An easy-to-use heterogeneous catalyst for the knoevenagel condensation

Article abstract of DOI:10.1139/v01-072

Physical mixtures of alkali and earth alkali metal carbonates and commercially available zeolites were investigated as solid catalysts for the Knoevenagel condensation. Best results for the model reaction between benzaldehyde and ethyl cyanoacetate were o

Full text of DOI:10.1139/v01-072

566
An easy-to-use heterogeneous catalyst for the
Knoevenagel condensation
Bernd Siebenhaar, Bruno Casagrande, Martin Studer, and Hans-Ulrich Blaser
Abstract: Physical mixtures of alkali and earth alkali metal carbonates and commercially available zeolites were inves-
tigated as solid catalysts for the Knoevenagel condensation. Best results for the model reaction between benzaldehyde
and ethyl cyanoacetate were obtained for a 1:4 mixture of Na2CO3 with 4 Å molecular sieves (MS). The effects of the
following parameters were investigated: structure of substrate, type and basicity of metal carbonate and zeolite, and
temperature. Between 50 and 90°C chemical yields up to >90% were obtained without continuous removal of water
and with reasonable catalyst activities and reaction times. Na2CO3 – MS 4 Å proved to be active for the condensation
of several aldehydes and ketones with a variety of active methylene components.
Key words: Knoevenagel condensation, solid basic catalysts, zeolite – sodium carbonate mixtures.
Résumé : On a évalué la possibilité d’utiliser des mélanges physiques de carbonates de métaux alcalins ou alcalinoter-
reux et de zéolites commercialement disponibles comme catalyseurs solides pour des condensations de Knoevenagel.
Les meilleurs résultats pour la réaction modèle entre le benzaldéhyde et le cyanoacétate d’éthyle ont été obtenus avec
un mélange 4:1 de Na2CO3 avec du MS 4 Å. On a étudié les effets des paramètres suivants: structure du substrat; type
et basicité du carbonate métallique et du zéolite; température. Entre 50 et 90°C, on a obtenu des rendements chimiques
allant jusqu’à plus de 90 % sans nécessité d’enlever l’eau de façon continue, avec des activités catalytiques et des
temps de réaction raisonnables. Le mélange Na2CO3 – MS 4 Å s’avère actif pour la condensation de plusieurs aldéhy-
des et cétones avec une grande variété de composés comportant un méthylène actif.
Mots clés : condensation de Knoevenagel, catalyseurs basiques solides, mélanges de zéolite – carbonate de sodium.
[Traduit par la Rédaction] Siebenhaar et al. 569
Introduction
and even though there are cases where the reaction occurs at
room temperature (14), some catalysts are not very active. In
this contribution we describe the application of a physical
mixture of molecular sieves (MS) and sodium carbonate as
very effective solid catalysts for the Knoevenagel condensa-
tion of several types of starting materials. The catalysts are
easy to prepare starting from commercially available materi-
als, are highly active and selective, and lead to very pure
condensation products at relatively low temperatures.
The Knoevenagel condensation is a valuable tool in syn-
thetic chemistry (1, 2). Starting from aldehydes or ketones
and activated methylene compounds the synthesis of a wide
variety of tri- or tetra-substituted olefins is possible (usually
trans products are favored). This type of reaction is classi-
cally carried out in presence of an organic bases such as
pyridine and piperidine and water is removed continuously.
While yields are generally good, relatively high tempera-
tures are needed and work up can be cumbersome (Fig. 1).
To overcome some of these problems, solid basic catalysts
were developed using zeolites (3, 4), clays (5, 6), alumina
(7, 8), as well as amines immobilized on montmorillonite
(9), silica (10, 11), and ion exchanged resins (12, 13). Al-
though many of these catalysts indeed have helped to solve
some of the problems mentioned above, they are not very
practical for the synthetic organic chemist. Most of them are
not available commercially, many are difficult to prepare,
Results and discussion
As already pointed out, zeolites have been used as solid
catalysts before (3, 4). However, in order to get reasonable
activities, quite elaborate modification of the commercially
available materials is usually necessary. On the other hand,
alkaline carbonates have also been used with good activity ,
but due to various side reactions, selectivities were reported
to be rather low (1, 15). We thought that a combination of a
metal carbonate with a readily available zeolite might elimi-
nate these deficiencies and a catalyst screening was carried
out with different carbonates and zeolites using the reaction
of benzaldehyde with ethyl cyanoacetoactetate as model re-
action. The results were very promising and selected results
are presented in Table 1 and Fig. 2. The most important find-
ing was that with several catalyst combinations, conversions
up to 99% and selectivities of 98 to 99% of ethyl
cyanocinnamate were reached at low temperature within
reasonable reaction times. No further Michael addition
Received September 20, 2000. Published on the NRC
Research Press Web site at http://canjchem.nrc.ca on
May 31, 2001.
Dedicated to Professor Brian James on the occasion of his
65th birthday.
B. Siebenhaar,1 B. Casagrande, M. Studer, and H.-U.
Blaser. Solvias AG, P.O. Box, CH-4002 Basel, Switzerland.
1Corresponding author (telephone: +41 61 686 64 26; fax:
+41 61 686 63 11; e-mail: bernd.siebenhaar@solvias.com).
Can. J. Chem. 79: 566–569 (2001)
© 2001 NRC Canada
DOI: 10.1139/cjc-79-5/6-566

Siebenhaar et al.
567
Fig. 1. Knoevenagel condensation.
Table 1. Effect of zeolite type, counter ion, temperature on conversion, and reaction time for the condensation of benzaldehyde and
ethyl cyanoacetate.
Conversion
(%) (5 min)
Conversion
(%) (max)
tmax
(min)
Zeolite
Metal
T (°C)
Comments
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
K
K
K
K
22
50
70
90
60
80
93
93
83
85
95
96
30
20
15
10
1 g zeolite
1 g zeolite
1 g zeolite
1 g zeolite
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
MS 4 Å
Li
Na
K
Rb
Cs
Ca
Ba
Sr
70
70
70
70
70
90
90
90
80
61
94
95
72
14
22
55
98
96
97
97
97
96
96
98
90
90
30
15
15
150
150
150
2 g zeolite
2 g zeolite
2 g zeolite
2 g zeolite
2 g zeolite
2 g zeolite
2 g zeolite
2 g zeolite
a
a
a
a
H-MOR
Na-X
Na-Y
SiO2
K
K
K
K
50
50
50
50
—
—
—
—
76a
78a
80a
70a
2 g mordenite, 0.45 g K2CO3
2 g zeolite X, 0.45 g K2CO3
2 g zeolite Y, 0.45 g K2CO3
2 g SiO2, 0.45 g K2CO3
Note: Reaction conditions: 0.1 mol substrates, 0.55 g metal carbonate.
aReaction time 15 min.
reactions to the product molecules were ever observed. As
expected, the strongest correlation was found between cata-
lyst activity (expressed as mmol/g catalyst * h) and the ba-
sicity of the two components (see Fig. 3), but the amount of
zeolite also plays a role. Similar dependencies have been re-
ported before (3). The overall preferred combination used
for further investigations was the easily available MS 4 Å
and K2CO3 at a weight ratio of ca. 1:4, respectively. This
means that the molecular sieve can absorb about 50% of the
water formed (pore volume of 0.45 mL g–1) (16), which
seems to be enough to allow high conversions under these
conditions. Control experiments in absence of molecular
sieves gave similar conversions but much lower yields due
to side reactions, confirming the documented observations
(1, 15) mentioned above.
To determine the scope and limitations of the new catalyst
system we investigated the effect of variations in the sub-
strate structure. On the one hand, this is important for the
preparative applications of the catalysts, and on the other
hand the dependence on the pKa of the methylene compo-
nent allows an indirect catalyst characterization (3, 5, 6).
The best results for each combination of starting materials
are listed in Table 2 and the following trends are noteworthy:
(i) The scope of the Na2CO3 – MS 4 Å combination is quite
broad, and a variety of different substrates can be condensed
with moderate to very high conversions and low to very high
yields. (ii) For the reaction with benzaldehyde, the catalyst
activity (see Fig. 3), as well as the product yields, are related
to the pKa of the starting methylene compound with a limit-
ing value of ca. 13; this is inferred to correspond to an ap-
proximate pKa value for the solid catalyst. (iii) As for the
classical version of the Knoevenagel condensation, products
are predominantly trans, and aldehydes are much more reac-
tive than ketones, which give generally low conversions but
acceptable selectivities.
Conclusions
As a result of their ready availability and very good over-
all catalytic performance, a 1:4 physical mixture of Na2CO3
with MS 4 Å is a very useful catalyst for the preparative
Knoevenagel condensation for a variety of aldehydes and ke-
tones with different active methylene compounds. The most
important parameters affecting the catalytic performance
were the structure of starting materials and the catalyst ba-
sicity. From the correlation between the catalyst activity and
the pKa of different methylene components, it is concluded
that the Na2CO3 – MS 4 Å catalyst has a pKa of approxi-
mately 13. Optimal reaction temperatures are between 50
and 90°C, and chemical yields of up to >90% can be ob-
tained without continuous removal of water and with reason-
able catalyst activities and reaction times.
Experimental
All organic starting materials were obtained from Fluka
(purum) and were used without further purification. The fol-
lowing reference compounds were used: benzylidene-
malononitrile (Aldrich), ethyl cyanocinnamate (Aldrich),
diethyl benzylidenemalonate (Fluka). The inorganic salts
© 2001 NRC Canada

568
Can. J. Chem. Vol. 79, 2001
Table 2. Best results at the optimal temperature for the Knoevenagel condensation with different substrates using a mixture of Na2CO3
and MS 4 Å.
Time
(h)
Conversion
(%)
Yield
(%)
Activity
(mmol/g catalyst * h)
Z1
Z2
pKa
R
R′
T (°C)
CN
CN
Ac
COOEt
Br
CN
CN
CN
CN
CN
~8
9
10.7
13.3
>14
9
9
9
9
Ph
Ph
Ph
Ph
H
H
H
H
H
70
90
90
130
120
30
25
50
50
0.25
0.25
0.5
1.5
6
3
1.25
2
98
94
63
69
0
59
90
90
63
97
872
736
282
102
0
43
161
99
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
93a
62a,b
61a,b
0
Ph
Vanillin
2-OH-Ph
C7H15
57a,b
58b
82b
35b
H
H
0.25
562
CH2CHO
CN
CN
CN
CN
COOEt
COOEt
COOEt
COOEt
9
9
9
BnCH2
PhCHCH2
Ph
Me
Me
Me
H
90
90
120
150
5
5
4
2
8
82
5
98c
8
4
36
3
80
5
97c
c
Ph
—
Note: Reaction conditions: 0.1 mol substrates, 0.45 g Na2CO3, 2 g MS 4 Å.
1
a>95% trans according to H NMR, not determined for the other substrates.
bIsolated yield after purification (see Experimental), product with >95% purity.
cReference experiment: β-alanine as homogeneous catalyst, with continuous removal of water with toluene (1).
Fig. 2. Condensation of benzaldehyde and ethyl cyanoacetate.
Fig. 3. Condensation of benzaldehyde with different methylene
compounds using a mixture of Na2CO3 and MS 4 Å at 70–90°C;
correlation between pKa and catalyst activity.
(a) Correlation between pH of different metal carbonates and
catalyst activity mmol/g catalyst * h); (b) correlation between
product yield and pH value of aqueous suspensions of different
zeolites. For the determination of the pH value see Experimental.
General procedure for Knoevenagel condensations
In a 50 mL three-necked flask with reflux condenser the
carbonyl compound (0.1 mol) and the methylene compound
(0.1 mol) were heated to reaction temperature. A mixture of
carbonate (0.45 g) and MS 4 Å (2.0 g) was added and the re-
action started immediately. After 0.25–4 h (depending on the
nature of the carbonyl and methylene compound) the hot re-
action mixture was filtered to remove the catalyst and yields
were determined by GLC. In many cases the crude product
was obtained with high yield and purity and did not need
further purification. Otherwise the crude product was dis-
solved in hot ethanol and slowly cooled down to room tem-
perature. Crystals of the product appeared and after filtration
and drying under vacuum the product was obtained with
high yield and purity.
Analytics
were p.A. grade and supplied by Fluka or Merck. The
zeolites used were obtained from Strem (H-mordenite, zeo-
lite X and Y) and from Merck (MS 4 Å).
The course of reaction was monitored by GLC (OV 101,
40°C, 10°C min–1; 220°C, 5°C min–1). Conversion was cal-
culated on the basis of peak area of the carbonyl compound,
© 2001 NRC Canada

Siebenhaar et al.
569
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Procedure for the determination of the pH values of
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© 2001 NRC Canada

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