Ultrasound promotes one-pot synthesis of 1,4-dihydropyridine and imidazo[1,2-a]quinoline derivatives, catalyzed by ZnO nanoparticles

Article abstract of DOI:10.1007/s11164-014-1624-7

Ultrasonic irradiation is being considered not only as a green approach but also as a powerful technique for the synthesis of 1,4-dihydropyridine and imidazo[1,2-a]quinoline derivatives. It can be carried out by using multicomponent reaction of cyclic ena

Full text of DOI:10.1007/s11164-014-1624-7

Res Chem Intermed
DOI 10.1007/s11164-014-1624-7
Ultrasound promotes one-pot synthesis of 1,4-
dihydropyridine and imidazo[1,2-a]quinoline
derivatives, catalyzed by ZnO nanoparticles
•
Mehdi Abaszadeh Mohammad Seifi Ali Asadipour
•
Received: 26 December 2013 / Accepted: 17 March 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract Ultrasonic irradiation is being considered not only as a green approach
but also as a powerful technique for the synthesis of 1,4-dihydropyridine and imi-
dazo[1,2-a]quinoline derivatives. It can be carried out by using multicomponent
reaction of cyclic enaminoketones, malononitrile, and aromatic aldehydes, in the
presence of catalytic amounts of zinc oxide nanoparticles, in EtOH, at 80 °C. The
preponderance of such a catalyst is due to its inexpensiveness, stability, and the
potential of being easily obtained. Furthermore, high conversions, short reaction
times, and cleaner reaction profiles are some of the advantages of this method.
Keywords Ultrasound irradiation ꢀ 1,4-Dihydropyridine and imidazo[1,2-
a]quinoline derivatives ꢀ Multicomponent reaction ꢀ ZnO nanoparticles
Introduction
Ultrasound irradiation has been increasingly used in organic synthesis in the last
three decades as an eco-friendly energy source. Compared to traditional methods,
this technique is more convenient and easily controlled [1–3]. Moreover, enhanced
reaction rates, formation of unadulterated products in high yields, easier
M. Abaszadeh (&)
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical
Sciences, 76175493 Kerman, Iran
e-mail: abaszadeh@kmu.ac.ir
M. Seifi
Najafabad Branch, Department of Chemistry, Faculty of Sciences, Islamic Azad University,
Najafabad, Esfahan, Iran
A. Asadipour
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences,
Kerman, Iran
123

M. Abaszadeh et al.
manipulation, and waste minimization are some prominent features of this approach
[4, 5]. More recently, ultrasonic irradiation has been used for the synthesis of
azeto[2,1-d] [1, 5] benzothiazepines [6], 1,3-dipolar cycloaddition [7], and
multicomponent reaction [8, 9] as a clean, practical, and usable protocol.
In this regard, multicomponent reactions (MCRs) are considered an invaluable
strategy for the synthesis of many novel compounds [8–11]. The MCRs strategy
depicted significant priorities over conventional linear-type synthesis, bringing
about three or more simple and flexible molecules brought together to rapidly
introduce structural complexity and diversity [12–15]. Because of the range of
readily available starting materials and the simplicity of one-pot procedures, MCRs
have been extensively used for the synthesis of heterocyclic compounds. Among
these, the multicomponent synthesis of polyfunctionalized heterocyclic compounds
has become more challenging in organic and medicinal chemistry [16, 17].
1,4-Dihydropyridines are an important class of compounds with a wide range of
biological activities [18]. Due to being pharmacologically active and acting as an
antitumor [19], calcium channel bloker [20], antitubercular [21], analgesic [22],
antithrombotic [23], anti-inflammatory [24], and anticonvulsant agent [25], they are
of many interests. Some of the marketed drug preparations containing 1,4-
dihydropyridine moieties are Nifedipine, Amlodipine, Oxodipine, etc. (Scheme 1).
In addition, imidazo[1,2-a]quinoline is a synthetically designed scaffold with a
broad range of biological activities. Some of its derivatives have pharmacological
properties such as antiallergic [26] and anxiolytic [27] activity (Scheme 1).
Nano-particles as heterogeneous catalysts have received considerable attention in
recent years owing to their interesting structures and outstanding catalytic activities
[28–31]. These nano-metal oxides have also shown high activity, strong oxidizing
power, recyclability, and long-term stability [32, 33]. Nano-crystalline metal oxides
such as nano-zinc oxide exhibit versatile applications as active adsorbents for gases
or destruction of hazardous chemicals [34, 35], and also as catalysts in various
organic transformations [8, 9, 36–39]. Hence, we decided to synthesize 1,4-
dihydropyridine and imidazo[1,2-a]quinoline derivatives, by using ultrasound
irradiation at EtOH and in the presence of catalytic amounts of zinc oxide nano-
particles.
Experimental
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 13C-NMR spectra were recorded on a Avance III
400 Bruker spectrometer at 400 and 100 MHz, respectively. Elemental analyses
were performed using a Heracus CHN-O-Rapid analyzer. The cyclic enaminoke-
tones 1a–d [43] and 1e, f [40] were prepared from the according to procedures
described in the literature.
123

Ultrasound promotes one-pot synthesis of 1,4-dihydropyridine
O
O
Cl
NO2
MeO2C
CO2Et
MeO2C
CO2Me
MeO2C
CO2Me
O
NH2
N
N
N
H
H
H
Nifedipine
Oxodipine
Amlodipine
OCH3
N
N
N
N
CO2Et
Antiallergic activity
CO2Et
Anxiolytic activity
Scheme 1 Some of the marketed drugs containing 1,4-dihydropyridine moieties and imidazo[1,2-
a]quinoline derivatives with biological activity
Preparation of ZnO nanoparticles
Zinc acetate dihydrate (2.19 g, 10 mmol) and CO(NH2)2 (12 g, 200 mmol) were
dissolved in deionized water (200 ml) at room temperature to form a transparent
solution, which was then refluxed for 12 h. It was cooled in an ice bath to stop the
reaction. The precipitate was centrifuged and washed with deionized water and
absolute EtOH, dried at 80 °C for 8 h, and then calcinated in a furnace in the
presence of air at 400 °C for 2 h [44].
General procedure for the preparation of 1,4-dihydropyridine (4a–l)
and imidazo[1,2-a]quinoline (4m–r) derivatives
A mixture of cyclic enaminoketones 1 (2 mmol), malononitrile 2 (2 mmol),
aldehyde 3 (2 mmol), and ZnO nanoparticles (10 mol %) in ethanol (10 ml) was
irradiated at 80 °C for the times reported in Table 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 from the reaction mixture by
centrifugation. Then, the reaction mixture was poured into ice-cold water; the crude
product was filtered, dried, and recrystallized from ethanol.
2-amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-
3-carbonitrile (4b)
Yellow crystals; IR (KBr, mmax,cm-1): 3,392, 3,328, 3,232 (NH2, NH), 2,192 (CN),
1
1,654 (C=O), 1,596 (C=C). H NMR (400 MHz, DMSO-d6) d: 8.82 (s, 1H, NH),
6.94 (d, 2H, JHH=4 Hz, CH–Ar), 6.71 (d, 2H, JHH = 4 Hz, CH–Ar), 5.65 (s, 2H,
3
3
2
NH2), 4.16 (s, 1H, CH), 3.61 (s, 3H, OCH3), 2.32 (d, JHH = 8 Hz, CH), 2.20 (d,
2
2
2JHH=8 Hz, CH), 2.08 (d, JHH=8 Hz, CH), 1.89 (d, JHH=8 Hz, CH), 0.92 (s, 3H,
123

M. Abaszadeh et al.
CH3), 0.81 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) d: 192.71 (C=O), 156.08,
153.27, 152.59, 137.96, 136.48, 132.71, 131.48, 113.35 (CN), 61.68 (C3), 55.63
(OCH3), 48.25 (CH2), 37.36 (CH2), 36.58 (CH), 32.69 (CMe2), 29.34 (CH3), 27.24
(CH3). Anal. calcd. for C19H21N3O2: C, 70.57; H, 6.55; N, 12.99 %. Found: C,
70.43; H, 6.48; N, 12.82 %.
2-amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (4c)
Yellow crystals; IR (KBr, mmax,cm-1): 3,392, 3,328, 3,232 (NH2, NH), 2,192 (CN),
1
1,654 (C=O), 1,596 (C=C). H NMR (400 MHz, DMSO-d6) d: 8.93 (s, 1H, NH),
3
7.45 (d, 2H, JHH=4 Hz, CH–Ar), 7.08 (d, 2H,3JHH=4 Hz, CH–Ar), 5.82 (s, 2H,
2
NH2), 4.30 (s, 1H, CH), 2.42 (d,2JHH=8 Hz, CH), 2.31 (d, JHH=8 Hz, CH), 2.18
(d,2JHH=8 Hz, CH), 1.98 (d,2JHH=8 Hz, CH), 1.02 (s, 3H, CH3), 0.90 (s, 3H, CH3).
13C NMR (100 MHz, DMSO-d6) d: 191.89 (C=O), 155.88, 154.12, 136.70, 134.34,
132.19, 131.79, 128.86, 113.41 (CN), 60.61 (C3), 49.59 (CH2), 40.89 (CH2), 39.91
(CH), 33.53 (CMe2), 30.22 (CH3), 28.82 (CH3). Anal. calcd. for C18H18BrN3O: C,
58.08; H, 4.87; N, 11.29 %. Found: C, 57.91; H, 4.75; N, 11.05 %.
2-amino-7,7-dimethyl-5-oxo-1-phenyl-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (4e)
Yellow crystals; IR (KBr, mmax,cm-1): 3,472, 3,344 (NH2), 2,176 (CN), 1,651
(C=O), 1,590 (C=C). 1H NMR (400 MHz, DMSO-d6) d: 7.63–7.12 (m, 9H, CH–Ar),
5.31 (s, 2H, NH2), 4.42 (s, 1H, CH), 2.21 (d, 2JHH=4 Hz, CH), 2.17 (d, 2JHH=4 Hz,
CH), 2.00 (d,2JHH=8 Hz, CH), 1.69 (d,2JHH=8 Hz, CH), 1.03 (s, 3H, CH3), 0.88 (s,
3H, CH3), 0.73 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) d: 193.76 (C=O),
156.23, 153.14, 135.02, 134.31, 132.25, 131.66, 130.79, 130.18, 127.77, 126.26,
120.94, 114.82 (CN), 62.70 (C3), 49.80 (CH2), 42.10 (CH2), 38.42 (CH), 34.51
(CMe2), 32.02 (CH3), 29.63 (CH3), 21.11 (CH3). Anal. calcd. for C25H25N3O: C,
78.30; H, 6.57; N, 10.96 %. Found: C, 78.08; H, 6.45; N, 10.83 %.
2-amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-1-phenyl-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (4f)
White crystals; IR (KBr, mmax,cm-1): 3,456, 3,328 (NH2), 2,160 (CN), 1,648 (C=O),
1
1,587 (C=C). H NMR (400 MHz, DMSO-d6) d: 7.63–7.23 (m, 9H, CH–Ar), 5.71
(s, 2H, NH2), 4.46 (s, 1H, CH), 2.21 (d, 2JHH=4 Hz, CH), 2.17 (d, 2JHH=4 Hz, CH),
2
2.01 (d, JHH=8 Hz, CH), 1.70 (d,2JHH=8 Hz, CH), 0.88 (s, 3H, CH3), 0.73 (s, 3H,
CH3). 13C NMR (100 MHz, DMSO-d6) d: 192.25 (C=O), 157.14, 154.66, 135.29,
133.27, 132.92, 131.62, 131.43, 128.36, 126.03, 122.88, 120.95, 114.95 (CN), 61.69
(C3), 49.75 (CH2), 43.22 (CH2), 38.58 (CH), 35.90 (CMe2), 31.69 (CH3), 29.50
(CH3). Anal. calcd. for C24H22BrN3O: C, 64.29; H, 4.95; N, 9.37 %. Found: C,
64.07; H, 4.78; N, 9.19 %.
123

Ultrasound promotes one-pot synthesis of 1,4-dihydropyridine
2-amino-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (4g)
Yellow crystals; IR (KBr, mmax,cm-1): 3,408, 3,328, 3,232 (NH2, NH), 2,176 (CN),
1
1,638 (C=O), 1,596 (C=C). H NMR (400 MHz, DMSO-d6) d: 8.96 (s, 1H, NH),
7.27–7.12 (m, 5H, CH–Ar), 5.75 (s, 2H, NH2), 4.34 (s, 1H, CH), 2.28–1.76 (m, 6H,
3CH2). 13C NMR (100 MHz, DMSO-d6) d: 192.94 (C=O), 156.59, 153.98, 137.94,
133.74, 132.82, 131.70, 130.29, 113.40 (CN), 62.12 (C3), 49.10 (CH2), 42.89 (CH2),
38.58 (CH), 25.40 (CH2). Anal. calcd. for C16H15N3O: C, 72.43; H, 5.70; N, 15.84 %.
Found: C, 72.29; H, 5.52; N, 15.67 %.
2-amino-5-oxo-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (4h)
Yellow crystals; IR (KBr, mmax,cm-1): 3,424, 3,328, 3,232 (NH2, NH), 2,176 (CN),
1
1,651 (C=O), 1,596 (C=C). H NMR (400 MHz, DMSO-d6) d: 8.93 (s, 1H, NH),
3
3
7.04 (d, 2H, JHH=4 Hz, CH–Ar), 7.01 (d, 2H, JHH=4 Hz, CH–Ar), 5.73 (s, 2H,
NH2), 4.30 (s, 1H, CH), 2.23 (s, 3H, CH3), 2.20–1.72 (m, 6H, 3CH2). 13C NMR (100
MHz, DMSO-d6) d: 192.58 (C=O), 155.97, 153.22, 138.00, 133.13, 132.73, 131.85,
129.64, 113.43 (CN), 62.29 (C3), 49.28 (CH2), 40.90 (CH2), 38.36 (CH), 26.12
(CH2), 21.57 (CH3). Anal. calcd. for C17H17N3O: C, 73.10; H, 6.13; N, 15.04 %.
Found: C, 72.89; H, 5.98; N, 14.88 %.
2-amino-4-(4-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (4i)
Yellow crystals; IR (KBr, mmax,cm-1): 3,392, 3,328, 3,232 (NH2, NH), 2,176 (CN),
1
1,657 (C=O), 1,600 (C=C). H NMR (400 MHz, DMSO-d6) d: 9.00 (s, 1H, NH),
3
3
7.31 (d, 2H, JHH= 4 Hz, CH–Ar), 7.14 (d, 2H, JHH=4 Hz, CH–Ar), 5.81 (s, 2H,
NH2), 4.35 (s, 1H, CH), 2.28–1.73 (m, 6H, 3CH2). 13C NMR (100 MHz, DMSO-
d6) d: 193.05 (C=O), 156.11, 154.01, 135.56, 133.77, 132.79, 131.57, 127.61,
114.94 (CN), 63.14 (C3), 48.92 (CH2), 41.40 (CH2), 37.29 (CH), 25.28 (CH2). Anal.
calcd. for C16H14ClN3O: C, 64.11; H, 4.71; N, 11.83 %. Found: C, 63.87; H, 4.59;
N, 11.69 %.
2-amino-5-oxo-1,4-diphenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (4j)
Pink crystals; IR (KBr, mmax,cm-1): 3,472, 3,296 (NH2), 2,176 (CN), 1,648 (C=O),
1,590 (C=C). 1H NMR (400 MHz, DMSO-d6) d: 7.52–7.09 (m, 10H, CH–Ar), 5.26
(s, 2H, NH2), 4.41 (s, 1H, CH), 2.21–1.49 (m, 6H, 3CH2).). 13C NMR (100 MHz,
DMSO-d6) d: 192.75 (C=O), 155.18, 153.49, 142.28, 140.33, 135.26, 131.61,
131.23, 131.08, 130.50, 125.88, 124.68, 114.06 (CN), 62.89 (C3), 49.12 (CH2),
41.75 (CH2), 38.34 (CH), 26.60 (CH2). Anal. calcd. for C22H19N3O: C, 77.40; H,
5.61; N, 12.31 %. Found: C, 77.18; H, 5.47; N, 12.13 %.
123

M. Abaszadeh et al.
2-amino-5-oxo-1-phenyl-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (4k)
Yellow crystals; IR (KBr, mmax,cm-1): 3,472, 3,328 (NH2), 2,192 (CN), 1,638
(C=O), 1,590 (C=C). 1H NMR (400 MHz, DMSO-d6) d: 7.61–7.11 (m, 9H, CH–Ar),
5.32 (s, 2H, NH2), 4.46 (s, 1H, CH), 2.27 (s, 3H, CH3), 2.22–1.56 (m, 6H, 3CH2).
13C NMR (100 MHz, DMSO-d6) d: 192.86 (C=O), 156.82, 154.27, 136.07, 135.51,
134.52, 134.14, 133.54, 131.63, 131.32, 128.85, 125.96, 115.44 (CN), 63.23 (C3),
48.69 (CH2), 41.24 (CH2), 37.69 (CH), 25.88 (CH2), 21.46 (CH3). Anal. calcd. for
C23H21N3O: C, 77.22; H, 5.96; N, 11.82 %. Found: C, 77.01; H, 5.78; N, 11.69 %.
2-amino-4-(4-chlorophenyl)-5-oxo-1-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (4l)
Brown crystals; IR (KBr, mmax,cm-1): 3,408, 3,328 (NH2), 2,176 (CN), 1,657
(C=O), 1,600 (C=C). 1H NMR (400 MHz, DMSO-d6) d: 7.61–7.41 (m, 5H, CH–Ar),
3
3
7.39 (d, 2H, JHH=4 Hz, CH–Ar), 7.30 (d, 2H, JHH=4 Hz, CH–Ar), 5.41 (s, 2H,
NH2), 4.51 (s, 1H, CH), 2.29–1.56 (m, 6H, 3CH2). 13C NMR (100 MHz, DMSO-
d6) d: 193.11 (C=O), 155.12, 153.68, 140.94, 135.16, 132.03, 130.87, 130.83,
129.94, 128.51, 127.47, 126.97, 115.35 (CN), 63.69 (C3), 49.28 (CH2), 41.52 (CH2),
38.14 (CH), 25.30 (CH2). Anal. calcd. for C22H18ClN3O: C, 70.30; H, 4.83; N,
11.18 %. Found: C, 70.04; H, 4.68; N, 10.99 % .
Results and discussion
There are several methods known for the synthesis of 1,4-dihydropyridine and
imidazo[1,2-a]quinoline derivatives; these compounds were conventionally pre-
pared using multicomponent reaction of cyclic enaminoketones, malononitrile, and
aromatic aldehydes [40–42]. Although, many reported methods are effective
enough, the use of expensive or poisonous catalysts, low yields, tedious work-up
O
Ar
CN
if R'= H, Ph
R
N
NH2
O
R
R'
O
CN
CN
EtOH, Nano ZnO
80°C, )))
4a-l
+
+
R
Ar
H
NH
R'
R
O
Ar
N
CN
3a-e
1a-f
2
if R'= CH2COOEt
R
NH
O
R
4m-r
Scheme 2 Synthesis of 1,4-dihydropyridine and imidazo[1,2-a]quinoline derivatives
123

Ultrasound promotes one-pot synthesis of 1,4-dihydropyridine
processes, long reaction times, and hazardous conditions make them less favorable.
In addition, the catalysts are not recyclable and are destroyed during the work-up
procedure. Therefore, the introduction of a mild, easy, efficient, and environmen-
tally benign method to synthesize 1,4-dihydropyridine and imidazo[1,2-a]quinoline
derivatives is still needed.
In order to synthesis 1,4-dihydropyridine and imidazo[1,2-a]quinoline deriva-
tives, we have investigated the multicomponent reaction of cyclic enaminoketones,
malononitrile, and aromatic aldehydes in EtOH, in the presence of catalytic amounts
of zinc oxide nanoparticles by using ultrasound irradiation (Scheme 2).
To optimize the reaction conditions, the reaction between 3-amino-5,5-
dimethylcyclohex-2-enone 1a, malononitrile 2, and benzaldehyde 3a was chosen
as a model reaction. When this multicomponent reaction was carried out in the
presence of ZnO nanoparticles (10 mol %), in ethanol, under ultrasound irradiation
and at 80 °C, the 2-amino-7,7-dimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroqui-
noline-3-carbonitrile 4a was obtained in 92 % yield within 30 min. This reaction
was also carried out in different solvents such as toluene and acetonitrile, and the
best results in terms of reaction time and yield of the desired product 4a, which was
obtained when the reaction was conducted in ethanol (Table 1, entries 1–3).
Decreasing the catalyst loading from 10 to 4 mol % significantly lowered the yield
of the reaction (Table 1, entries 4–6). The best catalyst loading was found at
10 mol %, which gave an excellent yield of 4a after only 30 min. It is worth
mentioning that the reaction temperature was optimized to 80 °C in ethanol
(Table 1, entries 7–9).
Table 1 Optimization of the model reaction between 3-amino-5,5-dimethylcyclohex-2-enone (1a),
malononitrile 2 and benzaldehyde (3a)
Entry
Solvent
Catalyst (mol %)
Temperature (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
EtOH
CH3CN
Toluene
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
10
10
10
8
80
80
80
80
80
80
70
60
r.t.
30
45
65
33
38
45
35
38
50
92
85
78
90
87
83
89
87
80
6
4
10
10
10
Table 2 Reusability of nano-
ZnO on the three-component
reaction for the synthesis of
(4a)
Entry
Time (min)
Yield (%)
1
2
3
4
50
38
40
35
67
88
85
89
123

M. Abaszadeh et al.
Table 3 Multicomponent reaction of cyclic enaminoketones (1a–f), malononitrile (2), and aromatic
aldehydes (3a–e)
O
Ar
O
Ar
CN
CN
R
R
N
NH2
N
NH
O
R
R
R'
4a-l
4m-r
Compd. no.
R
R0
Ar
Time Yield M.P. observed M.P. reported
(min) (%)
(°C)
(°C)
4a
4b
4c
4d
4e
4f
Me
Me
Me
H
H
H
C6H5
30
92
90
93
91
90
92
92
90
93
90
88
92
90
88
92
89
88
90
262–264
279–281
210 (dec.)
244–245
243–245
269–271
254 (dec.)
269–271
296–298
110 (dec.)
235 (dec.)
228–230
[300
265–267 [40]
4–CH3O–C6H4 35
4-Br-C6H4
C6H5
27
32
35
28
32
37
30
33
38
30
45
48
42
48
55
45
Me C6H5
Me C6H5
Me C6H5
246–248 [40]
4–CH3–C6H4
4–Br–C6H4
C6H5
4g
4h
4i
H
H
H
H
H
H
H
H
4–CH3–C6H4
4–Cl–C6H4
C6H5
H
4j
C6H5
C6H5
C6H5
4k
4l
4–CH3–C6H4
4–Cl–C6H4
4m
4n
4o
4p
4q
4r
Me CH2–COOEt C6H5
[300 [41]
Me CH2–COOEt 4–CH3–C6H4
Me CH2–COOEt 4–Cl–C6H4
[300
[300 [41]
[300
[300 [41]
H
H
H
CH2–COOEt C6H5
270–272
283–285
289–290
274–275 [41]
287–2289 [41]
290–291 [41]
CH2–COOEt 4–CH3–C6H4
CH2–COOEt 4–Cl–C6H4
We also attempted to reuse the catalysts by a variety of methods (Table 2). Direct
reuse of the catalysts (Table 2, entry 1) led to a greater than 25 % decrease in
activity, while washing of the catalysts with dichloromethane, ethyl acetate, and
chloroform prior to reuse also resulted in lower conversions (Table 2, entries 2–4).
This phenomenon probably arose because the reactant and product were not
completely desorbed from nano-ZnO and, therefore, the active sites were blocked.
According to our collected data, we decided to apply this method for synthesis of
1,4-dihydropyridine and imidazo[1,2-a]quinoline derivatives, using a multicompo-
nent reaction of cyclic enaminoketones, malononitrile, and aromatic aldehydes
under ultrasound irradiation and in the presence of Zno nanoparticles (Table 3).
Conclusions
In summary, we have reported an efficient procedure for the multicomponent
reaction of cyclic enaminoketones, malononitrile, and aromatic aldehydes, which
123

Ultrasound promotes one-pot synthesis of 1,4-dihydropyridine
leads to the synthesis of 1,4-dihydropyridine and imidazo[1,2-a]quinoline deriva-
tives. This reaction was carried out in the presence of ZnO nanoparticles
(10 mol %), in ethanol, by using ultrasound irradiation at 80 °C. The procedure
offers several advantages including high yields, operational simplicity, and clean
reaction conditions in comparison with existing methods, which makes it a useful
practical process for the synthesis of these compounds.
Acknowledgments The authors express their great appreciation toKermanUniversity ofMedical Sciences,
Pharmaceutics Research Center, Institute of Neuropharmacology for support of this investigation.
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