Indian Journal of Chemistry
Vol. 54B, November 2015, pp 1350-1354
ZnO Nanoparticles: An efficient green
reusable catalyst for the synthesis of
3-formyl benzopyranones chalcones by
Claisen-Schmidt reaction under
solvent-free condition
Subhash Chand & Jagir S Sandhu*
Department of Chemistry, Punjabi University,
Patiala 147 002, India
E-mail: [email protected]
Received 3 June 2015; accepted (revised) 1 September 2015
An efficient environmentally benign protocol is reported for
the production of benzopyranes based chalcones. In this protocol,
yield is very high, reaction time is very small, work up is very
simple, catalyst can be recycled, and it is free of any hazardous
by-product formation during workup.
Keywords: 3-Formyl benzopyran-4-one, ketones, Claisen-Schmidt
condensation, ZnO NP, chalcones, solvent free
Benzopyrans occupy a unique position of because of
their rich chemistry as well as biological significance1.
Development in chemical knowledge have been very
fast as they are the synthons for very highly reactive
dipoles and dienophiles2. The biological significance
is amply demonstration by the presence number of
molecules (Figure 1) in clinical process derived from
this motif. Some chromone based drug molecules 1-6
are already in the market as shown in Figure 1 with
their activity and trade name.
As far as chemical modification of this unit is
concerned, this molecule possesses three reactive sites
and to keep the pyran ring intact is a major problem,
which requires very careful handling to avoid rupture.
Hence, we were keen in the use of nanoparticles because
of their established green aspect and particularly report
here the use of already prepared zinc oxide nanoparticles (which are extensively used in organic
synthesis such as Knoevenagel reaction, Hantsch
condensastion, etc.)3-6. Here our focus was on the
Claisen-Schmidt reaction of 3-formyl benzopyran-4one keeping the pyran ring intact. Indeed we succeeded
and prepared the chalcone derivatives from this using
the protocol (Scheme I) and the desired chalcones
were obtained in excellent yield.
Chalcone molecules have a broad spectrum of biological activities, such as anti-bacterial7, antioxidant8,
anti-inflammatory9, antimalarial10, antileshmanial11,
anticancer12, and antitumor13. The following materials
can be used for the synthesis of chalcones. Catalysts
have been reported in the literature for the synthesis of
chalcones like aqueous sodium hydroxide14, potassium
hydroxide15,
zeolites16,
LiHDMS17,
calcined
18
NaNO3/natural phosphates , dry HCl (Ref 19),
TiCl4 (Ref 20), RuCl3 (Ref 21), BF3.Et2O (Ref 22),
SOCl2/EtOH (Ref 23), molecular iodine24, and
Brϕnsted acidic ionic liquid catalysts25, etc. Some recent
examples are ZrCl4/Al2O3 (Ref 26), Zn(L-proline)2
(Ref 27), (NaNO3/NP) (Ref 28), BiCl3 (Ref 29). In the
present protocol nanomaterial ZnO have been chosen,
since these materials have basic sites in high density,
nontoxic in nature and efficient green catalyst for the
production of vital organic compounds3-6. Because of
these features and its prospective applications in
synthetic chemistry it was decided to explore the
catalytic activities of ZnO based nanoparticles in the
synthesis of biologically important benzopyran chalcone
under solvent free conditions.
Results and Discussion
Initially, ZnO nanoparticles were used to catalyse
the Claisen-Schmidt reaction of 3-formylchromone
(10 mmol) with acetophenone (10 mmol) under different
reaction conditions (Scheme II). The best results were
obtained when the reaction was catalyzed by 5 mol%
of zinc oxide nanoparticles at 120°C using oil bath for
8 min under solvent-free conditions and the corresponding Claisen-Schmidt product 3a was isolated
with 95% yield (Table I). In order to optimize the yields,
Scheme II was carried out using different amounts of
catalyst (2, 5, 10, 15 and 20 mol%)(Table I). It was
observed that large amount of catalyst (>5 mol%) did
not affect the yields and reaction rate but an amount
less than 5 mol% considerably decreased the yield of
products.
Keeping the optimized reaction conditions, a variety
of 3-formylchromone were condensed with aetophenone
in presence of ZnO nanoparticles at 120°C under solventfree conditions to provide Claisen-Schmidt products
3a-r in excellent yields within short reaction times
(Table II).
Thereafter, the recyclability of the catalyst was
studied by using Scheme II. It was observed that the
NOTES
1351
Figure 1
Scheme I — ZnO NP catalysed Synthesis of chalcones 3a-r; ZnO NP, Solvent free
Scheme II — Synthesis of 3-formyl benzopyran-4-one chalcones
Table I — Optimization of catalyst amount in Claisen-Schmidt
reactiona
a
Entry
ZnO NP (mol %)
Yield (%)b
1
2
80
2
5
95
3
10
91
4
15
88
5
20
85
Reaction conditions: 3-Formyl chromone 1a (1 mmol) with
acetophenone 2a (1 mmol) and ZnO nanoparticles; heat under
solvent free condition for 10 min.
b
Isolated yields after recrystallization.
catalyst could be recovered and reused for a new set
of reactions. The reaction mixture with a minimum
quantity of solvent was centrifuged for 10 min at 5000
rpm. The supernatant was collected and the centrifuged
pellet is made up of ZnO nanoparticles. Finally, ZnO
nanoparticles were dried in the oven at 100°C. The
recovered catalyst was successfully recycled and
reused for five runs without further purification.
The synthesized compounds were well characterized
and their structures confirmed by spectral techniques
e.g. IR, 1H NMR and mass spectroscopy. For the
compound 3-(3-aryl-3-oxo1-propenyl)-4H-1benzopyran
3a, the yield is 95% and the absorption observed in IR
region is 1685 cm-1 for OCC and 1640 cm-1 for
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INDIAN J. CHEM., SEC B, NOVEMBER 2015
pyronyl CO, respectively. In the 1H NMR spectra, a
pair of doublets at δ 8.47 and 8.18 was found for the a
and b protons of chalcone system, the hydrogen
attached to C2 position of chromone appeared as a
singlet at δ 8.9, and other aromatic protons appeared
as a complex multiplet pattern at δ 7.64
Experimental Section
All starting materials were commercial products,
and were used without further purification. Yield refers
to yield of the isolated products. Melting points were
determined in open capillaries in paraffin bath and are
uncorrected. Nuclear magnetic resonance spectra
(1H NMR) were obtained on a 400 MHz Bruker
AVANCE II instrument in CDCl3 using TMS as a
standard. Infrared spectra were recorded using Shimadzu
FT-IR-8400s spectrophotometer with samples prepared
in KBr pellets.
General procedure for preparation of chalcones
A mixture of 3-formyl benzopyran-4-one (10 mmol,
1.74 g), acetophenone (10 mmol, 1.20 g), for the synthesis
of chalcone with ZnO (0.1 mmol) was heated at 120°C
for 7 min under solvent-free conditions. The reaction was
monitored via TLC using hexane:ethylacetate (9:1).
After the reaction completion, reaction mass was
cooled (15°C‒20°C) and stirred with ethanol (50 mL)
for 30 min. Thereafter, the reaction mass was centrifuged
for 10 min at 5000 rpm. The supernatant was collected
and solvent removed under reduced pressure. The
NOTES
obtained products were purified by re-crystallization
from EtOH. During centrifugation, the obtained pellet
consisted of ZnO nanoparticles, which was washed
with ethanol and dried in the oven at 100°C to recover
and reuse the catalyst. The products were confirmed
from their spectral data (IR, 1H NMR and mass spectra)
after comparison with authentic samples.
3-((E)-3-Oxo-3-phenylprop-1-enyl)-4H-chromen-4one 3a: Yield 95%. IR (KBr): 3050, 3010, 1680,
1640, 1573, 1512 cm-1; 1H NMR (400 MHz, CDCl3):
δ 8.47-8.43 (d, J = 15.52 Hz, 1H), 8.18-8.15 (d, J = 13.04
Hz, 1H), 8.9 (S, 1H), 7.82-7.62 (dd, J = 7.12 Hz, 2H,
Ar-H), 8.03-8.01 (d, J = 8.56 Hz, 2H, Ar-H), 7.64-7.49
(m, 5H, Ar-H); MS: m/z 276. Anal. Calcd for C18H11O3:
C, 78.25; H, 4.38; O, 17.38. Found: C, 78.13; H, 4.40;
O, 17.29%.
6-Chloro-3-((E)-3-oxo-3-phenylprop-1-enyl)-4Hchromen-4-one 3b: Yield 94%. IR (KBr): 3066, 3030,
1680, 1637, 1590 cm-1; 1H NMR (400 MHz, CDCl3):
δ 8.45-8.43 (d, J = 15.50 Hz, 1H), 8.15-8.12 (d, J = 13.01
Hz, 1H), 8.8 (S, 1H), 7.80-7.60 (d, J = 7.12 Hz, 2H,
Ar-H), 8.06-8.04 (d, J = 8.50 Hz, 1H, Ar-H), 8.95-8.97
(S, 1H, Ar-H), 7.66-7.50 (m, 5H, Ar-H); MS: m/z 310.
Anal. Calcd for C18H11ClO3: C, 69.58; H, 3.57; O, 15.45;
Cl, 11.41. Found: C, 69.66; H, 3.50; O, 17.35%.
3-((E)-3-Oxo-3-p-tolylprop-1-enyl)-4H-chromen4-one 3g: Yield 94%. IR (KBr): 2930, 3040, 3020, 1685,
1638, 1578 cm-1; 1H NMR (400 MHz, CDCl3): δ 8.44-8.40
(d, J = 15.50 Hz, 1H), 8.15-8.12 (d, J = 13.01 Hz, 1H),
8.7 (S, 1H), 7.80-7.60 (dd, J = 7.12 Hz, 2H, Ar-H),
8.03-8.01 (d, J = 8.56 Hz, 2H, Ar-H), 2.53(S, 3H,
Ar-CH3), 7.23-7.20 (d, J = 13.72, 2H, Ar-H ), 7.41-7.38
(d, J = 10.12, 2H, Ar-H); MS: m/z 290.3. Anal. Calcd
for C19H14O3: C, 78.61; H, 4.86; O, 17.38. Found: C,
78.66; H, 4.80; O, 17.35%.
Conclusions
In summary, we have developed a simple, rapid,
and environmentally benign protocol for the synthesis
of 3-formyl chromone chalcone via ZnO nanoparticles
catalysed Claisen Schmidt reaction. The present protocol
has the following salient features: (i) a variety of
biologically important aldehydes can be employed,
(ii) in contrast to known methods, this procedure does
not need volatile organic solvents, (iii) catalyst ZnO
nanoparticles shows an excellent catalytic activity by
activating both reactants without the formation of any
complexes or by-products, (iv) this method produces
excellent yields in shorter reaction time due to the
large suface area of the catalyst, (v) used catalyst can
1353
be recycled and reused many times without the
reduction in catalytic potential, (vi) furthermore, the
process is carried out with operational simplicity and
simple work-up procedures. These features place this
protocol at an advantage to the existing processes.
Acknowledgements
The authors are thankful to the Council of Scientific
and Industrial Research, New Delhi, India, for financial
assistance and to the Indian National Science Academy,
New Delhi, India, for additional financial support for this
research project.
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