Application of novel and reusable Fe3O4@CoII(macrocyclic Schiff base ligand) for multicomponent reactions of highly substituted thiopyridine and 4H-chromene derivatives

Article abstract of DOI:10.1002/aoc.5769

In this research study we designed and synthesized Co^II(macrocyclic Schiff base ligand containing 1,4-diazepane) immobilized on Fe₃O₄ nanoparticles as a novel, recyclable, and heterogeneous catalyst. The nanomaterial was f

Full text of DOI:10.1002/aoc.5769

Received: 11 October 2019
DOI: 10.1002/aoc.5769
Revised: 23 March 2020
Accepted: 7 April 2020
F U L L P A P E R
II
Application of novel and reusable Fe O @Co (macrocyclic
3
4
Schiff base ligand) for multicomponent reactions of highly
substituted thiopyridine and 4H-chromene derivatives
Hakimeh Ebrahimiasl
| Davood Azarifar
| Jamshid Rakhtshah |
Hassan Keypour | Masoumeh Mahmoudabadi
Department of Chemistry, Bu-Ali Sina
University, Hamedan, 65178, Iran
II
In this research study we designed and synthesized Co (macrocyclic Schiff
base ligand containing 1,4-diazepane) immobilized on Fe O nanoparticles as
3
4
Correspondence
a novel, recyclable, and heterogeneous catalyst. The nanomaterial was fully
characterized using various techniques such as Fourier-transform infrared
spectroscopy, scanning electron microscopy, transmission electron microscopy,
X-ray diffraction, energy-dispersiveX-ray spectroscopy, thermogravimetric
analysis, vibrating sample magnetometry, differential reflectance spectroscopy,
Brunauere–Emmette–Teller method, inductively coupled plasma, and elemen-
tal analysis (CHNS). Then, the catalytic performance was successfully investi-
gated in the multicomponent synthesis of 2-amino-4-aryl-6-(phenylsulfanyl)
pyridine-3,5-dicarbonitrile and 2-amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-
benzo[g]chromene-3-carbonitrile derivatives. Furthermore, the catalyst was
isolated using a simple filtration, and recovery of the nanocatalyst was demon-
strated five times without any loss of activity.
Hakimeh Ebrahimiasl and Davood
Azarifar, Department of Chemistry, Bu-
Ali Sina University, 65178 Hamedan, Iran.
Email: h_ebrahimiasl64@basu.ac.ir;
azarifar@basu.ac.ir
K E Y W O R D S
2
-amino-4-aryl-6-(phenylsulfanyl)pyridine-3,5-dicarbonitrile, 4H-benzo[g]chromene-
II
3
3 4
-carbonitrile derivatives, Fe O @Co (macrocyclic Schiff base ligand), magnetic nanoparticles,
multicomponent reaction
[
4–6]
1
| INTRODUCTION
providing functional groups on the surface.
The
design and a combination of coating functional groups
such as macrocyclic Schiff base ligand and MNPs can also
provide suitable heterogeneous systems.
In recent times, environmental catalysts and heteroge-
neous benign metals have attracted tremendous attention
[1]
in the world of organic synthesis.
Homogeneous
Multicomponent reactions (MCRs) are effective in the
synthesis of heterocycle compounds in organic chemis-
catalysts based on transition metals often involve a
monotonous catalyst separation step. Recently, magnetic
nanoparticles (MNPs), with important properties such as
high reusability, easy preparation, high surface area,
functionalization, facile catalyst separation by an external
magnet, and high loading capacity, have been extensively
used for the heterogenization of homogeneous cata-
[
7]
try. Recently, the synthesis of the three- and four MCRs
has been most reported because of their high sustainabil-
[
8–11]
ity and great ecofriendly conditions.
MCRs have
many advantages such as a simplified purification,
easy synthesis of compounds in a few steps, the forma-
tion of new bonds in one pot with a high atomic
economy, the reduction of by-products, and the ease
[2,3]
lysts.
The surface coating of MNPs may increase the
[
12–14]
chemical stability, avoiding aggregation in solutions and
of workup.
The combination of magnetic
Appl Organomet Chem. 2020;e5769.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
1 of 19
https://doi.org/10.1002/aoc.5769

2
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EBRAHIMIASL ET AL.
nanocatalysts and MCRs has emerged as a helpful strat-
egy in heterocycle systems.
2 | MATERIALS AND METHODS
Heteroaryl-substituted pyridines and chromenes
2.1 | General
through –NH and –CN functional groups in the second
2
and third positions are important heterocycle medical
All the solvents and reagents used in this work were pur-
chased from Merck Company and were used without fur-
ther purification. Analytical thin layer chromatography
scaffolds because of various pharmaceutical properties and
[15–23]
biological activities in natural product structures.
A
variety of approaches and methods have been established
for the synthesis of heteroaryl-substituted pyridines and
chromenes, especially one-pot, three-component reactions
was performed using the Merck silica gel GF2 plates.
54
1
13
The H NMR (DMSO-d , 400 and 250 MHz) and
C
6
NMR (DMSO-d , 250and 100 MHz) spectra were
6
[24,25]
of aldehydes, malononitrile, and nucleophiles.
In
recorded using BRUKER AVANCE instruments in
recent years, more-efficient catalysts such as ionic
DMSO-d as solvent. The X-ray diffraction (XRD) spectra
6
[26]
[27]
[28]
liquid,
Lewis
acid
ZnCl2,
NAP-MgO,
were recorded using a PANalytical X'Pert PRO instru-
ment. The microstructure of the material was assessed
using a scanning electron microscope (Zeiss Sigma VP
model) and a transmission electron microscope (Zeiss-
EM10C-100 KV model). The vibrating sample magnetom-
etry (VSM) was recorded using the LBKFB model
(Meghnatis Daghigh Kavir Company, Kashan, Iran). The
inductively coupled plasma (ICP) was recorded using an
LBKFB, PerkinElmer model. The thermogravimetric
analysis (TGA) was recorded using the SDT Q600 V20.9
Build 20 model.
[
29]
[30]
KF/alumina, ortho iodoxybenzoic acid, scandium(III)
triflate,
[31]
[32]
Et N,
3
and imidazole have been reported for
the synthesis of 2-amino-4-aryl-6-(phenylsulfanyl)pyri-
[
33]
dine-3,5-dicarbonitrile.
of methodologies for the synthesis of 2-amino-5,10-dioxo-
-aryl-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile
in the presence of heterogeneous catalysts such as basic
On the contrary, a wide range
4
[34]
[35]
[36]
[37]
ionic liquid,
and phosphates have been reported.
Continuing our efforts in the synthesis and design of
Na CaP O ,
nano-MgO,
MOF-5,
2
2 7
[
38]
[39]
novel nanomagnetic catalysts,
in this work, we
prepared macrocyclic Schiff base ligand immobilized on
2.2 | General procedure for preparation of
macrocyclic Schiff base ligand containing
1,4-diazepane
II
Fe O , denoted as Fe O @Co (macrocyclic Schiff
3
4
3 4
base ligand) and then fully characterized the cobalt-
supported macrocyclic Schiff base ligand containing
0
1
,4-diazepane. We studied the catalytic activity of
A
solution of 2,2 -(1,4-diazepane-1,4-diyl)dianiline
II
Fe O @Co (macrocyclic Schiff base ligand) as
a
(0.075 g, 0.25 mmol) in absolute ethanol (15 ml) was
added dropwise to solution of
3
4
heterogeneous, novel, and recyclable catalyst in one-pot
MCRs of 2-amino-4-aryl-6-(phenylsulfanyl)pyridine-3,-
a
2,3-dihydroxybenzaldehyde (0.075 g, 0.5 mmol) in etha-
nol (20 ml). Then, the mixture was stirred and refluxed
for 24 h. The resulting orange powder was obtained by
filtration; washed with 10 ml of ethanol, n-hexane, and
diethyl ether; and dried in vacuum to obtain macrocyclic
5
5
-dicarbonitrile
,10-dihydro-4H-benzo[g]chromene-3-carbonitrile. This
and
2-amino-5,10-dioxo-4-aryl-
method had many advantages (e.g., low cost, easy
availability, and good yields) compared with the
previous methods.
[
40]
Schiff base ligand (Scheme 1).
SCHEME 1 Synthesis of
macrocyclic Schiff base ligand
(
III)

EBRAHIMIASL ET AL.
3 of 19
2
.3 | General procedure for preparation of
2.5 | General procedure for synthesis of
2-amino-4-aryl-6-(phenylsulfanyl)pyridine-
,5-dicarbonitrile (1a–h)
Fe O @macrocyclic Schiff base ligand
3
4
3
First, the Fe O nanoparticles were synthesized according
3
4
[41]
to the process outlined in Taghizadeh et al.
0 mlround-bottom flask, a mixture of the macrocyclic
Schiff base ligand (III) (0.17 g, 0.5 mmol) and Fe O (0.5 g)
In a
A mixture of aldehyde (1.0 mmol), malononitrile
II
5
(2.0 mmol), Fe O @Co (macrocyclic Schiff base ligand)
3 4
(20 mg), and thiophenole (1.0 mmol) was stirred under
3
4
ꢀ
was added to in 25 ml of acetonitrile. The mixture was son-
icated for 1 h and stirred overnight. The residue was sepa-
rated from the mixture by magnetic decantation, rinsed
with acetonitrile several times, and dried in a vacuum.
solvent-free conditions at 100 C. The reaction mixture
was stirred under reflux conditions in the open air. The
progress of the reaction was monitored using TLC. After
the reaction was completed, the nanocatalyst was sepa-
rated from the reaction mixture using an external mag-
netic field and washed with ethanol several times. Finally,
the solid product was collected by recrystallization from
ethanol and dried to obtain a pure solid. The obtained
solid was pure enough for further characterization
(Table 2).
2
.4 | General procedure for preparation of
II
Fe O @Co (macrocyclic Schiff base ligand)
3
4
In the last step, complexation of the Fe O -supported
3
4
macrocyclic Schiff base ligand (III) with cobalt(II) was
accomplished by treatment of Fe O @macrocyclic
3
4
Schiff base ligand MNPs (0.5 g) with Co(Cl) .6H O
2.6 | General procedure for synthesis of
2-amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-
benzo[g]chromene-3-carbonitrile (2a–j)
2
2
(1 mmol) in ethanol (50 ml). The reaction mixture was
stirred for 24 h under reflux conditions. The precipitate
was isolated using a super magnet bar, rinsed with etha-
ꢀ
nol several times, and dried at 80 C overnight under vac-
A mixture of aldehyde (1.0 mmol), malononitrile
II
II
uum. The Fe O @Co (macrocyclic Schiff base ligand)
(2.0 mmol), Fe O @Co (macrocyclic Schiff base ligand)
3
4
3 4
was obtained as a brown solid (Scheme 2).
(20 mg), and 2-hydroxy-1,4-naphthoquinone (1.0 mmol)
II
SCHEME 2 Synthesis of Fe
3
O
4
@Co (macrocyclic Schiff base ligand)

4
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EBRAHIMIASL ET AL.
ꢀ
was stirred under solvent-free conditions at 100 C. The
reaction mixture was stirred under reflux conditions in
the open air. After the reaction was completed, the
nanocatalyst was separated from the reaction mixture
by using an external magnetic field and washed with
ethanol several times. Finally, the solid product was
collected by recrystallization from ethanol and dried to
obtain a pure solid. The obtained solid was pure
enough for further characterization (Table 3). The char-
acterization data for the catalyst and the titled products
are available online in the Supporting Information
section.
154.7, 134.0, 119.2, 116.7, 115.9, 115.5, 115.0, 112.1,
69.2 ppm.
3.4 | 2-Amino-4-(3-nitrophenyl)-
6-(phenylthio)pyridine-3,5-dicarbonitrile
(1c)
ꢀ
Yield 97%. Brown solid, m.p. 220–222 C. IR ν
(KBr):
max
3460, 3344, 3233, 2216, 1634, 1582, 1352, 1261,
−1 1
1067 cm ; H NMR (DMSO-d , 250 MHz) δ = 7.49–7.58
6
H
(m, 5H, Ar–H), 7.86–7.89 (m, 2H, Ar–H), 8.03–8.50 (bs,
13
2
H, NH ), 8.41–8.50 (m, 5H, Ar–H) ppm. C NMR
2
(
DMSO-d , 250 MHz) δ = 166.7, 160, 156.8, 148.1, 135.9,
6 c
3
3
| CHARACTERIZATION DATA
131.1, 130.2, 129.9, 127.5, 125.6, 124.1, 115.5, 115.2, 93.9,
7.8 ppm.
8
0
.1 | 3,3 -((1Z,1’Z)-(((1,4-diazepane-1,4-diyl)
bis(2,1-phenylene))bis(azanylylidene))
bis(methanylylidene))bis(benzene-1,2-diol)
3.5 | 2-Amino-6-(phenylthio)-4-(pyridin-
3-yl)pyridine-3,5-dicarbonitrile(1d)
(
III)
ꢀ
1
ꢀ
Yield 85%. Orange solid, m.p. 153 C. H NMR (DMSO-
Yield 96%. Light green solid, m.p. 228–230 C. IR ν
max
d6, 250 MHz) δH = 8.75 (s, 2H, OH), 8.66 (s, 2H, OH),
(KBr): 3408, 3376, 3247, 2213, 1650, 1575, 1551, 1480,
−
1
1
6
3
2
1
1
5
.57–6.75 (m, 14H, Ar–H), 6.57–6.66 (s, 2H, N=CH),
1329, 1294 cm ; H NMR (DMSO-d , 250 MHz)
6
.33–3.79 (m, 4H, CH ), 2.49–2.59 (m, 4H, CH ), 1.67 (M,
δH = 7.30–8.04 (m, 10H, Ar–H, NH ), 8.75 (m, 1H, Ar–
2
2
2
13
H, CH ) ppm. C NMR (DMSO-d , 250 MHz) δ = 193.2,
H) ppm.
2
6
c
64.0, 150.1, 147.6, 146.1, 133.1, 130.4, 128.6, 126.9, 123.3,
21.6, 119.9, 119.6, 119.3, 119.0, 58.0, 56.5, 55.1, 54.2,
3.5, 40.6, 40.2, 39.9, 39.6, 39.3, 27.5, 18.9 ppm. Mass
3.6 | 2-Amino-4-(4-nitrophenyl)-
6-(phenylthio)pyridine-3,5-dicarbonitrile
+
(EI) m/z = 522.23 [M ].
(1e)
ꢀ
3
.2 | 2-Amino-4-phenyl-6-(phenylthio)
Yield 98%. Yellow solid, m.p. 290–292 C. IR ν
(KBr):
max
pyridine-3,5-dicarbonitrile (1a)
3426, 3336, 3230, 2213, 1634, 1552, 1513, 1460, 1350,
262 cm ; H NMR (DMSO-d , 250 MHz) δ = 7.49–7.58
(m, 5H, Ar–H), 7.84–7.92 (m, 4H, Ar–H, NH ), 8.38–8.41
(m, 2H, Ar–H) ppm. C NMR (DMSO-d , 250 MHz)
−1 1
1
6
H
ꢀ
Yield 90%. Yellow solid, m.p. 230–232 C. IR νmax (KBr):
2
13
3
479, 3350, 3213, 3064, 2218, 1623, 1522, 1441,
6
−1
1
1
263,1034 cm ;
H
NMR (DMSO-d6, 250 MHz)
δc = 87.39, 93.45, 115.06, 115.39, 124.32, 127.37, 129.95,
δ = 7.48–7.55 (m, 10H, Ar–H), 7.79 (bs, 2H, NH ) ppm.
130.22, 130.69, 135.25, 140.66, 149.05, 157.16, 159.91,
H
3
2
1
13
C NMR (DMSO-d , 250 MHz) δ = 166.6, 160.1, 159.0,
166.70 ppm. C NMR (DMSO-d , 250 MHz) δ = 166.7,
6
c
6
c
1
1
35.2, 134.4, 130.8, 130.1, 129.9, 129.1, 128.8, 127.6, 115.7,
15.4, 93.9, 87.6 ppm.
159.9, 157.2, 149.0, 140.7, 135.2, 130.7, 130.2, 129.9, 127.4,
124.3, 115.4, 115.1, 93.4, 87.4 ppm.
3
.3 | 2-Amino-4-(4-(dimethylamino)
phenyl)-6-(phenylthio)pyridine-
,5-dicarbonitrile (1b)
3.7 | 2-Amino-4-(4-hydroxyphenyl)-
6-(phenylthio)pyridine-3,5-dicarbonitrile
(1f)
3
ꢀ
ꢀ
Yield 95%. Brown solid, m.p. 234–236 C. IR νmax (KBr):
Yield 98%. Yellow solid, m.p. 310–312 C. IR ν
(KBr):
max
3
1
414, 3335, 3117, 2210, 1613, 1568, 1521, 1387,
3406, 3334, 3247, 3117, 2219, 1650, 1572, 1479,
1295 cm ; H NMR (DMSO-d , 250 MHz) δ = 4.08 (bs,
6 H
−
1 1
−1 1
196 cm ; H NMR (DMSO-d , 250 MHz) δ = 3.07–3.31
6
H
(
m, 6H, CH ), 4.08 (bs, 2H, NH ), 6.80–8.01 (m, 9H) ppm.
2H, NH ), 7.29–7.46 (m, 9H, Ar–H), 10.01 (bs, 1H,
OH) ppm.
3
2
2
1
3
C NMR (DMSO-d , 250 MHz) δ = 161.9, 159.2, 158.6,
6
c

EBRAHIMIASL ET AL.
5 of 19
3
6
.8 | 2-Amino-4-(4-fluorophenyl)-
-(phenylthio)pyridine-3,5-dicarbonitrile
3.12 | 2-Amino-4-(4-methoxyphenyl)-
5,10-dioxo-5,10-dihydro-4H-benzo[g]
chromene-3-carbonitrile (2c)
(
1g)
ꢀ
ꢀ
Yield 97%. Yellow solid, m.p. 230–232 C. IR ν
(KBr):
Yield 96%. Brown solid, m.p. 244–246 C. IR ν
(KBr):
max
max
3
1
493, 3342, 3224, 2216, 1605, 1633, 1556, 1421,
3405, 3327, 3250, 3193, 2200, 1663, 1634, 1604, 1511,
1406, 1364, 1243, 1176 cm ; H NMR (DMSO-d6,
−
1 1
−1
1
261 cm ; H NMR (DMSO-d , 250 MHz) δ = 7.41–7.65
6
H
13
(m, 9H, Ar–H), 7.81 (bs, 2H, NH ) ppm. C NMR
250 MHz) δH = 3.85 (s, 3H, CH ), 4.53 (s, 1H, CH),
2
3
13
(DMSO-d , 250 MHz) δ = 87.72, 93.97, 115.40, 115.70,
6.81–8.00 (m, 10H, Ar–H, NH ) ppm. C NMR (DMSO-
6
c
2
1
1
1
16.13, 116.48, 127.58, 128.28, 129.92, 130.15, 130.79,
31.47, 131.60, 135.60, 135.25, 158.18, 160.08, 161.65,
65.60, 166.54 ppm.
d , 250 MHz) δ = 183.0, 158.8, 136.1, 135.0, 134.5, 131.5,
131.0, 129.3, 126.5, 126.2, 122.7, 119.8, 114.4, 58.2, 55.5,
36.1 ppm.
6
c
3
2
.9 | 2-Amino-6-(phenylthio)-4-(thiophen-
-yl)pyridine-3,5-dicarbonitrile (1h)
3.13 | 2-Amino-4-(4-(dimethylamino)
phenyl)-5,10-dioxo-5,10-dihydro-4H-
benzo[g]chromene-3-carbonitrile (2d)
ꢀ
Yield 96%. Yellow solid, m.p. 250–252 C. IR νmax
ꢀ
(KBr): 3488, 3347, 3213, 3075, 2215, 1726, 1650, 1623,
Yield 96%. Dark-orange solid, m.p. 250–252 C. IR ν
max
−1 1
1
548, 1401, 1256 cm ; H NMR (DMSO-d , 250 MHz)
(KBr): 3336, 3323, 3193, 2798, 2199, 1667, 1524, 1403,
6
−1
1
δH = 7.26–7.56 (m, 7H, Ar–H), 7.81 (bs, 2H, NH ),
1244, 715 cm ; H NMR (DMSO-d , 400 MHz)
2
6
13
7
2
1
1
2
1
.93–7.95 (m, 1H, Ar–H) ppm. C NMR (DMSO-d6,
50 MHz) δ = 87.31, 115.59, 115.83, 127.56, 128.35,
29.91, 130.16, 131.28, 131.74, 133.14, 133.14, 135.28,
51.37, 160.29, 167.13 ppm.
50 MHz) δ = 167.1, 160.3, 151.4, 135.3, 133.1, 131.7,
30.2, 129.9, 128.3, 127.6, 115.8, 115.6, 87.3 ppm.
δH = 8.04–8.03 (m, 1H, Ar–H), 7.88–7.81 (m, 3H, Ar–H),
7.25(s, 2H, NH ), 7.09–7.07 (d, 2H, Ar–H), 6.64–6.62 (d,
c
2
2H, Ar–H), 4.48 (s, 1H, CH), 2.50–2.49 (s, 6H, CH ) ppm;
3
13
13
C NMR (DMSO-d6,
C NMR (DMSO-d , 100 MHz) δ = 182.66, 176.99,
6
c
158.28, 149.52, 148.19, 134.52, 134.10, 131.10, 131.04,
130.53, 128.31, 126.03, 125.03, 122.66, 122.61, 119.58,
c
119.55, 112.42, 57.78, 35.45 ppm.
3
5
3
.10 | 2-Amino-5,10-dioxo-4-phenyl-
,10-dihydro-4H-benzo[g]chromene-
-carbonitrile (2a)
3.14 | 2-Amino-4-(4-chloro-3-nitrophenyl)-
5,10-dioxo-5,10-dihydro-4H-benzo[g]
chromene-3-carbonitrile (2e)
ꢀ
Yield 96%. Orange solid, m.p. 260–262 C. IR ν
(KBr):
max
ꢀ
3
400, 3220, 3191, 3052, 2198, 1635, 1687, 1405, 1366,
Yield 98%. Red-brown solid, m.p. 230–232 C. IR ν
max
−
1 1
1
244, 1178, 1070 cm ; H NMR (DMSO-d , 250 MHz)
(KBr): 3410, 3330, 3218, 2193, 1660, 1593, 1530, 1412,
6
−1
1
δH = 4.58 (s, 1H, CH), 7.19–8.05 (m, 11H, Ar–H, NH )
ppm. C NMR (DMSO-d , 250 MHz) δ = 183.0, 177.3,
1245, 716 cm ; H NMR (DMSO-d , 400 MHz)
2
6
13
δH = 8.04–8.02 (m, 1H, Ar–H), 7.88–7.85 (m, 1H, –Ar–H),
6
c
1
1
58.8, 149.4, 144.0, 135.0, 134.6, 131.5, 131.1, 129.0, 128.1,
27.5, 126.5, 126.2, 122.5, 119.7, 58.0, 37.0 ppm.
7.84–7.81 (m, 1H, Ar–H), 7.25 (s, 2H, NH ), 7.09–7.07 (d,
2
2H, Ar–H), 6.64–6.62 (d, 2H, Ar–H), 4.48 (s, 1H, CH)
13
ppm; C NMR (DMSO-d , 100 MHz) δ = 182.66, 176.99,
6
c
158.28, 149.52, 148.19, 134.52, 134.10, 131.10, 131.04,
3.11 | 2-Amino-5,10-dioxo-4-p-tolyl-
5,10-dihydro-4H-benzo[g]chromene-
3-carbonitrile (2b)
130.53, 128.31, 126.03, 125.77, 122.66, 122.61, 119.58,
119.55, 112.42, 57.78, 40.11 ppm.
ꢀ
Yield 95%. Orange solid, m.p. 240–242 C. IR ν
(KBr):
3.15 | 2-Amino-4-(furan-2-yl)-5,10-dioxo-
5,10-dihydro-4H-benzo[g]chromene-
3-carbonitrile (2f)
max
3
1
3
406, 3327, 3196, 2199, 1636, 1604, 1593, 1408, 1243,
110 cm ; H NMR (DMSO-d , 250 MHz) δ = 2.22 (s,
H, CH ), 4.54 (s, 1H, CH), 7.06–8.03 (m, 10H, Ar–H,
NH ) ppm. C NMR (DMSO-d , 250 MHz) δ = 183.0,
−
1 1
6
H
3
1
3
ꢀ
Yield 97%. Orange solid, m.p. 260–262 C. IR νmax
2
6
c
1
1
58.8, 149.2, 141.1, 136.7, 135.0, 134.6, 131.5, 131.1, 129.6,
28.0, 126.0, 126.2, 122.6, 119.8, 58.0, 36.5, 21.0 ppm.
(KBr): 3414.19, 3330, 2197, 1665, 1592, 1420, 1201,
−1 1
708 cm ; H NMR (DMSO-d , 400 MHz) δ = 8.05–8.03
6
H

6
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EBRAHIMIASL ET AL.
13
(m, 1H, Ar–H), 7.95–7.93 (m, 2H, Ar–H), 7.53 (d, 1H,
ppm. C NMR (DMSO-d , 250 MHz) δ = 183.0, 177.2,
6 c
Ar–H), 7.43 (s, 2H, NH ), 6.36–6.35 (m, 1H, Ar–H),
158.8, 151.4, 149.9, 147.0, 135.0, 134.7, 131.4, 131.1, 129.6,
126.5, 124.2, 121.1, 119.4, 56.9, 36.9 ppm.
2
13
6
.29–6.28 (d, 1H, Ar–H), 4.76 (s, 1H, CH) ppm;
C
NMR (DMSO-d , 100 MHz) δc = 182.28, 176.83,
6
1
1
1
59.27, 154.50, 149.23, 142.74, 134.71, 130.94, 130.54,
26.20, 125.92, 119.82, 119.78, 119.23, 119.20, 110.78,
06.46, 54.62 ppm.
3.17 | 2-Amino-4-(2,4-dichlorophenyl)-
5,10-dioxo-5,10-dihydro-4H-benzo[g]
chromene-3-carbonitrile (2h)
ꢀ
3
5
.16 | 2-Amino-4-(4-nitrophenyl)-
,10-dioxo-5,10-dihydro-4H-benzo[g]
Yield 97%. Red-brown solid, m.p. 280–282 C. IR ν
max
(KBr): 3467, 3341, 3167, 3073, 2202, 1670, 1592, 1248,
1199, 847, 717 cm ; H NMR (DMSO-d , 250 MHz)
δH = 5.10 (s, 1H, CH), 7.32–7.83 (m, 9H, Ar–H, NH )
ppm. C NMR (DMSO-d , 250 MHz) δ = 182.9, 177.2,
−
1
1
chromene-3-carbonitrile (2g)
6
2
ꢀ
13
Yield 97%. Orange solid, m.p. 230–232 C. IR νmax (KBr):
6
c
3
1
399, 3331, 3219, 2203, 1670, 1640, 1592, 1522, 1412,
158.8, 150.1, 140.6, 135.0, 134.6, 133.4, 132.7, 132.4, 131.3,
131.0, 129.1, 128.4, 126.5, 126.3, 121.2, 119.1, 56.3,
33.6 ppm.
−
1 1
302, 1245, 1077 cm ; H NMR (DMSO-d , 250 MHz)
6
δH = 4.79 (s, 1H, CH), 7.46–8.16 (m, 10H, Ar–H, NH2)
II
FIGURE 1 Field-emission scanning electron microscopy image of Fe
3
O
4
@Co (macrocyclic Schiff base ligand)
II
FIGURE 2 Transmission electron microscopy image of Fe
3
O
4
@Co (macrocyclic Schiff base ligand)

EBRAHIMIASL ET AL.
7 of 19
II
4
| RESULTS AND DISCUSSION
core/shell nanostructure Fe O @Co (macrocyclic Schiff
3 4
base ligand) was investigated as a novel, heteroge-
neous, and reusable Schiff base magnetic nanocatalyst
for the synthesis of highly substituted thiopyridine and
4H-chromene derivatives.
Macrocyclic Schiff base ligand (III) was synthesized by
0
the reaction of
a
solution of 2,2 -(1,4-diazepane-
1
2
,4-diyl)dianiline
,3-dihydroxybenzaldehyde(Scheme
(MNPs) were
3-chloropropyl)trimethoxysilane
(0.075
g,
0.25
mmol)
1).
modified
and
II
Fe O4
The synthesized Fe O @Co (macrocyclic Schiff base
3
3 4
nanoparticles
(
by
and
ligand) catalyst was characterized using Fourier-
transform infrared spectroscopy (FT-IR), scanning elec-
tron microscopy (SEM), transmission electron micros-
copy (TEM), XRD, energy-dispersiveX-ray spectroscopy
(EDX), TGA, VSM, differential reflectance spectroscopy
(DRS), ICP, and elemental analysis (CHNS).
II
Fe O @Co (macrocyclic Schiff base ligand). Cobalt(II)
3
4
was supported on the surface of Schiff base by the
reaction of cobalt chloride with ethanol under reflux
conditions (Scheme 2). Then, the catalytic activity of
FIGURE 3 (a) Thermogravimetric analysis (TGA) analysis of Fe
3
O
4
@macrocyclic Schiff base ligand; (b) TGA analysis of
II
Fe
3
O
4
@Co (macrocyclic Schiff base ligand)

8
of 19
EBRAHIMIASL ET AL.
FIGURE 4 X-ray powder
diffraction analyses of
II
3 4
Fe O @Co (macrocyclic Schiff base
ligand)
FIGURE 5 Energy-dispersiveX-ray
spectroscopy analyses of
II
Fe
3
O
4
@Co (macrocyclic Schiff base ligand)
3 4
FIGURE 6 (a) Vibrating sample magnetometry (VSM) analysis of Fe O @macrocyclic Schiff base ligand; (b) VSM analysis of
II
3 4
Fe O @Co (macrocyclic Schiff base ligand)

EBRAHIMIASL ET AL.
9 of 19
Field-emission
scanning
electron
microscopy
EDX analysis revealed the presence of Fe, O, N, C,
and Co elements in the nanomagnetic catalyst. The pres-
ence of the nitrogen and cobalt peaks in the EDX spec-
trum confirmed the immobilization of Schiff base
(
FESEM) was also used to verify the nanostructure of
II
Fe O @Co (macrocyclic Schiff base ligand). The FESEM
3
4
image revealed nanostructured morphology (Figure 1).
TEM revealed the particles having a relatively spherical
shape with an average size of ꢁ30 nm (Figure 2).
II
Co(II) complex on the surface of Fe O @Co (macrocyclic
3
4
Schiff base ligand) (Figure 5).
To investigate the stability and presence of the organic
II
structure on Fe O @Co (macrocyclic Schiff base ligand),
3
4
ꢀ
TGA was performed under N atmosphere at 25–600 C
2
for Fe O @macrocyclic Schiff base ligand and
3
4
II
Fe O @Co (macrocyclic Schiff base ligand) (Figure 3a,b).
3
4
The TGA curve in Figure 3a,b demonstrates a two mass
loss as it decomposed on heating. The TGA results showed
ꢀ
small amounts of weight loss below 100 C, which was
because of the removal of the physically adsorbed solvents
and moisture (2%). The mass loss of macrocyclic Schiff
ꢀ
base ligand was between five zones at above 200 C (for
[45]
3
a: 12.96 wt. % and 3b: 13.57 wt. %) (Figure 3).
X-ray powder diffraction (XRD) analysis is an effec-
tive technique used to identify the magnetite crystal
II
phase in Fe O @Co (macrocyclic Schiff base ligand).
3
4
II
The XRD diffraction pattern of Fe O @Co (macrocyclic
Schiff base ligand) exhibited several peaks at 2θ = 30.2 ,
5.6 , 43.3 , 53.7 , 57.3 , 62.9 , and 75.5 , which are
assigned to the (220), (311), (400), (422), (333), (440), and
622) crystallographic faces of magnetite, respectively.
These patterns were consistent with the standard Fe O
3
4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
(
3
4
FIGURE 8 Differential reflectance spectroscopy analysis of
[46]
II
XRD spectrum
(Figure 4).
3 4
Fe O @Co macrocyclic Schiff base ligand
FIGURE 7 Fourier-
transform infrared spectroscopy
3 4
image of (a) Fe O ,
(
b) macrocyclic Schiff base
3 4
ligand, (c) Fe O @macrocyclic
Schiff base ligand, and
II
(
d) Fe
3 4
O @Co (macrocyclic
Schiff base ligand)

10 of 19
EBRAHIMIASL ET AL.
3 4
FIGURE 9 (a) Brunauere–Emmette–Teller(BET) analysis of Fe O @macrocyclic Schiff base ligand; (b) BET analysis of
II
3 4
Fe O @Co (macrocyclic Schiff base ligand)
The magnetic property of the nanocatalyst was investi-
nanoparticles are illustrated in Figure 6. The saturation
magnetization of Fe O @(macrocyclic Schiff base ligand)
gated using the vibrating sample magnetometer. The mag-
netization curves for Fe O @(macrocyclic Schiff base
3
4
II
and Fe O @Co (macrocyclic Schiff base ligand) was found
3
4
3 4
II
−1
ligand) and Fe O @Co (macrocyclic Schiff base ligand)
to be 58.10 and 54.20 emu g , which was slightly lower
3
4
TABLE 1
Fe O @Co (macrocyclic Schiff base ligand)
3 4
Optimal conditions for the synthesis of 2-amino-4-phenyl-6-(phenylthio)pyridine-3,5-dicarbonitrile in the presence of
II
ꢀ
a
Entry
Amounts of catalyst (g)
Solvent
Temperature ( C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
0.01
0.01
0.01
0.01
0.02
0.02
–
Solvent free
rt
rt
120
120
80
20
25
2
H O
EtOH
rt
40
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
90
13
82
80
13
87
120
80
13
90
120
13
Trace
90
0.02
100
Note. Conditions of reaction: benzaldehyde (1 mmol), malononitrile (2 mmol), and thiophenol (1 mmol). rt, room temperature.
a
Isolated yield.

EBRAHIMIASL ET AL.
11 of 19
II
−1
TABLE 2
Comparative catalytic activity of Fe
3
O
4
@Co
than that of the Fe O nanoparticles (ꢁ66.64 emu g
3
4
[47]
(
macrocyclic Schiff base ligand) under optimal conditions
reported in Ghorbani-Choghamarani et al. ).
Figure 7 shows the FT-IR spectra of Fe O , macrocy-
clic Schiff base ligand, Fe O @macrocyclic Schiff base
ligand, and Fe O @Co (macrocyclic Schiff base ligand).
The O–H stretching vibration due to the hydroxy groups
3
4
Time
(min)
Yield
(%)
Entry Catalyst
3 4
II
II
3 4
1
Fe
base ligand)
Fe @(macrocyclic Schiff
3
O
4
@Co (macrocyclic Schiff
13
90
−
1
of Fe O is observed in the range of 2750–3450 cm for
all three compounds, Fe–O bending vibrations appearing
3
4
2
3
O
4
50
80
base ligand)
−1
at ꢁ567 cm (Figure 7a). The FT-IR spectrum of Fe O
3
4
3
4
Macrocyclic Schiff base ligand
240
45
48
60
nanoparticles (Figure 7b) demonstrated a strong and
Fe
3
O
4
−1
broad peak ꢁ3404 cm , which corresponded to OH
II
TABLE 3
Synthesis of 2-amino-4-aryl-6-(phenylsulfanyl)pyridine-3,5-dicarbonitrile in the presence of Fe
3
O
4
@ Co (macrocyclic Schiff
base ligand)
a
Entry
Aldehyde
Product
Time (min)
Turnover number
Yield (%)
Melting point (reference)
[42]
1
13
195.6
90
230–232
1a
[43]
2
20
206.5
95
290–292
1b
[43]
3
11
210.9
97
234–236
1c
[
43]
4
5
12
11
208.7
213.0
96
98
310–312
220–222
1d
[28]
1e
(
Continues)

12 of 19
EBRAHIMIASL ET AL.
TABLE 3 (Continued)
a
Entry
Aldehyde
Product
Time (min)
Turnover number
Yield (%)
Melting point (reference)
[28]
6
15
213.0
98
230–232
1f
[
42]
7
8
11
13
210.9
208.7
97
96
228–230
1
1
g
[44]
250–252
h
ꢀ
Note. Conditions of reaction: benzaldehyde (1 mmol), malononitrile (2 mmol), thiophenole (1 mmol), catalyst (0.02 g), 100 C, and
solvent-free condition.
a
Isolated yield.
II
SCHEME 3 The plausible reaction mechanism of Fe
-(phenylsulfanyl)pyridine-3,5-dicarbonitrile
3
O
4
@Co (macrocyclic Schiff base ligand) for the synthesis of 2-amino-4-aryl-
6

EBRAHIMIASL ET AL.
13 of 19
TABLE 4
Optimal conditions for the synthesis of 2-amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile in the
II
3 4
presence of Fe O @ Co (macrocyclic Schiff base ligand)
ꢀ
a
Entry
Amounts of catalyst (g)
Solvent
Solvent free
Temperature ( C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
0.01
0.01
0.01
0.01
0.02
0.02
–
rt
rt
100
100
80
25
20
2
H O
EtOH
rt
40
Solvent free
Solvent free
Solvent free
Solvent free
80
11
85
80
11
92
100
100
11
96
120
Trace
Note. Conditions of reaction: benzaldehyde (1 mmol), malononitrile (1 mmol), and 2-hydroxy-1,4-naphthoquinone (1 mmol). rt, room
temperature.
a
Isolated yield.
TABLE 5
Fe O @Co (macrocyclic Schiff base ligand)
3 4
Synthesis of 2-amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile in the presence of
II
a
Entry
Aldehyde
Product
Time (min)
Turnover number
Yield (%)
Melting point (reference)
[48]
1
11
208.7
96
260–262
2
2
a
b
[
48]
2
3
3
13
15
25
206.5
208.7
208.7
95
96
96
240–242
[48]
244–246
250–252
2c
[48]
2d
(
Continues)

14 of 19
EBRAHIMIASL ET AL.
TABLE 5 (Continued)
a
Entry
Aldehyde
Product
Time (min)
Turnover number
Yield (%)
Melting point (reference)
[49]
4
11
210.9
97
230–232
2
2
2
e
[
49]
5
6
11
11
210.9
210.9
97
97
260–262
230–232
f
[48]
g
[48]
7
11
210.9
97
280–282
2h
Note. Conditions of reaction: benzaldehyde (1 mmol), malononitrile (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol), catalyst (0.02 g),
ꢀ
1
00 C, and solvent-free condition.
a
Isolated yield.
stretching vibrations of the macrocyclic Schiff base ligand
600–800 nm range can be due to the complexation of Co
with organic ligand (Figure 8).
−
1
(
III). The peaks at ꢁ1630 and ꢁ1571 cm corresponded
to the azo-methine(C=N) vibration. The bands attributed
to C=N was found to shift to lower- and higher-
frequency regions after complexation, respectively. The
shift of the C=N band to a higher frequency and the
Brunauere–Emmette–Teller analysis revealed a surface
2
−1
area of 73.50 and 49.26 m g for Fe O @(macrocyclic
3
4
II
Schiff base ligand) and Fe O @Co (macrocyclic Schiff
3
4
base ligand) materials; both adsorption isotherm products
refer to multilayer adsorption by weak interactions with
low energy between adsorbed molecules and the adsorbent
with macropores, with a pore size of ꢁ16 nm (Figure 9).
ICP analysis was performed on the magnetic
−1
appearance of absorption bands at ꢁ630 and ꢁ587 cm
Fe–O bending vibrations) clearly confirmed the coating
of macrocyclic Schiff base ligand on the surface of Fe O
(
3
4
in Figure 7c,d. In summary, these results indicated that
II
the Schiff base was prepared and attached to the Fe O4
nanocatalyst to identify the cobalt content of Fe O @Co
3
3 4
NP surface.
(macrocyclic Schiff base ligand), which was found to be
1.365 wt. %. Elemental analysis before attaching cobalt
with Schiff base was found for C: 13.46, H: 1.32, and N:
3.73.
DRS is a surface analytical technique. Appearance of
a peak at 220 nm can be attributed to the presence of
organic molecules. Furthermore, a broad peak in the

EBRAHIMIASL ET AL.
15 of 19
5
| CATALYTIC STUDIES
completed, the catalyst was filtered, and thiophenole was
added to the reaction. Finally, no change was observed in
the progress of the reaction compared to the catalyst-free
synthesis conditions. Moreover, the catalytic activity of
After the catalyst was characterized, to find the best opti-
mal conditions, Fe O @Co (macrocyclic Schiff base
ligand) as a magnetic nanocatalyst was examined in the
synthesis of 2-amino-4-aryl-6-(phenylsulfanyl)pyridine-3,-
II
3
4
II
Fe O @Co (macrocyclic Schiff base ligand) was com-
3
4
pared with that of bare Fe O , macrocyclic Schiff base
3
4
5
-dicarbonitrile derivatives. From this point of view, the
ligand, and Fe O @macrocyclic Schiff base ligand in sep-
3 4
cyclocondensation of benzaldehyde (1.0 mmol),
malononitrile (2.0 mmol), and thiophenole (1.0 mmol)
was assessed as a model reaction under different optimal
conditions. The effect of the amount of catalyst, solvent,
and temperature was tested. First, we tried solvents such
arate experiments conducted under the same optimal
conditions. The resulting yields, provided in Table 2,
II
clearly indicated that Fe O @Co (macrocyclic Schiff
3
4
base ligand) had a relatively higher catalytic activity com-
pared with that of Fe O , macrocyclic Schiff base ligand,
3
4
as EtOH, H O, and solvent-free conditions. Solvent-free
and Fe O @macrocyclic Schiff base ligand.
3 4
2
condition was the most effective condition for this, and
product 1a was obtained in 90 % yield (Table 1, entry 8).
In the next step, the effect of temperature and amount of
catalyst in the progressing reaction was examined. As
To generalize this methodology, we subjected a series of
2-amino-4-aryl-6-(phenylsulfanyl)pyridine-3,5-dicarbonitrile
II
in the presence of Fe O @Co (macrocyclic Schiff base
3
4
ꢀ
ligand) as a heterogeneous magnetic nanocatalyst at 100 C
and solvent-free conditions. Many types of aldehydes,
electron-donating and electron-withdrawing, were used to
obtain the corresponding products with a good yield
(Table 3).
observed in Table 1, the best result was obtained at
ꢀ
1
00 C. Also, the amount of catalyst revealed a significant
effect on the synthesis product. Best results were
obtained in the presence of 0.02 g of catalyst (Table 1,
entry 8). Hot-filtration test was also performed to observe
the possibility of Co leaching from the support. There-
fore, after the reaction of aldehyde and malononitrile was
The
plausible
reaction
mechanism
of
II
Fe O @Co (macrocyclic Schiff base ligand) is demon-
3
4
strated in Scheme 3. Malononitrile and carbonyl group in
SCHEME 4 The plausible
reaction mechanism of
II
Fe
3
O
4
@Co (macrocyclic Schiff
base ligand) for the synthesis of
2
5
-amino-5,10-dioxo-4-aryl-
,10-dihydro-4H-benzo[g]
chromene-3-carbonitrile

16 of 19
EBRAHIMIASL ET AL.
aldehyde are activated by a catalyst. The role of a catalyst
is observed in the Knoevenagel-type condensation of
aldehydes with active methylene compounds and in the
Michael-type addition of intermediates to obtain the final
2a yielded 96% (Table 4, entry 6). Varying derivatives of
2a–j were also synthesized using different aldehydes
under similar reaction conditions, and the results are
summarized in Table 5.
[28]
product.
Formation of the desired products could be
A plausible mechanism for the three-component reac-
tion between the aldehydes, malononitrile, and different
phenolic reagents for the synthesis of the corresponding
2-amino-4H-chromene derivatives is shown in Scheme 4.
It is probable that the initial step involved the condensa-
tion reaction between the aldehyde and malononitrile in
explained by the formation of the arylidene molecule and
then the Michael addition of malononitrile on the
double bond of the arylidene moiety forming the inter-
mediate that underwent cyclization by the nucleophilic
attack of thiophenole on the cyanocarbon; the resulting
compound underwent aromatization to form the final
products.
II
the presence of Fe O @Co (macrocyclic Schiff base
3
4
ligand) as
a
Lewis acid catalyst to generate
II
The use of Fe O @Co (macrocyclic Schiff base
arylidenemalononitrile (I). In the following step, the
resulting intermediate (I) underwent a Michael-type
addition reaction with 2-hydroxynaphthalene-1,4-dione
under catalytic acceleration to produce the adduct (II).
Finally, enolization of (II) occurred to yield the interme-
diate (III), undergoing intramolecular nucleophilic cycli-
3
4
ligand) for the synthesis of 2-amino-5,10-dioxo-4-aryl-
,10-dihydro-4H-benzo[g]chromene-3-carbonitrile was
5
investigated by checking the amount of the catalyst, tem-
perature, and solvent. The same results will be obtained
in the case of 2-hydroxy-1,4-naphthoquinone as a nucleo-
phile. Interestingly, the expected corresponding product
[
50]
zation to obtain the respective products.
FIGURE 10 (a) Vibrating sample magnetometry analyses of the catalyst after recycling; (b) energy-dispersiveX-ray spectroscopy
analyses of the catalyst after recycling; (c) Fourier-transform infrared spectra of the catalyst after recycling

EBRAHIMIASL ET AL.
17 of 19
FIGURE 11 The recycling experiment of
II
Fe
3
O
4
@Co (macrocyclic Schiff base ligand) in
the condensation of (a) benzaldehyde (1 mmol),
malononitrile (2 mmol), and thiophenole
(
1 mmol); (b) benzaldehyde (1 mmol),
malononitrile (1 mmol), and 2-hydroxy-
1
,4-naphthoquinone (1 mmol)
Hot-filtration test was also performed to observe the
synthesis of the highly substituted thiopyridine and 4H-
chromene derivatives with aldehyde, malononitrile, and
thiophenole (or 2-hydroxy-1,4-naphthoquinone). The
possibility of Co leaching from the support. Therefore,
after the reaction of aldehyde and malononitrile was
completed, the catalyst was filtered, and thiophenole was
added to the reaction. Finally, no change was observed in
the progress of the reaction compared to the catalyst-free
synthesis conditions.
ICP–MS analysis of the catalyst, after five consecutive
cycles, was performed, and the results showed no signifi-
cant change in the weight percentage of Co compared to
the pristine form of the catalyst.
Fe O4 MNPs were prepared, and macrocyclic Schiff
3
base ligand containing 1,4-diazepane was immobilized
on its surface; then cobalt was supported on the surface
of the macrocyclic Schiff base ligand. This catalyst was
characterized using FT-IR, SEM–EDX, XRD, TEM,
TGA, VSM, DRS, and ICP techniques. XRD patterns
were consistent with the standard Fe O4 XRD spec-
3
trum. EDX analysis revealed the presence of the Fe, O,
N, C, and Co elements in the nanomagnetic catalyst.
The VSM value of the catalyst was found to be
The FT-IR, VSM, and XRD pattern of the catalyst
were studied after recycling (Figure 10). The results
showed no significant changes.
−1
54.20 emu g , which was slightly lower than that of
The recyclability of the catalyst was assessed for
the reaction of benzaldehyde with malononitrile and
Fe O4 nanoparticles. FT-IR analysis revealed that the
3
Schiff base was prepared and attached to the Fe O NP
3
4
thiophenole (or 2-hydroxy-1,4-naphthoquinone) as a
surface. TEM revealed particles having with a relatively
spherical shape with an average size of ꢁ30 nm. This
catalyst can be recovered and reused five times. All the
products were obtained in good yields and with high
purity. The high yields, operational ease, practicality,
and applicability to a number of substrates render this
method a valuable substitute to other previously used
approaches.
ꢀ
model reaction in solvent-free condition at 100
C
II
using 0.02 g of Fe O @Co (macrocyclic Schiff base
3
4
II
ligand). After the reaction was completed, Fe O @Co
3
4
(macrocyclic Schiff base ligand) was conveniently
removed from the product using an external magnet,
and the remaining solution was decanted. The recov-
ered catalyst was washed using ethanol to remove the
residual product, dried under vacuum, and recycled in
further reactions. As shown in Figure 11, the catalyst
was used for more than five runs without any signifi-
cant loss of activity.
ACKNOWLEDGMENTS
The authors are grateful for technical supports to carry
out this project from the Research Council of the Bu-Ali
Sina University.
6
| CONCLUSION
II
In this work, an effective Fe O @Co (macrocyclic
CONFLICT OF INTEREST
3
4
Schiff base ligand) catalyst was developed for the
There are no conflicts to declare.

18 of 19
EBRAHIMIASL ET AL.
ORCID
D. T. Lima, P. Tongwa, J. Altig, W. F. A. Steelant,
S. V. Slambrouck, M. Y. Antipin, A. Kornienko, Bioorg. Med.
Chem. Lett. 2012, 22, 5195.
Hakimeh Ebrahimiasl https://orcid.org/0000-0001-
6
690-5820
[
17] (a) I. Pevet, C. Brulé, A. Tizot, A. Gohier, F. Cruzalegui,
Davood Azarifar https://orcid.org/0000-0002-7331-2748
Hassan Keypour https://orcid.org/0000-0001-9973-241X
J. A. Boutin, S. Goldstein, Bioorg. Med. Chem. 2011, 19, 2517.
(
b) S. Singh, J. Tiwari, D. Jaiswal, A. K. Sharma, J. Singh,
V. Singh, J. Singh, Curr. Organocatal. 2018, 5, 51.
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