Iodine-catalyzed efficient synthesis of chalcones by grinding under solvent-free conditions

Article abstract of DOI:10.1139/V09-106

Chalcones are useful intermediates in organic synthesis and exhibit a large number of different biological activities. Chalcones have been synthesized in high yields by Claisen-Schmidt condensation of substituted acetophenones with various aromatic aldehydes in the presence of 10 mol% of iodine at room temperature by grinding under solvent-free conditions.

Full text of DOI:10.1139/V09-106

1209
Iodine-catalyzed efficient synthesis of chalcones
by grinding under solvent-free conditions
Hongshe Wang and June Zeng
Abstract: Chalcones are useful intermediates in organic synthesis and exhibit a large number of different biological activities.
Chalcones have been synthesized in high yields by Claisen–Schmidt condensation of substituted acetophenones with various
aromatic aldehydes in the presence of 10 mol% of iodine at room temperature by grinding under solvent-free conditions.
Key words: iodine, chalcones, Claisen–Schmidt condensation, grinding, solvent-free.
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Resume : Les chalcones sont des intermediaires importants en synthese organique et elles presentent un grand nombre d’acti-
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vites biologiques diverses. On a realise la synthese de chalcones avec des rendements eleves, par le biais d’une condensation
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de Claisen–Schmidt d’acetophenones substituees avec divers aldehydes aromatiques, en presence de 10 moles % d’iode, a la
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temperature ambiante, par simple broyage dans des conditions sans solvant.
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Mots-cles : iode, chalcones, condensation de Claisen–Schmidt, broyage, sans solvant.
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[Traduit par la Redaction]
under solvent-free conditions is an environment-friendly
method for the organic synthesis reactions.
Introduction
Chalcones and their derivatives are useful intermediates in
organic synthesis.1 Many chalcone derivatives display inter-
esting pharmacological and biological activities.2 Therefore,
much attention has been paid to the synthesis of chalcones.
Traditionally, chalcones are obtained via Claisen–Schmidt
condensation carried out using alkaline hydroxides as cata-
lysts.3 However, the poor selectivity, generation of wastes,
and laborious separation techniques make these catalysts
practically inconvenient. Thus, more efficient methods have
been developed for the synthesis of chalcones, which in-
clude the use of NaOH,4 FeCl3Á6H2O,5 SOCl2/EtOH,6
BF3ÁEt2O,7 sulfonic-acid-functionalized organosilica materi-
als,8 ZrCl4,9 bamboo char sulfonic acid,10 and ionic liquid11
microwave12 and ultrasonic irradiation.13 However, some of
the previously reported procedures have various disadvan-
tages, such as long reaction times, special efforts needed to
prepare the catalysts, high temperatures, and the use of ex-
pensive reagents and hazardous solvents. Thus, there is
scope for further improvement involving more environment-
friendly and milder reaction conditions.
In recent years, molecular iodine has been considered as
an inexpensive and readily available catalyst for a variety
of organic transformations.15 In continuation to our work on
studying iodine-catalyzed reactions,16 we report herein an
efficient and convenient procedure for the synthesis of chal-
cones from substituted acetophenones and various aromatic
aldehydes via Claisen–Schmidt condensation in the presence
of a catalytic amount of iodine at room temperature by
grinding under solvent-free conditions (Scheme 1).
Results and discussion
To determine the efficiency of this procedure, we carried
out the reaction of acetophenone with benzaldehyde using
various other Lewis acids, such as InCl3, FeCl3, ZnCl2,
(NH4)2Fe(SO4)2, Bi(NO3)3, Al2(SO4)3, and Mg(ClO4)2 at
room temperature by grinding under solvent-free conditions
(Table 1). Among these catalysts, I2 was found to be the
most effective catalyst for this conversion. As for the amount
of the catalyst used, we found that 10 mol% of I2 is sufficient
to promote reaction efficiently (Table 2). No reaction was ob-
served when acetophenone was reacted with benzaldehyde
under similar conditions in the absence of I2 even after grind-
ing for 180 min. Any excess of I2 beyond this loading did not
show any further increase in conversion and yield. Use of less
than the required catalyst loading resulted in low yields.
With the increasing public concern over environmental
pollution, it is of great importance for chemists to come up
with new approaches that are less hazardous to human health
and environment. The use of environmentally benign sol-
vents, like water, and solvent-free reactions represent very
powerful green chemical technology procedures from both
the economical and synthetic points of view.14 Grinding
Received 14 March 2009. Accepted 8 June 2009. Published on the NRC Research Press Web site at canjchem.nrc.ca on 4 August 2009.
H. Wang1 and J. Zeng. Shaanxi Key Laboratory for Phytochemistry, Department of Chemistry and Chemical Engineering, Baoji
University of Arts and Sciences, Baoji 721013, P. R. China.
1Corresponding author (e-mail: hongshewang@126.com).
Can. J. Chem. 87: 1209–1212 (2009)
doi:10.1139/V09-106
Published by NRC Research Press

1210
Can. J. Chem. Vol. 87, 2009
Table 2. Effect of different amounts of iodine on the
reaction of benzaldehyde with acetophenone.
Scheme 1.
Entry
I2 (mol%)
Time (min)
Yielda(%)
1
2
3
4
5
6
0
1
5
10
15
20
180
20
10
5
5
5
0
46
73
91
92
91
Table 1. Claisen–Schmidt condensation of acetophenone with
benzaldehyde catalyzed by different catalysts.
Note: The reaction was carried out at room temperature
by grinding under solvent-free conditions.
aIsolated yield.
Entry
Catalyst (mol%)
InCl3 (50)
FeCl3 (50)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
20
20
20
20
20
20
10
5
30
30
20
20
40
55
72
91
TMS as an internal standard. Mass spectra were measured
by HP5973 spectrometer. IR spectra were measured on a
Nicolet FTIR-750 spectrometer. The benzaldehyde was dis-
tilled prior to use. All other reagents were commercially
available products and were used without further purifica-
tion.
ZnCl2 (50)
(NH4)2Fe(SO4)2 (50)
Bi(NO3)3 (50)
Al2(SO4)3 (50)
Mg(ClO4)2 (30)
I2 (10)
Note: The reaction was performed with 1 mmol of benzaldehyde and
1 mmol of acetophenone by grinding at room temperature.
General procedure for the synthesis of chalcones
aIsolated yield.
A mixture of acetophenone (1 mmol), benzaldehyde
(1 mmol), and iodine (0.1 mmol) was ground in a mortar
with a pestle (the mortar and pestle are thoroughly cleaned
between runs) at room temperature until the reaction was
completed (monitored by TLC). The reaction mixture was
treated with 5% aqueous sodium thiosulfate. The precipi-
tated products were then separated, washed with water, and
recrystallized from ethanol to afford the pure products.
Except for compounds 3d, 3e, 3h, and 3l, all the products
are known compounds. The spectroscopic and physical data
for all known compounds corresponded to those given in the
literatures.
To explore the generality of this method, a series of chal-
cones were prepared under the optimized reaction condi-
tions. By this method, the reactions were carried out simply
by mixing a variety of substituted acetophenones and substi-
tuted benzaldehydes in the presence of a catalytic amount
(10 mol%) of iodine at room temperature by grinding under
solvent-free conditions, and the results are summarized in
Table 3. The components of the mixture were ground to-
gether in a mortar with a pestle for several minutes. In all
the cases, the reactions proceeded smoothly to afford the
corresponding products in good-to-excellent yields using
ethanol recrystallization. Their physical properties were de-
3-(4-N,N-Dimethylaminophenyl)-1-phenyl-2-propen-1-one
(3d)
IR (KBr) n: 2922, 1649, 1565, 1529 cm–1. 1H NMR
(400 MHz, CDCl3) d: 3.05 (s, 6H), 6.73 (d, J = 8.0 Hz,
2H), 7.35 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H),
7.55 (m, 3H), 7.80 (d, J = 16.0 Hz, 1H), 8.00 (d, J =
5.6 Hz, 2H). 13C NMR (CDCl3, 100 MHz) d: 42.31, 110.13,
111.06, 119.11, 123.24, 128.23, 129.06, 133.10, 139.07,
145.19, 162.16, 190.08. MS (EI) m/z (%): 251 (M+, 100),
250 (34), 236 (2), 222 (11), 207 (11), 174 (43), 105 (16).
Anal. calcd. for C17H17NO: C, 81.27; H, 6.77; N, 5.59.
Found: C, 81.16; H, 6.86; N, 5.67.
termined, and the structures were confirmed by H and 13C
1
NMR, IR, and MS. All acetophenones and benaldehydes
with either electron-withdrawing or electron-donating substi-
tutes, such as nitro, and methoxy groups on aromatic rings
produced a satisfactory yield ranging from 83% to 95%. It
was found from H NMR spectral data that all chalcones
were with trans configuration.
In conclusion, we have developed a new methodology to
prepare a variety of chalcones in the presence of a catalytic
amount of iodine at room temperature by grinding under sol-
vent-free conditions. The advantages, such as the easy pro-
cedure, shorter reaction times, green and clean to the
environment, mild reaction conditions, and high yields,
make our method an attractive alternative to the preparation
of chalcones.
1
3-(2-Hydroxyphenyl)-1-phenyl-2-propen-1-one (3e)
IR (KBr) n: 3386, 1662, 1591, 1562, 1498, 1392, 800,
1
762 cm–1. H NMR (400 MHz, CDCl3) d: 6.60 (m, 3H),
7.23 (d, J = 16.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.54
(m, 3H), 7.71 (d, J = 16.0 Hz, 1H), 8.01 (d, J = 8.0 Hz,
2H), 9.68 (s, 1H). 13C NMR (CDCl3, 100 MHz) d: 110.96,
111.63, 119.79, 123.91, 128.62, 129.32, 129.86, 131.05,
133.53, 138.61, 145.11, 162.84, 166.17, 190.87. MS (EI) m/
z (%): 224 (M+, 66), 207 (100), 206 (2), 222 (16), 147 (71),
119 (31), 105 (65). Anal. calcd. for C15H12O2: C, 80.36; H,
5.36. Found: C, 80.23; H, 5.45.
Experimental
Melting points were determined on an XT4A electrother-
1
mal apparatus equipped with a microscope. H NMR and
13C NMR spectra were recorded on a Bruker Avance 400
spectrometer (1H: 400 MHz, 13C: 100 MHz) in CDCl3 with
Published by NRC Research Press

Wang and Zeng
Table 3. Synthesis of chalcones catalyzed by iodine.
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Entry
1
2
3
4
5
6
7
8
Product
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
R1
H
H
H
H
H
R2
H
Time (min)
5
5
5
8
5
5
5
10
8
Yielda (%)
Mp (lit.) (8C)
57–58 (56–57)7
94–95 (93–94)5
143–144 (144–145)5
102–103
91
90
92
88
89
90
95
87
92
91
85
83
4-CH3
3-NO2
4-N(CH3)2
2-OH
H
142–143
4-CH3
4-NO2
2,4-(OCH3)2
4-Br
3-OCH3
2,4-(OH)2
2,4-(OCH3)2
54–55 (53–54)17
118–119 (117–119)13
168–170
H
3-NO2
4-OH
2-NO2
4-N(CH3)2
4-OCH3
9
179–181 (180–182)13
88–90 (99–90)13
181–183 (180–182)13
33–35
10
11
12
10
10
10
Note: All the reactions were performed with 10 mol% of iodine at room temperature by grinding under solvent-free conditions.
aIsolated yields.
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1-(2,4-Dimethoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one
(3h)
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IR (KBr) n: 3055, 2965, 2843, 1658, 1605, 1573, 1403,
1
813, 646 cm–1. H NMR (400 MHz, CDCl3) d: 3.90 (s, 3H),
3.98 (s, 3H), 6.50 (m, 2H), 7.48 (m, 4H), 7.61 (d, J =
16.0 Hz, 1H), 7.82 (d, J = 16.0 Hz, 1H), 8.01 (d, J =
8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d: 55.96, 114.98,
120.66, 121.73, 125.06, 126.98, 129.09, 130.05, 134.64,
139.13, 142.60, 145.43, 164.44, 191.87. MS (EI) m/z (%):
313 (M+, 58), 296 (30), 285 (83), 165 (100), 151 (33).
Anal. calcd. for C17H15NO5: C, 65.18; H, 4.79; N, 4.40.
Found: C, 65.11; H, 4.71; N, 4.55.
1-(2,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-
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IR (KBr) n: 3050, 1651, 1600, 1573, 1510, 1441, 1330,
1015, 980, 821, 772, 680 cm–1. 1H NMR (400 MHz,
CDCl3) d: 3.86 (s, 6H), 3.97 (s, 3H), 6.36 (m, 2H), 6.95 (d,
J = 8.0 Hz, 2H), 7.40 (d, J = 16.0 Hz, 1H), 7.51 (d, J =
8.0 Hz, 2H), 7.80 (d, J = 16.0 Hz, 1H), 8.00 (d, J = 8.0 Hz,
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119.43, 121.21, 128.75, 129.87, 130.11, 133.89, 140.03,
144.30, 161.64, 163.54, 190.77. MS (EI) m/z (%): 298 (M+,
100), 283 (82), 255 (10). Anal. calcd. for C18H18O4: C,
72.48; H, 6.04. Found: C, 72.33; H, 6.03.
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Acknowledgments
This work was financially supported by the Educational
Committee of Shaanxi Province (Nos. 08JZ09 and
09JK332) and Baoji University of Arts and Sciences (No.
Zk064).
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