Preparation and characterization of silica-supported magnetic nanocatalyst and application in the synthesis of 2-amino-4H-chromene-3-carbonitrile derivatives

Article abstract of DOI:10.1080/24701556.2016.1241266

Silica-supported magnetic nanoparticles were simply prepared in high yields and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and energy-dispersive X-ray spectr

Full text of DOI:10.1080/24701556.2016.1241266

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Preparation and characterization of silica-supported magnetic nanocatalyst and
application in the synthesis of 2-amino-4H-chromene-3-carbonitrile derivatives
Ali Maleki*and Sepide Azadegan
Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran
University of Science and Technology, Tehran 16846-13114, Iran
*E-mail: maleki@iust.ac.ir
Silica-supported magnetic nanoparticles were simply prepared in high yields and characterized by Fourier transforms infrared
spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM)
and energy-dispersive X-ray spectroscopy (EDX) analyses. Then, Fe O @SiO core-shell was used as a reusable and efficient
3
4
2
heterogeneous nanocatalyst in a one-pot three-component condensation of various aromatic aldehydes, malononitrile and 1,3-
dicarbonyl compounds to yield 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile derivatives as worthy
structures under mild reaction conditions and easy work-up procedure.
Keywords
Nanocatalyst, Fe O @SiO , core-shell, multicomponent reaction, chromene.
3
4
2
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Introduction
Multicomponent reactions (MCRs) are an important tool in organic synthesis as they
often allow the circumvention of multistep procedures by combining three or more
molecules into one structure in a single step. An additional asset of the MCR approaches
are the significant increase of the combinatorial possibilities, since a modification of final
product is easily accomplished by implementing minor changes in the reaction setup; this
1
obviously allows considerable savings in time and resources. Moreover, MCR is a
2
3,4
powerful tool in the synthesis of biologically active compounds such as drug delivery,
5
6
7
magnetic resonance imaging, biomolecular sensors, bioseparation, and magneto-
8
thermal therapy.
2
-Amino-4H-chromenes and their derivatives are of significant importance as they
9
10
possess a wide range of biological activities such as antimicrobial, sex pheromone,
1
1
12
antitumor, cancer therapy and central nervous system activity. Moreover, some of
1
3,14
these compounds could be used as inhibitors
-amino-4H-chromene-3-carbonitriles as the structural units also find applications as
cognitive enhancers in treatment of neurodegenerative diseases like Alzheimer’s as well
(Figure 1). Many compounds containing
2
1
5
as for Parkinson’s disease. In addition, these compounds have applications in
1
6
17
fluorescence markers cosmetics and pigments.
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There are various literature reports on the synthesis of 2-amino-4H-chromene-3-
1
8--21
carbonitrile derivatives.
Most of the methods reported for the synthesis of these
valuable compounds suffer from one or more drawbacks such as harsh reaction
2
2--26
conditions, low yields, long reaction times or expensive catalysts.
Along with other
reaction parameters such as solvent type, the nature of the catalyst plays a significant role
in determining yield, selectivity, and general applicability. Thus, development of an
inexpensive, general, and reusable catalyst by using MCRs strategy for the synthesis of 2-
amino-4H-chromene-3-carbonitriles is an issue of interest.
In continuation of our research on the introduction of new recoverable nanocatalysts in
2
7--32
organic synthesis,
one-pot synthesis
carbonitrile derivatives 4a-p via condensation of various aromatic aldehydes
malononitrile and 1,3-dicarbonyl compounds in the presence of Fe O @SiO core-
in this work, we report convenient and facile multicomponent,
of 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-
1
,
2
3
3
4
2
shell nanostructure as an efficient, eco-friendly, superparamagnetic and heterogeneous
catalyst (Scheme 1). According to our literature survey, this is the first report on the
application of the present heterogonous composite nanocatalyst in the synthesis of 2-
amino-4H-chromene-3-carbonitrile derivatives.
Results and discussion
3
2
Fe O nanoparticles and Fe O @SiO nanocomposite were prepared by co-precipitation
3
4
3
4
2
3
3
and modified Strober methods, respectively. As can be seen in Figure 2, the
comparative FT-IR spectra of the Fe O , SiO and Fe O @SiO magnetic nanocatalyst can
3
4
2
3
4
2
3
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1
verify the preparation of the expected product. The vibration band at 575 cm is induced
1
by structure Fe--O vibration. The Si--OH vibration peak at 952 cm and the Si--O--Si
1
vibration peak at around 1095 cm were also observed, indicating that the SiO shell was
2
successfully composed onto the surfaces of Fe O nanoparticles.
3
4
To clarify the morphology of the nanocatalyst, SEM images of Fe O @SiO are
3
4
2
presented in Figure 3. As it obvious, obtained catalyst has a uniform and spherical
2
7
morphology. In addition, as it proved in our previous work and also in the literature
3
3
report, this nanocatalyst has core-shell structure.
Figure 4 shows the results of the XRD patterns analysis of the magnetite silica-
supported Fe O @SiO nanoparticles. The results are suitably in accordance with
3
4
2
standard patterns of an inverse cubic spinel Fe O crystal structure, showing diffraction
3
4
peaks at the predicted 2θ angles. The intense and sharp peaks indicated that Fe O crystals
3
4
are highly crystalline. As can be seen, the resulted nanomaterials show only typical
diffraction peaks of magnetite nanoparticles and there is no deviation raised from specific
peaks attributable to the composite nanostructure.
The TEM images shown in Fig. 5 revealed that the silica--magnetite composites made as
supports of the catalyst had good spherical morphologies and arranged core--shell structures; and
the average particles size was 59.13 nm.
Furthermore, to confirm elemental composition of the Fe O @SiO core-shell structures an
3
4
2
energy-dispersive X-ray spectroscopy (EDX) spectra of the nanocatalyst was provided and
indicated the presence of Si, O and Fe elements in the nanocomposite (Fig. 6).
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Initially, to optimize the reaction conditions for the synthesis of 2-amino-4H-
chromene-3-carbonitriles we have studied various parameters on the reaction of 3-
nitrobenzaldehyde (1 mmol), dimedone (1 mmol) and malononitrile (1 mmol) as a pilot
test. First, the effect of catalyst amount on the reaction yield was studied. It was found
that using 0.005 g of the Fe O @SiO nanocatalyst is sufficient to complete the reaction
3
4
2
and give 4a after 35 min in 98% yield in 5 mL of EtOH as a green solvent at room
temperature.
To compare the efficiency of ethanol, several solvents with different polarities were
tested using the model reaction in the presence of Fe O @SiO . As it obvious from the
3
4
2
results, it was found that ethanol is the superior solvent for this study than MeOH, H O,
2
CH CN, CH Cl and also solvent-free in the presence of 0.005 g of Fe O @SiO catalyst
3
2
2
3
4
2
at room temperature.
Finally, a comparison was made between the present work and others which were
reported earlier for the synthesis of 4a. The results summarized in Table 1 clearly
demonstrate the superiority of the present work over all the earlier reported ones in
energy consuming, high yield products along with green medium.
In order to investigate the scope and limitations of the present protocol and to show the
application of Fe O @SiO in synthesis of substituted 2-amino-4H-chromene-3-
3
4
2
carbonitriles, a variety of their derivatives were synthesized under the optimized
conditions from the three-component reaction of dimedone or 1,3-cyclohezanedione,
diverse aldehyde and malononitrile at room temperature. The summarized results in Table
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2
show that all products were obtained in high-to-excellent yields after appropriate
reaction times.
The suggested possible mechanism for the formation of 2-amino-4-aryl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile derivatives 4a-p is shown in Scheme 2. In the
4
0, 41
proposed mechanism, Fe O @SiO , as a Lewis acid,
can increases the electrophilicity
and also dimedone by means of a strong
is the result of Lewis acid-catalyzed Knoevenagel
condensation between the aldehyde and dimedone. This molecule acts as a Michael
acceptor. Subsequent attack of malononitrile makes the open-chain intermediate
Finally, an intramolecular cyclization of intermediate gave the desired products
3
4
2
of the carbonyl groups on the aldehyde
1
3
4
2
coordinate bond. Molecule
5
2
6.
7
4.
To study the catalyst reusability, the model reaction was carried out by using 0.005 g
of Fe O @SiO . After completion of the reaction, nanoparticles were separated by using
3
4
2
an external magnet and washed with ethanol and water, dried and reused in another set of
reaction. It was observed that the catalyst can be reused for five times without any
significant reduction in product yield (Figure 7). In addition, no extra care should be
taken in order to store or handle the catalyst in recovery process; because, it does not have
any air or moisture sensitive nature.
Conclusions
In summary, we have developed a simple, green and extremely efficient protocol for the
synthesis of 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile scaffolds by
condensation between aromatic aldehyde, malononitrile and 1,3-dicarbonyl compounds in
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presence of nano-Fe O @SiO as an environmentally friendly and reusable superparamagnetic
3
4
2
nanocatalyst with facile preparation process.
Experimental section
General
All the solvents, chemicals and reagents were purchased from Merck, Sigma and Aldrich.
Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected.
Fourier transforms infrared spectroscopy (FT-IR) spectra were recorded on a Shimadzu
1
13
IR-470 spectrometer by the method of KBr pellet. H and C NMR spectra were recorded
on a Bruker DRX-500 Avance spectrometer at 500 and 125 MHz, respectively. Scanning
electron micrograph (SEM) images were taken with Zeiss-DSM 960A microscope with
attached camera. The crystalline phase of the nanoparticles were recognized by means of
X-ray diffraction (XRD) measurements using Cu Kα radiation (λ = 1.54 A˚, 40 kV, 40
mA) on a STOE powder diffraction system in the 2θ range of 10--80°. Transmission
electron microscopy (TEM) images were obtained through Zeiss EM 900 electron
microscope operating at 80 kV. Energy-dispersive X-ray spectroscopy (EDX) spectra
were recorded on Numerix DXP--X10P.
Preparation of Fe O nanoparticles
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4
Fe O nanoparticles were prepared by co-precipitation of Fe O from a mixture of FeCl
3
4
3
4
2
2
and FeCl (1:2, molar ratio) upon addition of NH ·H O. In a typical reaction, 1.72 g FeCl
3
3
2
and 4.7 g FeCl were mixed in 80 mL de-ionized water and heated to 80°C in a three
3
7
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necked flask. While vigorously stirring the reaction mixture, 10 mL of NH ·H O was
3
2
introduced by syringe and the heating continued for 40 min. Black precipitate was
produced immediately by adding NH ·H O. The precipitation reaction is as follows:
3
2
2
3

Fe 2Fe 8OH Fe O 4H O
3
4
2
The obtained Fe O precipitate was washed repeatedly with de-ionized water until pH
3
4
value decreased to 7 and then dried at 80°C in an oven.
Preparation of core-shell Fe O @SiO nanoparticles
3
4
2
The synthesis of core-shell Fe O @SiO nanoparticles was performed by modifying the
3
4
2
Strober method via the hydrolysis of tetraethylorthosilicate (TEOS) in the presence of
Fe O nanoparticles. In a typical synthesis of 60 nm core-shell Fe O @SiO nanoparticles
3
4
3
4
2
(
with a silica shell thickness of 20 nm), 45 mg as-prepared 20 nm hydrophilic Fe O4
3
nanoparticles were dispersed in 16 mL of water by using an ultrasonic water bath, then
mixing with 2 mL of aqueous ammonia solution (25 wt%) and 80 mL of ethanol. Next,
0
.8 mL of TEOS was added drop wise into the Fe O nanoparticle solution under violent
3 4
stirring at room temperature. The stirring continued at room temperature for 24 h. The
products were separated by an external magnet and washed with water several times. The
final product was collected and dried at 50°C.
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General procedure for the synthesis of 2-amino-4H-chromene-3-carbonitrile
derivatives 4a-p
A reaction mixture of an aldehyde
or 1,3-cyclohezanedione 3b (1 mmol) were added to EtOH (5 mL) including nano-
Fe O @SiO (0.005 g); and stirred at room temperature for the appropriate time. After
1 (1 mmol), malononitrile 2 (1 mmol), and dimedone
3
a
3
4
2
completion of the reaction (TLC monitoring), the catalyst was separated easily by an
external magnet and reused as such for the next experiments. Most of the products were
isolated pure just by recrystallization from hot EtOH and no more purification was
needed.
Spectral data of 2-amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile 4d
1
Colourless crystals: mp 200-202°C. FT-IR (KBr) (υ , cm ): 3392, 3323, 3190, 2962,
max
1
2
192, 1654. H NMR (500 MHz, DMSO--d ): δ (ppm) = 0.94 (3H, s, CH ), 1.03 (3H, s,
6
3
CH ), 1.03-1.07 (2H, m, CH ), 2.10 (1H, d, J = 16.0 Hz, CH ), 2.25 (1H, d, J = 16.0 Hz,
3
2
2
CH ), 4.18 (1H, s, CH), 7.06 (2H, br s, NH ), 7.12 (2H, d, J = 8.1 Hz, H-Ar), 7.48 (2H, d,
2
2
1
3
J = 8.1 Hz, H-Ar). C NMR (125 MHz, DMSO-d ): δ (ppm) = 27.7, 29.1, 32.6, 36.0,
6
40.5, 50.8, 58.6, 113.1, 120.3, 120.5, 130.3, 132.0, 145.0, 159.3, 163.5, 196.6.
Acknowledgements
The authors gratefully acknowledge the partial financial support from the Research
Council of the Iran University of Science and Technology.
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References
1
2
P. A. Gale, C.-H. Lee, A. Cukalovic, J.-C. M. R. Monbaliu and C. V Stevens, in Synthesis
of Heterocycles via Multicomponent Reactions I, Springer, 2010, 39, 161.
M. M. Gupta, M. M. Gupta, Rajnikant, V. K. Gupta, P. A. Gale and C.-H. Lee, New J.
Chem., 2015, 39, 3578.
3
4
Y. Zhu, Y. Fang and S. Kaskel, J. Phys. Chem. C, 2010, 114, 16382.
T. Neuberger, B. Schöpf, H. Hofmann, M. Hofmann and B. Von Rechenberg, J. Magn.
Magn. Mater., 2005, 293, 483.
5
Q. A. Pankhurst, J. Connolly, S. K. Jones and J. J. Dobson, J. Phys. D. Appl. Phys., 2003,
3
6, R167.
6
7
8
D. L. Graham, H. A. Ferreira and P. P. Freitas, TRENDS Biotechnol., 2004, 22, 455.
D. Wang, J. He, N. Rosenzweig and Z. Rosenzweig, Nano Lett., 2004, 4, 409.
A. Jordan, R. Scholz, P. Wust, H. Fähling and R. Felix, J. Magn. Magn. Mater., 1999,
2
01, 413.
9
1
M. M. Khafagy, A. H. F. A. El-Wahab, F. A. Eid and A. M. El-Agrody, IL Farmaco,
002, 57, 715.
2
0 G. Bianchi and A. Tava, Agric. Biol. Chem., 1987, 51, 2001.
10
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ACCEPTED MANUSCRIPT
1
1
1 S. J. Mohr, M. A. Chirigos, F. S. Fuhrman and J. W. Pryor, Cancer Res., 1975, 35, 3750.
2 D. R. Anderson, S. Hegde, E. Reinhard, L. Gomez, W. F. Vernier, L. Lee, S. Liu, A.
Sambandam, P. A. Snider and L. Masih, Bioorg. Med. Chem. Lett., 2005, 15, 1587.
1
1
3 T. H. V Huynh, B. Abrahamsen, K. K. Madsen, A. Gonzalez-Franquesa, A. A. Jensen
and L. Bunch, Bioorg. Med. Chem., 2012, 20, 6831.
4 J.-L. Wang, D. Liu, Z.-J. Zhang, S. Shan, X. Han, S. M. Srinivasula, C. M. Croce, E. S.
Alnemri and Z. Huang, Proc. Natl. Acad. Sci., 2000, 97, 7124.
1
1
1
5 L. Bonsignore, G. Loy, D. Secci and A. Calignano, Eur. J. Med. Chem., 1993, 28, 517.
6 E. R. Bissell, A. R. Mitchell and R. E. Smith, J. Org. Chem., 1980, 45, 2283.
7 M. A. Sofan, F. M. El-Taweel, A. G. A. Elagamey and M. H. Elnagdi, Liebigs Ann.
Chem., 1989, 935.
1
1
8
9
J. K. Rajput, P. Arora, G. Kaur and M. Kaur, Ultrason Sonochem., 2015, 26, 229.
V. M. Joshi, R. L. Magar, P. B. Throat, S. U. Tekale, B. R. Patil, M. P. Kale and R. P.
Pawar, Chin. Chem. Lett., 2014, 25, 455.
2
0
Z. Vafajoo, H. Veisi, M. T. Maghsoodlou and H. Ahmadian, C. R. Chim., 2014,
1
7, 301.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2
1
R. L. Magar, P. B. Thorat, V. B. Jadhav, S. U. Tekale, S. A. Dake, B. R. Patil and R. P.
Pawar, J. Mol. Catal. A, 2013, 374–375, 118.
2
2
2
J. M. Khurana, B. Nand and P. Saluja, Tetrahedron, 2010, 66, 5637.
3 A. Shaabani, R. Ghadari, S. Ghasemi, M. Pedarpour, A. H. Rezayan, A. Sarvary and S.
W. Ng, J. Comb. Chem., 2009, 11, 956.
2
2
2
2
2
2
3
3
3
3
4 S. Makarem, A. A. Mohammadi and A. R. Fakhari, Tetrahedron Lett., 2008, 49, 7194.
5 G. W. Kabalka, B. Venkataiah and B. C. Das, Synlett, 2004, 2194.
6 G. Yang, C. Luo, X. Mu, T. Wang and X.-Y. Liu, Chem. Commun., 2012, 48, 5880.
7 A. Maleki, Helv. Chim. Acta, 2014, 97, 587.
8 A. Maleki and R. Paydar, RSC Adv., 2015, 5, 33177.
9 A. Maleki, M. Aghaei and N. Ghamari, Chem. Lett., 2015, 44, 259.
0 A. Maleki, Tetrahedron, 2012, 68, 7827.
1 A. Maleki, Tetrahedron Lett., 2013, 54, 2055.
2 A. Maleki and M. Kamalzare, Catal. Commun., 2014, 53, 67.
3 C. Hui, C. Shen, J. Tian, L. Bao, H. Ding, C. Li, Y. Tian, X. Shi and H.-J. Gao,
Nanoscale, 2011, 3, 701.
12
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ACCEPTED MANUSCRIPT
3
4 kapil S. Pandit, P. V Chavan, U. V Desai, M. A. Kulkarni, P. P. Wadgaonkar, kapil S.
Pandit, P. V Chavan, M. A. Kulkarni and P. P. Wadgaonkar, New J. Chem., 2015, 39,
4
452.
3
3
3
3
5 L.-M. Wang, J.-H. Shao, H. Tian, Y.-H. Wang and B. Liu, J. Fluor. Chem., 2006, 127,
7.
9
6 S. Balalaie, M. Bararjanian, M. Sheikh-Ahmadi, S. Hekmat and P. Salehi, Synth.
Commun., 2007, 37, 1097.
7 O. H. Qareaghaj, S. Mashkouri, M. R. Naimi-Jamal and G. Kaupp, RSC Adv., 2014, 4,
4
8191.
8 U. Desai, kapil S. Pandit, P. V Chavan, M. a. Kulkarni and P. P. Wadgaonkar, New J.
Chem., 2015, 39, 4452.
3
4
9 R. J. Kalbasi and N. Mosaddegh, Catal. Commun., 2011, 12, 1231.
0 B. Mirhosseini-Eshkevari, M. A. Ghasemzadeh and J. Safaei-Ghomi, Res. Chem.
Intermed., 2014, 1.
4
4
1
A. Maleki, R. Rahimi and S. Maleki, Environ. Chem. Lett., 2016, 14, 195.
2 A. Akbari, Heterocycl. Commun., 2013, 19, 425.
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Table 1. A comparison of some catalysts effects with the present nanocatalyst on the
model reaction.
En
try
Temperatu Tim Yield
Catalyst
re (°C)
80
e
75m
in
(%)
80
SiO --
2
1
2
2
Cu(II)
SiO2
80
4h
60
Nano-
Fe O @SiO
3
5m
in
3
r.t.
98
3
4
2
4
5
6
-
80
r.t.
60
4.5h
2h
52
91
90
3
4
THAM
3
5
Re(PFO)3
4h
14
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Table 2. Synthesis of 2-amino-4H-chromene-3-carbonitriles 4a-p by using nano-
Fe O @SiO .
3
4
2
Mp (°C)
Reporte
1
,3-
Time
a
Entr
y
Yield
(%)
Aldehyde
Dicarbonyl
compound
Product
(min)
Found
d
3
-NO2-
213-
214
213-
1
2
3a
3a
35
98
3
6
C H CHO
217
6
4
4
4
a
2
-NO2-
218-
220
220-
40
40
97
3
7
C H CHO
221
6
4
b
4
-NO2-
180-
182
178-
3
4
3a
3a
97
95
2
C H CHO
179
6
4
4
c
4
-Br-
200-
202
196-
40
3
7
C H CHO
198
6
4
4
d
15
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4
-Cl-
212-
214
213-
5
3a
40
91
3
6
C H CHO
215
6
4
4
4
4
e
f
2
-Cl-
289-
291
290-
6
7
3a
3a
40
45
89
83
2
C H CHO
291
6
4
2
2
29-
31
231-
C H CHO
6
5
3
6
235
g
4
-Me-
220-
222
217-
8
9
3a
3a
55
11
86
87
3
8
C H CHO
219
6
4
4
4
h
4
-MeO-
200-
202
196-
3
8
C H CHO
5
198
6
4
i
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4
-HO-
13
205-
206
204-
1
1
1
0
1
2
3a
3b
3b
83
91
89
3
6
9
7
C H CHO
5
205
6
4
4
j
3
-NO2-
204-
205
201-
35
40
3
C H CHO
203
6
4
4
4
4
4
k
4
-NO2-
222-
225
223-
3
C H CHO
225
6
4
l
4
-Br-
239-
242
238-
1
1
3
4
3b
3b
45
45
94
88
3
7
C H CHO
240
6
4
m
4
-Cl-
221-
223
220-
3
9
C H CHO
222
6
4
n
17
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4
-MeO-
11
197-
199
199-
1
5
3b
95
82
3
7
C H CHO
5
202
6
4
4
4
o
4
-HO-
13
244-
247
244-
1
6
3b
3
7
C H CHO
5
246
6
4
p
a
Isolated yield.
18
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Fig. 1. Examples of 2-amino-4H-chromene-3-carbonitrile-based biological and
pharmaceutical compounds
19
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Fig. 2. FT-IR spectra of Fe O , SiO and Fe O @SiO nanocatalyst.
3
4
2
3
4
2
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Fig. 3. SEM image of Fe O @SiO nanocatalyst.
3
4
2
21
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Fig. 4. XRD pattern of Fe O @SiO nanocatalyst.
3
4
2
22
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Fig. 5. TEM image of Fe O @SiO core-shell structures.
3
4
2
23
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Fig. 6. EDX of the Fe O @SiO nanocatalyst.
3
4
2
24
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Fig. 7. Recycling of the nanocatalyst for the synthesis of 4a
.
25
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Scheme 1. Fe O @SiO catalyzed MCRs leading to chromenes 4a-p
.
3
4
2
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Scheme 2. The proposed mechanism for the formation of 2-amino-4H-chromene-3-carbonitriles
4
a-p.
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