A simple and efficient method for selective single aldol condensation between arylaldehydes and acetone

Article abstract of DOI:10.1081/SCC-200048425

A simple and efficient method has been developed for selective single aldol condensation between acetone and various aromatic/heterocyclic aldehydes using aqueous sodium hydroxide at 5-10°C.

Full text of DOI:10.1081/SCC-200048425

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A Simple and Efficient Method
for Selective Single Aldol
Condensation Between
Arylaldehydes and Acetone
a
a
Satya Paul & Monika Gupta
a
Department of Chemistry, University of Jammu,
Jammu, 180 006, India
Version of record first published: 28 Jul 2007.
To cite this article: Satya Paul & Monika Gupta (2005): A Simple and Efficient
Method for Selective Single Aldol Condensation Between Arylaldehydes and Acetone,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:2, 213-222
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Synthetic Communications , 35: 213–222, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048425
A Simple and Efficient Method for Selective
Single Aldol Condensation Between
Arylaldehydes and Acetone
Satya Paul and Monika Gupta
Department of Chemistry, University of Jammu, Jammu, India
Abstract: A simple and efficient method has been developed for selective single aldol
condensation between acetone and various aromatic/heterocyclic aldehydes using
aqueous sodium hydroxide at 5–108C.
Keywords: Acetone, aldol condensation, aqueous sodium hydroxide, arylaldehydes,
chalcones, selectivity
INTRODUCTION
[1]
The aldol condensation is an important method for forming C 22 C bond. The
reaction involves the condensation of arylaldehydes with ketones. Both
[2]
[2,3]
acidic
and basic
catalysts have been used with variable results,
however, under classical aldol condensation reaction conditions including
basic media, dimer, polymer, and self-condensation products often formed
as well. Recently, improved methods have been reported for this type of
[4]
reaction, which results in the synthesis of chalcones and related enones.
The method was simple and works well for the condensation of arylaldehydes
0
0
and ketones. However, in acetone where a and a -H are present, reaction
didn’t stop at one a-carbon atom but extends for a also; as a result, double
condensation reaction takes place. So there is a need to develop a simple
and selective procedure for single aldol condensation between acetone and
arylaldehydes to benzylidene acetone, because these compounds are
Received in India November 8, 2004
Address correspondence to Satya Paul, Department of Chemistry, University of
Jammu, Jammu 180 006, India. Fax: þ91-191-2505086; E-mail: paul7@rediffmail.com

214
S. Paul and M. Gupta
[
5–8]
important intermediates in the synthesis of various natural products
[
and
9–11]
heterocyclic compounds.
In continuation of our interest
[
12–15]
to devise economic and environmen-
tally friendly procedures for organic reactions, we report a simple and
selective procedure for the single aldol condensation between acetone and
aryl/heterocyclic aldehydes using aqueous sodium hydroxide at 5–108C.
In 1999, Kad et al. reported rate enhancement in aldol condensation under
[17]
microwave irradiation using aqueous sodium hydroxide.
In this method,
single aldol condensation has been reported in acetone and arylaldehydes.
However, the method is limited to small number of aldehydes and also
workup is not so simple because it requires extraction with organic
solvents. Our method is much more superior than other reported methods
because no energy-consuming device is required, pure products crystallize
out, and there is no need of further purification. This method is general and
can be applied to both aromatic and hereocyclic aldehydes. Furthermore,
the formation of Cannizaro product of aromatic aldehydes and self-
condensation products of ketones was negligible.
We have successfully applied our new method for the synthesis of single
chalcones from acetone and aromatic as well as heterocyclic aldehydes. First,
the aldol condensation between benzaldehyde and acetone was examined
under different conditions to get single chalcones selectively such as 1 : 2, 1 : 3,
and 1 : 4 ratio of benzaldehyde and acetone, respectively, using 1) ethanolic
sodium hydroxide under microwave irradiation; 2) ethanolic sodium
hydroxide under stirring at room temperature; 3) aqueous sodium hydroxide
under stirring at room temperature; and 4) aqueous sodium hydroxide under
microwave irradiation. It has been found that in all cases, dichalcones were
formed. However, when the reaction of benzaldehyde and acetone in 1 : 4 ratio
was carried out by using aqueous sodium hydroxide at 5–108C, we were able
to get single chalcones as pure product in nearly quantitative yield. Thus, in all
other examples, 1 : 4 equivalents of aldehyde and acetone were used in
aqueous sodium hydroxide at 5–108C. Among 2-chloro-3-formylquinolines
(entries 18 and 19) and 2-aryl-3-formylindoles (entries 16 and 17), quinoline
ring deactivates, while indole ring activates the –CHO group. In cinnamalde-
hydes (entries 12–15), the electron-withdrawing and electron-releasing
groups have little effect on the rate of the reaction, whereas in aromatic
aldehydes, no specific structure-reactivity relationship can be drawn.
EXPERIMENTAL
General
All reagents were obtained from commercial sources and used without further
1
purification unless mentioned elsewhere. H NMR spectra were recorded in

Selective Single Aldol Condensation Method
215
CDCl on Jeol JNM-PMX 60 NMR spectrometer (60 MHz) using TMS as
3
internal standard (chemical shifts in d ppm) and IR spectra as KBr pellets
2
1
on Hitachi 270–30 spectrophotometer (nmax in cm ). Elemental analysis
was determined on Elemental Analysensysteme GmbH Vario EL. Melting
points were determined by using Buchi melting point apparatus and are
uncorrected. Purity of all analytical samples was checked by TLC.
General Procedure for Single Aldol Condensation Between
Acetone and Arylaldehydes
Arylaldehyde (1 mmol) and acetone (4 mmol) were taken in a borosil beaker
(
100 mL) containing 15 mL of 10% aqueous sodium hydroxide solution. The
beaker containing the reaction mixture was covered with a watch glass, and
the reaction mixture was maintained at 5–108C using crushed ice. The
reaction mixture was stirred after every interval of 15 min). After the appro-
priate time (Table 1), the solid product so obtained was filtered, washed
with water until the washings were neutral. It was dried and crystallized
from EtOAc: pet. ether, or EtOH.
1
The structures of the products were confirmed by IR, H NMR, elemental
analysis, and comparison with authentic samples prepared according to
literature methods.
Spectral and Analytical Data of Some Selected Compounds
Entry 10
1
H NMR (CDCl ): d 2.7 (s, 3H), 6.7 (d, J ¼ 13.8 Hz, 1H, –CH 55 C), 7.2–7.9
3
2
m, 4H, Ar-H & –CH 55 ); IR (KBr, nmax in cm ): 1665 (C 55 O). Anal. calcd.
1
(
for C H Cl O: C, 56.00%; H, 3.70%. Found: C, 55.78%; H, 3.63%.
1
0
8
2
Entry 11
1
H NMR (CDCl ): d 2.8 (s, 3H), 6.8 (d, J ¼ 14.2 Hz, 1H, –CH 55 C), 7.2–7.85
3
2
m, 4H, Ar-H & –CH 55 ); IR (KBr, nmax in cm ): 1670 (C 55 O). Anal. calcd.
1
(
for C H Cl O: C, 56.00%; H, 3.70%. Found: C, 55.58%; H, 3.73%.
1
0
8
2
Entry 12
1
H NMR (CDCl ): d 2.65 (s, 3H), 6.82 (d, J ¼ 14.0 Hz, 1H, –CH 55 C), 7.0–
3
2
.72 (m, 6H, Ar-H & 2x –CH 55 ); IR (KBr, nmax in cm ): 1630 (C 55 O). Anal.
1
7
calcd. for C H BrClO: C, 52.50%; H, 3.70%. Found: C, 55.78%; H, 3.53%.
1
2 10

216
S. Paul and M. Gupta

Selective Single Aldol Condensation Method
217

218
S. Paul and M. Gupta

Selective Single Aldol Condensation Method
219

220
S. Paul and M. Gupta
Entry 13
1
H NMR (CDCl ): d 2.7 (s, 3H), 6.78 (d, J ¼ 14.0 Hz, 1H, –CH 55 C), 7.2–
3
2
1
7
Anal. calcd. for C H Cl O: C, 60.00%; H, 4.10%. Found: C, 60.18%; H,
.72 (m, 6H, Ar-H & 2x –CH 55 ); IR (KBr, n
in cm ): 1620 (C 55 O).
max
1
2
10
2
3
.95%.
Entry 14
1
H NMR (CDCl ): d 2.74 (s, 3H), 6.57 (d, J ¼ 13.0 Hz, 1H, –CH 55 C),
3
2
1
7.2–8.2 (m, 4H, Ar-H & 2x –CH 55 ); IR (KBr, n
C 55 O). Anal. calcd. for C H ClNO : C, 57.30%; H, 3.90%; N, 5.5%.
in cm ): 1630
max
(
Found: C, 57.38%; H, 3.98%; N, 5.56.
12 8 3
Entry 15
1
H NMR (CDCl ): d 2.72 (s, 3H), 6.56 (d, J ¼ 13.0 Hz, 1H, –CH 55 C),
3
2
1
7.3–8.6 (m, 5H, Ar-H & 2x –CH 55 ); IR (KBr, n
C 55 O). Anal. calcd. for C H Cl O: C, 43.10%; H, 2.60%. Found: C,
in cm ): 1630
max
(
12 9 3
4
2.98%; H, 2.48%.
Entry 16
1
H NMR (CDCl ): d 2.58 (s, 3H), 6.55 (d, J ¼ 12.5 Hz, 1H, –CH 55 C),
3
7.1–7.68 (m, 10H, Ar-H & –CH 55 ), 8.6 (bs, 1H, indole NH); IR (KBr,
nmax in cm ): 1650 (C 55 O). Anal. calcd. for C H NO: C, 81.81%; H,
2
1
18
14
5
.70%; N, 5.3%. Found: C, 81.88%; H, 5.78%; N, 5.26%.
Entry 17
1
H NMR (CDCl ): d 2.64 (s, 3H), 6.52 (d, J ¼ 12.5 Hz, 1H, –CH 55 C),
3
7.25–7.72 (m, 10H, Ar-H & –CH 55 ), 8.63 (bs, 1H, indole NH); IR (KBr,
nmax in cm ): 1660 (C 55 O). Anal. calcd. for C H NClO: C, 73.21%; H,
2
1
18
14
4
.70%; N, 4.70%. Found: C, 73.18%; H, 4.76%; N, 4.66%.
Entry 18
1
H NMR (CDCl ): d 2.54 (s, 3H), 6.54 (d, J ¼ 14.0 Hz, 1H, –CH 55 C),
3
2
1
7
Anal. calcd. for C H ClNO: C, 67.53%; H, 4.30%; N, 6.0%. Found: C,
.2–8.4 (m, 5H, Ar-H & –CH 55 ); IR (KBr, n
in cm ): 1650 (C 55 O).
max
1
3 10
6
7.38%; H, 4.37%; N, 5.96%.

Selective Single Aldol Condensation Method
221
Entry 19
1
H NMR (CDCl ): d 2.35 (s, 3H, CH ), 2.72 (s, 3H, COCH ), 6.55
3
3
3
(
d, J ¼ 12.5 Hz, 1H, –CH 55 C), 7.2–8.4 (m, 4H, Ar-H & –CH 55 ); IR (KBr,
2
1
n
4
in cm ): 1650 (C 55 O). Anal. calcd. for C H ClNO: C, 68.80%; H,
14 12
max
.90%; N, 5.7%. Found: C, 68.73%; H, 4.98%; N, 5.56%.
Entry 20
1
H NMR (CDCl ): d 2.48 (s, 3H), 6.8 (d, J ¼ 13.0 Hz, 1H, –CH 55 C), 6.5–8.0
3
2
m, 10H, Ar-H & –CH 55 ); IR (KBr, nmax in cm ): 1665 (C 55 O). Anal. calcd.
1
(
for C H ClN O : C, 62.0%; H, 3.80%; N, 11.4%. Found: C, 62.08%; H,
1
9
14
3 3
3
.98%; N, 5.56.
Entry 21
1
H NMR (CDCl ): d 2.47 (s, 3H), 6.77 (d, J ¼ 13.0 Hz, 1H, –CH 55 C),
3
2
1
6
Anal. calcd. for C H BrClN O: C, 58.0%; H, 3.50%; N, 4.0%. Found: C,
.7–8.1 (m, 10H, Ar-H & –CH 55 ); IR (KBr, n
in cm ): 1660 (C 55 O).
max
1
9
14
2
5
7.89%; H, 3.48%; N, 4.06%.
CONCLUSION
We have developed a simple, safe, and economic method for selective single
aldol condensation between acetone and aryl/heterocyclic aldehydes. In
addition, high yields of the products, ease of workup and low cost make
the above method advantageous in comparison to other existing methods.
ACKNOWLEDGMENT
Monika Gupta thanks CSIR, New Delhi, for the Junior Research Fellowship
award.
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