Indian Journal of Chemistry
Vol. 51B, November 2012, pp 1623-1627
Note
Microwave enhanced Claisen-Schmidt
condensation: A green route to chalcones
Jayant P Singh, Mangalshree Dulawat, Neetu Jaitawat,
Sumer S Chundawat, Anju Devpura & Shiv S Dulawat*
Department of Chemistry, B N P G College, M L Sukhadiya
University, Udaipur 313 001, India
E-mail: jayantratnawat@gmail.com
Received 16 May 2011; accepted (revised) 10 September 2012
Chalcones have been synthesized under microwave irradiation
by Claisen-Schmidt condensation between 4-piperidino-
acetophenone and appropriately substituted benzeldehydes using
NaOH-Al2O3 under solvent free conditions. Neat reactions on
microwave irradiation (MWI) under solvent free conditions result
in enhancement of yield and reaction rates. High conversion is
obtained in absence of solvent. The protocol offers several
advantages such as simple procedure, fast reaction rate, mild
reaction conditions and excellent yield. Structure elucidation of
synthesized compounds has been accomplished by elemental
analysis and spectral data. All the compounds have been screened
for antimicrobial activity by the cup-plate method.
Keywords: Chalcones, microwave irradiation, green
chemistry, antimicrobial activity
The members of chalcone1 and flavonoid family have
attracted a great deal of interest due to their application
as antimicrobial2-4, anti-inflammatory5,6, antifungal,
antiviral7, anti parasitic, antileishmanial8,
antitubercular9-11, and anticancer12-14 pharmacological
agents15,16. In addition, these compounds are of high
interest due to their use as starting materials in the
synthesis of a series of heterocyclic compounds like
isoxazole, quinolinones, thiadiazines, benzofuranones,
benzodiazepines, tetrahydro-2-chromens, flavones, etc.
These are important intermediates in many addition
reactions of nucleophiles due to inductive polarization
of carbonyl group at the β-position. These findings
explain the significant interest of scientists in this
particular group of compounds.
Several strategies for the synthesis of these systems
based on the formation of carbon-carbon bond have
been reported. Among them, direct aldol condensation
and Claisen-Schmidt condensation17 still occupy
prominent position. The main method for the
synthesis of chalcones is the Claisen-Schmidt
condensation in the presence of alkaline bases.
Conventional methods present several hurdles,
such as toxic reagents, waste disposal problem, strong
acidic or basic conditions and low selectivity that
pose environmental hazards. In this respect solid
phase synthesis under microwave irradiation is
considered as an eco-friendly alternative.
Under the frame-work of “Green Chemistry” an
environmentally benign solvent free synthesis18 of
chalcones has been developed by condensing 4-
piperidinoacetophenone and substituted benzelde-
hydes using microwave irradiation in the presence of
basic alumina as inorganic solid support.
The structures of the various synthesized
compounds were assigned on the basis of IR, 1H
NMR, mass spectral data and elemental analysis.
These compounds were also screened for their
antimicrobial activity.
Results and Discussion
Antimicrobial activity
All the synthesized compounds 5a-h (Scheme I)
were screened for their in vitro antibacterial activity at
a concentration of 200 µg/mL in DMF against Gram-
positive B. subtilis and Gram negative E. coli, K.
pneumonia and Pseudomonas bacteria as well as
antifungal activity against Candida albicans and
Aspergillus fungi by the paper disc diffusion method.
The zone of inhibition was measured in mm. Standard
drugs Cipro and Flucanazole were used as reference
compounds. The zone of inhibition was compared
with the standard drugs after 24 hr. of incubation at
25°C. All the compounds 5a-h exhibited moderate to
good activity against the test organisms. The results
are summarized in Table I.
Experimental Section
All the melting points are uncorrected and were
recorded using open ended capillaries. Thin layer
chromatography of synthesized compounds was
performed on silica gel-G plates using hexane-ethyl
acetate (7:3) solvent system and iodine vapour as
visualizing agent.
The IR spectra were recorded on Digilab FTS-14 or
Perkin-Elmer 157P spectrophotometer in KBr (νmax in
cm-1). 1H NMR was recorded on acetone-d6 on a
1624 INDIAN J. CHEM., SEC B, NOVEMBER 2012

O O
MWI
F + N
CH3 Anhyd. K2CO3/ DMSO CH3
N
H

1 2 3

O O O
(i), (ii), (iii), (iv)
N N
+
CH3

R
3 4a-h 5a-h
R
4, 5 R 4, 5 R
a 4-OCH3 e 4-N(CH3)2
b 3,4-OCH3 f 4-OH
c 3,4,5-OCH3 g 2-Cl
d 3-NO2 h 4-Cl
Scheme I — Reagents: (i) Aq. NaOH/EtOH/RT, (ii) Aq. NaOH/EtOH/MWI,
(iii) Basic alumina/MWI, (iv) Anhyd. K2CO3/MWI

Table I — Antimicrobial activity of compounds 5a-h (zone of inhibition in mm)

Bacteria Fungi
Compd
B. subtilis K. pneumonia E. coli Pseudomonas C. albicans Aspergillus
5a 16 13 13 26 10 -
5b 13 12 12 24 12 -
5c 10 10 10 25 12 -
5d 16 14 12 23 10 12
5e 13 10 12 23 12 10
5f 16 23 16 32 17 26
5g 12 21 18 23 14 12
5h 13 19 19 23 14 10
Cipro (Std.) 36 32 32 35 - -
Flucanazole (Std.) - - - - 27 18
Control (DMF) 00 00 00 00 00 00

Varian CFT-20 or Brucker DRX-300 (300 MHz)
spectrometer using TMS as internal standard
(chemical shift in δ ppm). FAB mass spectra were
recorded on Jeol SX-102 spectrometer. All
compounds gave satisfactory elemental analysis and
spectral data. All the reactions were carried out in a
domestic microwave oven (Kenstar, output energy
1200 W, frequency 2450 MHz, Model No. MO9760).
4-Piperidinoacetophenone 3 was synthesized in-
house under MWI.
Synthesis of 4-piperidinoacetophenone 3
Synthesis of 4-piperidinoacetophenone 3 was
performed using 4-fluoroacetophenone 1 (0.02 mol)
and piperidine 2 (0.017 mol) using K2CO3 (0.017
mol) and DMSO (15 mL) under microwave
irradiation at 25% microwave power (300 W) for a
period of 5 min. On completion of reaction (TLC), the
reaction mixture was treated with ice-cold water to
obtain the precipitate of the product 3 leaving behind
K2CO3 dissolved in water. The product was filtered,
washed with water and purified by recrystallization
from n-heptane to afford analytical samples of
compound 3.
General procedure for synthesis of chalcones, 5a-h
Method (A)
Conventional solution phase
A solution of 4-piperidinoacetophenone 3 (0.01
mol) and different substituted benzeldehyde 4a-h
 NOTES 1625

Table II — Comparison of reaction time and yield of compounds 5a-h

Compd R m.p. (°C) Method-A Method-B Method-C Method-D

a (hr)/b a (min)/b a (min)/b a (min)/b
5a 4-OCH3 144 5/81 5/86 2/97 3/91
5b 3,4-OCH3 155 7/79 5/82 2/92 3/88
5c 3,4-OCH3 158 7/77 5/81 3/90 3/82
5d 3-NO2 177 4/83 3/88 2/93 2/86
5e 4-N(CH3)2 200 10/67 6/79 4/86 4/80
5f 4-OH 190 12/71 5/81 3/91 5/78
5g 2-Cl 108 12/62 6/76 5/88 4/74
5h 4-Cl 186 12/68 6/79 5/89 5/83
a = Time (min) and b = Yield (%)

(0.01 mol) in ethanol (25 mL) was stirred at RT for a
period specified as in Table II in the presence of 30%
NaOH solution (8 mL). After that, the sodium salt of
chalcone was decomposed by ice cold 2N HCl (2-3
mL). The separated chalcone was filtered, washed
with water (2 × 50 mL) and purified by
recrystallization from ethanol to afford analytical
samples of compounds 5a-h.
Method (B)
One pot solution phase MWI (Aq. NaOH)
To a solution of 4-piperidinoacetophenone 3 (0.01
mol), substituted benzeldehydes 4a-h (0.01 mol) in
ethanol (25 mL) was added into a 100 mL Borosil
flask fitted with a funnel as a loose top. NaOH
solution (40%, 3 mL) was added and the reaction
mixture was subjected to microwave irradiation at
25% microwave power (300 W) for a period specified
as in Table II with short interval of 30 sec to 1 min to
avoid excessive evaporation of solvent. The reaction
mixture was cooled and neutralized with 2N HCl (2-3
mL). The separated product was filtered, washed with
water (2 × 50 mL) and purified by recrystallization
from ethanol to afforded analytical samples of
compounds 5a-h.
Method (C)
One pot solid phase MWI (Basic alumina)
A mixture of 4-piperidinoacetophenone 3 (0.01
mol) and substituted benzeldehydes 4a-h (0.01 mol)
was dissolved in ethanol (10 mL) and taken in a 100
mL Borosil flask. To this basic alumina (4.0 g) was
added and the reactants were properly mixed with the
help of a glass rod. The adsorbed material was dried
in air and irradiated inside the microwave oven at low
power level (30%) for a period specified as in
Table II. On completion of reaction (TLC), the
mixture was cooled to RT and product was extracted
with ethanol (2 × 20 mL). The solvent was removed
under reduced pressure and the crude solid was
purified by recrystallization from ethanol to afforded
analytical samples of compounds 5a-h.
Method (D)
One pot solid phase MWI (Anhydrous K2CO3)
Equimolar amounts of 4-piperidinoacetophenone 3
(0.01 mol) and substituted benzeldehydes 4a-h (0.01
mol) were dissolved in ethanol (10 mL) in a 100 mL
Borosil flask. To this anhyd. K2CO3 (4 g) was added
with constant stirring. The adsorbed material was
dried in air and irradiated inside the microwave oven
at low power level (30%) for a period specified as in
Table II. On completion of reaction (TLC), the
reaction mixture was treated with ice-cold water to
obtain the precipitate of the product 5a-h leaving
behind K2CO3 dissolved in water. The product was
filtered, washed with water and purified by
recrystallization from ethanol to afforded analytical
samples of compounds 5a-h.
The compounds synthesized by the above
procedure were found to be identical to those obtained
by method A, B, C and D on the basis of their m.p.
and IR spectra. The characterization data of
synthesized compounds 5a-h as well as compound 3
are given below.
3: Light yellow flakes, yield 90%, +ve nitrogen
test, m.p. 87°C. Anal. Calcd for C13H17NO (203): C,
76.81; H, 8.43. Found: C, 76.21; H, 8.41%. 1H NMR
(acetone-d6): δ 1.60-2.74 (m, piperidine-H), 2.52 (3H,
s, -COCH3), 6.90-8.09 (m, Ar-H); IR (KBr): 3065
(Ar-H), 1650 (C=O), 1602, 1517, 1456, 1424 cm-1
(C=C/Ar); MS (EI): m/z 204 (M+1), 203 (M+), 189,
174, 160, 78, 55, 40.
1626 INDIAN J. CHEM., SEC B, NOVEMBER 2012
5a: Yellow crystals, m.p. 144°C. Anal. Calcd for
C21H23NO2 (321.4): C, 78.47; H, 7.21. Found: C,
77.82; H, 6.92%. 1H NMR (acetone-d6): δ 1.62-2.76
(m, piperidine-H), 3.87 (3H, s, -OCH3), 6.92-8.10 (m,
Ar-H), 7.60 (1H, d, -CO-CH=), 8.02 (1H, d, =CH-
Ar); IR (KBr): 3061 (Ar-H), 1655 (C=O), 1596, 1507,
1461, 1420 (C=C/Ar), 1015 (CH=CH trans), 817,
720, 678 cm-1 (substituted phenyl); MS (EI): m/z 322
(M+1), 321 (M+), 291, 207, 132,78.
5b: Yellow crystals, m.p. 155°C. Anal. Calcd for
C22H25NO3 (351.44): C, 75.19; H, 7.17. Found: C,
74.96; H, 7.01%. 1H NMR (acetone-d6): δ 1.64-2.72
(m, piperidine-H), 3.84, 3.82 (6H, s, -OCH3), 6.90-
8.04 (m, Ar-H), 7.35 (1H, d, -CO-CH=), 8.13 (1H, d,
=CH-Ar); IR (KBr): 3054 (Ar-H), 1658 (C=O), 1600,
1509, 1458 (C=C/Ar), 996, 954 (CH=CH trans), 893,
770, 724, 632 cm-1 (substituted phenyl); MS (EI): m/z
352 (M+1), 351 (M+), 321, 290, 215, 132, 78, 65, 53.
5c: Yellow crystals, m.p. 158°C. Anal. Calcd for
C23H27NO4 (381.46): C, 72.42; H, 7.13. Found: C,
72.01; H, 6.94%. 1H NMR (acetone-d6): δ 1.60-2.69
(m, piperidine-H), 3.85 (9H, s, -OCH3), 7.1-8.08 (m,
Ar-H), 7.05 (1H, d, -CO-CH=), 7.98 (1H, d, =CH-
Ar); IR (KBr): 3040 (Ar-H), 1650 (C=O), 1606, 1502,
1481 (C=C/Ar), 1026, 966 (CH=CH trans), 878, 864,
787, 706 cm-1 (substituted phenyl); MS (EI): m/z 382
(M+1), 381 (M+), 350, 321, 290, 207, 136, 80, 60, 45.
5d: Orange crystals, m.p. 177°C. Anal. Calcd for
C20H20N2O3 (336.38): C, 71.41; H, 5.99. Found: C,
71.07; H, 5.42%. 1H NMR (acetone-d6): δ 1.59-2.62
(m, piperidine-H), 7.04-7.96 (m, Ar-H), 7.35 (1H, d, -
CO-CH=), 8.13 (1H, d, =CH-Ar); IR (KBr): 3052
(Ar-H), 1645 (C=O), 1595, 1505, 1462 (C=C/Ar),
1320 (Ar-NO2), 1009 (CH=CH trans), 818, 731, 670,
610 cm-1 (substituted phenyl); MS (EI): m/z 336 (M+),
290, 277, 190, 118, 103, 78, 65, 26.
5e: Yellow crystals, m.p. 200°C. Anal. Calcd for
C22H26N2O (334.45): C, 79.0; H, 7.84. Found: C,
78.63; H, 7.21%. 1H NMR (acetone-d6): δ 1.49-2.60
(m, piperidine-H), 2.82 (6H, s, ter.- amine-H), 7.11-8.0
(m, Ar-H), 7.25 (1H, d, -CO-CH=), 8.0 (1H, d, =CH-
Ar); IR (KBr): 3068 (Ar-H), 1661 (C=O), 1599, 1501,
1454 (C=C/Ar), 998, 956 (CH=CH trans), 878, 864,
787, 704 cm-1 (substituted phenyl); MS (EI): m/z 335
(M+1), 334 (M+), 321, 305, 287, 208, 130, 77, 68, 24.
5f: Orange crystals, m.p. 190°C. Anal. Calcd for
C20H21NO2 (307.39): C, 78.15; H, 6.89. Found: C,
78.00; H, 6.19%. 1H NMR (acetone-d6): δ 1.54-2.70
(m, piperidine-H), 6.87-8.07 (m, Ar-H), 7.40 (1H, d, -
CO-CH=), 8.16 (1H, d, =CH-Ar), 8.36 (1H, phenolic
H); IR (KBr): 3292 (Ar-OH), 3062 (Ar-H), 1650
(C=O), 1590, 1516, 1490, 1454 (C=C/Ar), 1005
(CH=CH trans), 818, 735, 690, 625 cm-1 (substituted
phenyl); MS (EI): m/z 308 (M+1), 305 (M-2), 290,
206, 131, 116, 77, 41, 30.
5g: Yellow crystals, m.p. 108°C. Anal. Calcd for
C20H20ClNO (325.83): C, 73.72; H, 6.19. Found: C,
73.20; H, 5.98%. 1H NMR (acetone-d6): δ 1.68-2.72
(m, piperidine-H), 6.98-8.0 (m, Ar-H), 7.25 (1H, d, -
CO-CH=), 7.96 (1H, d, =CH-Ar); IR (KBr): 3052
(Ar-H), 1645 (C=O), 1595, 1490, 1453 (C=C/Ar),
1024 (CH=CH trans), 861, 760, 694 cm-1 (substituted
phenyl); MS (EI): m/z 327 (M+1), 326 (M+), 291,
208, 121, 76, 45.
5h: Yellow crystals, m.p. 186°C. Anal. Calcd for
C20H20ClNO (325.83): C, 73.72; H, 6.19. Found: C,
73.28; H, 5.94%. 1H NMR (acetone-d6): δ 1.64-2.68
(m, piperidine-H), 7.11-8.2 (m, Ar-H), 6.98 (1H, d, -
CO-CH=), 7.98 (1H, d, =CH-Ar); IR (KBr): 3060
(Ar-H), 1654 (C=O), 1602, 1498, 1487 (C=C/Ar),
1005 (CH=CH trans), 849, 772, 701 cm-1 (substituted
phenyl); MS (EI): m/z 327 (M+1), 326 (M+), 293,
207, 125, 104, 77, 41, 30.
Conclusion
The proposed microwave-assisted methodology on
inorganic solid support provides an easier, facile,
practically convenient and eco-friendly one-pot
synthesis of bio-active chalcones 5a-h as compared to
existing conventional methods. Significant
antimicrobial activity was observed with compound
5f against bacteria and fungi.
Acknowledgement
Authors are thankful to the concerned authorities of
M L Sukhadia University and B N P G College,
Udaipur, Rajasthan for providing laboratory facilities.
Thanks are also due to the Director, CDRI, Lucknow
for providing analytical and spectral data and Head,
Department of Pharmacology, R N T Medical
College, Udaipur for antibacterial screening results.
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