CuO nanoparticles: An efficient and recyclable nanocatalyst for the rapid and green synthesis of 3,4-dihydropyrano[c]chromenes

Article abstract of DOI:10.1016/j.cclet.2011.06.003

Copper oxide nanoparticles showed excellent catalytic activity through three-component condensation reaction of aldehydes, malononitrile, and 4-hydroxycoumarin for the synthesis of 3,4-dihyropyrano[c]chromenes in water medium in excellent yields and very

Full text of DOI:10.1016/j.cclet.2011.06.003

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1419–1422
www.elsevier.com/locate/cclet
CuO nanoparticles: An efficient and recyclable nanocatalyst for the
rapid and green synthesis of 3,4-dihydropyrano[c]chromenes
*
Hossein Mehrabi , Maryam Kazemi-Mireki
Department of Chemistry, Vali-e-Asr University of Rafsanjan, 77176, Rafsanjan, Iran
Received 4 May 2011
Available online 29 July 2011
Abstract
Copper oxide nanoparticles showed excellent catalytic activity through three-component condensation reaction of aldehydes,
malononitrile, and 4-hydroxycoumarin for the synthesis of 3,4-dihyropyrano[c]chromenes in water medium in excellent yields and
very short reaction times.
# 2011 Hossein Mehrabi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 3,4-Dihydropyrano[c]chromene; Nanoparticle; Three-component condensation; 4-Hydroxycoumarin
Dihydropyrano[c]chromenes are of considerable interest due to their widespread biological properties, such as
spasmolytic, diuretic, anticoagulant, anti-cancer, and anti-anaphylactic activity. In addition, they can be used as
cognitive enhancers, for the treatment of neurodegenerative diseases, including Alzheimer’s disease, amyotrophic
lateral sclerosis, Huntington’s disease, Parkinson’s disease, AIDS associated dementia and Down’s syndrome as well
as for the treatment of schizophrenia and myoclonus [1–7].
3,4-Dihydropyrano[c]chromenes have already been prepared in the presence of organic bases like piperidine or
pyridine in an organic solvent, i.e. ethanol and pyridine [8],or catalysed by KF-montmorillonite [9]. They are also
prepared in the presence of diammonium hydrogen phosphate and heteropolyacid in aqueous ethanol [10,11]. Also,
phase transfer catalysts same as tetrabutylammonium bromide and sodium dodecyl sulfate in aqueous medium are as
well reported [12,13].
Copper oxide nanoparticles have been of considerable interest due to the role of CuO in catalysis, gas sensors and
semiconductors [14,15]. CuO nanoparticles were found to be the effective catalysts for CO and NO oxidation as well
as for the oxidation of volatile organic chemicals such as methanol [16–18]. Also, the application of copper oxide
nanoparticles for organic reactions has attracted immense attention in recent years [19–22]. Because this class of
catalysts appears as one of the most promising solutions toward efficient reactions under mild and environmentally
benign conditions in the context of green chemistry [23,24].
In continuation of our interests to develop environmentally benign protocols [13], we decided to use nanosized
copper oxide as catalyst for preparation of 3,4-dihydropyrano[c]chromenes by three-component condensation of
aromatic aldehydes, malononitrile and 4-hydroxycoumarin in water as reaction medium.
* Corresponding author.
E-mail address: mehraby_h@yahoo.com (H. Mehrabi).
1001-8417/$ – see front matter # 2011 Hossein Mehrabi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.06.003

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H. Mehrabi, M. Kazemi-Mireki / Chinese Chemical Letters 22 (2011) 1419–1422
1. Experimental
All chemicals were purchased from Aldrich and Merck with high-grade quality, and used without any purification.
All melting points were obtained by Bamslead Electrothermal 9200 apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded in DMSO-d6 on a Bruker 500 MHz spectrometer. Infrared spectra were recorded by Bruker FT-
IR Equinax-55 spectrophotometer in KBr with absorption in cmÀ1. All products were characterized by their spectra
and physical data.
1.1. Synthesis of nano-CuO
Solution of NaOH (100 mL, 0.1 mol/L) was added to solution of Cu(CH3COO)2Á2H2O (0.1 mol/L) in ethanol/
water. The obtained mixtures were sonicated for 30 min with 30 W ultrasound power. To investigate the role of
surfactants on the size and morphology of nanoparticles, we used 1 g of polyvinyl alcohol (PVA) in the reaction. The
morphology, structure and size of the samples were investigated by Scanning Electron Microscopy (SEM). Fig. 1
indicates that the original morphology of the particle was approximately spherical with the diameter varying between
35 and 103 nm.
1.2. General procedure for synthesis of 3,4-dihydropyrano[c]chromenes
A mixture of aromatic aldehyde (1 mmol), malononitrile (1 mmol), 4-hydroxycoumarin (1 mmol), and CuO
nanoparticles (15 mol%) in water (10 mL) was refluxed for appropriate time. Upon completion, monitored by TLC,
the reaction mixture was allowed to cool to room temperature. The mixture was extracted with ethyl acetate
(2 mL Â 5 mL) and the organic phase was dried, filtered, and excess ethyl acetate was distilled off (filtration of both
organic and aqueous phases led to the recovery of solid CuO). The residue was recrystalized from ethanol to afford the
pure product.
2d: Mp: 260–262 oC; IR (KBr): ymax 3378, 3292, 2194, 1716, 1677, 1605, 1507, 1379 cmÀ1, 1H NMR (500 MHz,
DMSO-d6): d 4.47 (s, 1H, CH), 7.07 (dd, 2H, J1 = 8.4 Hz, J2 = 8.0 Hz, HAr), 7.31 (dd, 2H, J1 = 8.4 Hz, J2 = 7.8 Hz,
HAr), 7.38 (br s, 2H, NH2), 7.41 (d, 1H, J = 8.3 Hz, HAr), 7.46 (t, 1H, J = 7.6 Hz, HAr), 7.67 (t, 1H, J = 7.5 Hz, HAr),
7.88 (d, 1H, J = 7.5 Hz, HAr). 13C NMR (125 MHz, DMSO-d6): d 36.26, 57.89, 103.76, 112.92, 115.11, 116.47,
119.02, 123.50, 129.59, 132.85, 139.45, 152.12, 153.36, 157.93, 159.45, 160.23, 162.16.
2. Results and discussion
To find the optimal conditions, we studied synthesis of 2-amino-5-oxo-4-phenyl-4H,5H-pyrano[3,2-c]- chromene-
3-carbonitrile 2a from the condensation of 4-hydroxycoumarine, benzaldehyde and malononitrile under various
reaction conditions (Table 1).
Fig. 1. SEM image of synthesized CuO nanoparticles.

H. Mehrabi, M. Kazemi-Mireki / Chinese Chemical Letters 22 (2011) 1419–1422
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Table 1
Optimization of the nanoparticles catalysed model reaction for synthesis of 3,4-dihydropyrano[c]chromenes under aqueous medium at reflux condition.
Entry
Catalyst (15 mol%)
Time (min)
Yield (%)a
1
2
3
4
5
6
7
Non
1440
10
25
80
90
92
93
93b
88
MgO
ZnO
10
NiO
10
CuO
6
CuO
35
CuO bulk
180
a
Yield are related to isolated pure products.
b
Reaction was carried out at room temperature.
We examined this reaction in the absence and presence of several nanoparticle catalysts. It was found that when the
reaction was carried out without any catalysts resulted in 25% of product after 24 h (Table 1, entry 1). While good
results were obtained in the presence of MgO, ZnO and NiO nanoparticles after 10 min (Table 1, entries 2–4). Among,
when CuO nanoparticles were used in this reaction system, the yields of products were the best (Table 1, entry 5). On
the optimized of amount of catalyst, we found that 15 mol% of CuO nanoparticles could effectively catalyze the
reaction for synthesis of the desired product. With inclusion of 5 and 10 mol% of CuO nanoparticles the reaction took
longer time. Using more than 15 mol% CuO nanoparticles has less effect on the yield and time of the reaction. The
effect of temperature was studied by carrying out the model reaction in the presence of CuO nanoparticles (15 mol%).
It was observed that the time was increased (Table 1, entry 6) at room temperature. Commercially available CuO bulk
also was evaluated for the synthesis of 2a. Clearly, the reaction time using CuO nanoparticles have been reduced with
higher yield than CuO bulk (Table 1, entries 5 and 7).
To generalize this methodology, we subjected a series of other aromatic aldehydes having electron-donating as well
as electron-withdrawing substituent’s to obtain the corresponding 3,4-dihydropyrano[c]chromene under the optimized
reaction condition (Table 2).
As can be seen from Table 2, electronic effects and the nature of substituents on the aromatic ring did show effects
in terms of reaction time. When aromatic aldehydes containing electron-donating groups (such as methyl, methoxyl,
Table 2
Synthesis of 3,4-dihyropyrano[c]chromenes by condensation of aldehydes, 4-hydroxycoumarin and malononitrile using CuO nanoparticles (15 mol%)
NH2
OH
CN
CuO nanoparticles (15mol%)
O
NC
+
+
as catalyst. ArCHO
.
Ar
H2O, Reflux
NC
O
O
O
1 a-m
O
2 a-m
Entry
Ar
Product
Time (min)
Yield (%)a
Melting point (8C)/(lit.)
1
C6H5
2a
2b
2c
2d
2e
2f
6
3
93
90
88
90
95
93
89
92
98
95
97
93
95
259–261(258–260) [10]
257–259(255–256) [10]
260–261(262–264) [11]
263–264(260–262) [13]
246–249(245–247) [8]
259–260(258–260) [10]
247–250(249–251) [12]
261–263(264–266) [13]
250–251(250–252) [8]
253–255(257–259) [11]
233–236(232–234) [9]
225–228(228–230) [13]
267–269(266–268) [8]
2
4-O2NC6H4
3-O2NC6H4
4-FC6H4
3
3
4
6
5
3-ClC6H4
5
6
4-ClC6H4
6
7
4-BrC6H4
2g
2h
2i
6
8
2-CH3C6H4
4-CH3C6H4
2,4-Cl2C6H3
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-(CH3)2NC6H4
9
9
12
3
10
11
12
13
2j
2k
2l
12
15
15
2m
a
Yield are related to isolated pure products.

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H. Mehrabi, M. Kazemi-Mireki / Chinese Chemical Letters 22 (2011) 1419–1422
Table 3
Recycling of CuO nanoparticles in the model reaction.
Run
Catalyst recovery (%)
Yield 2a (%)c
1a
2b
3b
4b
96
94
89
85
93
91
90
88
a
Reaction performed in the presence of 1a (1 mmol), malononitrile (1 mmol), 4-hydroxycoumarin (1 mmol), 15 mol% of CuO nanoparticles, and
H2O (10 mL).
b
Recovered catalyst used.
c
Yield are related to isolated pure products.
or dimethylamino group) were employed, a longer reaction time was required than those of electron-withdrawing
groups (such as nitro or halides group) on aromatic rings.
To check the recyclability of the catalyst, after completion of reaction, the reaction mixture was allowed to cool at
room temperature and the solid was filtered off and washed with water (2 mL Â 10 mL). The catalyst was recovered
from the methanol solution by centrifugation, dried under vacuum and reused for further catalytic reactions. The
catalyst maintained its good level of activity even after being recycled four times as shown in Table 3.
3. Conclusions
We have reported an efficient procedure through three-component coupling of aldehydes, malononitrile, and 4-
hydroxycoumarin for the synthesis of 3,4-dihyropyrano[c]chromenes using CuO nanoparticles as a reusable, non-
toxic and inexpensive heterogeneous nanocatalyst. The major advantage of this method is the ease of the work-up; i.e.,
the products can be isolated without chromatography. The method also offers some other advantages such as clean
reaction, low loading of catalyst, high yields of products and very short reaction times, which make it a useful and
attractive strategy for the synthesis of 3,4-dihyropyrano[c]chromenes.
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