An efficient and environment friendly procedure for the synthesis of arylmethylenemalononitrile catalyzed by strong base anion-exchange resin in water

Article abstract of DOI:10.1081/SCC-200025621

Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by strong base anion-exchange resin in water results aryl- methylenemalononitrile in 74-98% yield at room temperature.

Full text of DOI:10.1081/SCC-200025621

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An Efficient and Environment
Friendly Procedure
for the Synthesis of
Arylmethylenemalononitrile
Catalyzed by Strong Base
Anion‐Exchange Resin in
Water
Tong‐Shou Jin a , Jian‐She Zhang a , Ai‐Qing Wang a
& Tong‐Shuang Li a
a Department of Chemistry, College of Chemistry
and Environmental Science, Hebei University, No.
88 Hezuo Road, Baoding, 071002, Hebei Province,
P.R. China
Published online: 10 Jan 2011.
To cite this article: Tong‐Shou Jin , Jian‐She Zhang , Ai‐Qing Wang & Tong‐Shuang
Li (2004): An Efficient and Environment Friendly Procedure for the Synthesis
of Arylmethylenemalononitrile Catalyzed by Strong Base Anion‐Exchange
Resin in Water, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:14, 2611-2616
To link to this article: http://dx.doi.org/10.1081/SCC-200025621
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 14, pp. 2611–2616, 2004
An Efficient and Environment Friendly
Procedure for the Synthesis of
Arylmethylenemalononitrile Catalyzed
by Strong Base Anion-Exchange
Resin in Water
*
Tong-Shou Jin, Jian-She Zhang, Ai-Qing Wang, and
Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, Hebei Province, P.R. China
ABSTRACT
Knoevenagel condensation of malononitrile with aromatic aldehydes
catalyzed by strong base anion-exchange resin in water results aryl-
methylenemalononitrile in 74–98% yield at room temperature.
Key Words: Strong base anion-exchange resin; Synthesis; Knoevenagel
condensation; Arylmethylenemalononitrile.
*
Correspondence: Tong-Shou Jin, Department of Chemistry, College of Chemistry and
Environmental Science, Hebei University, No. 88 Hezuo Road, Baoding 071002,
Hebei Province, P.R. China; E-mail: orgsyn@mail.hbu.edu.cn.
2611
DOI: 10.1080/SCC-200025621
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2612
Jin et al.
INTRODUCTION
Arylmethylenemalononitrile is an important precursor of potentially bio-
active pyrimidine derivatives.[1] Preparation of arylmethylenemalononitrile by
the conventional method is completed via Knoevenagel condensation between
malononitrile and various aromatic aldelhydes using organic bases (primary,
secondary and tertiary amines; ammonia; and ammonium salts).[2] Subse-
quently, the use of Al2O3,[3] silica gel functionalized with amino groups,[4]
ZnCl2,[5] CdI2,[6] K3PO4,[7] usy zeolite,[8] xonotlite,[9] and KF/Al2O3
has
[10]
been reported. More recently, the Knoevenagel reaction carried out by micro-
wave irradiation[11] and grinding method[12] was applied for this purpose to
obtain relatively better results.
Base anion exchange resin is a type of solid base. It has been widely used
in synthetic organic chemistry.[13–16] To our knowledge, there is no report of
using strong base anion-exchange resin as a catalyst in the Knoevenagel con-
densation under various conditions. Thus, we wish to report the synthesis of
arylmethylenemalononitrile catalyzed by strong base anion-exchange resin
in water (Sch. 1).
When a series of aromatic aldehydes were treated with malononitrile
under catalyst of strong base anion-exchange resin in water, the corresponding
arylmethylenemalononitrile were synthesized, and the results are summarized
in Table 1.
We have examined the effects of the solvent through some experiments.
As a model reaction, the reaction of 4-nitrobenzaldehyde with malononitrile in
various solvents including water, ethanol, acetonitrile, dichloromethane,
cyclohexane, and 1,4-dioxane was investigated. All of the solvents gave a
quantitative yield, for example, water gave the 98% yield, ethanol 98%, aceto-
nitrile 95%, dichloromethane 86%, cyclohexane 81%, and 1,4-dioxane 76%.
Solvents such as water, ethanol, and acetonitrile gave satisfactory results,
while water is obviously a better choice for safety, economy, and friendly
environment. Thus we can conclude that on the system, strong base anion-
exchange resin in water is the most effective for the reactions.
We have found that the present procedure gave better to excellent yields
and need shorter reaction time than reported methods. For example, in the
reaction catalyzed by xonotlite,[9] 3d and 3k were obtained in 65% and
Scheme 1.

Procedure for Synthesis of Arylmethylenemalononitrile
2613

2614
Jin et al.
70% yield, respectively, for 24 hr, whereas the present procedure results in
94% yield of the 3d within 1 hr and results 87% yield of the 3k within
1.5 hr respectively. The Knoevenagel condensation reaction was carried
out at room temperature and no Michael addition product was detected. It is
apparent that the condensation can be finished in milder conditions and higher
yield catalyzed by strong base anion-exchange resin in water. The electronic
effect of substituents also affects the rates of the reaction. The derivatives of
benzaldehyde bearing electron-withdrawing substituents had higher reaction
rates compared to those with electron-releasing groups.
We have also found that 4-hydroxybenzaldehyde and 2-hydroxybenzal-
dehyde give different results in terms of the reaction rate and the yield.
4-Hydroxybenzaldehyde reacted with malononitrile to give the product 3j in
98% yield after 2.0 hr of reaction time, whereas 2-hydroxybenzaldehyde
reacted with malononitrile to give the product 3i in 74% yield after 2.5 hr of
reaction time. We proposed that the explanation for this result should be
that the intramolecular hydrogen bond formed in 2-hydroxybenzaldehyde
reduces the activity of aldehyde group, which results in the deactivation of
2-hydroxybenzaldehyde.
The catalysts need no regeneration and could be reused five times for the
preparation of arylmethylenemalononitrile without significant loss of activity.
For example, 4-nitrobenzoaldehyde reacted with malononitrile in the presence
of strong base anion-exchange resin to give the product 3h in quantitative
yield (98%) after 0.8 hr of reaction time, and under the equal time the recycled
catalysts also gave a quantitative yield, the first recycled catalysts gave 98%
yield, the second 97% yield, the third 97% yield, the fourth 96% yield, and
the fifth 97% yield.
In conclusion, we have developed a practical Knoevenagel condensation
procedure for the preparation of arylmethylenemalononitrile. This method has
the advantages of operational simplicity, high yield, and short reaction time. It
is a non-toxic, non-corrosive, non-pollutive, recyclable, and environmental
friendly catalyst.
EXPERIMENTAL
Strong base anion-exchange resin was prepared as follows. Original
chloro-anion-exchange resin was washed with deionized H2O, then exchanged
with 10% NaOH until chloride was absent, finally washed with deionized H2O
until it was neutral, dried under room temperature, and stored in a desiccator
until use. Liquid aldehydes were purified by distillation prior to use. All the
products were characterized by their melting points and comparison with lit-
erature values.

Procedure for Synthesis of Arylmethylenemalononitrile
General Procedure
2615
A mixture of the aromatic aldehyde 1 (2 mmol) and malononitrile 2
(2 mmol) in deionized H2O (15 mL) was stirred in the presence of strong
base anion-exchange resin (100 mg) at room temperature for the length of
time as indicated in Table 1. The progress of the reaction was monitored by
TLC. After completion of the reaction, appropriate amount of ethyl acetate
was added to the reaction mixture, and the strong base anion-exchange resin
was filtered off. The catalyst was washed with ethyl acetate (3 Â 10 mL),
and the filtrate was evaporated under reduced pressure to get the crude
product. Further purification was achieved by recrystallization from 95%
ethanol or by column chromatography on silica gel using petroleum ether
and ethyl acetate as eluent to afford the pure product 3.
ACKNOWLEDGMENTS
The project was supported by the National Natural Science Foundation of
China (29872011 and 29572039), Educational Ministry of China, Educational
Department of Hebei Province (990104), and the Science and Technology
Commission of Hebei Province.
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Received in Japan January 19, 2004