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Chemistry Letters Vol.32, No.10 (2003)
Efficient and Clean Aldol Condensation Catalyzed by Sodium Carbonate in Water
Ze Zhang, Ya-Wei Dong, and Guan-Wu WangÃ
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
(Received July 15, 2003; CL-030635)
Efficient and environmentally friendly synthesis of chal-
practically pure form simply by Buchner filtration of the final
¨
cone and azachalcone was performed by aldol condensation
of aldehydes with ketones in pure water catalyzed by sodium
carbonate. In this convenient methodology, side reactions were
avoided and thus high yields were achieved.
aqueous reaction mixture after cooling to room temperature.12
In spite of the extremely low aqueous solubility of both ketones
and aldehydes used, the reaction can still be carried out effi-
ciently. The yields and reaction conditions for the aldol reac-
tions of acetophenone and 2-acetylpyridine with various aro-
matic aldehydes are summarized in Table 1.
Noticeably, the aldol reaction of acetophenone can be car-
ried out in refluxing condition without the occurrence of any
side reaction in most cases. But for the aldol reaction of 2-ace-
tylpyridine, it is not the case. To avoid the side reaction, it is
necessary to control the temperature at 70 ꢀC or below.
To investigate the effect of applied base on this aldol reac-
tion, we performed the reaction of 4-nitrobenzaldehyde with 2-
acetylpyridine in EtOH–H2O systems catalyzed by sodium car-
bonate and sodium hydroxide, respectively (Table 2).
From Table 2, it can be seen that Na2CO3 is a superior base
to NaOH in all EtOH–H2O media and that this reaction is fa-
voured in pure water although it involves the elimination of a
molecule of water. Side reactions were obviously avoided in
water compared in EtOH and EtOH–H2O (1:1).
Based on their crucial role as intermediates in organic syn-
thesis1 and their chemical flexibility as synthons for the produc-
tion of five- or six-membered-ring compounds,2 the synthesis of
chalcones and azachalcones has been extensively investigated
over the past decades. Traditionally, the synthesis of these com-
pounds is achieved from aromatic aldehyde and ketone with
NaOH or KOH as the base in hydroalcoholic medium,2–7 or
strong bases in organic solvents.8 Under these conditions, the al-
dol reactions give mixtures of ketols and ꢀ; ꢁ-unsaturated ke-
tones,5 and by-products from Michael addition, Cannizzaro re-
action, and other side reactions are often formed.4,7 It should be
noted that Toda et al. reported the first example of aldol conden-
sation in the absence of solvent.5 For the stringent and growing
environmental regulations, organic chemists are requested to
develop clean, economical, and environmental safer methodol-
ogies. One of the most promising approaches is to utilize water
as reaction medium. In recent years there has been increasing
recognition that water is an attractive medium for many organic
reactions.9 The formation of chalcones from the reactions of ar-
omatic ketones and cyclohexanone with aromatic aldehydes in
water catalysed by NaOH has been reported.10 However, in
these reactions ketols were obtained and were even the main
products in some cases. More recently, Kourouli et al.11 report-
ed the synthesis of ꢀ; ꢁ-unsaturated ketones by aldol condensa-
tion of liquid aldehydes with ꢁ-ketoacids in pure water with
KOH as the base. Nevertheless, this protocol has the disadvan-
tages of relatively low yield and tedious preparation of ketoacid
from ketoester. To the best of our knowledge, there has been no
report on the synthesis of chalcone and azachalcone by aldol
condensation of aromatic aldehydes with ketones catalyzed by
sodium carbonate in pure water.
In conclusion, we have found that chalcone and azachal-
Table 1. Aldol condensations of ketones with aldehydes cata-
lyzed by 25 mol% Na2CO3 in water
Product
(3)a
R
X
Temp. Time Yieldb
/ꢀC
/h
/%
3a
3b
3c
3d
3e
4-NO2C6H4
3-NO2C6H4
4-NCC6H4
3,4-ClC6H4
4-ClC6H4
CH
CH
CH
CH
CH
100
100
60c
100
100
100
70c
100
70
1
7
697
3
8
10
4
32
0.5
1.5
5
98
97
98
84
88
92
61
98
98
95
98
87
89
94
68
3f
3,4-CH2O2C6H3 CH
3gd
3hd
3i
2-pyridine
Ph
CH
CH
N
N
N
N
N
N
N
4-NO2C6H4
3-NO2C6H4
4-NCC6H4
3,4-ClC6H4
4-ClC6H4
3,4-CH2O2C6H3
2-pyridine
Ph
3j
3k
3l
3m
3n
3od
3pe
70
The aldol condensations of ketones 1 with aldehydes 2 in
water catalyzed by sodium carbonate were found to afford
ꢀ; ꢁ-unsaturated ketones 3 in high yields (Scheme 1).
This protocol does not require the use of any organic sol-
vent and only 25% molar equivalent of Na2CO3 is enough for
this aldol condensation. In fact, the products were isolated in
c
6
0
70
70
70
70
4
28
10
1
N
25c
25
aProducts were properly characterized by mp, IR, H NMR
and 13C NMR. bIsolated yield. cHigher temperature leads
to obvious side reaction. dIt is necessary to let the final reac-
tion mixture stand overnight due to the relatively low melt-
1
O
O
Na2CO3/ H2O
X
X
R
R-CHO
+
X=CH 100 °C
X=N 70°C
e
ing point of the product. Isolated by column chromatogra-
X=CH, N
phy on silica gel along with 21% of 3-phenyl-3-hydroxy-1-
(2-pyridyl)-1-propanone. A black mixture was obtained
due to side reactions under heating conditions.
1
2
3
Scheme 1.
Copyright Ó 2003 The Chemical Society of Japan
Zhang, Ze
