SnCl4-functionalized nano-Fe3O4 encapsulated-silica particles as a novel heterogeneous solid acid for the synthesis of 1,4-dihydropyridine derivatives

Article abstract of DOI:10.1039/c5ra12734c

A novel type of green heterogeneous solid acid was prepared by the immobilization of SnCl₄ on the surface of Fe₃O₄@SiO₂ (Fe₃O₄@SiO₂-SnCl₄) and characterized by Fourier

Full text of DOI:10.1039/c5ra12734c

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SnCl4-Functionalized nano-Fe3O4 encapsulated-silica particles
as a novel heterogeneous solid acid for synthesis of
1,4-dihydropyridine derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Abdolhamid Bamoniri*, Sara Fouladgar
A novel type of green heterogeneous solid acid was prepared by the immobilization of SnCl4 on the surface of Fe3O4@SiO2
(Fe3O4@SiO2-SnCl4) and characterized by Fourier transform-infrared spectroscopy (FT-IR), X-ray diffraction (XRD), vibrating
sample magnetometer (VSM), field emission-scanning electron microscope (FE-SEM), energy dispersive X-ray (EDX), N2
adsorption-desorption (BET) and transmission electron microscope (TEM). The activity of this solid acid was probed via the
synthesis of 1,4-dihydropyridine derivatives of three or four components coupling reaction of aldehyde, 1,3-dicabonyl
compound, and ammonium acetate under ultrasonic irradiation and yeilded excellent results with easy work-up in short
time. 1,4-dihydropyridine derivatives were characterized by FT-IR and 1HNMR
.
that
the
1,4-dihydropyridines
exhibit
significant
pharmacological and biological functions such as calcium
channel blocking9, anti-anginal10, antitumor11, anti-
Introduction
13
inflammatory12,
antitubercular14,
analgesic15
and
Industrial chemistry is broadly adopting the conception of
green chemistry to meet the essential scientific challenges of
protecting the environment and human health while
preserving commercial viability.1 As one of the breakthroughs
progresses in the field of green processes based on
sonochemistry, it has increasingly been considered as a simple,
clean and convenient method2-5 and so chemists are focusing
on its use for the synthesis of organic compounds Similarly,
multicomponent reactions (MCRs) work as an efficient and
important tool in modern synthetic organic chemistry. These
reactions which consist of two or more synthetic steps, are
carried out without the separation of any intermediates, so as
to reduce time and to save both energy and raw materials.6, 7
The Hantzsch reaction, which provides 1,4-dihydropyridines as
products, is one of the most well-known MCRs. There is always
something new on this old topic.8 This is mainly due to the fact
17
antithrombotic activites.16,
Moreover 1,4-dihydropyridine
skeleton is the parent nucleus of many commercial drugs such
as amlodipine, nifedipin, nimodipin, felodipine, isradipine, and
nicardipine. Thus, 1,4-dihydropyridines have attracted the
attention of many chemists and pharmacologists. As a result,
various methods to prepare these compounds have been
reported.18-24
More recently, the design of magnetical catalysts has
attracted a great deal of attention because these catalysts
improve the efficient separation of catalysts by magnetic
decantation after the reaction leading to improved
reusability.25-27 The combination of this concept with that of
nano materials holds a significant potential in advanced
catalysts with improved activities and selectivities providing
high specific surface area to volume ratio and higher surface
area affording more active sites. Thus making MNPs have
emerged as a new class of nano catalysts.28, 29 MNPs are one of
the most extensively considered materials in research fields
including biotechnology, biomedicine and catalysis. These are
generally inert and, for this reason, ideal for imaging and
separation in biological systems.30, 31 They have been used as a
Department of Organic Chemistry, Faculty of Chemistry, University of
Kashan,Kashan, I.R. Iran. E-mail: bamoniri@kashanu.ac.ir
† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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useful support in a variety of heterogeneous catalysts for EDX spectroscopy (XL30, Philips microscope). The specific surface
various organic reactions.32-34 MNPs of Fe3O4 are an efficient
area was evaluated by the BET method using N2 adsorption at –196
°C using an automated gas adsorption analyzer (TriStar II 3020
V1.03, Micromeritics).
and important alternative to conventional heterogeneous
catalyst supports due to their magnetic properties which
facilitate the separation of the catalyst upon reaction and produce a
Synthesis of Fe3O4@SiO2-SnCl4 MNPs
very active surface area for adsorptions or immobilization of metals
and ligands.4, 35 Nano-Fe3O4 (Fe3O4 NPs) is chemically stable, readily
Fe3O4 nanoparticles were prepared by a known procedure,
chemical co-precipitation method reported in the literature.44,
45
available, and easy to prepare, and low in toxicity and cost.
Briefly, FeCl3·6H2O (2.7 g) and FeCl2·4H2O (1 g) with molar ratio of
However, pure Fe3O4 NPs suffer from some inherent limitations:
2:1, were dissolved in concentrated HCl, 1.2 M (100 mL, 0.12 mol)
they are oxidized and easily lose their magnetism when used under
through ultrasonic method for 30 min. Then, ammonia 1.25 M (150
acidic conditions and they are easy to agglomerate and lose
dispersibility.36, 37 The above inherent limitations of Fe3O4 NPs has
mL, 0.19 mol) was injected into the reaction mixture under vigorous
stirring at 80 ˚C for 1 h under atmosphere nitrogen. The black
led to use of
a suitable protective coating. Silica has been
magnetic nanoparticles of Fe3O4 (magnetite) were formed.
Afterwards, the reaction mixture was cooled. The precipitate was
isolated using the magnetic field and washed thoroughly with water
until the supernatant liquid reached neutrality (pH ~7).
considered as one of the most ideal coating layers for Fe3O4 NPs
due to its chemical stability, biocompatibility, flexibility and
reactivity with numerous coupling agents.38 The iron-oxide with a
layer of silica not only stabilizes the nanoparticles in solution but
also offers sites for surface modification with various biomedical
ligands in biological applications,39,40 Bi2WO6, TiO2 in photocatalyst
application41,42 and γ-mercapto-propyl-trimethoxy-silane for
extracted various ions metal from water in a wide pH range.43
To the best of our knowledge, To the best of our knowledge,
the grafting of SnCl4 on Fe3O4 coated with SiO2 has not been
reported previously.In this study, we report, for the first time, the
successful synthesis of Fe3O4@SiO2-SnCl4 as a new catalyst for the
synthesis of 1,4-dihydropyridines. We attempted to perform one-
pot synthesis of 1,4-dihydropyridine derivatives through three and
four component coupling reaction of aldehydes, 1,3-dicabonyl
compounds, and ammonium acetate in the presence of
Fe3O4@SiO2-SnCl4 as an efficient eco-friendly catalyst under
ultrasound irradiation.
The synthesized Fe3O4 MNPs were used for coating with a silica
shell following the reported method.46 Fe3O4 MNPs (1 g) were
diluted by the consecutive addition of water (20 mL), ethanol (60
mL), and concentrated aqueous ammonia (2 mL, 25 wt%). The
resultant dispersion was homogenized through ultrasonic method.
A solution of tetraethylorthosilicate (TEOS) (0.5 mL) in ethanol (10
mL) was then added to the dispersion in a drop-wise manner at
room temperature under vigorous stirring for 16 h. Fe3O4@SiO2 was
collected by an external magnet, washed three times with ethanol
(30 mL) and dried under vacuum at 70 ˚C for 6 h.
In the last step, Fe3O4@SiO2 (0.65 g) was dispersed in CHCl3
(10 mL) using ultrasonic method for 30 min. Subsequently, SnCl4
(0.16 mL, 0.001 mol) was added drop-wise to dispersed solution of
Fe3O4@SiO2 at room temperature under vigorous stirring over a
period of 30 min. The resulting suspension was separated using an
external magnet, washed with chloroform (20 mL) and dried at
room temperature to obtain the brown solid presented nano
Fe3O4@SiO2–SnCl4
Experimental
Materials and apparatus
Chemicals and solvents were purchased from Merck and Aldrich
companies. FT-IR spectra were run on a Nicolet Magna 550
spectrometer using KBr pellets. NMR spectra were recorded at 400
MHz (1H) on a Bruker DRX-400 Avance spectrometer in CDCl3 as a
solvent. Melting points were obtained with a micro melting point
Acidic capacity of Fe3O4@SiO2-SnCl4
100 mg of Fe3O4@SiO2-SnCl4 accurately weighted placed in
conical flask containing about 10 mL of water and 3 drops of
phenolphthalein TS and then titrated with NaOH (0.1 M) VS until
solution remained light pink for 30 seconds.
apparatus (Electrothermal, Mk3) and used uncorrected.
A
multiwave ultrasonic generator (Sonicator 3000; Bandelin MS 72,
Germany), equipped with a convertor/transducer and titanium
oscillator (horn), 12.5 mm in diameter, operating at 20 kHz with a
maximum power output of 60 W, was used for the ultrasonic
irradiation. The ultrasonic generator automatically adjusted the
power level. The morphology of the synthesized samples and
catalyst were studied by a Mira ІІ LMU Tescan FE-SEM made in
Czech Republic. XRD patterns were recorded on a Philips Xpert MPD
diffractometer equipped with a Cu Kα anode (λ=1.54 A˚) in the 2θ
range from 10 to 80˚. Magnetization of the samples was recorded
as a function of the applied magnetic field sweeping between ±10
kOe at room temperature. All measurements were performed on a
vibrating sample magnetometer device (Meghnatis Daghigh Kavir
Co., Kashan Kavir, Iran). Fe3O4@SiO2-SnCl4 average size and
distribution were analyzed by TEM using a Philips CM120 with a
LaB6 cathode and accelerating voltage of 120 kV. Elemental
composition of the above mentioned MNPs was investigated by
General procedure for the synthesis of 1,4-dihydropyridines
Method I (∆)
A
mixture of an aryl aldehyde (1 mmol), 1,3-dicarbonyl
compound (2 mmol), ammonium acetate (1.5 mmol) and
Fe3O4@SiO2-SnCl4 (25 mg) was refluxed in ethanol (5 mL) near 75 °C
for the stipulated time mentioned in table 3. The progress of the
reaction was monitored by TLC (EtOAc: petroleum ether 7: 3). After
completion of the reaction, the catalyst was separated by an
external magnet and reused for the next experiment. The filtrate
was poured into crushed ice obtaining solid product, recrystallized
from ethanol to get pure crystalline 1,4-dihydropyridines derivative
.
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ARTICLE
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-3,4,6,7-
tetrahydroacridine1,8(2H,5H,9H,10H) -dione (compound 4g) Yellow
Method II (US)
In a round-bottom flask, a mixture of an aryl aldehyde (1 solid, FT-IR (KBr, υ cm-1) 3279 (NH) , 1644 (C=O, dimedone), 1486
mmol), 1,3-dicarbonyl compound (2 mmol), ammonium acetate (C=C, aromatic), 1145 (C-Cl). 1H NMR (CDCl3, 400 MHz) δ: 7.27 (d, J =
(1.5 mmol) and Fe3O4@SiO2-SnCl4 (18mg) in ethanol (5 mL) was 8 Hz, 2H, Ar-H), 7.17 (d, J = 8 Hz, 2H, Ar-H), 6.79 (s, 1H, NH), 5.05 (s,
sonicated at 20 kHz frequency and 40W power at room 1H, CH), 2.13- 2.37 (m, 8H, 4 CH2), 1.08 (s, 6H, 2 CH3), 0.96 (s, 6H, 2
temperature for the stipulated time which was confirmed by TLC CH3).
3,3,6,6-Tetramethyl-9-(4-nitrophenyl)-3,4,6,7-
and worked-up as described in method I
.
tetrahydroacridine-1,8(2H,5H,9H,10H)-dione
(compound
4h)
Yellow-orange solid, FT-IR (KBr, υ cm-1) 3384 (NH), 1643 (C=O,
Spectral data for selected compounds
1
dimedone), 1514 (NO2), 1481 (C=C, aromatic), 1344 (NO2). H NMR
2,6-Dimethyl-4-phenyl-1,4-dihydropyridine-3,5-
(CDCl3, 400 MHz) δ: 8.07 (d, J = 8.3 Hz, 2H, Ar-H), 7.51(d, J = 8.3 Hz,
2H, Ar-H), 6.13 (s, 1H, NH), 5.15 (s, 1H, CH), 2.14- 2.45 (m, 8H, 4
CH2), 1.10 (s, 6H, 2 CH3), 0.96 (s, 6H, 2 CH3).
diethylcarboxylate (compound 4a) Yellowish solid, FT-IR (KBr, υ
cm-1): 3342 (NH), 1689 (C=O, ester), 1487 (C=C, aromatic), 1212 (C-
O). 1H NMR (CDCl3, 400 MH) δ: 7.28 (d, J= 7 Hz, 2H. Ar-H), 7.21 (t, J=
6.9 Hz, 2H. Ar-H), 7.13 (d, J= 6.9 Hz, 1H, Ar-H), 5.54(s, 1H, NH), 4.99
(s, 1H, CH), 4.09(q, J = 6.8 Hz, 4H, 2 OCH2), 2.34 (s, 6H, 2CH3), 1.22
(t, J = 6.8 Hz, 6H, 2CH3CH2).
2,7,7-Trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylic acid ethyl ester (compound 4i)
Yellowish solid, FT-IR (KBr, υ cm-1): 3289 (NH), 1698 (C=O, ester),
1640 (C=O, dimedone), 1485 (C=C, aromatic), 1215 (C-O). 1H NMR
(CDCl3, 400 MHz) δ: 7.30 (d, J = 7.5 Hz, 2H, Ar-H), 7.19 (t, J = 7.5 Hz,
2H, Ar-H), 7.09 (t, J = 7.2 Hz, 1H, Ar-H), 6.44 (s, 1H, NH), 5.05 (s, 1H,
CH), 4.06 (q, J =7.2 Hz, 2H, OCH2), 2.35 (s, 3H, CH3), 2.13–2.30 (m,
4H, 2 CH2), 1.18 (t, J =7.2 Hz, 3H, CH3CH2), 1.07 (s, 3H, CH3), 0.93 (s,
3H, CH3).
2,6-Dimethyl-4-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-
diethylcarboxylate (compound 4b) Yellow solid, FT-IR (KBr, υ cm-1):
1
3343 (NH), 1689 (C=O, ester), 1489 (C=C, aromatic), 1211 (C-O). H
NMR (CDCl3, 400 MH) δ: 7.20 (d, J= 7.9 Hz, 2H. Ar-H), 6.75 (d, J= 7.9
Hz, 2H, Ar-H), 5.54(s, 1H, NH), 4.93 (s, 1H, CH), 4.10(q, J = 7.4 Hz,
4H, 2 OCH2), 3.76 (s, 3H, OCH3), 2.33 (s, 6H, 2CH3), 1.23 (t, J = 7.4 Hz,
6H, 2CH3CH2).
2,7,7-Trimethyl-5-oxo-4-(4-methoxyphenyl)-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylic acid ethyl ester (compound 4j)
Yellow solid, FT-IR (KBr, υ cm-1): 3279 (NH), 1700 (C=O, ester), 1645
(C=O, dimedone), 1497 (C=C, aromatic), 1217 (C-O). 1H NMR (CDCl3,
400 MHz) δ: 7.73 (d, J =8 Hz, 2H, Ar-H), 7.10 (d, J= 8 Hz, 2H, Ar-H),
5.99 (s, 1H, NH), 4.99 (s, 1H, CH), 4.06 (q, J= 6.8 Hz, 2H, OCH2), 3.73
(s, 3H, OCH3), 2.36 (s, 3H, CH3), 2.13–2.34 (m, 4H, 2 CH2), 1.20 (t, J=
6.8 Hz, 3H, CH3CH2), 1.07 (s, 3H, CH3), 0.94 (s, 3H, CH3).
2,6-Dimethyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-
diethylcarboxylate (compound 4c) Yellowish solid, FT-IR (KBr, υ cm-
1): 3356 (NH), 1695 (C=O, ester), 1486 (C=C aromatic), 1214 (C-O),
1
1117 (C-Cl). H NMR (CDCl3, 400 MH) δ: 7.22 (d, J= 8 Hz, 2H. Ar-H),
7.17 (d, J= 8 Hz, 2H, Ar-H), 5.55(s, 1H, NH), 4.96 (s, 1H, CH), 4.08(q, J
= 7.2 Hz, 4H, 2 OCH2), 2.34 (s, 6H, 2CH3), 1.22 (t, J = 7.2 Hz, 6H,
2CH3CH2)
2,7,7-Trimethyl-5-oxo-4-(4-chlorophenyl)-1,4,5,6,7,8-
2,6-Dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-
diethylcarboxylate (compound 4d) Colorless solid, FT-IR (KBr, υ cm-
1): 3327 (N-H), 1696 (C=O, ester), 1517 (NO2), 1486 (C=C, aromatic),
1345 (NO2), 1213 (C-O); 1H NMR (CDCl3, 400 MH) δ (ppm): 8.09 (d, J
= 7.9 Hz, 2H, Ar-H), 7.45 (d, J= 7.9 Hz, 2H, Ar-H), 5.63 (s, 1H, NH),
5.10 (s, 1H, CH), 4.08 (q, J = 7.4 Hz, 4H, 2 OCH2), 2.37 (s, 6H, 2 CH3),
1.24 (t, J = 7.4 Hz, 6H, 2 CH3CH2).
hexahydroquinoline-3-carboxylic acid ethyl ester (compound 4k)
Yellow solid, FT-IR (KBr, υ cm-1): 3276 (NH), 1703 (C=O, ester), 1645
1
(C=O, dimedone), 1490 (C=C, aromatic), 1217 (C-O), 1158 (C-Cl). H
NMR (CDCl3, 400 MHz) δ: 7.26 (d, J =6.9 Hz, 2H, Ar-H), 7.16 (d, J= 6.9
Hz, 2H, Ar-H), 6.00 (s, 1H, NH), 5.02 (s, 1H, CH), 4.06 (q, J= 6.8 Hz,
2H, OCH2), 2.38 (s, 3H, CH3), 2.13–2.31 (m, 4H, 2 CH2), 1.19 (t, J= 6.8
Hz, 3H, CH3CH2), 1.08 (s, 3H, CH3), 0.93 (s, 3H, CH3).
3,3,6,6-Tetramethyl-9-4-phenyl-3,4,6,7-tetrahydroacridine
1,8(2H,5H,9H,10H)-dione (compound 4e) Yellowish solid, FT-IR (KBr,
υ cm-1): 3279(NH), 1641 (C=O, dimedone), 1484 (C=C, aromatic). 1H
NMR (CDCl3, 400 MHz) δ: 7.33 (d, J = 7.5 Hz, 2H, Ar-H), 7.19 (t, J =
7.5 Hz, 2H, Ar-H), 7.07 (t, J = 7.5 Hz, 1H, Ar-H), 6.68 (s, 1H, NH), 5.08
(s, 1H, CH), 2.14–2.39 (m, 8H, 4 CH2), 1.08 (s, 6H, 2 CH3), 0.97 (s, 6H,
2 CH3).
2,7,7-Trimethyl-5-oxo-4-(4-nitrophenyl)-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylic acid ethyl ester (compound 4l)
Yellow solid, FT-IR (KBr, υ cm-1): 3279 (NH), 1702 (C=O, ester), 1647
(C=O, dimedone), 1516 (NO2), 1344 (NO2); 1H NMR (CDCl3, 400
MHz) δ (ppm): 8.08 (d, J =7.9 Hz, 2H, Ar-H), 7.48 (d, J= 7.9 Hz, 2H,
Ar-H), 5.91 (s, 1H, NH), 5.15 (s, 1H, CH), 4.05 (q, J= 7.1 Hz, 2H,
OCH2), 2.42 (s, 3H), 2.10–2.36 (m, 4H, 2 CH2), 1.17 (t, J= 7.1 Hz, 3H,
CH3CH2), 1.09 (s, 3H, CH3), 0.91 (s, 3H, CH3).
3,3,6,6-Tetramethyl-9-(4-methoxyphenyl)-3,4,6,7-
tetrahydroacridine-1,8 (2H,5H,9H,10H) -dione (compound 4f)
Yellow solid, FT-IR (KBr, υ cm-1) 3279 (NH), 1640 (C=O, dimedone),
1482 (C=C aromatic), 1224 (C-O); 1H NMR (CDCl3, 400 MHz) δ (ppm):
7.23 (d, J = 8.3 Hz, 2H, Ar-H), 6.72 (d, J = 8.3 Hz, 2H, Ar-H), 6.51 (s,
1H, NH), 5.02 (s, 1H, CH), 3.70 (s, 3H, OCH3), 2.14- 2.37 (m, 8H, 4
CH2), 1.08 (s, 6H, 2 CH3), 0.96 (s, 6H, 2 CH3).
Results and discussion
This research was performed in two steps. Firstly, Fe3O4@SiO2-
SnCl4 MNPs were prepared and identified by FT-IR, XRD, VSM,
FE-SEM, EDS, and TEM techniques. In the second step, 1,4-
dihydropyridine derivatives were synthesized by aryl
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aldehydes, 1,3-dicarbonyl compounds, and ammonium acetate The phase and purity of the different stepwise synthesized
under reflux and ultrasound irradiation methods and then materials in this work from magnetite Fe3O4 to final catalyst
characterized by their melting points using FT-IR, 1HNMR Fe3O4@SiO2-SnCl4 were determined by XRD patterns (Figure 3). XRD
spectroscopy.
pattern of Fe3O4 exhibited peaks at 2θ=30.43, 35.80, 43.40, 53.98,
57.46, 62.99, and 74.51° (Figure 3a). The diffraction peaks in this
pattern can be in accord with standard pattern of an inverse cubic
Preparation and characterization of Fe3O4@SiO2–SnCl4
Fe3O4@SiO2-SnCl4 was prepared by
convenient method (Figure1).
a
simple, low cost and spinel of Fe3O4.50 The strong and sharp peaks indicated phase purity
of Fe3O4 nanoparticles. Silica coated magnetite nano particles
exhibited a broadened pattern due to the non-crystalline nature at
2θ= 20-30 corresponding to amorphous phase of SiO2 and also
30.33, 35.79, 43.36, 53.82, 57.36, 62.99 and 74.62° which
corresponded to Fe3O4 structure (Figure 3b).The XRD pattern of
Fe3O4@SiO2-SnCl4 in figure 3c showed a much broader diffraction
pattern and increased the noise to that of figure 3b, which seems to
link to SnCl4 on the surface of Fe3O4@SiO2. Moreover, characteristic
peaks of Fe3O4 were observed in three samples, indicating that the
binding process did not induce any phase change.
Fig. 1. The schematic diagram for synthesis and suggested structure of
Fe3O4@SiO2-SnCl4
In order to recognize the molecular structures of Fe3O4,
Fe3O4@SiO2, and Fe3O4@SiO2– SnCl4 MNPs, FT-IR analysis of the
three mentioned samples was performed (Figure 2). Fe3O4 was
identified by bands at 443 and 582 cm-1 due to Fe–O vibrations in
octahedral and tetrahedral sites47 (Figure 1a). The FT-IR spectrum of
Fe3O4@SiO2 (Figure 2b) displays characteristic peaks at 1094 and
802 cm-1 corresponding to symmetrical and asymmetrical vibrations
of Si–O–Si, respectively. Weak band at 469 cm-1 corresponds to the
Si–O–Fe stretching vibrations of the Fe3O4@SiO2. These outcomes
indicate that SiO2 is immobilized on the surface of Fe3O4. The
successful covalent linking of the SnCl4 on the surface of
Fe3O4@SiO2 was confirmed by the appearance of a new band at 563
cm-1, which originates from the absorption of O-Sn (Figure
2d).48,49
Fig. 3. XRD patterns of (a) Fe3O4, (b) Fe3O4@SiO2, and (c) Fe3O4@SiO2-SnCl4
The energy dispersive X-ray (EDX) from the Fe3O4@SiO2-SnCl4
(Figure 4) provided the presence of the expected elements in the
structure of this catalyst and confirmed supporting of SnCl4 on
Fe3O4@SiO2. The elemental compositions of Fe3O4@SiO2-SnCl4 were
found to be 52.80, 31.33, 0.82, 5.30 and 9.76% for Fe, O, Si, Sn and
Cl, respectively.
Fig. 4. EDX patterns of Fe3O4@SiO2-SnCl4
Fig. 2. FT-IR spectra of (a) Fe3O4, (b) Fe3O4@SiO2, (c) SnCl4 and (d) Fe3O4@SiO2-
SnCl4
The BET specific surface area of Fe3O4@SiO2-SnCl4 in this study was
59.0467 m2/g. In order to identify the possible structure of
Fe3O4@SiO2-SnCl4, we determined acidic capacity of this catalyst by
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titration producing HCl in water. We found that 0.1 g of the catalyst
produced 0.324 mmol of H+ or Cl−. Also, for the determination of
the loading amounts of the Sn on the Fe3O4@SiO2-SnCl4 by the
addition of 1 mL aqueous solution of NaOH (0.2 M) to 0.1 g of
catalyst and hot water. The nanomagnetic catalyst was separated
with external magnet from the obtained Sn(OH)4 solution. The
solution was evaporated to obtain a dry Sn(OH)4 powder. The
calculated loading amount of Sn in the catalyst was 0.138 mmol g-1.
According to the above data and EDX data, the molar ratio of Sn:Cl,
were investigated 1:2 and the possible structure of Fe3O4@SiO2-
SnCl4 was proposed as shown in figure 5.
Fig. 7. SEM images of (a) Fe3O4, (b) Fe3O4@SiO2, and (c) Fe3O4@SiO2-SnCl4
Transmission electron microscopy (TEM) image of the synthesized
catalyst was recorded as depicted in figure 8. According to this
image, the catalyst was approximately 28 nm in size.
Fig. 5. Suggested structure of Fe3O4@SiO2-SnCl4
The magnetization curve for synthesized Fe3O4, Fe3O4@SiO2,
and Fe3O4@SiO2–SnCl4 nanoparticles is shown in figure 6.
Room temperature specific magnetization (M) versus applied
magnetic field (H) indicated the magnetization as a function of
applied magnetic field. The saturation magnetization of the
Fe3O4 nanoparticles was about 53.52 emu/g, which decreased
to 40.98 emu/g after supporting Fe3O4 with SiO2 and to 31.05
emu/g after supporting Fe3O4@SiO2with SnCl4. The decrease of
the saturation magnetization after surface coating of Fe3O4
confirms the presence of a diamagnetic outer shell (SiO2 or
SiO2-SnCl4).
Fig. 8. TEM image of Fe3O4@SiO2-SnCl4
Evaluation of the catalytic activity of Fe3O4@SiO2–SnCl4
To obtain appropriate conditions for the synthesis of 1,4-
dihydropyridines, different reaction conditions have been
examined. At the outset, the reaction was carried out with
benzaldehyde, ethyl acetoacetate, dimedone and ammonium
acetate as a model reaction (Scheme 1).
O
Ph
O
O
O
O
O
O
EtO
Fe3O4@SiO2-SnCl4
NH4OAc
H
+
+
EtO
N
H
Scheme 1. Standard model reaction
We studied the effect of various solvents such as H2O, EtOH,
DMF, CH3CN, and CHCl3 on a model reaction under ultrasound
irradiation (40W power). The results are summarized in table 1.
It was found that ethanol was the best choice for the model
reaction.
Table 1 Optimization of the model reaction using various solvents under
ultrasound irradiation
Fig. 6. VSM patterns of (a) Fe3O4, (b) Fe3O4@SiO2, and (c) Fe3O4@SiO2-SnCl4
Entry Solvent Time (min) Yield (%)a
The FE-SEM images of the Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2–
SnCl4 nanoparticles are displayed in figure 7. These images
evidently show the surface morphology of three kinds of
1
2
3
4
5
CH3CN
CHCl3
DMF
Water
EtOH
5
5
5
5
5
74
75
85
89
98
synthesized MNPs with
a nearly spherical shape. Although
Fe3O4@SiO2 and Fe3O4@SiO2-SnCl4 still keep the morphological of
Fe3O4, they are slightly larger in particle size.
aIsolated yields. benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol),
dimedone (1 mmol), ammonium acetate (1.5 mmol) and Fe3O4@SiO2-SnCl4
(18mg).
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In order to examine the scope and generality of this procedure in
these methodologies, a number of aromatic aldehydes containing
both electron-withdrawing and electron-donating groups in the
para position were used with ammonium acetate and ethyl
acetoacetate or/and dimedone in the presence of Fe3O4@SiO2-
SnCl4 in ethanol under reflux and ultrasound irradiation conditions.
By comparing obtained data for different condition from Table 3,
reveal that ultrasound irradiation method leads to interesting effect
concerning the synthesis of 1,4-dihydropyridines.
In order to study the effects of Fe3O4@SiO2-SnCl4 on the model
reaction, catalytic behaviour of Fe3O4@SiO2-SnCl4 was
compared under reflux or and ultrasound irradiation
conditions (Table 2). The obtained results showed that, in the
absence of catalyst, no significant product was obtained and in
the presence of Fe3O4@SiO2-SnCl4 the reaction was carried out
with high yields (Entry 1). Also the results in table 1 exhibit the
optimum amount of the catalyst was 25 mg under reflux
condition, and 18 mg under ultrasound irradiation (Entry 6).
Notably, the increase of the catalyst in reflux and ultrasound
irradiation conditions did not show any significant changes in
yield and time of reaction (Entry 7).
In all cases, when the reactions were carried out under
ultrasound irradiation, the times of the reactions were shorter and
the yields of the products were higher than reflux method. Also, the
amount of catalyst was decreased under ultrasound irradiation. This
should be explained based on the phenomenon of cavitation
produced by ultrasound irradiation. Moreover this method,
particularly when considering the basic green chemistry concepts, is
more environmental friendly. As can be seen from the results in
Table 3, aromatic aldehydes with substituents carrying either
electron-donating or electron-withdrawing groups reacted
successfully with 1,3-dicabonyl compounds to afford the
corresponding 1,4-dihydropyridines in excellent yields. However,
using dimedone instead of ethyl acetoacetate affects the yield and
reaction time due to acidity of the methylenic protons.
Table 2 Optimization of the model reaction using Fe3O4@SiO2-SnCl4 under reflux (І)
and ultrasound irradiation (ІІ)
Method I (∆)
Catalyst/ (g)
Method II (US)
Catalyst/ (g)
Entry
Time (min)
none
Yield (%)a
Time (min)
none
Yield (%)a
1
2
200
SnCl4 / 0.13
30
trace
20
SnCl4 / 0.13
10
trace
49
56
The proposed mechanism for the formation of 1,4-
dihydropyridines in the presence of Fe3O4@SiO2-SnCl4, which can
act as Lewis acid catalyst (empty π orbital of Sn in Fe3O4@SiO2-
SnCl4) is depicted in scheme 2.
BF3·Et2O / 0.13
BF3·Et2O / 0.13
3
4
30
50
10
55
TiCl4 / 0.13
TiCl4 / 0.13
30
45
10
50
SnCl4·SiO2 / 0.50
30 55
Fe3O4@SiO2-SnCl4/ 0.005 Fe3O4@SiO2-SnCl4/ 0.005
25 65 84
Fe3O4@SiO2-SnCl4/ 0.010 Fe3O4@SiO2-SnCl4/ 0.010
23 73 89
Fe3O4@SiO2-SnCl4/ 0.020 Fe3O4@SiO2-SnCl4/ 0.015
18 85 91
Fe3O4@SiO2-SnCl4/ 0.025 Fe3O4@SiO2-SnCl4/ 0.018
SnCl4·SiO2 / 0.50
5
6
78
10
8
7
6
Scheme 2. Proposed mechanism for the synthesis of 1,4-dihydropyridines
8
9
As can be seen, an acid–base interaction between Fe3O4@SiO2-
5
SnCl4 and oxygen in carbonyl bond forms
corresponding
Knoevenagel product (I) and enamine (II). In the following, Michael
addition is occurred between enamine and Knovenagel product for
the formation of an open chain intermediate (III). The dipolar
transition state is undergone cyclodehydration to furnish the
desired product. Moreover, reaction in heterogeneous systems
which proceeds via ionic intermediate is influenced predominantly
through the mechanical effects of cavitation
14
Fe3O4@SiO2-SnCl4/ 0.030 Fe3O4@SiO2-SnCl4/ 0.025
14 94 96
95
5
98
10
5
aIsolated yields. benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), dimedone (1 mmol)
and ammonium acetate (1.5 mmol) in ethanol (5 mL)
Table 3 Synthesis of 1,4-dihydropyridine derivatives under reflux conditions and sonication (methods I and II)
6 | RSC Adv.., 2014, 00, 1-3
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ARTICLE
O
O
Ar
O
Method I
Fe3O4@SiO2-SnCl4 / EtOH , reflux
Method I I
Fe3O4@SiO2-SnCl4 / EtOH , U.S.
NH4OAc
ArCHO
+
O
+
N
H
1,3-dicarbonyls
Product
Time(min) / Yield (%)a
M. P. (oC)
Entry
R
Method I (∆)b
Method II (US)c
Found
Reported
158-16051
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Dimedone
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Dimedone
1
2
C6H5
25 / 91
6 / 96
6 / 92
5 / 96
4 / 97
4 / 96
4 / 93
3 / 97
3 / 98
5 / 98
5 / 94
4 / 96
3 / 98
157-160
4a
4b
4c
4d
4e
4f
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
C6H5
18 / 89
23 / 95
20 / 92
22 / 93
12 / 94
15 / 93
15 / 95
14 / 95
15 / 90
18 / 96
18 / 95
160-162
145-147
130-132
189-191
269-271
297-299
285-287
225-227
258-260
245-246
240-242
161-16351
147-14851
129-13151
190-19252
270-27252
299-23053
286-28853
228-22954
260-26254
245-24654
241-24254
3
4
5
Dimedone
Dimedone
6
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
C6H5
Dimedone
Dimedone
7
4g
4h
4i
Dimedone
Dimedone
8
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Dimedone
9
Dimedone
10
11
12
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
4i
Dimedone
4k
4l
Dimedone
aIsolated yields. arylaldehyde (1 mmol), 1,3-dicarbonyl compounds (2 mmol), ammonium acetate (1.5 mmol) in ethanol (5 mL)
b Fe3O4@SiO2-SnCl4(25mg).
cFe3O4@SiO2-SnCl4(18mg).
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Consequently, it is essential for the solid acid to maintain of the catalyst make this methodology a valid contribution to
strong acidity even after recycling and the most important benefits the existing processes in the field of one-pot multicomponent
for commercial applications. Thus, after the completion of the Hantzsch reaction.
reaction, the catalyst was separated by an external magnet. The
recovered catalyst was washed with chloroform (30 mL) and dried
Acknowledgements
at room temperature without further purification to use for the
next run in current reaction under identical condition. It was found
that the catalyst could be reused for five times without any
appreciable loss of its activity (Figure9).
The authors are grateful to University of Kashan for supporting this
work by Grant No. (159189/34)
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SnCl4-functionalized nano-Fe3O4 encapsulated-silica particles as a novel heterogeneous
solid acid for synthesis of 1,4-dihydropyridine derivatives
Abdolhamid Bamoniri*, Sara Fouladgar
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 8731751167, Iran
E-mail: bamoniri@kashanu.ac.ir
A simple and general synthetic method for the synthesis of 1,4-dihydropyridines via three- or
four-component condensation of aldehydes, 1,3-dicarbonyl compounds, and ammonium acetate
under ultrasonic irradiation were developed by using Fe3O4@SiO2-SnCl4 as an efficient catalyst.