Evaluation of magnetically recyclable nano-Fe3O4 as a green catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono and bis 1,4-dihydropyridine derivatives

Article abstract of DOI:10.1007/s11164-015-2220-1

Magnetically separable Fe₃O₄ nanoparticles were used as an environmental friendly catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono- and bis-1,4-dihydropyridine derivatives via three-component reactions of aromatic aldehydes and malononitrile with cyclic β-dicarbonyls or cyclic β-enaminoketones respectively. These reactions were carried out in EtOH and at reflux. Fe₃O₄ nanoparticles can be magnetically separated from the reaction mixture by a magnet and recycled without significant loss of catalytic activity.

Full text of DOI:10.1007/s11164-015-2220-1

Res Chem Intermed
DOI 10.1007/s11164-015-2220-1
Evaluation of magnetically recyclable nano-Fe3O4
as a green catalyst for the synthesis of mono- and bis-
tetrahydro-4H-chromene and mono and bis
1,4-dihydropyridine derivatives
Bagher Amirheidari1 Mohammad Seifi2
•
•
Mehdi Abaszadeh3
Received: 6 June 2015 / Accepted: 7 August 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract Magnetically separable Fe3O4 nanoparticles were used as an environ-
mental friendly catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene
and mono- and bis-1,4-dihydropyridine derivatives via three-component reactions
of aromatic aldehydes and malononitrile with cyclic b-dicarbonyls or cyclic b-
enaminoketones respectively. These reactions were carried out in EtOH and at
reflux. Fe3O4 nanoparticles can be magnetically separated from the reaction mixture
by a magnet and recycled without significant loss of catalytic activity.
Keywords Fe3O4 nanoparticles Á Tetrahydro-4H-chromenes Á 1,4-
Dihydropyridines Á Three-component reaction
Introduction
Multicomponent reactions (MCRs) are useful to make complex molecules with
reliable synthetic yield, frequently with high stereoselectivity, and easily accessible
reactants [1–3]. Improvement of MCRs can result in useful synthetic methods to
produce many organic compounds potentially applicable in current organic,
bioorganic, and medicinal chemistry [4–6].
Due to their unique chemical and biological properties, bis-heterocyclic
compounds have attracted much attention in recent years [7–9]. Particularly, bis-
&
Mehdi Abaszadeh
abaszadeh@kmu.ac.ir
1
2
3
Herbal and Traditional Medicine Research Center, Kerman University of Medical Sciences,
Kerman, Iran
Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
Najafabad, Esfahan, Iran
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of
Medical Sciences, Kerman 76175493, Iran
123

B. Amirheidari et al.
heterocyclic compounds, which exhibit various biological activities, including
antibacterial, fungicidal, tuberculostatic, and antiamoebic properties [10–12], play
important roles in the drug discovery processes and analysis of drugs in late
development.
In this context, the three-component reaction of aromatic aldehydes and
malononitrile with cyclic b-dicarbonyls or cyclic b-enaminoketones has been one
of the most well-studied MCRs in recent years. The reaction affords formation of
mono- and bis-tetrahydro-4H-chromene and mono- and bis-1,4-dihydropyridine
derivatives, respectively.
Tetrahydro-4H-chromenes due to their lucrative biological and pharmacological
properties are used as a momentous class of heterocyclic compounds in the
pharmaceutical applications such as anticancer [13], antimalarial [14], antileish-
manial [15], antibacterial [16], antifungal [17], antianaphylactic [18], antiallergenic
[19], diuretic [20], and hypotensive [21] agents.
Also, 1,4-dihydropyridines are of an important class of compounds with a wide
range of biological activities [22]. Due to being pharmacologically active and acting
as antitumor [23], calcium channel blocker [24], antitubercular [25], analgesic [26],
antithrombotic [27], anti-inflammatory [28], anticonvulsant agents [29], they are of
many interests.
Applications of tetrahydro-4H-chromene and 1,4-dihydropyridine derivatives
necessitates the advancement in the environmentally friendly procedures to
synthesize these compounds by three-component reaction of aromatic aldehydes
and malononitrile with cyclic b-dicarbonyls or cyclic b-enaminoketones, respec-
tively. There are various catalytic systems for the synthesis of tetrahydro-4H-
chromene [30–39] and 1,4-dihydropyridine [40, 41] derivatives by MCR, but these
systems suffer from disadvantages like the use of toxic organic solvents, costly
catalysts, existence of transition metals, difficult work up, time-consuming reaction,
and low yield. Thus, a simple and green synthesis of tetrahydro-4H-chromenes and
1,4-dihydropyridines needs to be carried out without association of these catalytic
systems.
The field of nanocatalysis is a rapidly growing field, which involves the use of
nanoparticles as catalysts for a variety of homogeneous and heterogeneous catalysis
applications, owing to their remarkably different and unique properties, which
include a high surface area, easy recovery, and nanosize [42, 43]. Nanocatalysts are
esteemed as materials of enormous surface areas and with new investigation,
developments may offer expanding catalytic abilities [44–46]. Heterogeneous
catalysis characterizes one of the oldest commercial practices of nanoscience,
nanoparticles of metals and other compounds have been extensively used for
important chemical reactions. Fe3O4 nanoparticles (Fe3O4 NPs) have been used as
recyclable catalysts in the development of sustainable methodologies [47] for
synthesis of compounds such as xanthenes [48], oximes [49], quinoxalines [50],
fused azo-linked pyrazolo[4,3-e]pyridines [51], 1,8-dioxo-decahydroacridine [52],
propargylamines [53] and many more, because of their significant characteristics
such as the ease of magnetic separation from the reaction mixture, non-toxicity, and
being widely accessible. But Fe3O4 NPs has never been used in the synthesis of
tetrahydro-4H-chromene (4a–x) and 1,4-dihydropyridine (7a–t) derivatives. Hence,
123

Evaluation of magnetically recyclable nano-Fe3O4 as a green…
we set about to synthesize the aimed compounds in refluxing EtOH by using Fe3O4
NPs as a catalyst for the first time.
Results and discussion
To optimize the reaction conditions, a methodical study considering different
variables affecting the reaction time and yield was carried out for the three-
component reaction of benzaldehyde 1a, malononitrile 2, and dimedone 3a in the
presence of Fe3O4 NPs as catalysts for preparing compound 2-amino-7,7-dimethyl-
5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile 4a (Scheme 1). The
results are shown in Table 1.
We used some polar and nonpolar solvents in this reaction for which the best
results in terms of reaction time and yield of the desired product 4a was obtained
when the reaction was conducted in ethanol (Table 1, entry 1–4). We also optimized
the quantity of the catalysts. The best results were obtained when the reactions were
carried out in the presence of 30 mol% Fe3O4 NPs (Table 1, entry 5–8). We also
attempted to reuse the catalyst; the catalyst was easily separated from the reaction
mixture by an external magnet and reused (after washing with ethanol and dried) for
three consecutive runs, and no obvious diminishing activity was observed (Table 1,
entry 9–11).
Relying on our collected data, we decided to apply this method for synthesis of
tetrahydro-4H-chromene (4a–k, m–w) and 1,4-dihydropyridine (7a–d, f–i, k–n,
p–s) derivatives by a three-component reaction of aromatic aldehydes (1a–k)
and malononitrile (2) with cyclic b-dicarbonyls (3a, b) or cyclic b-enaminoketone
(6a–d) respectively, in EtOH, under reflux, and in the presence of Fe3O4 NPs
(30 mol%) (Scheme 2; Tables 2, 3).
We were stimulated by this success, so the versatility of the reaction was
explored further by extending the procedure to the synthesis of bis-tetrahydro-4H-
chromene (4l, x) and bis-1,4-dihydropyridine derivatives (7e, j, o, t) via reaction of
para phthalaldehyde (1l) with two equiv. malononitrile (2) and b-dicarbonyls (3a,
b) or cyclic b-enaminoketone (6a–d) under similar conditions (Scheme 3; Tables 2,
3).
A plausible mechanism for the nano Fe3O4 catalyzed is illustrated in Scheme 4.
The nano Fe3O4 facilitates the Knoevenagel condensation and Michael addition
through coordination of its Fe3? with O of the carbonyl group and with N from CN.
Scheme 1 Three-component reaction of benzaldehyde 1a, malononitrile 2, and dimedone 3a in the
presence of Fe3O4 NPs as catalysts for a model reaction
123

B. Amirheidari et al.
Table 1 Optimization of the
model reaction between
benzaldehyde 1a, malononitrile
2, and dimedone 3a
Entry
Solvent
Catalyst (mol%)
Time (min)
Yield (%)
1
EtOH
CH3CN
EtOAc
Toluene
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
30
30
30
30
15
20
25
35
30
30
30
5
20
35
60
22
15
10
5
93
88
82
65
85
87
90
93
91
90
89
2
3
4
5
6
7
8
9a
10b
11c
6
a
First run
7
b
Second run
9
c
Third run
Scheme 2 Synthesis of tetrahydro-4H-chromene (4a–k, m–w) and 1,4-dihydropyridine (7a–d, f–i, k–n,
p-s) derivatives
Conclusions
In summary, we have reported the use of magnetically separable Fe3O4 nanoparticles
for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono- and bis-1,4-
dihydropyridine derivatives via the three-component reaction of aromatic aldehydes
and malononitrile with cyclic b-dicarbonyls or cyclic b-enaminoketones, respectively.
These reactions were carried out in EtOH at reflux. Recycling of the catalyst, high
yields, short reaction times, and clean reaction conditions are advantages of this
procedure that make it a useful practical process for the synthesis of these compounds.
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Evaluation of magnetically recyclable nano-Fe3O4 as a green…
Table 2 Three-component reaction of aromatic aldehydes (1a–k), malononitrile (2) and dimedone (3a)
or 1,3-cyclohexanedione (3b)
R
R
R
R
O
Ar
O
O
O
CN
R
O
O
NH2
R
NC
NH2
H2N
CN
4a-k, m-w
4l, x
Compd.
no.
R
Ar
Time
(min)
Yield
(%)
M. P.
observed (°C)
M. P. reported
(°C)
4a
4b
4c
4d
4e
4f
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
C6H5
5
4
93
94
95
94
95
91
90
88
90
89
89
88
92
93
94
93
94
91
89
87
89
88
88
88
231–232
215–217
175–178
221–222
181–182
218–220
200–202
225–228
221–222
227–229
206–207
[300 (dec.)
230–231
223–226
220–222
248–250
234–237
223–225
189–191
256–258
237–239
210–211
229–230
[300 (dec.)
234–236 [30]
216–218 [30]
178–179 [32]
222–224 [30]
180–182 [30]
219–221 [30]
201–203 [30]
226–228 [30]
220–222 [30]
226–228 [30]
206–207 [38]
[300 (dec.) [39]
229–231 [32]
225–227 [32]
221–223 [32]
248–250 [38]
235–237 [32]
224–226 [31]
190–192 [32]
257–259 [31]
237–239 [38]
210–211 [38]
229–230 [38]
4-Cl-C6H4
2,4-(Cl)2-C6H3
4-Br-C6H4
4
5
4-NO2-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-OH-C6H4
Furan-2-yl
4
6
4g
4h
4i
7
9
9
4j
Thiophen-2-yl
Pyridin-3-yl
p-Phthalaldehyde
C6H5
10
10
13
6
4k
4l
4m
4n
4o
4p
4q
4r
4s
H
4-Cl-C6H4
5
H
2,4-(Cl)2-C6H3
4-Br-C6H4
4
H
5
H
4-NO2-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-OH-C6H4
Furan-2-yl
4
H
7
H
8
4t
H
10
12
13
13
15
4u
4v
4w
4x
H
H
Thiophen-2-yl
Pyridin-3-yl
p-Phthalaldehyde
H
H
Experimental section
General
Melting points were measured on a Electrothermal-9100 apparatus and are
uncorrected. IR spectra were recorded on a Brucker FT-IR Tensor 27 infrared
1
spectrophotometer. H NMR and spectra were recorded on a Avance III 400 MHz
123

B. Amirheidari et al.
Table 3 Three-component reaction of aromatic aldehydes (1a–g), malononitrile (2) and cyclic
enaminoketones (6a–d)
R
R
R
R
O
Ar
O
O
CN
R
R'
N
N
R'
N
NH2
R
H2N
CN
7e, j, o, t
NC
NH2
R'
7a-d, f-i, k-n, p-s
Compd.
no.
R
R0
Ar
Time
(min)
Yield
(%)
M. P.
observed (°C)
M. P. reported
(°C)
7a
7b
7c
7d
7e
7f
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
H
C6H5
12
15
10
13
15
10
12
8
91
89
92
90
89
92
91
93
91
90
90
89
92
89
88
91
89
93
90
89
262–264
279–281
210 (dec.)
248–250
191 (dec.)
244–245
243–245
269–271
265–267
200 (dec.)
254 (dec.)
269–271
296–298
287–289
260 (dec)
110 (dec.)
235 (dec.)
228–230
237–238
230 (dec.)
265–267 [40]
279–281 [41]
210 (dec.) [41]
H
4-CH3O-C6H4
4-Br-C6H4
Pyridin-3-yl
p-Phthalaldehyde
C6H5
H
H
H
C6H5
C6H5
C6H5
C6H5
C6H5
H
246–248 [40]
243–245 [41]
269–271 [41]
7g
7h
7i
4-CH3-C6H4
4-Br-C6H4
Pyridin-3-yl
p-Phthalaldehyde
C6H5
11
13
15
17
12
15
17
12
15
10
13
15
7j
7k
7l
254 (dec.) [41]
269–271 [41]
296–298 [41]
H
H
4-CH3-C6H4
4-Cl-C6H4
7m
7n
7o
7p
7q
7r
7s
H
H
H
H
Pyridin-3-yl
p-Phthalaldehyde
C6H5
H
H
H
C6H5
C6H5
C6H5
C6H5
C6H5
110 (dec.) [41]
235 (dec.) [41]
228–230 [41]
H
4-CH3-C6H4
4-Cl-C6H4
H
H
Pyridin-3-yl
p-Phthalaldehyde
7t
H
Bruker spectrometer. The cyclic enaminoketones 6a–d [54] were prepared from
according to procedures described in the literature.
Preparation of Fe3O4 nanoparticles
To a solution of FeCl2Á4H2O (2.5 g) and FeCl3Á6H2O (6 g) in 30 mL deionized
water was added dropwise 1.0 mL of concentrated hydrochloric acid at room
temperature. The solution was added into 300 mL of 1.5 mol/L NaOH, and then the
solution was stirred vigorously at 70 °C until precipitation. Afterwards, the prepared
magnetic nanoparticles were separated magnetically, washed with deionized water,
and then dried at 70 °C for 8 h [48].
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Evaluation of magnetically recyclable nano-Fe3O4 as a green…
Scheme 3 Synthesis of bis-tetrahydro-4H-chromene (4l, x) and bis-1,4-dihydropyridine (7e, j, o,
t) derivatives
General procedure for the preparation of mono- and bis-tetrahydro-4H-chromene
(4a–x) and mono- and bis-1,4-dihydropyridine (7a–t) derivatives
A mixture of aromatic aldehydes 1a–k (2 mmol) [if para phthalaldehyde 1l
(1 mmol)], malononitrile 2 (2 mmol), cyclic b-dicarbonyls 3a, b or cyclic b-
enaminoketones 6a–d (2 mmol) and Fe3O4 nanoparticles (30 mol%) in ethanol
(10 mL) was refluxed for the time reported in Table 2, 3 (the progress of the
reaction being monitored by TLC and was used hexane/ethyl acetate as an eluent).
After completion of the reaction, the catalyst was separated magnetically from the
reaction mixture. Then the reaction mixture was poured into ice-cold water; the
crude product was filtered, dried, and recrystallized from ethanol.
4,40-(1,4-Phenylene)bis(2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboni-
trile) (4x) Yellow powder; IR (KBr, mmax/cm-1): 3456, 3392 (NH2), 2192 (CN),
1
1680 (C=O), 1593 (C=C). H NMR (400 MHz, DMSO-d6): 7.38 (s, 4H, CH-Ar),
7.04 (s, 4H, 2NH2), 4.11 (s, 2H, 2CH), 3.31–1.32 (m, 12H, 6CH2). 13C NMR
(100 MHz, DMSO-d6): 195.21 (C=O), 163.27 (C2), 157.12 (C8a), 146.47 (C–Ar),
128.63 (CH-Ar), 121.11 (C4a), 114.08 (CN), 62.25 (C3), 48.98 (CH2), 43.87 (CH2),
37.89 (C4), 26.14 (CH2). Anal. calcd. for C26H22N4O4: C, 68.71; H, 4.88; N,
12.33 %. Found: C, 68.49; H, 4.69; N, 12.14 %.
2-Amino-7,7-dimethyl-5-oxo-4-(pyridin-3-yl)-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (7d) Yellow powder; IR (KBr, mmax/cm-1): 3472, 3360, 3312 (NH2,
NH), 2192 (CN), 1699 (C=O), 1606 (C=C). H NMR (400 MHz, DMSO-d6): 9.07
(s, 1H, NH), 8.27 (s, 1H, CH-Ar), 7.78–7.25 (m, 3H, CH-Ar), 5.38 (s, 2H, NH2),
1
2
4.43 (s, 1H, CH), 2.27 (d, 1H, JHH = 4 Hz, CH), 2.21 (d, 1H, JHH = 4 Hz, CH),
2
123

B. Amirheidari et al.
Scheme 4 Plausible mechanism for the nano Fe3O4 catalyzed
2.07 (d, 1H, 2JHH = 8 Hz, CH), 1.78 (d, 1H, 2JHH = 8 Hz, CH), 1.07 (s, 3H, CH3),
0.91 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6): 192.21 (C=O), 164.78 (C2),
158.14 (C8a), 153.25, 137.02, 135.14, 130.54, 128.11, 124.32 (C4a), 114.21 (CN),
63.70 (C3), 49.74 (CH2), 41.89 (CH2), 38.25 (C4), 35.28 (CMe2), 32.21 (CH3),
28.98 (CH3). Anal. calcd. for C17H18N4O: C, 69.37; H, 6.16; N, 19.03 %. Found: C,
69.15; H, 5.98; N, 18.84 %.
4,40-(1,4-Phenylene)bis(2-amino-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile) (7e) Yellow powders; IR (KBr, mmax/cm-1): 3472, 3296, 3232
(NH2, NH), 2176 (CN), 1648 (C=O), 1590 (C=C). 1H NMR (400 MHz, DMSO-d6):
8.98 (s, 2H, 2NH), 7.71 (s, 4H, CH-Ar), 5.27 (s, 4H, 2NH2), 4.43 (s, 2H, 2CH), 2.51
2
2
(d, 2H, JHH = 8 Hz, 2CH), 2.35 (d, 2H, JHH = 8 Hz, 2CH), 2.18 (d, 2H,
2
2JHH = 8 Hz, 2CH), 1.61 (d, 2H, JHH = 8 Hz, 2CH), 1.01 (s, 6H, 2CH3), 0.92 (s,
6H, 2CH3). 13C NMR (100 MHz, DMSO-d6): 193.92 (C=O), 167.87 (C2), 160.34
123

Evaluation of magnetically recyclable nano-Fe3O4 as a green…
(C8a), 144.70 (C–Ar), 128.82 (CH-Ar), 121.20 (C4a), 114.08 (CN), 61.28 (C3),
52.48 (CH2), 46.91 (CH2), 43.74 (C4), 32.04 (CMe2), 30.26 (CH3), 27.77 (CH3).
Anal. calcd. for C30H32N6O2: C, 70.84; H, 6.34; N, 16.52 %. Found: C, 70.63; H,
6.16; N, 16.33 %.
2-Amino-7,7-dimethyl-5-oxo-1-phenyl-4-(pyridin-3-yl)-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile (7i) Pale orange powders; IR (KBr, mmax/cm-1): 3392, 3312
(NH2), 2192 (CN), 1670 (C=O), 1587 (C=C). H NMR (400 MHz, DMSO-d6):
1
8.12–7.07 (m, 9H, CH-Ar), 5.53 (s, 2H, NH2), 4.43 (s, 1H, CH), 2.23 (d, 1H,
2
2
2JHH = 4 Hz, CH), 2.18 (d, 1H, JHH = 4 Hz, CH), 2.01 (d, 1H, JHH = 8 Hz,
2
CH), 1.77 (d, 1H, JHH = 8 Hz, CH), 0.93 (s, 3H, CH3), 0.85 (s, 3H, CH3). 13C
NMR (100 MHz, DMSO-d6): 192.65 (C=O), 166.05 (C2), 160.06 (C8a), 157.05,
152.25, 135.29, 133.15, 132.47, 131.62, 131.27, 126.25, 123.58, 121.20 (C4a),
114.32 (CN), 62.69 (C3), 49.78 (CH2), 43.58 (CH2), 39.02 (C4), 35.87 (CMe2),
31.76 (CH3), 29.54 (CH3). Anal. calcd. for C23H22N4O: C, 74.57; H, 5.99; N,
15.12 %. Found: C, 74.35; H, 5.80; N, 14.92 %.
4,40-(1,4-Phenylene)bis(2-amino-7,7-dimethyl-5-oxo-1-phenyl-1,4,5,6,7,8-hexahy-
droquinoline-3-carbonitrile) (7j) Yellow powders; IR (KBr, mmax/cm-1): 3472,
3328 (NH2), 2192 (CN), 1638 (C=O), 1590 (C=C). H NMR (400 MHz, DMSO-
1
3
d6): 7.63–7.58 (m, 8H, CH-Ar), 7.43 (d, 2H, JHH = 4 Hz, CH-Ar), 7.24 (d, 4H,
3JHH = 4 Hz, CH-Ar), 5.32 (s, 4H, 2NH2), 4.47 (s, 2H, 2CH), 2.20 (d, 2H,
2
2
2JHH = 8 Hz, 2CH), 2.15 (d, 2H, JHH = 8 Hz, 2CH), 2.07 (d, 2H, JHH = 8 Hz,
2
2CH), 1.77 (d, 2H, JHH = 8 Hz, 2CH), 0.89 (s, 6H, 2CH3), 0.77 (s, 6H, 2CH3).
13C NMR (100 MHz, DMSO-d6): 194.90 (C=O), 165.04 (C2), 151.08 (C8a),
150.19, 144.41, 136.24, 130.27, 129.71, 126.78, 121.01 (C4a), 113.78 (CN), 60.57
(C3), 49.28 (CH2), 46.56 (CH2), 40.93 (C4), 35.91 (CMe2), 31.98 (CH3), 28.85
(CH3). Anal. calcd. for C42H40N6O2: C, 76.34; H, 6.10; N, 12.72 %. Found: C,
76.13; H, 5.91; N, 12.54 %.
2-Amino-5-oxo-4-(pyridin-3-yl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (7n)
Pale yellow powders; IR (KBr, mmax/cm-1): 3456, 3392, 3232 (NH2, NH), 2192
(CN), 1680 (C=O), 1593 (C=C). 1H NMR (400 MHz, DMSO-d6): 8.81 (s, 1H, NH),
8.03 (s, 1H, CH-Ar), 7.68–7.33 (m, 3H, CH-Ar), 5.75 (s, 2H, NH2), 4.41 (s, 1H,
CH), 2.31–1.74 (m, 6H, 3CH2). 13C NMR (100 MHz, DMSO-d6): 192.25 (C=O),
166.02 (C2), 160.14 (C8a), 156.22, 148.27, 141.59, 137.47, 131.22, 120.75 (C4a),
113.14 (CN), 62.02 (C3), 48.01 (CH2), 37.12 (CH2), 36.58 (C4), 27.03 (CH2). Anal.
calcd. for C15H14N4O: C, 67.65; H, 5.30; N, 21.04 %. Found: C, 67.43; H, 5.12; N,
20.85 %.
4,40-(1,4-Phenylene)bis(2-amino-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboni-
trile) (7o) Yellow powders; IR (KBr, mmax/cm-1): 3392, 3328, 3232 (NH2, NH),
2176 (CN), 1657 (C=O), 1600 (C=C). 1H NMR (400 MHz, DMSO-d6): 8.90 (s, 2H,
2NH), 6.97 (s, 4H, CH-Ar), 5.56 (s, 4H, 2NH2), 4.84 (s, 2H, 2CH), 2.77–1.28 (m,
12H, 6CH2). 13C NMR (100 MHz, DMSO-d6): 193.89 (C=O), 169.41 (C2), 159.96
(C8a), 149.80 (C–Ar), 128.67 (CH-Ar), 121.25 (C4a), 115.09 (CN), 62.21 (C3),
123

B. Amirheidari et al.
49.82 (CH2), 43.70 (CH2), 36.54 (C4), 25.82 (CH2). Anal. calcd. for C26H24N6O2:
C, 69.01; H, 5.35; N, 18.57 %. Found: C, 68.80; H, 5.17; N, 18.38 %.
2-Amino-5-oxo-1-phenyl-4-(pyridin-3-yl)-1,4,5,6,7,8-hexahydroquinoline-3-car-
bonitrile (7s) Cream powders; IR (KBr, mmax/cm-1): 3392, 3328 (NH2), 2192
(CN), 1658 (C=O), 1593 (C=C). 1H NMR (400 MHz, DMSO-d6): 8.23 (s, 1H, CH-
Ar), 7.99–7.35 (m, 8H, CH-Ar), 5.78 (s, 2H, NH2), 4.42 (s, 1H, CH), 3.13–1.87 (m,
6H, 3CH2). 13C NMR (100 MHz, DMSO-d6): 191.97 (C=O), 166.48 (C2), 160.15
(C8a), 150.12, 142.35, 138.72, 135.28, 134.34, 132.19, 131.79, 128.86, 125.68,
121.14 (C4a), 113.78 (CN), 62.61 (C3), 49.47 (CH2), 40.25 (CH2), 39.59 (C4),
28.26 (CH2). Anal. calcd. for C21H18N4O: C, 73.67; H, 5.30; N, 16.36 %. Found: C,
73.45; H, 5.12; N, 16.17 %.
4,40-(1,4-Phenylene)bis(2-amino-5-oxo-1-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile) (7t) Yellow powders; IR (KBr, mmax/cm-1): 3408, 3328 (NH2), 2176
(CN), 1638 (C=O), 1596 (C=C). H NMR (400 MHz, DMSO-d6): 7.36–7.32 (m,
1
3
6H, CH-Ar), 7.20 (d, 2H, JHH = 4 Hz, CH-Ar), 7.99 (s, 4H, CH-Ar), 5.03 (s, 4H,
2NH2), 4.24 (s, 2H, 2CH), 2.26–1.41 (m, 12H, 6CH2). 13C NMR (100 MHz,
DMSO-d6): 195.15 (C=O), 165.12 (C2), 152.34 (C8a), 150.91, 144.58, 136.23,
130.04, 129.66, 126.82, 121.25 (C4a), 114.05 (CN), 60.48 (C3), 49.11 (CH2), 42.74
(CH2), 35.95 (C4), 27.76 (CH2). Anal. calcd. for C38H32N6O2: C, 75.48; H, 5.33; N,
13.90 %. Found: C, 75.27; H, 5.15; N, 13.72 %.
Acknowledgments The authors express their great appreciation to the Pharmaceutics Research Center,
Institute of Neuropharmacology, Kerman University of Medical Sciences, for supporting this
investigation.
References
1. J. Zhu, Multicomponent Reactions (Wiley-VCH, Weinheim, 2005)
2. L.F. Tietze, Chem. Rev. 96, 115 (1996)
3. L.F. Tietze, U. Beifuss, Angew. Chem. 105, 137 (1993)
4. D.A. Horton, G.T. Bourne, M.L. Smythe, Chem. Rev. 103, 893 (2003)
5. A.S. Al-bogami, Res. Chem. Intermed. (2013). doi:10.1007/s11164-013-1171-7
6. R. Sandaroos, S. Damavandi, Res. Chem. Intermed. 39, 4167 (2013)
7. R.M. Shaker, Arkivoc ix, 59 (2006)
8. F. Bellina, R. Rossi, Tetrahedron 62, 7213 (2006)
9. M. Abaszadeh, M. Seifi, Org. Biomol. Chem. 12, 7859 (2014)
10. P.D. Mehta, N.P.S. Sengar, A.K. Pathak, Eur. J. Med. Chem. 45, 5541 (2010)
11. A.R. Bhat, F. Athar, A. Azam, Eur. J. Med. Chem. 44, 426 (2009)
12. P.F. Iqbal, H. Parveen, A.R. Bhat, F. Hayat, A. Azam, Eur. J. Med. Chem. 44, 4747 (2009)
13. S.J. Mohr, M.A. Chirigos, F.S. Fuhrman, J.W. Pryor, Cancer Res. 35, 3750 (1975)
14. J. Davoll, J. Clarke, E.F. Eislager, J. Med. Chem. 15, 837 (1972)
15. T.N. Shwetaa, S. Gupta, Bioorg. Med. Chem. Lett. 14, 3913 (2004)
16. A.M. El-Agrody, M.H. El-Hakium, M.S. Abd El-Latif, A.H. Fekry, E.S.M. El-Sayed, K.A. El-
Gareab, Acta Pharm. 50, 111 (2000)
17. V.K. Ahluwalia, R. Batla, A. Khurana, R. Kumar, Indian J. Chem. Sec. B. 29, 1141 (1990)
18. J.L. Wang, D. Liu, Z.J. Zhang, S. Shan, X. Han, S.M. Srinivasula, C.M. Croce, E.S. Alnemri, Z.
Huang, Proc. Natl. Acad. Sci. U.S.A. 97, 7124 (2000)
19. L. Bonsignore, G. Loy, D. Secci, A. Calignano, Eur. J. Med. Chem. 28, 517 (1993)
20. M. Kidwai, S. Saxena, M.K.R. Khan, S.S. Thukral, Bioorg. Med. Chem. Lett. 15, 4295 (2005)
123

Evaluation of magnetically recyclable nano-Fe3O4 as a green…
21. D. Heber, C. Heers, U. Ravens, Pharmazie 48, 537 (1993)
22. D.M. Stout, A. Meyers, Chem. Rev. 82, 223 (1982)
23. R. Boer, V. Gekeler, Drugs Fut. 20, 499 (1995)
24. M. Ramesh, W.V. Matowe, J. Med. Chem. 41, 509 (1998)
25. S.R. Pattan, A.N. Parate, Indian. J. Heterocycl. Chem. 12, 387 (2003)
26. Y.S. Sadanandam, M.M. Shetty, Eur. J. Med. Chem. 29, 975 (1994)
27. K. Cooper, M.J. Fray, J. Med. Chem. 35, 3115 (1992)
28. S.R. Agudoawu, E.E. Knaus, J. Heterocycl. Chem. 37, 303 (2000)
29. A. Shafiee, N. Rastakari, Daru 12, 81 (2004)
30. M.G. Dekamin, M. Eslami, A. Maleki, Tetrahedron 69, 1074 (2013)
31. H.R. Safaei, M. Shekouhy, A. Shirinfeshan, S. Rahmanpur, Mol. Divers. 16, 669 (2012)
32. M. Seifi, H. Sheibani, Catal. Lett. 126, 275 (2008)
33. T.S. Jin, J.C. Xiao, S.J. Wang, T.S. Li, X.R. Song, Synlett, 2001 (2003)
34. C. Lu, X.J. Huang, Y.Q. Li, M.Y. Zhou, W. Zheng, Monatsh. Chem. 140, 45 (2009)
35. S. Abdolmohammadi, S. Balalaie, Tetrahedron Lett. 48, 3299 (2007)
36. M.R. Naimi-jamal, S. Mashkouri, A. Sharifi, Mol. Divers. 14, 473 (2010)
37. M.M. Heravi, B. Baghernejad, H.A. Oskooie, J. Chin. Chem. Soc. 55, 659 (2008)
38. M. Abaszadeh, M. Seifi, Lett. Org. Chem. 12, 271 (2015)
39. F. You-Jiana, M. Chun-Baoa, G. Yuanb, T. Shu-Jiang, F. Fang, S. Da-Qing, Chin. J. Chem. 22, 622
(2004)
40. B.V. Lichitsky, A.A. Dudinov, M.M. Krayushkin, Arkivoc ix, 73 (2001)
41. M. Abaszadeh, M. Seifi, A. Asadipour, Res. Chem. Intermed. 41, 5129 (2014)
42. S. Sa, M.B. Gawande, A. Velhinho, J.P. Veiga, N. Bundaleski, J. Trigueiro, A. Tolstogouzov,
O.M.N.D. Teodoro, R. Zboril, R.S. Varma, P.S. Branco, Green Chem. 16, 3494 (2014)
43. M.B. Gawande, A.K. Rathi, I.D. Nogueira, R.S. Varma, P.S. Branco, Green Chem. 15, 1895 (2013)
44. D. Wang, D. Astruc, Chem. Rev. 114, 6949 (2014)
45. M.B. Gawande, R. Luque, R. Zboril, Chem. Cat. Chem. 6, 3312 (2014)
46. M.B. Gawande, Y. Monga, R. Zboril, R.K. Sharma, Coord. Chem. Rev. 288, 118 (2015)
47. M.B. Gawande, P.S. Brancoa, R.S. Varma, Chem. Soc. Rev. 42, 3371 (2013)
48. M.A. Ghasemzadeh, J. Safaei-Ghomi, S. Zahedi, J. Serb. Chem. Soc. 78, 769 (2013)
49. B. Zeynizadeh, M. Karimkoshteh, J. Nanostruct. Chem. 3, 57 (2013)
50. H.Y. Lu¨, S.H. Yang, J. Deng, Z.H. Zhang, Aust. J. Chem. 63, 1290 (2010)
51. M. Nikpassand, L. Zare, T. Shafaati, S. Shariati, Chin. J. Chem. 30, 604 (2012)
52. M.A. Ghasemzadeh, J. Safaei-Ghomi, H. Molaei, C. R. Chim. 15, 969 (2012)
53. T. Zeng, W.W. Chen, C.M. Cirtiu, A. Moores, G. Song, C.J. Li, Green Chem. 12, 570 (2010)
54. Z. Karimi-Jaberi, Z. Takmilifard, Eur. Chem. Bull. 2, 211 (2013)
123