A straightforward method for the synthesis of functionalized trisubstituted alkenes through Na2S/Al2O3 catalyzed knoevenagel condensation

Article abstract of DOI:10.1002/jccs.200700219

Na₂S/Al₂O₃ catalyzed the Knoevenagel condensation between an aldehyde and an active methylene compound to yield various trisubstituted alkenes.

Full text of DOI:10.1002/jccs.200700219

Journal of the Chinese Chemical Society, 2007, 54, 1557-1560
1557
A Straightforward Method for the Synthesis of Functionalized
Trisubstituted Alkenes through Na2S/Al2O3 Catalyzed Knoevenagel
Condensation
Majid M. Heravi,* Khadijeh Bakhtiari, Shima Taheri and Hossein A. Oskooie
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
Na2S/Al2O3 catalyzed the Knoevenagel condensation between an aldehyde and an active methylene
compound to yield various trisubstituted alkenes.
Keywords: Knoevenagel condensation; Na2S; Al2O3; Active methylene compound; Arylidenes;
Trisubstituted alkenes.
The synthesis of arylidene derivatives has attracted
considerable attention from organic chemists for many
years because many of them have significant biological ac-
tivity. Moreover, benzylidene malononitriles have been re-
ported to be effective anti-fouling agents, fungicides and
insecticides.1 They are important intermediates for the syn-
thesis of various organic compounds.1
3-nitronezaldehyde with malononitrile, in the presence of a
catalytic amount of Na2S (20 mol %) in refluxing dichloro-
methane. After 1.5 h, 99% yield of the product was ob-
tained. In order to investigate the effect of the alumina on
the reaction time, the reaction was repeated in the presence
of Na2S (20 mol %) and basic Al2O3 (0.05 g). Interestingly,
we have obtained 99% yield of 1,1-dicyano-2-phenylethyl-
ene after only 5 min at room temperature.
The Knoevenagel reaction is a venerable reaction and
it is the most simple and straightforward method used to
produce substituted alkenes. Classically, the process con-
sists of the condensation of aldehydes with active methy-
lene compounds in the presence of a variety of reagents and
gives good yields of arylidenes or alkylidenes. Several
weak bases2-4 or Lewis acid5-6 catalysts have been used in
the Knoevenagel condensations. It can also be performed
in heterogeneous media.7-10
After optimizing the reaction conditions, various aro-
matic aldehydes reacted very well with malononitrile and
ethylcyanoacetate as active methylene compounds to give
the corresponding arylidenes in good to excellent yields
(Scheme I). More interestingly, the reaction is highly
stereoselective affording alkenes in E-geometry.
Scheme I
The preparation of sodium sulfide adsorbed onto alu-
mina (Na2S/Al2O3) was first describes by Regen11 who
used it to prepare dialkyl sulfides from primary alkyl hal-
ides. Pagni and Kabala12 later reported its use in the synthe-
sis of cyclic sulfides from straight chain a,w-dibromides. It
is also used as a reagent for the facile synthesis of 2,11-
dithia[3,3]metacyclophanes.13
In continuation of our interest in catalytic14-23 and
Knoevenagel reactions,24-27 in the present study, we report
the sodium sulfide adsorbed onto basic alumina (Na2S/
Al2O3) as a highly efficient catalyst for condensation of al-
dehydes with active methylene compounds such as mal-
ononitrile and ethylcyanoacetate under heterogeneous con-
ditions. We first performed the Knoevenagel reaction of
Knoevenagel condensation involving various aro-
matic carbonyl compounds with malononitrile and ethyl-
cyanoacetate as the active methylene compounds was car-
ried out with Na2S/Al2O3 at room temperature and under re-
flux conditions. The aromatic aldehydes readily condensed
with malononitrile, while with ethylcyanoacetate, the reac-
tion is slightly slower. This may be attributed to the fact that
abstraction of a proton from the active methylene group of
ethylcyanoacetate is more difficult due to its lower activity.
* Corresponding author. E-mail: mmh1331@yahoo.com

1558 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Heravi et al.
Table 1. Knoevenagel condensation catalyzed by Na2S/Al2O3
Time
Entry
m.p. (°C)
Found Reported
R1
R2
R3
Condition
Yield (%)a
(min)
1
C6H5-
H
H
CN
CN
20
Reflux
Reflux
90
83-84
8328
16431
-
2
4-Cl-C6H4-
2-NO2-C6H4-
3-NO2-C6H4-
4-NO2-C6H4-
4-CH3-C6H4-
2-CH3O-C6H4-
4-CH3O-C6H4-
C6H5-HC=CH-
C6H5-
30
90
166-167
141-142
101-103 104-10529
161-162 159-16028
3
H
CN
10
room temperature
room temperature
room temperature
Reflux
98
4
H
CN
5
99
5
H
CN
5
97
6
H
CN
55
96
137-138
80
13532
7835
11528
12832
-
7
H
CN
45
Reflux
97
8
H
CN
10
Reflux
94
113-114
122-123
-
9
H
CN
5
Reflux
98
10
11
12
13
14
15
16
17
18
19
20
21
22
C6H5
CH3
H
CN
24 hours
Reflux
No reaction
C6H5-
CN
24 hours
Reflux
No reaction
-
-
C6H5-
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
25
Reflux
90
50-51
87-89
102
130
169
93-94
70
5228
8734
9635
128-13233
17034
9228
6934
80-8428
11630
-
4-Cl-C6H4-
2-NO2-C6H4-
3-NO2-C6H4-
4-NO2-C6H4-
4-CH3-C6H4-
2-CH3O-C6H4-
4-CH3O-C6H4-
HC=CH-C6H5
C6H5-
H
45
Reflux
90
H
7
room temperature
room temperature
room temperature
Reflux
96
H
5
95
H
7
65
95
H
94
H
60
Reflux
90
86
H
30
Reflux
85
H
5
Reflux
96
115
-
C6H5
CH3
24 hours
24 hours
Reflux
No reaction
No reaction
C6H5-
Reflux
-
-
a Yields refer to the isolated pure products.
It can be seen from Table 1 that all reactions proceed selec-
tively to the dehydrated products without any side reaction.
No self-condensation, Cannizaro products or hydrated prod-
ucts of Knoevenagel adducts were obtained.
present work in comparison with some reported proce-
dures, we compared the results of the synthesis of olefinic
compounds in the presence of HZSM-5,24 Proline,36 RE-
NaY zeolite37 and Na2S/Al2O3 with respect to the reaction
times and yield of products (Table 2). The results show that
Na2S/Al2O3 promotes the reaction more effectively than
HZSM-5. Reaction in the presence of other catalysts in Ta-
ble 2 required longer reaction times.
As shown in Table 1, aromatic aldehydes containing
both electron donating or withdrawing groups gave the de-
sired products in good to excellent yields in the reaction
time ranging from 5 to 65 minutes. Deactivated aldehydes
such as nitrobenzaldehyde isomers and 4-chlorobenzalde-
hyde required shorter reaction times due to the electron
withdrawing groups (Table 1, entries 2-5, 13-16). More-
over, the steric hindrance seems to have significant effects
on the reaction times and yields (Table 1, entries 7-8, 18-
19). We also investigated Knoevenagel condensation of ke-
tones with malononitrile and ethylcyanoacetate. No reac-
tions occurred under the conditions in which aldehydes
gave almost quantitative conversions.
In summary, we have demonstrated the Na2S/Al2O3
catalyzed condensation between various aldehydes and ac-
tive methylene compounds in a heterogeneous system. This
method offers some advantages in terms of simplicity of
performance, easy work-up, use of inexpensive, available
and easy to handle catalysts and high yields of products and
Table 2. Comparison of the synthesis of trisubstituted alkenes
using different catalysts
The use of Na2S/Al2O3 as catalyst in this reaction al-
lowed us to perform the condensation under mild condi-
tions. In this case, yields were excellent. The salient fea-
tures of this reaction are the following: a) use of inexpen-
sive and readily available catalyst b) and simplicity of per-
formance and work-up. In order to show the merit of the
Entry
Catalyst
Time
Yield (%)
Ref.
1
2
3
4
HZSM-5
Proline
5-12 (h)
Over night
8-18 (h)
60-80
24
36
66-100
78-100
86-99
RE–NaY Zeolite
Na2S/Al2O3
37
5-65 (min)
This work

Synthesis of Functionalized Trisubstituted Alkenes
relatively short reaction times.
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1559
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MMH is thankful to the Azzahra University Research
Council for partial financial support.
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Oskooie, H. A. J. Mol. Catal. A. Chem. 2006, 244, 8.
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M. Indian J. Chem., B. 1999, 38, 857.
Received March 5, 2007.
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