ZnAl2O4–Bi2O3 composite nano-powder as an efficient catalyst for the multi-component, one-pot, aqueous media preparation of novel 4H-chromene-3-carbonitriles

Article abstract of DOI:10.1007/s11164-015-2269-x

Abstract: A composite structure of ZnAl₂O₄–Bi₂O₃ nanopowder was prepared from the reaction of a watery solution of Zn(NO₃)₂, Al(NO₃)₃, and Bi(NO₃)₃ with a dilute solution of amino ethanol in water via a simple precipitation-complexation method. The as-prepared composite was used for the one-pot synthesis of 2-amino-4-aryl-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile and 2-amino-4-aryl-6-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile derivatives. This procedure is very simple and affords excellent yields. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-015-2269-x

Res Chem Intermed
DOI 10.1007/s11164-015-2269-x
ZnAl O –Bi O composite nano-powder as an efficient
2
4
2
3
catalyst for the multi-component, one-pot, aqueous
media preparation of novel 4H-chromene-3-
carbonitriles
1
Majid Ghashang
Received: 18 May 2015 / Accepted: 8 September 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract A composite structure of ZnAl O –Bi O nanopowder was prepared from the
2
4
2 3
reaction of a watery solution of Zn(NO ) , Al(NO ) , and Bi(NO ) with a dilute solution of
3 3
3
2
3 3
amino ethanol in water via a simple precipitation-complexation method. The as-prepared
composite was used for the one-pot synthesis of 2-amino-4-aryl-7-(pyrrolidin-1-yl)-4H-
chromene-3-carbonitrile, 2-amino-4-aryl-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile,
2
-amino-4-aryl-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile,
piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile and 2-amino-4-aryl-6-(1H-pyrrol-1-
2-amino-4-aryl-6-(2-
(
yl)-4H-chromene-3-carbonitrile derivatives. This procedure is very simple and affords
excellent yields.
&
Majid Ghashang
ghashangmajid@gmail.com
1
Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
P.O. Box 517, Najafabad, Esfah a¯ n, Iran
123

M. Ghashang
Graphical Abstract
N
O
NH2
CN
OH
Ar
N
O
NH
2
N
CN
OH
Ar
O
ZnAl O -Bi O
3
2
4
2
N
NH2
CN
N
composite
nano-powder
+
Ar-CHO + CH (CN)2
2
OH
H O/EtOH; Reflux
2
Ar
N
N
O
NH2
OH
N
CN
OH
Ar
O
N
NH2
N
CN
Ar
Keywords ZnAl O –Bi O nanopowder Á 2-Amino-4H-chromene Á 4-(2-
2
4
2 3
(
Piperidin-1-yl)ethyl)phenol Á 3-(Piperidin-1-yl)phenol Á 3-(1H-Pyrrol-1-yl)phenol
Introduction
H-Chromenes containing phenolic or amino functionalized structures are present
4
in a wide range of natural and synthetically occurring products with important
biological activities. An intensified family of 4H-chromenes has been recently
reported and is shown to possess anti-cancer, anti-inflammatory, antioxidant, anti-
HIV, antibacterial, and analgesic property activities [1–6]. Recently, Cai and
coworkers reported that 4H-chromenes were identified as potent apoptosis inducers.
Also, they mentioned that these compounds are highly active in the growth
inhibition MTT assay, including for paclitaxel resistant, p-glycoprotein over-
expressed and MES-SA/DX5 tumor cells. Functionally, they were found to be
potent inhibitors of tubulin polymerization and to effectively inhibit the binding of
colchicine to tubulin. In addition, several 4H-chromenes were also found to be
effective vascular disrupting agents (VDAs) [7]. Thus, the development of synthetic
routes for producing the 4H-chromenes is, therefore, a rewarding endeavor.
Generally, the more common procedures for the preparation of chromene
derivatives involved multi-component reaction of aldehydes, malononitrile/b-keto
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
esters and diverse enolizable C–H-activated acidic compounds, phenols and a- or b-
naphthols. The extensive research published on this procedures has been mostly
focused on the use of Lewis and Brønsted acid catalysts such as potassium
phthalimide-N-oxyl [8], 2,2,2-trifluoroethanol [9], N,N-dimethylamino-functional-
ized basic ionic liquid [10], Fe O -chitosan nanoparticles [11], MgO [12],
3
4
triethylbenzylammonium chloride (TEBA) [13], Fe(DS)3 [14], SO3H-bearing
carbonaceous solid catalyst (PEG-SAC) [15], etc. These methods have the
advantages of high yields, and mild reaction conditions and some disadvantages
of using toxic solvents and expensive catalysts. However, the discovery of new
synthetic methodologies that facilitate the preparation of organic compounds is of
great interest. On the other hand, development of new methods to synthesize these
compounds using environmentally friendly (’green’) catalysts or to synthesize new
derivatives of these compounds is in demand.
Therefore, as a part of our incessant efforts on the use of heterogeneous catalysts
in multi-component reactions [16–20], the scope of the present work was extended
for the multi-component condensation reaction of aldehydes, diverse phenols and
malononitrile to afford a variety of 4H-chromene-3-carbonitrile derivatives using
ZnAl O –Bi O composite nanopowder as a new green, environmentally friendly
2
4
2 3
catalyst (Scheme 1).
Experimental
All reagents were purchased from Merck and Aldrich and used without further
purification. Field emission scanning electron microscope (FE-SEM) images were
obtained on an Hitachi S-4160. N adsorption measurements of the catalyst were
2
carried out using micro-metrics adsorption equipment (Quantachrome instrument,
model Nova 2000, USA), with N (99.99 %) as the analysis gas, and the catalyst
2
samples were slowly heated to 120 °C for 3 h under nitrogen atmospheric. The total
pore volume was obtained from the maximum amount of nitrogen gas adsorbed at
partial pressure P/P0 = 0.999. Dynamic light scattering (DLS) measurement was
OH
ZnAl O -Bi O
2 4 2 3
composite
nano-powder
R2
O
NH2
CN
+
2
Ar-CHO + CH (CN)2
R1
H O/EtOH; Reflux
2
R1
R2
Ar
N
N
a
R = H; R =
1 2
c
R = H; R =
1
2
N
b
R = H; R =
2 1
N
d
R = H; R =
1
2
N
e
R = H; R =
2
1
Scheme 1 Preparation of 4H-chromene-3-carbonitriles using ZnAl
2
O
4
2 3
–Bi O composite nanopowder
123

M. Ghashang
done using a Malvern Zetasizer Nano ZS (ZEN 3600) instrument. Nuclear magnetic
resonance (NMR) spectra were recorded on a Bruker Avance DPX 400-MHz
instrument. The spectra were measured in deuterated dimethyl sulfoxide (DMSO-
d6) relative to trimethylsilane (TMS, 0.00 ppm). Melting points were determined in
open capillaries with a Buchi 510 melting point apparatus. Thin layer chromatog-
raphy (TLC) was performed on silica gel plates (Polygram SIL G/UV 254).
Preparation of ZnAl O –Bi O composite nanopowder
2
4
2
3
A solution of Zn(NO ) (10 mmol), Al(NO ) (10 mmol), and Bi(NO3) (20 mmol)
3
3
2
3 3
was prepared by dissolving these salts in 200 ml of water (solution A). 20 g of urea
was added to solution A. The 2-aminoethanol solution was prepared by dissolving
the 2-aminoethanol (150 mmol) in 100 ml of water (solution B). Solution (B) was
slowly added drop-wise to solution (A) under vigorous magnetic stirring. The
mixture was continuously stirred for another 60 min. The resulting precipitate was
filtered, washed with water several times and dried in an oven at 100 °C for 5 h and
finally calcined at 700 °C for 3 h.
Synthesis of 3-(pyrrolidin-1-yl)phenol and 3-(piperidin-1-yl)phenol
A mixture of 3-aminophenol (1 mmol) and 1,4-dichlorobutane/1,5-dichloropantane
(
1.1 mmol) was refluxed in dry toluene for 24 h and then cooled to room
temperature and, subsequently, triethyl amine (2 mmol) and sodium carbonate
1 mmol) in 10 ml distilled water were added to the mixture. The reaction mixture
(
was refluxed for another 24 h. After completion of the reaction, the solvent was
reduced and the organic portion was extracted with CH Cl . The solvent was
2
2
evaporated and the crude product (70–75 %) was purified using silica gel column
chromatography with petroleum ether/ethyl acetate as the eluent.
3
-(Pyrrolidin-1-yl)phenol
1
Proton NMR [ H-NMR, 400 MHz, deuterated chloroform (CDCl )]: d = 1.96–2.02
3
(
m, 4 H), 3.33–3.44 (m, 4H), 6.58 (d, J = 7.8, 1H), 6.77 (s, 1H), 6.97 (d, J = 7.8,
H), 7.19 (t, J = 7.8, 1H), 10.13 (s, 1H, OH) ppm.
1
3
-(Piperidin-1-yl)phenol
1
H-NMR (400 MHz, CDCl ): d = 1.44–1.48 (m, 2H), 1.84–2.03 (m, 4H),
3
3
.05–3.12 (m, 4H), 6.56 (d, J = 7.8, 1H), 6.74 (s, 1H), 6.96 (d, J = 7.8, 1H),
.18 (t, J = 7.8, 1H), 10.09 (s, 1H, OH) ppm.
7
Synthesis of 4-(2-(piperidin-1-yl)ethyl)phenol
A mixture of 4-hydroxyphenethyl-4-methylbenzenesulfonate (1 mmol) and piper-
idine (1 mmol) was refluxed in dry toluene for 24 h and then cooled to room
temperature; subsequently, triethyl amine (1 mmol) and sodium carbonate (1 mmol)
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
in 10 ml water were added to the mixture. The reaction mixture was refluxed for
another 24 h. After completion of the reaction, the solvent was reduced and the
organic portion was extracted with CH Cl . The solvent was evaporated and the
2
2
crude product (77 %) was purified using silica gel column chromatography with
petroleum ether/ethyl acetate as the eluent.
4
-(2-(Piperidin-1-yl)ethyl)phenol
1
H-NMR (400 MHz, CDCl ): d = 1.43–1.47 (m, 2H), 1.69–1.75 (m, 4 H),
3
2
.45–2.53 (m, 4H), 2.60–2.67 (m, 2H), 2.83–2.89 (m, 2H), 6.72 (d, J = 7.9, 2H),
.03 (d, J = 7.9, 2H), 10.36 (s, 1H, OH) ppm.
7
Synthesis of 3-(1H-pyrrol-1-yl)phenol and 4-(1H-pyrrol-1-yl)phenol
To a solution of amine (1 mmol) in water (5 ml) was added tetrahydro-2,5-
dimethoxyfuran (1.1 mmol) and ZnAl O –Bi O composite nanopowder (0.1 g).
2
4
2 3
The reaction mixture was stirred at reflux condition for 24 h (TLC-monitored).
After completion of the reaction, the aqueous solution was extracted with CH Cl
2
2
(
3 9 10 ml) and dried with anhydrous sodium sulfate. The pure product was
achieved by using silica gel column chromatography with petroleum ether/ethyl
acetate as the eluent, after solvent removal.
3
-(1H-pyrrol-1-yl)phenol
1
H-NMR (400 MHz, DMSO-d ): d = 6.39–6.41 (dd, J = 2.7, 1.0 Hz, 2H), 6.74 (d,
6
J = 8.0 Hz, 1H), 7.07(s, 1H), 7.39–7.48 (m, 2H), 7.87–7.89 (dd, J = 2.7, 1.0 Hz,
2
H), 11.21 (s, 1H, OH) ppm.
4
-(1H-pyrrol-1-yl)phenol
1
H-NMR (400 MHz, DMSO-d ): d = 6.38–6.40 (dd, J = 2.7, 1.0 Hz, 2H), 7.06 (d,
6
J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.86–7.88 (dd, J = 2.7, 1.0 Hz, 2H),
1.17 (s, 1H, OH) ppm.
1
General procedure for the synthesis of 2-amino-7-hydroxy-4-aryl/alkyl-4H-
chromene-3-carbonitriles
A mixture of aldehydes (1 mmol), phenols (1 mmol), malononitrile (1 mmol), and
ZnAl O –Bi O nanopowder (0.1 g) in H O/ethanol (EtOH, 6 ml/4 ml) was
2
4
2
3
2
refluxed (80 °C) for the appropriate time. The progress of the reaction was
monitored by TLC (Tables 1, 2). After completion of the reaction, the reaction
mixture was dissolved in hot ethanol. The catalyst was removed by simple filtration.
The solvent was concentrated and the crude products were purified by recrystal-
lization from EtOH. The spectral data of compounds a1–8, b1–3, c1–4, d1–2 and e1–2
are given below:
123

M. Ghashang
Table 1 Optimization of the reaction conditions in the synthesis of 2-amino-4-phenyl-7-(pyrrolidin-1-
yl)-4H-chromene-3-carbonitrile
a
Entry
Catalyst (g)
T (°C)
Solvent (10 ml)
Time (h)
3Yield (%)
1
2
3
4
5
6
7
8
9
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.025
0.1
r.t.
H
2
O
24
24
24
24
24
24
24
24
24
24
15
24
12
12
20
10
10
30
–
r.t.
EtOH
CH CN
r.t.
3
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
50 °C
80 °C
80 °C
80 °C
80 °C
EtOH
n-Hexane
CH
2
3
Cl
2
–
CH
CN
45
35
30
55
70
65
89
85
EtOAc
H
H
H
H
H
H
2
2
2
2
2
2
O
1
1
1
1
1
a
1
2
3
4
5
O/EtOH (6 ml/4 ml)
O/EtOH (6 ml/4 ml)
O/EtOH (6 ml/4 ml)
O/EtOH (6 ml/4 ml)
O/EtOH (6 ml/4 ml)
0.25
Isolated yields
2
-Amino-4-phenyl-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct a ) Melting point: 187–189 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.95–2.07 (m, 4 H), 3.35–3.47 (m, 4H), 4.63 (s, 1H, CH), 6.49 (s, 1H), 6.79
1
(
d, J = 7.9, 1H), 6.95 (m, 4H), 7.15 (d, J = 7.9, 1H), 7.23 (t, J = 7.8, 1H), 7.35 (t,
3
1
J = 7.8, 2H) ppm; Carbon-13 NMR ( C-NMR, 100 MHz, DMSO-d ): d = 25.8,
6
4
1
7
6.7, 47.9, 57.4, 99.6, 114.8, 120.3, 128.2, 128.9, 129.1, 129.6, 130.7, 141.6, 144.9,
55.9, 163.7, ppm [Found: C, 75.84; H, 6.21; N, 13.42 % C H N O; requires: C,
2
0 19 3
5.69; H, 6.03; N, 13.24 %].
2
-Amino-7-(pyrrolidin-1-yl)-4-p-tolyl-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct a ) Melting point: 195–197 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.94–2.08 (m, 4H), 2.28 (s, 3H, CH ), 3.31–3.46 (m, 4H), 4.68 (s, 1H, CH),
2
3
6
.47 (s, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.96 (s, 2H, NH ), 7.04–7.08 (m, 4H), 7.15
2
1
3
(
d, J = 8.0 Hz, 1H) ppm; C-NMR (100 MHz, DMSO-d ): d = 21.5, 25.9, 44.9,
6
4
1
7
7.9, 57.8, 101.3, 119.9, 114.7, 126.9, 128.0, 129.5, 129.7, 140.1, 141.9, 145.1,
56.1, 163.5 ppm [Found: C, 76.31; H, 6.51; N, 12.79 % C H N O; requires: C,
2
1 21 3
6.11; H, 6.39; N, 12.68 %].
2
-Amino-7-(pyrrolidin-1-yl)-4-o-tolyl-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct a ) Melting point: 178–180 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.96–2.11 (m, 4H), 2.24 (s, 3H, CH ), 3.35–3.48 (m, 4H), 4.66 (s, 1H, CH),
3
3
6
.46 (s, 1H), 6.77 (d, J = 8.0 Hz, 1H), 6.91 (s, 2H, NH ), 7.00–7.18 (m, 5H) ppm;
C-NMR (100 MHz, DMSO-d ): d = 19.9, 25.8, 45.7, 47.7, 57.6, 102.1, 114.8,
2
1
3
6
1
19.8, 123.6, 126.9, 127.8, 129.3, 129.9, 131.6, 132.9, 140.2, 145.7, 156.8,
63.4 ppm [Found: C, 76.28; H, 6.51; N, 12.85 % C H N O; requires: C, 76.11;
1
H, 6.39; N, 12.68; %].
2
1 21 3
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
2 3 2 4
Table 2 Preparation of 4H-chromene-3-carbonitriles using Bi O –ZnAl O composite nano-powder
Entry
1
Aldehyde
Product
Time (h)
12
Yield (%)a
89
CHO
a
1
a
2
a
3
2
3
CHO
15
20
88
85
CHO
4
5
6
7
CHO
a
4
a
5
a
6
a
7
12
15
20
12
90
89
75
91
Cl
Cl
CHO
Cl
CHO
Cl
CHO
NO 2
8
9
CHO
a
8
10
86
O2N
CHO
b
b
15
15
89
92
1
1
0
CHO
2
Cl
1
1
2
CHO
CHO
b
3
14
17
88
85
O
2
2
N
N
1
c
1
O
1
1
1
3
4
5
CHO
c
c
c
2
20
20
20
79
80
85
CHO
3
4
CHO
Cl
Cl
Cl
1
1
6
7
CHO
d
1
2
20
18
87
80
CHO
d
1
1
8
9
CHO
e
e
1
20
20
81
79
CHO
2
a
Isolated yield; all product are new and were characterized on the basis of their NMR and elemental
analysis (CHN)
123

M. Ghashang
2
-Amino-4-(4-chlorophenyl)-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product a4) Melting point: 203–205 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.95–2.09 (m, 4H), 3.36–3.49 (m, 4H), 4.68 (s, 1H, CH), 6.48 (s, 1H), 6.79
(
J = 7.9 Hz, 2H), 7.49 (d, J = 7.9 Hz, 2H) ppm; C-NMR (100 MHz, DMSO-d6):
d, J = 8.1 Hz, 1H), 6.99 (s, 2H, NH ), 7.16 (d, J = 8.1 Hz, 1H), 7.36 (d,
1
2
3
d = 25.6, 47.4, 46.7, 57.5, 102.1, 114.1, 120.3, 127.8, 129.2, 129.4, 129.6, 135.8,
142.1, 145.0, 156.0, 163.5 ppm [Found: C, 68.39; H, 5.32; N, 12.14 %
C H ClN O; requires: C, 68.28; H, 5.16; N, 11.94; %].
2
0
18
3
2
-Amino-4-(2,4-dichlorophenyl)-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product a5) Melting point: 216–218 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.96–2.07 (m, 4H), 3.34–3.46 (m, 4H), 4.82 (s, 1H, CH), 6.48 (s, 1H), 6.80
(
1
d, J = 8.0 Hz, 1H), 6.96 (s, 2H, NH ), 7.15–7.18 (m, 2H), 7.50–7.55 (m, 2H) ppm;
2
3
C-NMR (100 MHz, DMSO-d ): d = 25.7, 46.9, 47.5, 57.6, 101.2, 113.9, 120.7,
6
1
27.9, 128.4, 128.6, 129.3, 129.8, 133.2, 136.0, 144.8, 148.3, 156.2, 163.5 ppm
[Found: C, 62.33; H, 4.56; N, 10.99 % C H Cl N O; requires: C, 62.19; H, 4.44;
20 17 2 3
N, 10.88; %].
2
-Amino-4-(2-dichlorophenyl)-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product a6) Melting point: 201–203 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.96–2.08 (m, 4H), 3.35–3.47 (m, 4H), 4.79 (s, 1H, CH), 6.49 (s, 1H), 6.81
(
d, J = 8.1 Hz, 1H), 6.92 (s, 2H, NH ), 7.15 (d, J = 8.1 Hz, 1H), 7.30–7.48 (m,
2
1
3
4
1
1
6
H) ppm; C-NMR (100 MHz, DMSO-d ): d = 25.6, 45.9, 47.6, 57.9, 99.9, 113.8,
6
20.4, 127.8, 128.5, 129.3, 129.5, 130.5, 130.8, 133.2, 144.9, 148.3, 156.0,
63.4 ppm [Found: C, 68.41; H, 5.27; N, 12.07 % C H ClN O; requires: C,
8.28; H, 5.16; N, 11.94 %].
2
0
18
3
2
-Amino-4-(3-nitrophenyl)-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct a ) Melting point: 223–225 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.96–2.11 (m, 4H), 3.35–3.47 (m, 4H), 4.96 (s, 1H, CH), 6.47 (s, 1H), 6.79
7
(
J = 7.9 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 8.19–8.22 (m, 2H) ppm; C-NMR
d, J = 8.0 Hz, 1H), 6.97 (s, 2H, NH ), 7.17 (d, J = 8.0 Hz, 1H), 7.44 (t,
2
1
3
(
100 MHz, DMSO-d ): d = 25.5, 46.1, 47.7, 58.2, 100.8, 113.9, 116.5, 117.6,
6
1
6
19.9, 127.6, 127.9, 128.4, 129.3, 140.9, 141.5, 144.9, 156.2, 163.4 ppm [Found: C,
6.55; H, 5.29; N, 15.56 % C H N O ; requires: C, 66.29; H, 5.01; N, 15.46; %].
2
0 18 4 3
2
-Amino-4-(4-nitrophenyl)-7-(pyrrolidin-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct a ) Melting point: 217–219 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.99–2.03 (m, 4H), 3.35–3.46 (m, 4H), 4.73 (s, 1H, CH), 6.47 (s, 1H), 6.80
8
(
J = 7.8 Hz, 2H), 8.11 (d, J = 7.8 Hz, 2H) ppm; C-NMR (100 MHz, DMSO-d6):
d, J = 8.0 Hz, 1H), 6.98 (s, 2H, NH ), 7.16 (d, J = 8.0 Hz, 1H), 7.44 (d,
2
1
3
d = 25.6, 44.7, 47.6, 58.1, 102.0, 114.2, 121.0, 123.9, 127.8, 128.6, 129.3, 141.7,
144.9, 148.2, 156.0, 163.4 ppm [Found: C, 66.51; H, 5.27; N, 15.54 % C H N O ;
20 18 4 3
requires: C, 66.29; H, 5.01; N, 15.46; %].
2
-Amino-4-phenyl-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct b ) Melting point: 231–233 °C; H-NMR (400 MHz, DMSO-d6):
1
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
d = 1.47–1.59 (m, 2H), 1.71–1.82 (m, 4H), 2.44–2.73 (m, 6H), 2.89–3.99 (m, 2H),
.66 (s, 1H, CH), 6.62 (d, J = 7.9 Hz, 1H), 6.86 (s, 1H), 6.93 (s, 2H, NH ), 6.99 (d,
4
J = 7.9 Hz, 1H), 7.24–7.35 (m, 5H) ppm; C-NMR (100 MHz, DMSO-d6):
2
1
3
d = 23.7, 26.5, 36.2, 46.4, 51.8, 57.6, 61.9, 112.7, 120.3, 127.7, 127.8, 128.6, 128.7,
128.9, 129.3, 136.7, 141.9, 150.3, 163.4 ppm [Found: C, 76.98; H, 7.23; N, 11.84 %
C H N O; requires: C, 76.85; H, 7.01; N, 11.69 %].
2
3 25 3
2
-Amino-4-(4-chlorophenyl)-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile
1
(Table 2,
Product b2) Melting point: 239–241 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.46–1.56 (m, 2H), 1.71–1.81 (m, 4H), 2.46–2.76 (m, 6H), 2.90–3.03 (m, 2H),
4
J = 8.0 Hz, 1H), 7.39 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 7.8 Hz, 2H) ppm; C-NMR
.69 (s, 1H, CH), 6.63 (d, J = 8.0 Hz, 1H), 6.88 (s, 1H), 6.96 (s, 2H, NH ), 6.98 (d,
2
1
3
(
100 MHz, DMSO-d ): d = 24.0, 26.4, 36.1, 47.3, 51.6, 57.9, 61.8, 112.6, 120.8,
6
1
7
27.7, 127.8, 129.0, 129.3, 129.6, 135.7, 136.8, 141.7, 149.8, 163.5 ppm [Found: C,
0.31; H, 6.41; N, 10.81 % C H ClN O; requires: C, 70.13; H, 6.14; N, 10.67 %].
2
3
24
3
2
-Amino-4-(4-nitrophenyl)-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile
1
(
Table 2, Product b3) Melting point: 257–259 °C; H-NMR (400 MHz, DMSO-
d6): d = 1.45–1.54 (m, 2H), 1.72–1.83 (m, 4H), 2.46–2.76 (m, 6H), 2.88–3.01 (m,
2
H), 5.23 (s, 1H, CH), 6.64 (d, J = 8.0 Hz, 1H), 6.86 (s, 1H), 6.95 (s, 2H, NH2),
.00 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 7.9 Hz, 2H), 8.12 (d, J = 7.9 Hz, 2H) ppm;
7
1
3
C-NMR (100 MHz, DMSO-d ): d = 24.5, 26.6, 36.1, 48.7, 51.4, 58.1, 61.5,
6
1
12.7, 121.3, 123.8, 127.7, 127.9, 128.6, 129.3, 136.9, 141.5, 148.3, 149.8,
63.5 ppm [Found: C, 68.51; H, 6.11; N, 13.98 % C H N O requires: C, 68.30;
1
H, 5.98; N, 13.85 %].
2
3 24 4 3;
2
-amino-4-(4-nitrophenyl)-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product c1) Melting point: 212–214 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.46–1.59 (m, 2H), 1.79–1.93 (m, 4H), 3.07–3.10 (m, 4H), 5.11 (s, 1H, CH),
6
.48 (s, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.97 (s, 2H, NH ), 7.15 (d, J = 8.0 Hz, 1H),
2
1
3
.42 (d, J = 7.9 Hz, 2H), 8.10 (d, J = 7.9 Hz, 2H) ppm; C-NMR (100 MHz,
7
DMSO-d ): d = 24.2, 256.0, 45.2, 49.6, 59.5, 99.8, 114.1, 117.5, 120.4, 127.8,
6
1
28.9, 129.3, 140.7, 141.9, 154.6, 156.1, 163.4 ppm [Found: C, 67.15; H, 5.51; N,
5.01 % C H N O ; requires: C, 67.01; H, 5.36; N, 14.88 %].
1
2
1 20 4 3
2
-Amino-4-(phenyl)-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct c ) Melting point: 189–191 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.46–1.59 (m, 2H), 1.79–1.92 (m, 4H), 3.06–3.09 (m, 4H), 4.71 (s, 1H, CH),
2
6
.49 (s, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.99 (s, 2H, NH ), 7.11–7.36 (m, 6H) ppm;
2
1
3
C-NMR (100 MHz, DMSO-d ): d = 24.2, 25.9, 46.0, 49.7, 57.9, 98.8, 113.9,
6
1
7
19.9, 127.8, 128.8, 128.6, 128.9, 129.3, 141.7, 154.9, 156.1, 163.3 ppm [Found: C,
6.23; H, 6.54; N, 12.77 % C H N O; requires: C, 76.11; H, 6.39; N, 12.68 %].
2
1 21 3
2
-Amino-7-(piperidin-1-yl)-4-p-tolyl-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct c ) Melting point: 190–192 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.47–1.59 (m, 2H), 1.81–1.93 (m, 4H), 2.28 (s, 3H), 3.08–3.11 (m, 4H), 4.70
3
(
s, 1H, CH), 6.48 (s, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.98–7.20 (m, 7H, aromatic and
123

M. Ghashang
1
3
NH ) ppm; C-NMR (100 MHz, DMSO-d ): d = 21.4, 24.3, 26.0, 46.2, 49.6, 57.7,
2
6
9
1
7
8.3, 113.8, 120.3, 127.1, 128.1, 129.4, 129.7, 139.9, 141.5, 154.8, 155.9,
63.4 ppm [Found: C, 76.63; H, 6.90; N, 12.37 % C H N O; requires: C,
2
2 23 3
6.49; H, 6.71; N, 12.16 %].
2
-Amino-4-(4-chlorophenyl)-7-(piperidin-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product c4) Melting point: 196–198 °C; H-NMR (400 MHz, DMSO-d6):
d = 1.46–1.58 (m, 2H), 1.83–1.95 (m, 4H), 3.08–3.11 (m, 4H), 4.75 (s, 1H, CH),
6
.49 (s, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.94 (s, 2H, NH ), 7.17 (d, J = 8.0 Hz, 1H),
2
1
.37 (d, J = 7.9 Hz, 2H), 7.47 (d, J = 7.9 Hz, 2H) ppm; C-NMR (100 MHz,
3
7
DMSO-d ): d = 24.1, 25.9, 47.0, 49.7, 58.1, 98.8, 114.2, 120.3, 127.8, 129.1, 129.5,
6
1
29.9, 135.7, 142.1, 154.9, 156.2, 163.4 ppm [Found: C, 69.19; H, 5.70; N, 11.60 %
C H ClN O; requires: C, 68.94; H, 5.51; N, 11.49 %].
2
1
20
3
2
-Amino-4-phenyl-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct d1) Melting point: 145–147 °C; H-NMR (400 MHz, DMSO-d ): d = 4.66
6
(
s, 1H, CH), 6.41–6.43 (dd, J = 2.7, 1.0, 2H), 6.91–7.47 (m, 10H), 7.91–7.93 (dd,
1
3
J = 2.7, 1.0 Hz, 2H) ppm; C-NMR (100 MHz, DMSO-d ): d = 46.9, 58.3, 99.8,
6
1
11.1, 114.2, 119.8, 120.7, 127.8, 128.6, 128.9, 129.4, 129.6, 141.6, 142.3, 156.2,
63.4 ppm [Found: C, 76.81; H, 4.99; N, 13.59 % C H N O; requires: C, 76.66;
1
H, 4.82; N, 13.41 %].
2
0 15 3
2
-Amino-4-(4-chlorophenyl)-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product d2) Melting point: 157–159 °C; H-NMR (400 MHz, DMSO-d6):
d = 4.69 (s, 1H, CH), 6.43–6.45 (dd, J = 2.7, 1.0, 2H), 6.90–7.49 (m, 9H),
1
3
7
.90–7.92 (dd, J = 2.7, 1.0 Hz, 2H) ppm; C-NMR (100 MHz, DMSO-d6):
d = 47.3, 58.2, 99.3, 110.8, 114.6, 119.7, 120.1, 127.8, 129.3, 129.7, 129.9, 135.8,
41.9, 142.6, 155.8, 163.5 ppm [Found: C, 69.32; H, 4.17; N, 12.25 %
C H ClN O; requires: C, 69.07; H, 4.06; N, 12.08 %].
1
2
0
14
3
2
-Amino-4-phenyl-6-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile (Table 2, Pro-
1
duct e1) Melting point: 123–125 °C; H-NMR (400 MHz, DMSO-d ): d = 4.71
6
(
s, 1H, CH), 6.42–6.44 (dd, J = 2.7, 1.0, 2H), 6.96–7.37 (m, 10H), 7.90–7.92 (dd,
1
3
J = 2.7, 1.0 Hz, 2H) ppm; C-NMR (100 MHz, DMSO-d ): d = 46.7, 57.9, 108.8,
6
1
11.3, 117.0, 119.5, 119.9, 123.8, 128.6, 128.9, 129.5, 129.7, 132.6, 141.7, 149.8,
63.4 ppm [Found: C, 76.77; H, 4.96; N, 13.55 % C H N O; requires: C, 76.66;
1
H, 4.82; N, 13.41 %].
2
0 15 3
2
-Amino-4-(4-chlorophenyl)-6-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile (Table 2,
1
Product e2) Melting point: 133–135 °C; H-NMR (400 MHz, DMSO-d6):
d = 4.73 (s, 1H, CH), 6.44–6.46 (dd, J = 2.7, 1.0, 2H), 6.95 (s, 2H, NH ),
7
2
1
3
.15–7.48 (m, 7H), 7.90–7.92 (dd, J = 2.7, 1.0 Hz, 2H) ppm; C-NMR (100 MHz,
DMSO-d ): d = 46.9, 58.0, 108.6, 110.9, 116.9, 119.6, 120.1, 123.7, 129.1, 129.4,
6
130.2, 132.6, 136.2, 142.1, 150.0, 163.5 ppm [Found: C, 69.25; H, 4.21; N, 12.24 %
C H N O; requires: C, 69.07; H, 4.06; N, 12.08 %].
2
0 14 3
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
Results and discussion
The XRD pattern was used to identify the phase and the composition of the
ZnAl O –Bi O composite nano-powder (Fig. 1). The XRD pattern can be indexed
2
4
2 3
to cubic ZnAl O (01-071-0968) and monoclinic a-Bi2O3 (00-027-0053) phases.
2
4
The diffraction peaks related to a-Bi O are 25.75, 26.91, 27.39, 28.01, 33.03,
2
3
3
3.23, 35.04, 37.57, 46.29, 48.59, 52.38 and 54.80 [2h°] which are matched well
with monoclinic a-Bi O . The peaks shown in 31.24, 36.84, 55.66, 59.36, 65.24
2
3
[
broad diffraction peaks imply that the crystalline grains are on the nanoscale. An
2h°] are connected to ZnAl O which has been crystallized as a cubic system. The
2
4
average crystal size of a-Bi O and ZnAl O particles was estimated using the
2
3
2 4
Scherrer equation as 86 and 76, respectively.
The morphological evolution of the Bi O –ZnAl O composite nano-powder was
2
3
2 4
further studied using FE-SEM images of calcined powder and the results are
revealed in Fig. 2. As shown in Fig. 2, the particles are relatively agglomerated and
are uniform in shape and size distribution.
The specific surface area measurements of the Bi O –ZnAl O composite nano-
2
3
2 4
powder were evaluated by the Brunauer–Emmett–Teller (BET) method and also the
total pore volume and average pore diameter were determined at 200 °C for
300 min. The results are given in Table 3. These results show that the catalyst has a
good specific surface area. The average diameter of the nanoparticles is 80 nm.
Dynamic light scattering (DLS) analysis was used to determine the particle size
distribution of Bi O –ZnAl O composite nano-powder. Before analysis, the sample
2
3
2 4
-
1
was diluted in ethanol (1 g l ) and sonicated for 2 h. Figure 3 shows the size
distribution of nanopowder. Focusing on the results, the intensity-average diameter
determined by DLS is approximately 77 nm.
2 3 2 4
Fig. 1 XRD pattern of Bi O –ZnAl O composite nano-powder calcined at 700 °C
123

M. Ghashang
2 3 2 4
Fig. 2 FE-SEM micrographs of Bi O –ZnAl O composite nano-powder
The catalytic activity of Bi O –ZnAl O composite nano-powder was examined
2
3
2 4
on the condensation reaction of 3-(pyrrolidin-1-yl)phenol (1 mmol), malononitrile
1 mmol) and benzaldehyde (1 mmol) as a tentative experiment in different
(
1
23

2 4 2 3
ZnAl O –Bi O composite nano-powder as an efficient catalyst for…
Table 3 Specific surface area,
average pore diameter and total
2
Specific surface area (m / Pore diameter
Pore volume (cc/
g)
g)
(nm)
2 3 2 4
pore volume of Bi O –ZnAl O
composite nanopowder
4
3.87
82.05
0.039
conditions, including variable solvent, temperature and catalyst dosage (Table 1).
The progress of the reaction was monitored by TLC. After completion of the
reaction, a work-up afforded the product 2-amino-4-phenyl-7-(pyrrolidin-1-yl)-4H-
chromene-3-carbonitrile in low yields at room temperature and did not afford the
product in non-polar solvents (Table 1, entries 1–3 and 5,6). Investigation of the
procedure at higher temperatures showed that a significant change was observed in
the relative yields, and reaction times decrease under these conditions (Table 1,
entries 4 and 7–12). It is worth mentioning that the best result was obtained in
aqueous medium. In another experiment, the effect of different catalyst dosages was
examined and it was found that the yield of the reaction increases with increasing
the quantity of the catalyst (Table 1, entries 12–15). The optimal catalyst amount
was found to be 0.1 g. The use of lesser amounts of the catalyst afforded lower
product yield. On the other hand, the use of quantities higher than 0.1 g of the
catalyst did not provide any significant increase in the reaction yield.
To study the scope and limitations of this procedure, a series of experiments were
carried out using a variety of aromatic aldehydes. The results are shown in Table 2.
The reactions worked well with almost all the aldehydes. However, aromatic
aldehydes bearing electron-withdrawing groups showed better reactivity and the
reactions were completed in less time.
2 3 2 4
Fig. 3 Particle size distribution of Bi O –ZnAl O composite nanopowder
123

M. Ghashang
We further investigated the one-pot three-component condensation reaction of
different phenol compounds, including 4-(2-(piperidin-1-yl)ethyl)phenol, 3-(piper-
idin-1-yl)phenol, 3-(1H-pyrrol-1-yl)phenol and 4-(1H-pyrrol-1-yl)phenol with aro-
matic aldehydes and malononitrile, and the results are summarized in Table 2. The
procedures for the preparation of these compounds are described in the experimental
section. We applied the above optimal reaction conditions (Table 1) for these
reactions. As shown in Table 2, all reactions preceded well and afforded the
products in high yields.
Conclusion
In summary, a simple precipitation–complexation method has been applied for the
preparation of Bi O –ZnAl O composite nano-powder. The as-prepared sample
2
3
2 4
was characterized using XRD, FE-SEM, BET and DLS analyses. In continuance, a
high yielding one-pot condensation reaction of different phenols, aromatic
aldehydes and malononitrile for the synthesis of 2-amino-4-aryl-7-(pyrrolidin-1-
yl)-4H-chromene-3-carbonitrile, 2-amino-4-aryl-7-(piperidin-1-yl)-4H-chromene-3-
carbonitrile, 2-amino-4-aryl-7-(1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile, 2-amino-
4-aryl-6-(2-(piperidin-1-yl)ethyl)-4H-chromene-3-carbonitrile and 2-amino-4-aryl-6-
(
1H-pyrrol-1-yl)-4H-chromene-3-carbonitrile derivatives using Bi O –ZnAl O com-
2
3
2 4
posite nano-powder was developed. Various aromatic aldehydes afforded the
corresponding products in high yields.
Acknowledgments The authors are indebted to the Islamic Azad University, Najafabad Branch for
financial support of this research.
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