Efficient synthesis of chalcones by a solid base catalyst

Article abstract of DOI:10.1081/SCC-200065006

A simple and efficient heterogeneous procedure has been developed for the synthesis of chalcones (α,β-unsaturated ketones) by the Claisen-Schmidt condensation between arylaldehydes and ketones using Mg-Al-O^tBu hydrotalcite (HT-O^tBu) as catalyst. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200065006

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Efficient Synthesis of
Chalcones by a Solid Base
Catalyst
M. Lakshmi Kantam a , B. Veda Prakash a & Ch.
Venkat Reddy a
a Inorganic Chemistry Division, Indian Institute of
Chemical Technology, Hyderabad, India
Version of record first published: 16 Aug 2006.
To cite this article: M. Lakshmi Kantam , B. Veda Prakash & Ch. Venkat Reddy (2005):
Efficient Synthesis of Chalcones by a Solid Base Catalyst, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
35:14, 1971-1978
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Synthetic Communicationsw, 35: 1971–1978, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200065006
Efficient Synthesis of Chalcones by a Solid
Base Catalyst
M. Lakshmi Kantam, B. Veda Prakash, and
Ch. Venkat Reddy
Inorganic Chemistry Division, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: A simple and efficient heterogeneous procedure has been developed
for the synthesis of chalcones (a,b-unsaturated ketones) by the Claisen–Schmidt
condensation between arylaldehydes and ketones using Mg-Al-OtBu hydrotalcite
(HT-OtBu) as catalyst.
Keywords: Arylaldehydes, chalcones, hydrotalcites, solid base
INTRODUCTION
Chalcones constitute an important group of natural products[1] and some of
them possess anticancer,[2] antimalarial,[3] antimicrobial,[4] and antiinflamma-
tory[5] activities. Chalcones also serve as precursors for the synthesis of
different classes of flavonoids.[6]
The Claisen–Schmidt condensation (CSC) is an important C-C bond-
forming reaction for the synthesis of chalcones. Generally it is carried out
by alkaline hydroxides or NaOEt.[6,7] Recently, the solid bases have been con-
sidered for possible replacement of soluble bases to offer environmentally
benign technologies. In this context, heterogeneous basic catalysts, such as
Received in India March 21, 2005
Address correspondence to M. Lakshmi Kantam, Inorganic Chemistry Division,
Indian Institute of Chemical Technology, Hyderabad 500007, India. Fax: þ91-40-
27160921; E-mail: mlakshmi@iict.res.in
1971

1972
M. L. Kantam, B. V. Prakash, and Ch. V. Reddy
alumina,[8] Ba(OH)2,
hydrotalcites,[10] MgO, and natural phosphates
[9]
modified with sodium nitrate[11] have been used as potential catalysts for
the CSC reaction.
We designed and developed the Mg-Al-OtBu hydrotalcite (HT-OtBu), a
solid base, by an exchange of nitrate anion of HT with KOtBu in our
laboratory that displayed manifold activity in various organic transform-
ations.[12] Herein, we report an efficient synthesis of simple and substituted
chalcones by using HT-OtBu as a catalyst[12] (Scheme 1).
RESULTS AND DISCUSSION
Taking the CSC reaction between benzaldehyde and acetophenone as a
model reaction, we compared the activity of HT-OtBu catalyst with
different hydrotalcite catalysts, such as Mg-Al-F and Mg-Al-NO3
(calcined), under similar reaction conditions (Table 1). With HT-OtBu, the
reaction proceeded with quantitative yields at a faster rate, whereas with
Mg-Al-F, Mg-Al-NO3 (calcined or uncalcined), and Mg-Al-NO3 (calcined
or uncalcined) catalysts, moderate yields were obtained after 12 h. Thus,
HT-OtBu proved to be an active catalyst for CSC reaction.
The CSC reaction was carried out with a variety of substituted
benzaldehydes and substituted acetophenones to produce chalcones in good
to excellent yields with HT-OtBu catalyst (Scheme 1, Table 2) and by-
products such as aldols are not observed in our reaction conditions. We
have successfully synthesized the a,b-unsaturated aromatic heterocyclic
compounds (Table 2, entries 2, 7) in good to quantitative yields. The rate of
furaldehyde was relatively fast compared with simple aldehydes whereas
the rate of the reaction is slightly slower when heteroaromatic ketone and
tetralone were used in place of simple aromatic ketones (Table 2, entries 2, 3).
Furthermore, the HT-OtBu catalyst was used for four cycles and gave 98,
83, 71, and 70% conversion as measured by NMR, respectively. The
decreased activity in recycles may be attributed to the water formed during
the reaction.
In conclusion we have developed a convenient procedure for the prep-
aration of simple and substituted chalcones with shorter reaction times.
Scheme 1.

Efficient Synthesis of Chalcones
1973
Table 1. CSC reaction between benzaldehyde and acetophenone using various
Mg-Al hydrotalcite catalystsa
Entry
Catalyst
Time (h)
Yield (%)b
1
2
3
4
5
6
7
HT-OtBu
KOtBu
Mg-Al-F hydrotalcite
3.5
3.5
12
98c
98d
60
Mg-Al-NO3 hydrotalcite (uncalcined)
Mg-Al-NO3 hydrotalcite (calcined)
Mg-Al-CO3 hydrotalcite (uncalcined)
Mg-Al-CO3 hydrotalcite (calcined)
12
12
50
67
12
12
46
65
aReaction conditions: aldehyde (1 mmol), acetophenone (1.2 mmol), and catalyst
(0.05 g) in toluene (5 ml) reflux.
1
bDetermined by H NMR spectroscopic integration.
t
cHT-OtBu (0.05 g, 5.2 mol% of BuO2).
dSoluble base (5.2 mol%) was charged in place of hydrotalcites.
EXPERIMENTAL
Preparation of the Catalysts
The preparation of HT-NO3 (Mg/Al, 3/1) was based on a literature
procedure.[12] HT-NO3 (Mg/Al, 3/1) was calcined at 723 K in flow of air
for 6 h (temperature raised 25 K min21) and cooled to room temperature in
a flow of dry nitrogen to obtain calcined HT. The calcined HT (1.214 g)
was added to a solution of KOtBu (0.1 M) prepared by dissolving KOtBu
(1.12 g, 10 mmol) in freshly dried THF (100 ml). The solution was stirred
for 24 h in a nitrogen atmosphere and then filtered under nitrogen. A white
solid, HT-OtBu (1.432 g), was obtained and was washed with excess of
THF (300 ml admixed with 0.1% of decarbonated water). This protocol
restores the partial layered structure of the HT.[12]
General Experimental and Reusability Procedure
In a typical procedure, toluene (5 ml), aldehyde (1 mmol), and acetophenone
(1.2 mmol) were refluxed under stirring in the presence of HT-OtBu
(0.050 g, 5.2 mol%) catalyst. The reaction was continued until the completion
of the reaction, as monitored by TLC. After the completion of the reaction, the
catalyst was filtered and the filtrate was concentrated to obtain the crude
product. The crude product was purified by column chromatography
(hexane/ethyl acetate, 9/1, v/v). The reusability of the catalyst was carried
out by adopting the following protocol under similar experimental conditions
as described previously. After the completion of reaction, the catalyst was
allowed to settle and the supernatant solution was pumped out from the

Table 2. Claisen–Schmidt condensation reaction catalyzed by HT-OtBu catalyst
Entry
Aldehyde
Ketone
Product
Time (h)
3.5
Yield (%)a
1
90
(70b)[13]
2
3
4
8.0
5.0
2.0
77[14]
88[14]
85[15]
5
2.0
91[15]

6
7
8
1.5
1.0
5.0
92[16]
92[14]
90[17]
9
2.0
1.5
87[15]
10
91[18]
(continued)

Table 2. Continued
Entry
Aldehyde
Ketone
Product
Time (h)
Yield (%)a
11
2.0
93[19]
12
2.0
91[20]
aIsolated yields, H NMR spectra are in accordance with the literature data (ref. nos. in brackets).
bYield after fourth cycle by NMR.
1

Efficient Synthesis of Chalcones
1977
reaction flask. The catalyst was washed with toluene and allowed to settle and
the supernatant solution was pumped out. Fresh quantities of benzaldehyde
and acetophenone were introduced. The HT-OtBu was thus reused for three
cycles with the identical protocol. All compounds are known and their
proton NMR spectra and mass data are in accordance with the literature data.
ACKNOWLEDGMENT
B. V. P and Ch. V. R thank the Council of Scientific and Industrial Research
(CSIR), India, for providing fellowships.
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