred until HCl gas evolu-
tion stopped. Then, the mixture was fltered and washed
with dichloromethane (30 mL) and methanol (30 mL)
and dried at room temperature to obtain the nanocompos-
ite as brown solid.
In situ preparation of MgFe2O4/cellulose
At frst, cellulose was dissolved in a solution of NaOH,
urea and H2O which was precooled to −8 °C. The result-
ing solution was centrifuged at 2000 rpm for 30 min for
degasifcation. The cellulose solution was cast onto a glass
plate. Then, 500 mL H2SO4 (5 wt%) was added for 5 min
for the coagulation and regeneration of the cellulose flms.
The resulting flms were washed with running water and
subsequently with distilled water. The wet flms obtained
were immersed in a 500 mL mixture of aqueous FeCl3 and
MgCl2 (2:1) for 24 h. Then, the flms were immersed in
500 mL of aqueous NaOH (4 mol/L) for 30 min and were
then rinsed with hot water for several times. Subsequently,
the precipitate was dried at 80 °C within 24 h.
Synthesis of polysubstituted 1,2,5,6‑tetrahydropyridines
4a–l
First, β-ketoester (0.5 mmol) and 0.01 g of the nano-
composite were added to aromatic amine (1 mmol) and
stirred till the formation of enamine (as monitored by
TLC). Then, 1 mmol of aromatic aldehyde was added
and stirred for appropriate time under solvent-free condi-
tions at 80 °C. Upon completion, ethyl acetate was added
to the mixture for dissolving the product. So, the nano-
composite can be removed easily by an external magnet.
After evaporating the solvent, the crystalline product was
obtained from hot ethanol.
Synthesis of 3,4‑dihydropyrimidine‑2‑(1H)‑ones
derivatives 6a–j
An aromatic aldehyde (1 mmol), urea (1 mmol),
β-ketoester (1 mmol) and the nanocomposite (0.02 g)
were heated at 90 °C. After completion of the reaction,
the mixture was dissolved in ethyl acetate for separating
the nanocatalyst by an external magnet. After evaporating
the solvent, the crystalline product was obtained from hot
ethanol.
Fig. 7 Recyclability studies of the nanocatalyst in the synthesis of
the products 4c and 6c
1 3

J IRAN CHEM SOC
Spectral data for the selected product
addition, when we used cellulose/SO3H as a catalyst, the
yield of the product was low. Therefore, it can be con-
cluded that they have synergistic effect to increase the yield
of the reaction.
Ethyl
1‑phenyl‑4‑(phenylamino)‑2,6‑di‑p‑tolyl‑1,2,5,6
‑tetrahydropyridine‑3‑carboxylate 4c (Table 3, entry
3) Yellow solid; IR (KBr): 3442, 3055, 3029, 2979,
2921, 2869, 1649, 1593, 1500, 1369, 1326, 1253, 1174,
Supporting information
1
1070, 1034 cm−1; H NMR (500 MHz, CDCl3): δ 1.45 (t,
J = 6.9 Hz, 3H, CH2CH3), 2.31 (s, 3H, CH3), 2.32 (s, 3H,
CH3), 2.75 (d, J = 14.7 Hz, 1H, CH2), 2.85 (dd, J = 15.0,
5.4 Hz, 1H, CH2), 4.29–4.34 (m, 1H, OCH2CH3), 4.41–4.46
(m, 1H, OCH2CH3), 5.10 (s, 1H, CH), 6.29 (d, J = 6.6 Hz,
2H, ArH), 6.40 (s, 1H, CH), 6.52 (d, J = 8.0 Hz, 2H, ArH),
6.58 (t, J = 7.0 Hz, 1H, ArH), 7.04–7.06 (m, 11H, ArH),
7.20–7.21 (m, 2H, ArH), 10.27 (s, 1H, NH).
Electronic Supplementary Information includes DLS dia-
gram and FT-IR spectra of the MgFe2O4/cellulose/SO3H
nanocomposite and selected H NMR copies of the prod-
1
ucts. This material is available electronically online.
Acknowledgements The authors gratefully acknowledge the partial
support from the Research Council of the Iran University of Science
and Technology.
Compliance with ethical standards
5‑Ethoxycarbonyl‑6‑methyl‑4‑(4‑methylphenyl)‑3,4‑dihy-
dropyrimidine‑2(1H)‑one 6c (Table 5, entry 3) White
solid; IR (KBr): 3245, 3118, 2979, 2929, 2869, 1704, 1649,
1461, 1222, 781 cm−1; 1H NMR (500 MHz, CDCl3): δ 1.22
(t, J = 7.1 Hz, 3H, CH3), 2.36 (s, 3H, CH3), 2.38 (s, 3H,
CH3), 4.11 (q, J = 7.1 Hz, 2H, OCH2), 5.41 (d, J = 2.4 Hz,
1H, CH), 5.68 (s, 1H, NH), 7.16 (d, J = 7.8 Hz, 2H, ArH),
7.25 (d, J = 7.9 Hz, 2H, ArH), 8.02 (s, 1H, NH).
Confict of interest The authors declare that they have no confict of
interest.
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