ZnO nanoparticle as catalyst for efficient green one-pot synthesis of coumarins through Knoevenagel condensation

Article abstract of DOI:10.1007/s12039-011-0133-0

Green chemistry protocols with the reusability of the nano particle as catalyst in the synthesis of coumarins is described. The zinc oxide (ZnO) nanoparticles functions as highly effective catalyst for the reactions of various o-hydroxy benzaldehydes with 1,3-dicarbonyl compounds under microwave and thermal conditions to afford the corresponding coumarins in moderate to good yields. The catalyst is inexpensive, stable, can be easily recycled and reused for several cycles with consistent activity. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0133-0

c
J. Chem. Sci. Vol. 123, No. 5, September 2011, pp. 615–621. ꢀ Indian Academy of Sciences.
ZnO nanoparticle as catalyst for efficient green one-pot synthesis
of coumarins through Knoevenagel condensation
B VINAY KUMAR, HALEHATTY S BHOJYA NAIK∗, D GIRIJA and B VIJAYA KUMAR
Department of Studies and Research in Industrial Chemistry, School of Chemical Sciences,
Kuvempu University, Shankaraghatta 577 451, India
e-mail: hsb_naik@rediffmail.com
MS received 27 September 2010; revised 26 April 2011; accepted 27 June 2011
Abstract. Green chemistry protocols with the reusability of the nano particle as catalyst in the synthesis
of coumarins is described. The zinc oxide (ZnO) nanoparticles functions as highly effective catalyst for the
reactions of various o-hydroxy benzaldehydes with 1,3-dicarbonyl compounds under microwave and thermal
conditions to afford the corresponding coumarins in moderate to good yields. The catalyst is inexpensive,
stable, can be easily recycled and reused for several cycles with consistent activity.
Keywords. Knoevenagel condensation; o-hydroxy benzaldehyde; zinc oxide (ZnO); catalyst;
green chemistry.
1. Introduction
due to their acid-base and redox properties. Recently,
bulk Zinc oxide has been employed as a heteroge-
neous catalyst for various organic transformations.11
The recent literature survey reveals that nano ZnO12 as
heterogeneous catalyst has received considerable atten-
tion because of its inexpensive, non-toxic catalyst and
has environmental advantages i.e., minimum execution
time, low corrosion, waste minimization, recycling of
the catalyst, easy transport and disposal of the catalyst.
In recent years, in biological field the potential utility
of ZnO nanoparticle in the treatment of cancer have
been reported by many researchers. Owing to numer-
ous advantages associated with this eco-friendly nature,
it has been explored as a powerful catalyst for several
organic transformations.13
Intensive studies have been recently focused on the
development of catalytic systems owing to their impor-
tance in synthetic organic chemistry. One of the
most attractive synthetic strategies favoured by organic
chemists is the use of heterogeneous catalyst in increas-
ing the efficiency of a wide range of organic synthesis.
Heterogeneous catalysis is being used in the fine-
chemicals industry because of the need for more
environmentally friendly production technology. This
tendency is assisted by the availability of novel catalytic
materials and modern techniques of creating and inves-
tigating specific active sites on catalyst surfaces.1,2 In
the field of fine chemical production, important steps in
the synthesis of relatively large and complex molecules
include carbon–carbon bond forming reactions such as
Knoevenagel condensations or Michael additions.
The Knoevenagel condensation, is one of the most
useful and widely employed methods for carbon–
carbon formation in organic synthesis, with numerous
applications in the synthesis of fine chemicals,3 hetero
Diels–Alder reactions,4 and carbocyclic as well as het-
erocyclic compounds of biological significance.5 The
reactions are usually catalysed by bases6 such as piperi-
dine, pyridine, ammonia or sodium ethoxide in organic
solvents. In recent years, metal oxides constitute the
largest family of catalyst in heterogeneous catalysis7–10
Further, coumarin and their derivatives have attracted
considerable interest in recent times because of their
promising biological activities as antibacterial, antico-
agulant, pesticidal, fungicidal and antimicrobial.14–18
Moreover, coumarins are structural units of several
natural products and feature widely in pharmacolog-
ically active compounds.19,20 Thus, synthesis of this
heterocyclic nucleus is of much current importance.
Coumarins have been synthesized by several routes
including Pechmann,21 Perkin,22 Knoevenagel,23
Reformatsky24 and Wittig reactions.25
Previously, Philip Kisanga and co-workers26 had
reported a new method for the preparation of some
∗For correspondence
615

616
B Vinay Kumar et al.
substituted coumarins by Knoevenagel condensa- point was determined by open capillaries are uncor-
tion of aromatic aldehydes with dicarbonyl com- rected. Thin-layer chromatography was performed
pounds under solvent-free condition using a promoter using commercially prepared 60-mesh silica gel plates
P(RNCH2CH2)3N (where R=Me, i-Pr) as a catalyst and visualization was effected with short wavelength
and also Dipak Prajapati and co-worker28 reported new UV light (254 nm). The IR spectra were recorded on
method for preparation of some coumarin derivatives by a Shimadzu model impact 400D FT-IR spectropho-
1
Knoevenagel condensation of aromatic aldehydes with tometer using KBr pellets. H NMR were recorded on
active methylene compounds under solvent-free condi- a Bruker AC-300F 400 MHz spectrometer in CDCl3
1
tions using molecular iodine as catalyst, but it needed using TMS as an internal standard with H resonant
a long reaction time and had to have a high reaction frequency of 400 MHz.
temperature.
Zn dust (Qualigens Fine Chemicals, AR grade, 325
Hence, in continuation of our quest in organic synthe- mesh, 99.90% purity), o-hydroxy benzaldehydes and
sis by different methods with the use of nano catalyst, 1,3-dicarbonyl compounds were commercially, pro-
we report an easy and rapid catalytic application of zinc cured from HiMedia Laboratories Pvt. Ltd., and used
oxide nanoparticle for one-pot synthesis of coumarins without any further purification.
via Knoevenagel condensation under MW irradiation
conditions.
2.1 Catalyst preparation
Zinc oxide nanoparticle used in the experiments was
produced according to the procedure29 with modi-
2. Experimental
Microwave irradiation was carried out in a microwave fication in following manner. Zinc powder 0.019 g
single-mode reactor (Biotage, Initiator). The melting
(0.3 mmol) in dust form was sonicated for 2 h with
Table 1. Knoevenagel condensation of 2-hydroxy aldehydes with various β-dicarbonyl
compounds in the presence of ZnO under microwave (MW 300 W, 120◦C) and thermal (ꢀ,
100◦C) conditions.
Time (min)
Yield (%)a
Observed
M.P. (◦C)
Literature
M.P. (◦C)
Entry
Product
MW
ꢀ
MW
ꢀ
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
4a
4b
5
6
4
5
5
6
5
5
7
7
5
7
9
6
8
6
6
5
36
43
52
45
54
60
51
53
72
52
37
48
54
48
52
51
34
57
92
90
86
92
90
92
93
87
88
90
62
85
92
95
93
93
92
91
85
83
73
88
85
86
87
78
76
87
45
78
85
87
82
85
81
87
95
93–9426
122–124
232–234
89–91
175
122–124
114–116
79
152–154
227–230
172–174
168
121–12326
233–23427
88–9026
173–17426
120–12526
115–11626
77–7826
9
151–15326
228–22926
174–17527
166–16727
20433
10
11
12
13
14
15
16
17
18
206
233–235
179–181
220–222
186–188
297
231–23333
178–17933
22033
187–18826
298–29926
aIsolated yield
Reaction attempted in a single-mode microwave reactor (Biotage Initiator)

ZnO nanoparticle as catalyst for efficient green one-pot synthesis
617
pound (2 mmol) and nano zinc oxide (10 mol%) was
added. The vial was sealed with an aluminum cap fit-
ted with a pressure and temperature-calibrated Teflon
seal. The vial was inserted into the cavity of the
microwave reactor, and the reaction mixture was irra-
diated with monomode irradiation at 120◦C and 9.6
bar for the time indicated in (table 1). The reaction
progress was monitored by TLC. After completion of
reaction, the reaction mixture was cooled to room tem-
perature and solidified within an hour. The resulting
solidified mixture was diluted with ethyl acetate (5 mL)
and the catalyst was separated. The filtrate obtained
was washed twice with water and evaporation of the
solvent under reduced pressure. It yielded the crude
product, which was further purified by recrystalliza-
tion. The same procedure was used for synthesis of
derivatives. All synthesized coumarin derivatives were
characterized using analytical techniques such as IR
and 1H NMR. Also the identity of these compounds was
established by comparison of their melting point with
those of reported samples (table 1).26,27,33
Figure 1. XRD pattern of the ZnO nanoparticle.
4 mL of n-butanol. To the above solution, 1.2 mL of tri-
ethanolamine (TEA) was added slowly. It was then son-
icated for ten more minutes. Finally, the mixture was
irradiated in a closed vessel mono-mode microwave
reactor at 140◦C and 10.9 bar for 6 min. The obtained
white solid suspension was centrifuged, washed sev-
eral times with distilled water and vacuum dried. It was
then calcined at 900◦C for 1 h and can be stored for
extended period of time. The sample was then charac-
terized using scanning electron microscopy (SEM), and
X-ray powder diffraction (XRD) techniques.
3. Results and discussion
In general, the nanoparticle is considered to be more
reactive because it offers higher surface area and low
coordinating sites. The surface area of the catalyst
increases tremendously when size decreases to nano
levels which are responsible for the higher catalytic
activity. Studies on interaction of alcohols with Zn
metal has revealed that C–O bond of the alcohol is read-
ily cleaved on zinc metal surface giving hydrocarbons
and the oxide species on the metal surface.30
2.2 General experimental procedure for the synthesis
The structure directing additive is a common
approach to control morphology, as shown by the effect
of coumarins
A 2–5 ml microwave reactor vial was charged with o- of ethylene diamine in hydrothermal ZnO nanorod syn-
hydroxy benzaldehyde (2 mmol), 1,3-dicarbonyl com thesis. Di- and tri-organic amines as well as long chain
Figure 2. Scanning electron microscopy (SEM) image of synthesized ZnO nanoparticle.

618
B Vinay Kumar et al.
O
R4
R3
R1
R3
R1
O
R4
ZnO (10% mol)
Microwave or Thermal
+
EtO
O
O
OH
R2
3 (a - p)
R2
1
2
R1
R2
R3
R4
3a
3b
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CO2Et
COMe
CO2Et
CO2Et
COMe
CO2Et
COMe
CO2Et
COMe
CN
H
3c OH
OH
OMe
OMe
H
3d
3e
H
H
3f OMe
3g OMe
3h Et2N
3i Et2N
3j Et2N
H
H
H
H
3k
H
OH
H
CO2Et
CO2Et
3l OH
3m
3n
3o
H
H
H
H
H
Cl COMe
Br COMe
H
H
NO2 COMe
OH COMe
3p
H
Scheme 1. Synthesis of coumarins by Knoevenagel condensation under microwave and thermal condition.

ZnO nanoparticle as catalyst for efficient green one-pot synthesis
619
which shows ZnO to be in nanostructure. This may
be the results of the presence of small amount of tri-
ethanolamine, which acts as stabilizer. These nanopar-
ticles are generally in random and not uniform, very
similar to those described in the literature.30
Table 2. Optimization of the ZnO nanoparticles catalysed
model reaction for synthesis of ethyl 2-oxo-2H-chromene-
3-carboxylate (3a).
Entry
Catalyst (mol %)
Yields(%)a
1
2
3
4
5
6
7
No catalyst
-
Although numerous methods to achieve coumarins
by Knoevenagel condensation are known, newer meth-
ods continue to attract attention for their experi-
mental simplicity and effectiveness. Thus, we have
been interested in the development of method for
Knoevenagel condensation that would avoid the use of
added acids and bases, are easy to perform and are
economical for application to large scale preparations.
The experimental reaction is presented in scheme 1.
To obtain the optimal reaction conditions, the syn-
thesis of ethyl 2-oxo-2H-chromene-3-carboxylate (3a)
was used as a model reaction. A mixture of o-hydroxy
benzaldehyde (2 mmol), ZnO (10 mol %) and diethyl
malonate (2.5 mmol) was irradiated in microwave oven
or heated in an oil bath in different solvents (4 mL).
A control experiment was conducted in the absence
of zinc oxide nanoparticle catalyst; for ethyl 2-oxo-
2H-chromene-3-carboxylate (3a) the reaction did not
proceed and the substrate remained unchanged, while
good results were obtained in the presence of ZnO
nanoparticles (table 2).
On the optimized of amount of catalyst, we found
that 10 mol% of ZnO nanoparticles could effectively
catalyze the reaction for synthesis of the desired prod-
uct. With the inclusion of 5 mol% of ZnO nanoparticles
the reaction took longer time. Using more than 20 mol%
ZnO nanoparticles has less effect on the yield and time
of the reaction. It is remarkable that the reaction carried
out by changing the size of the particles from nanoparti-
cles to bulk resulted in a drop in the catalytic activity. It
is interesting to note that the ZnO nanoparticle catalyst
catalyses the reaction in excellent yield within a shorter
reaction time than the bulk (table 2).
ZnO nano (5%)
ZnO nano (10%)
ZnO nano (20%)
ZnO nano (10%)
ZnO nano (10%)
ZnO bulk (10%)
55
90b
65
85c
52d
26
aIsolated yield
bReaction was carried out at 120◦C
cReaction was carried out at 100◦C
dReaction was carried out at 140◦C
glycols are reported to promote rod-like morpholo-
gies, as has increasing the base content during synthe-
sis.31 Thus, triethanol amine used as size stabilizer and
found effective in directing the morphology of ZnO
nanoparticle.
The obtained particles were characterized by X-ray
powder diffraction (XRD) (figure 1). The XRD pat-
tern of the newly prepared zinc oxide nanoparticles
showed the presence of peaks, which corresponds to
hexagonal wurtzite structure.32 The size of the particles
has been computed from the width of first peak using
Debye Scherrer formula
D = K λ/β COS θ,
here K is constant, λ is the wavelength of X-rays
employed radiation (1.54056 Å), β is corrected full
width at half maximum and θ is Bragg angle. The 2θ
value to be 19.0104. The crystallite size of the powder
particles is calculated as about 30 nm.
The morphology of the sample was investigated
with scanning electron microscopy (SEM) figure 2
Table 3. Comparative synthesis of compound 3a using solution versus the solvent-free
conditions under microwave (MW, 300 W, max. 120◦C) and thermal (ꢀ, 100◦C) conditions.
Time (min)
Yield (%)a
Entry
Solvents
MW
ꢀ
MW
ꢀ
1
2
3
4
5
6
No solvent
DMF
Acetonitrile
Dioxane
Methanol
Ethanol
6
36
90
15
20
16
72
84
85
11
18
12
66
79
20
18
14
10
8
180
190
120
96
56
aIsolated yield

620
B Vinay Kumar et al.
In order to select the appropriate microwave range of electron-donating and electron-withdrawing
power, the model reaction was examined at different functional groups afforded the corresponding products
microwave powers (100–400W) with controlled tem- in good yields.
perature (max. 140◦C) in the presence of ZnO nanopar-
ticles. The reaction was also examined at 60–140◦C in
3.1 Regeneration of catalyst
thermal conditions. Higher yield and shorter reaction
time were attained at 120◦C.
To examine the reusability, the catalyst recovered by fil-
tration from the reaction mixture o-hydroxy benzalde-
hyde and diethyl malonate after dilution with ethyl
acetate was reused as such for subsequent experiments
(up to four cycles) under similar reaction conditions.
The observed fact that yields of the product remained
comparable in these experiments (figure 3), established
the recyclability and reusability of the catalyst without
significant loss of activity.
To compare the efficiency of the solvent-free ver-
sus solution conditions, the reaction was examined in
several solvents under microwave and thermal con-
ditions. Thus, a mixture of 2-hydroxy benzaldehyde
(2 mmol), ZnO (0.4 mmol) and β-dicarbonyl compound
(2.5 mmol) was irradiated in microwave oven (300 W,
max. 120◦C) or heated in an oil bath (100◦C) in differ-
ent solvents. The results are depicted in table 3. As it
is clear from table 3, lower yields and longer reaction
times were observed in solution conditions. Therefore,
the solvent-free method is more efficient.
To investigate the versatility and capability of our
method, the reactions of o-hydroxy benzaldehyde was
examined with diethyl malonate compounds under both
microwave and thermal conditions (table 1). As table 3
indicates, the reactions proceeded efficiently and the
desired products were obtained in good to excellent
yields.
4. Conclusions
From the experimental results, we found that the mono-
mode microwave-assisted method has been success-
fully used for fast synthesis of nano-ZnO catalyst. The
use of triethanolamine has a significant influence on
the morphology of ZnO. We have developed an effi-
cient, facile and environmentally acceptable synthetic
methodology for the synthesis of coumarin derivatives
using nano-ZnO catalyst under solvent-free condition.
The advantages of this environmentally benign and safe
protocol include a simple reaction setup, very mild
reaction conditions, high product yields, short reac-
tion times, and the possibility for reusing the catalyst,
chemoselectivity and solvent-free conditions.
In order to investigate the scope of this reaction, a
variety of different substituted o-hydroxy benzaldehyde
and different 1,3-dicarbonyl compounds were subjected
to this reaction (table 1, entries 1–18). A variety of
substituted o-hydroxy benzaldehyde possessing a wide
Acknowledgement
The authors are thankful to University Grants Com-
mission (UGC) for financial support by sanctioning
the Major Research Project (F. No. 33-322/2007 (SR)
Dated: 28-02-2008).
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