Aldol condensations catalyzed by PEG400 and anhydrous K2CO 3 without solvent

Article abstract of DOI:10.1081/SCC-200054198

Aldol condensations of aromatic aldehydes with ketones under solvent-free conditions to synthesize α,β-unsaturated ketones in good to excellent yields using PEG400 and powdered anhydrous K₂CO₃ as catalysts at 90°C and 120°C are described. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054198

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Aldol Condensations Catalyzed by PEG400
and Anhydrous K CO Without Solvent
2
3
a
a
b
a
Yu‐Qing Cao , Zhi Dai , Rui Zhang & Bao‐Hua Chen
a
College of Chemistry and Environmental Science, Hebei University, Hebei,
P.R. China
b
Hebei Changtian Pharma, Baoding, P.R. China
Version of record first published: 16 Aug 2006
To cite this article: Yu‐Qing Cao, Zhi Dai, Rui Zhang & Bao‐Hua Chen (2005): Aldol Condensations Catalyzed
by PEG400 and Anhydrous K CO Without Solvent, Synthetic Communications: An International Journal for
2
3
Rapid Communication of Synthetic Organic Chemistry, 35:8, 1045-1049
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Synthetic Communications , 35: 1045–1049, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054198
Aldol Condensations Catalyzed by PEG400
and Anhydrous K CO Without Solvent
2
3
Yu-Qing Cao and Zhi Dai
College of Chemistry and Environmental Science, Hebei University,
Hebei, P.R. China
Rui Zhang
Hebei Changtian Pharma, Baoding, P.R. China
Bao-Hua Chen
College of Chemistry and Environmental Science, Hebei University,
Hebei, P.R. China
Abstract: Aldol condensations of aromatic aldehydes with ketones under solvent-free
conditions to synthesize a,b-unsaturated ketones in good to excellent yields using
PEG400 and powdered anhydrous K
described.
2 3
CO as catalysts at 90 8C and 120 8C are
Keywords: Aldol condensation, anhydrous K CO , PEG400, solvent-free
2
3
a,b-Unsaturated ketones are very important intermediates in organic synthesis
and some of them exhibit important pharmacological and biological activities.
Aldol condensation is a common approach to prepare a,b-unsaturated ketones
and is usually carried out in organic solvents catalyzed by strong acids,
[1]
[2]
bases, or some metal salts.
Organic synthesis in the absence of solvent is a powerful tool for the gen-
eration of structurally diverse molecules because of its low pollution, special
Received in Poland October 15, 2004
Address correspondence to Yu-Qing Cao, College of Chemistry and Environmental
Science, Hebei University, Hebei, P.R. China. E-mail: chemistry_hbu@yahoo.com

1
046
Y.-Q. Cao et al.
[3]
selectivity, and ease of setup and workup. It was reported in earlier litera-
tures that Aldol condensation reactions in the absence of solvent under
[4]
microwave irradiation afforded high yields of products in a short time.
Up until now, this was suitable only for small-scale preparation, not for
large-scale industrial preparation. Polyethylene glycols (PEG) have been
widely used as phase-transfer catalysts in many organic reactions because
of their stability, low cost, environmental friendliness, and easy availability.
It has been proved that PEGs incorporating 7–9 units are more effective in
þ
þ
[5]
catalyzing reactions in which K or Na salts participated. Especially
because of their liquid property and the two terminal hydroxy groups, PEG
400–600 are more suitable for solid–liquid organic reactions under solvent-
free conditions.
[6]
In the continuation of our previous work, we report a practical and
convenient approach for the Aldol condensations catalyzed by anhydrous
K CO and PEG400 in satisfactory yields without solvent. The reactions are
2
3
shown in Scheme 1 and the results are summarized in Table 1.
As shown in Table 1, longer reaction periods were needed in the reactions
for the products with high melting points. Higher yields could be obtained in
the condensation of ketones and aldehydes with electron-withdrawing groups
in the aromatic ring, such as –Cl, –Br, and NO , than with electron-donating
2
groups, such as –CH and –OCH , mainly because the aldehyde group with
3
3
electron-donating groups in the aromatic ring was easily oxidized. The reason
that the condensation of aromatic aldehydes has higher yields and longer
reaction periods with cyclopentanone than with cyclohexanone remains to
be investigated further.
When the reaction was carried out in the ratio of 1:1 (aromatic aldehyde/
0
cycloalkanone), the main products were a,a -bis (substituted benzylidene)
cycloalkanones with less a-mono (substituted benzylidene) cycloalkanones.
The condensation of aromatic aldehydes with acetone in the ratio of 1:1
Scheme 1.

Table 1. Aldol condensation of aromatic aldehydes with ketones in solvent-free condensations
mp, 8C
Entry
Aldehyde
Ketone
Time (h)
Yield (%)
Found
Lit.
b
[7]
a
b
c
d
e
f
C
6
H
5
CHO
4-CH
4-CH OC H CHO
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetone
2
85
82
84
90
91
82
86
84
89
85
87
86
94
93
88
88
89
91
93
90
91
89
78
116–117
199–200
169–170
146–147
158–159
143–144
179–180
164–165
188–189
183–184
135–136
209–210
179–180
223–224
54–55
117
202
170
147
159
144
a
[7]
[7]
[8]
[7]
[9]
3
C
6
H
4
CHO
3
a
3
3
6 4
a
4-ClC
4-NO
Furfural
6
H
4
CHO
CHO
2.5
2.5
a
2
C
6
H
4
a
3
a
[10]
[9]
g
h
i
Cinnamaldehyde
Furfural
3
2.5
180
a
165
a
[8]
C
6
H
5
CHO
3
3.5
189
a
[10]
[10]
[10]
[10]
[10]
[10]
[10]
[10]
[11]
[11]
[12]
j
4-CH C H CHO
184
136
210
180
223
55
3
3
3
6
4
b
k
l
3-CH
4-CH
6
C H
4
CHO
CHO
3
3.5
a
OC
6
H
4
a
m
n
o
p
q
r
3-BrC H CHO
6
3
3.5
4
a
4-ClC
6
H
4
CHO
b
C
4-CH C H CHO
6
H
5
CHO
2
b
2
95–96
96
3
6
4
b
4-CH
3
OC
6
H
4
CHO
2
75–76
76
b
4-ClC H
4-NO C H CHO
6
4
CHO
2
2.5
111–112
164–165
39–40
112
165
41
a
s
2
6 4
b
t
C H CHO
5
2
1.5
6
b
[12]
[13]
[13]
u
v
w
4-CH
furfural
C H CHO
3
6
C H
4
CHO
Acetone
Acetone
2-Butanone
27–28
33–34
36–37
28–29
33–35
37–38
b
2
2.5
b
6
5
a
b
The reactions were processed at 1208C and 908C.

1
048
Y.-Q. Cao et al.
provided the main product a-mono (substituted benzylidene) acetone. When
0
the ratio of aromatic aldehydes to acetones was 2:1, a,a -bis (substituted ben-
zylidene) acetone was obtained in the yield of only 53%, possibly because of
some by-products being formed. The condensation of benzaldehyde with
2-butanone was selective and the main product was 4-phenyl-3-methyl-3-
buten-2-one with less 5-phenyl-4-penten-3-one because of thermodynamic
dominating.
Effects of alkalies on the condensation were apparently different. Taking
the reactions of benzaldehyde with cyclopentanone as an example, the yields
using K CO , Na CO , KF, or KOH as bases were respectively 85%, 68%,
2
3
2
3
55%, and 38% under the same reaction conditions.
Using PEG400 as phase-transfer catalyst allowed us to perform the con-
densation under mild conditions without solvent. The amount of PEG400 was
–5 mol% to aromatic aldehydes (larger amounts were used in the reactions
3
for the products with higher melting points). A longer reaction period
would be necessary with less PEG400 and more products would be lost
during the course of washing with water with the larger amount of PEG400.
In summary, a novel method for Aldol condensation catalyzed by
PEG400 and anhydrous K CO without solvent was developed. The advan-
2
3
tages of our method are safety, high selectivity, environmental friendliness,
and ease of workup.
EXPERIMENTAL
Thin layer chromatography (TLC) was GF254 with petroleum ether/diethyl
ether (2:1) as eluent. Aromatic aldehydes and ketones were obtained from
commercial suppliers and were not purified. Melting points were determined
on a microscopy apparatus and are uncorrected.
Typical procedure for the synthesis of compound a: A mixture of benzal-
dehyde (0.2 mol), cyclohexanone (0.1 mol), anhydrous K CO (0.01 mol), and
2
3
PEG-400 (2 mL) were put into a 50-ml, three-necked, round-bottomed flask
equipped with a mechanical stirrer and drying tube filled with KOH. The
reaction was processed with vigorous stirring and heating at the assigned
temperature. The completion of the reaction was monitored by TLC. The
reaction mixture was cooled and treated with cool water. The product was
filtered, dried, recrystallized with ethanol, and identified by comparison of
melting point.
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