On water: An efficient Knoevenagel condensation using 12-tungstophosphoric acid as a reusable green catalyst

Article abstract of DOI:10.1080/00397910600770631

12-Tungstphosphoric acid is found to be an efficient, environmentally attractive, and reusable catalyst for Knoevenagel condensation of malononitrile and ethylcyanoacetate with various aldehydes. Copyright Taylor & Francis Group, LLC.

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On Water: An Efficient Knoevenagel
Condensation using 12‐Tungstophosphoric
Acid as a Reusable Green Catalyst
Hossien A. Oskooie a , Majid M. Heravi a , Fatemeh Derikvand a , Marzieh
Khorasani a & Fatemeh F. Bamoharram b
a Department of Chemistry, School of Sciences, Azzahra University, Vanak,
Tehran, Iran
b Department of Chemistry, School of Sciences, Azad University, Mashad,
Iran
Version of record first published: 16 Feb 2007
To cite this article: Hossien A. Oskooie, Majid M. Heravi, Fatemeh Derikvand, Marzieh Khorasani & Fatemeh
F. Bamoharram (2006): On Water: An Efficient Knoevenagel Condensation using 12‐Tungstophosphoric Acid as
a Reusable Green Catalyst, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 36:19, 2819-2823
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Synthetic Communicationsw, 36: 2819–2823, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600770631
On Water: An Efficient Knoevenagel
Condensation using 12-Tungstophosphoric
Acid as a Reusable Green Catalyst
Hossien A. Oskooie, Majid M. Heravi, Fatemeh Derikvand,
and Marzieh Khorasani
Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
Fatemeh F. Bamoharram
Department of Chemistry, School of Sciences, Azad University,
Mashad, Iran
Abstract: 12-Tungstphosphoric acid is found to be an efficient, environmentally
attractive, and reusable catalyst for Knoevenagel condensation of malononitrile and
ethylcyanoacetate with various aldehydes.
Keywords: Aqueous media, Knoevenagel condensation, rapid reactions, reusable
catalysts, 12-tungstophosphoric acid
Water is a desirable solvent for chemical reactions for reasons of cost, safety,
and environmental concerns, and the study of organic reactions in aqueous
solvents has an intriguing history.[1]
Knovenagel condensation of carbonyl compounds on molecules
containing an active methylene group is one of the most important methods
for the preparation of substituted alkenes.[2] This reaction between carboxylic
compounds and methylene malonic esters produces several important
products that include nitriles used in anionic polymerization and a-b-
unsaturated ester intermediates employed in the synthesis of several
Received in the U.K. December 11, 2005
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
2819

2820
H. A. Oskooie et al.
therapeutic drugs (e.g., niphedipine and nitredipine) and pharmacological
products (calcium channel blockers and antihypertensives). As an important
carbon–carbon forming reaction, Knoevenagel condensation has been exten-
sively studied. Alkali metal hydroxides (e.g., NaOH and KOH), pyridine, and
piperidine are the traditional catalysts used in this reaction. The reaction can
be catalyzed with Lewis acids, TiCl4/base,[3] ZnCl2,[4] Clays,[5] and modified
Mg-Al.[6] Recently Bigi and his coworkers reported Knoevenagel conden-
sation in refluxing water in the absence of a catalyst with in 1 h.[7]
However, they did not claim the reaction of ethyl acetoesters with carbonyl
compounds under the same conditions. In connection with our studies on
implementing organic reactions in an ecofriendly manner,[8–10] we explored
the catalytic Knoevenagel condensation in water. In recent decades, an appli-
cable industrial catalyst that is ecofriendly, green, and simply recycled in the
reaction mixture has been sought. Green chemistry has been defined as a set of
principles that reduces or eliminates the use or generation of hazardous
substances throughout the entire life of chemical materials.[1] Using hetero-
polyacids (HPAs) and their salts, which are low in toxicity, highly stable in
humidity, recyclable, and stable in air, have found more attention. They
show very high catalytic activities for acid-catalyzed reactions. HPAs are
usually insoluble in nonpolar solvents but soluble in polar solvents; the poor
solubility of HPAs in reaction products improves product selectivity and
also allows easy separation of the reaction and the product.[11]
We have recently started on the catalytic properties of heteropolyacids,
which are cheap, reusable, and easily available catalysis.[12] In continuation
of our work on the catalytic properties of heteropolyacids here in, we have
developed a convenient, efficient, and ecofriendly procedure for Knoevenagel
condensation using a catalytic amount of H3PW12O40 (Scheme 1).
To start our investigation, we studied different solvent effects on the
course of the reaction of benzaldehyde with malononitrile. From the results
given in Table 1, it follows that the best solvent for this reaction is water.
Only low yields of products were isolated after conventional heating in
CH2Cl2 and CHCl3. Yields and times were the same for the reaction in
water and Dimethyl formamide (DMF), but water is an excellent solvent in
terms of cost, availability, and environmental impact.
A variety of different aromatic aldehydes, containing electron-withdrawing
or donating groups and heterocyclic aldehydes, were subjected to this reaction
to investigate the generality of this methodology. All results are summarized in
Table 2. In the presence of HPA, the reaction times for malononitrile are shorter
Scheme 1.

12-Tungstophosphoric Acid
Table 1. Knovenagel reaction of benzal-
2821
dehyde with malonitrile in different solvents
under reflux
Solvent
Reaction time (h)
Yield
DMF
1
95
80
95
97
CHCl3
CH3CN
H2O
8
1.5
0.25
(5–15 min) than those reported by Bigi and colleagues (60 min). However,
the condensation with ethylcyanoacetate has been overlooked, so we studied
the Knoevenagel reaction with ethylcyanoacetate in aqueous media. In the
absence of HPA the reaction of 4-chlorobenzaldehyde as a model substance
with ethylcyanoacetate in aqueous media completed after 135 min. When the
catalyst was added, the reaction was completed after 60 min.
Our studies showed, in this reaction heteropolyacid is reusable and could
be used for at least 3 runs for the condensation reaction. After removing
the catalyst and washing that with diethylether, it could be reused and
subjected to a second run of the same reaction. The results of the first exper-
iment and our subsequent experiments were almost consistent in yield (96%,
94%, and 90%).
It is worthwhile mentioning that Knoevenagel condensation with ketones
in this condition does not occur. We used acetophenone as an example of
ketones that did not react in these conditions even after a prolonged
reaction time (24 h).
Table 2. Knoevenagel condensation using a catalytic amount of H3PW12O40 as
catalyst in aqueous media
Mp (8C)
Time
(min)
Yield
(%)
Entry
R
x
Found
87
Lit.
84[13]
1
2
3
4
5
Ph-
CN
CN
CN
CN
CN
15
5
91
92
91
92
91
4-MeO Ph-
4-Me Ph-
4-Cl Ph-
114
114[13]
135[13]
163[14]
Viscous
10
15
15
137–139
169
184
4-OH Ph-
liquid[15]
6
7
Furyl-
CN
15
90
92
85
87
89
89
70–72
100–102
136–137
92–93
88
72[13]
96[16]
2-NO2 Ph-
3- NO2 Ph-
4-Cl Ph-
COOEt
COOEt
COOEt
COOEt
8
90
60
128–132[17]
86[17]
9
10
4-MeO Ph-
120
88[17]

2822
H. A. Oskooie et al.
Our studies showed that in this reaction HPA is reusable for at least 5 runs
of the condensation reaction.
In summary, we have developed a novel, ecofriendly, and efficient
method for Knoevenagel condensation using HPA as an inexpensive, green,
and reusable catalyst in water. The advantages of the present method are
simplicity of workup, high yields, short reaction times, recyclability of the
catalyst, and the most important, use of water as solvent.
EXPERIMENTAL
The reagent is commercially available. All of the products are known
compounds and identified by melting-point and spectroscopic data.
General Procedure
A mixture of aldehyde (10 mmol), malononitrile or ethylcyanoacetate
(10 mmol), and H3PW12O40 (1 mol%) in water (10 mL) was refluxed. Upon
completion of the reaction, as monitored by TLC, the reaction mixture was
cooled to room temperature. The precipitated solid was filtered and recrysta-
lized from absolute EtOH to obtain pure products. 12-Tungstophosphoric acid
was soluble in water and was separated by filtration: by evaporation of filtrate
and washing with diethyl ether, the catalyst could be recycled and reused in
the same reaction.
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