Efficient knoevenagel condensation catalyzed by 2-hydroxyethylammonium acetate under solvent-free conditions at room temperature

Article abstract of DOI:10.1080/00397910802632530

An efficient method for Knoevenagel condensation of aromatic aldehydes with malononitrile or ethyl cyanoacetate has been developed using the inexpensive and environmentally friendly ionic liquid 2-hydroxyethylammonium acetate as catalyst. The reactions we

Full text of DOI:10.1080/00397910802632530

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Efficient Knoevenagel
Condensation Catalyzed by
2-Hydroxyethylammonium
Acetate Under Solvent-
Free Conditions at Room
Temperature
Zhongqiang Zhou a , Jiangyong Yuan a & Rong Yang a
a Key Laboratory of Catalysis and Materials Science
of Hubei Province, College of Chemistry and
Materials Science, South-Central University for
Nationalities, Wuhan, China
Available online: 27 Apr 2009
To cite this article: Zhongqiang Zhou, Jiangyong Yuan & Rong Yang (2009): Efficient
Knoevenagel Condensation Catalyzed by 2-Hydroxyethylammonium Acetate Under
Solvent-Free Conditions at Room Temperature, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:11,
2001-2007
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Synthetic Communications1, 39: 2001–2007, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802632530
Efficient Knoevenagel Condensation Catalyzed
by 2-Hydroxyethylammonium Acetate Under
Solvent-Free Conditions at Room Temperature
Zhongqiang Zhou, Jiangyong Yuan, and Rong Yang
Key Laboratory of Catalysis and Materials Science of Hubei Province,
College of Chemistry and Materials Science, South-Central University
for Nationalities, Wuhan, China
Abstract: An efficient method for Knoevenagel condensation of aromatic
aldehydes with malononitrile or ethyl cyanoacetate has been developed using
the inexpensive and environmentally friendly ionic liquid 2-hydroxyethylammo-
nium acetate as catalyst. The reactions were carried out under solvent-free condi-
tions at room temperature in short periods with simple workup procedure and
good to excellent yields.
Keywords: Aromatic aldehydes, ionic liquid, Knoevenagel condensation,
methylene compounds
The Knoevenagel condensation is a very useful reaction and has been
widely employed for the generation of double bonds from a carbonyl com-
pound and an active methylene compound. This reaction is usually cata-
lyzed by organic bases.[1] In the past two decades, the use of Al2O3,[2]
ZnCl2,[3] CdI2,[4] I2–K2CO3,[5] K3PO4,[6] KF–Al2O3,[7] AlPO4–Al2O3,[8]
H2O=cetyltriethylammonium bromide (CTMAB),[9] montmorillonite
K10–ZnCl2,[10] zinc acetate,[11] diammonium hydrogen phosphate,[12]
USY zeolite,[13] xonotlite,[14] silica gel,[15] silica gel functionalized with
Received August 12, 2008.
Address correspondence to Zhongqiang Zhou, Key Laboratory of Catalysis
and Materials Science of Hubei Province, College of Chemistry and Materials
Science, South-Central University for Nationalities, Wuhan 430074, China.
E-mail: zhou-zq@hotmail.com
2001

2002
Z. Zhou, J. Yuan, and R. Yang
amino groups,[16] aminopropyl–functionalized MCM-41,[17] ionic liquid–
functionalized silica gel,[18] ionic liquid–functionalized SBA-15,[19] basic
ionic liquid,[20] and others[21–32] have been reported. In spite of their poten-
tial utility, some of these methods are limited by low yields, long reaction
times, harsh conditions, expensive reagents, and use of toxic solvents.
Thus, there is an increasing interest in the development of new catalysts
under mild reaction conditions with cleaner reaction profiles, good yields,
less catalyst load, and simple experimental and isolation procedures.
Solvent-free organic synthesis has received considerable attention as
a result of growing worldwide concerns about chemical wastes and future
resources.[33] Ionic liquids have attracted increasing interest in recent
years because of their properties of nonvolatility, nonflammability, ther-
mal stability, low toxicity and reusability. A variety of catalytic reactions
have been successfully conducted with ionic liquids as catalysts or
solvents.[34,35] In this article, we report a simple and very efficient
Knoevenagel condensation reaction of aromatic aldehydes with active
methylene compounds catalyzed by 2-hydroxyethylammonium acetate
ionic liquid under solvent-free conditions at room temperature
(Scheme 1).
2-Hydroxyethylammonium acetate ionic liquid was easily prepared
from cheaply available acetic acid and 2-aminoethanol by a simple
acid–base reaction.[36] Initially, we examined the effects of catalyst load
on the condensation of benzaldehyde and ethylcyanoacetate. The results
are summarized in Table 1. The yield increased with the increase of cat-
alyst load, and the optimum molar ratio of 2-hydroxyethylammonium
acetate to the substrate was about 20% (entry 3). Further increasing
the amount of 2-hydroxyethylammonium acetate did not led to greater
yield (entry 4). Subsequently, Knoevenagel condensation of ethylcyanoa-
cetate and malononitrile with a variety of aromatic aldehydes with
20 mol % of 2-hydroxyethylammonium acetate as catalyst was investi-
gated. Results listed in Table 1 show efficient Knoevenagel condensation
of aromatic aldehydes with active methylene compounds in the presence
of 2-hydroxyethylammonium acetate. Aromatic aldehydes with electron-
donating or electron withdrawing substituents could react very well with
malononitrile, and good to excellent yields were achieved in a very
Scheme 1. Knoevenagel condensation of aromatic aldehydes with ethyl cyanoace-
tate and malononitrile.

Ionic Liquid–Catalyzed Knoevenagel Condensation
2003
Table 1. Knoevenagel condensation catalyzed by 2-hydroxyethylammonium
acetatea
Time
(min)b
Yield
(%)c
Entry
R1
R2
1d
2e
3
C6H5
C6H5
C6H5
C6H5
4-CH3OC6H4
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-(CH3)2NC6H4
4-NO2C6H4
2-Furyl
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–COOEt
–CN
180
30
25
25
30
2
2
2
2
3
60
1
2
2
1
1
1
1
2
63
76
80
80
90
85
95
95
95
95
90
93
84
85
96
94
92
91
95
85
4f
5
6
7
8g
9h
10i
11
12
13
14
15
16
17
18
19
20
C6H5CH¼CH
C6H5
4-CH3OC6H4
4-ClC6H4
–CN
–CN
–CN
–CN
4-CH3C6H4
4-(CH3)2NC6H4
C6H5CH¼CH
–CN
1
aUnless otherwise indicated, the reaction was carried out using 2-hydroxyethyl-
ammonium acetate (3 mmol), aldehyde (15 mmol), and active methylene com-
pound (15 mmol). All the products are known compounds and were identified
by comparison of their melting points and spectral data with those reported.
bThe mixture was stirred at room temperature. After the mixture solidified, the
workup was performed.
cIsolated yield.
dThe amount of 2-hydroxyethylammonium acetate is 0.75 mmol.
eThe amount of 2-hydroxyethylammonium acetate is 1.5 mmol.
fThe amount of 2-hydroxyethylammonium acetate is 4.5 mmol.
gThe second run.
hThe third run.
iThe fourth run.
short reaction time. The less-active methylene compounds such as
ethylcyanoacetate also reacted with the aldehydes to give the correspond-
ing products with good to excellent yields in short periods. The reuse of 2-
hydroxyethylammonium acetate was studied, and 4-methylbenzaldehyde
and ethyl cyanoacetate were chosen as the substrates. It was shown that

2004
Z. Zhou, J. Yuan, and R. Yang
ionic liquid retained strong catalytic activity for four runs (entries
7–10). In this methodology; reactions were completed in a short time
and with excellent yields; workup procedure is simple. In addition, all
the reactions were carried out at room temperature with constant stirring
(i.e., using mild reaction conditions). Another attractive feature of this
methodology is the use of recyclable ionic liquid as catalyst under
solvent-free conditions, primarily avoiding toxic organic solvent in the
whole procedure and thus decreasing both the cost of the synthesis and
the amount of waste flow.
In summary, we have demonstrated a simple and very efficient
Knoevenagel condensation reaction of one aromatic aldehyde with each
active methylene compounds to obtain condensation products in good
to excellent yields under mild reaction conditions using the inexpensive
and environmentally friendly ionic liquid 2-hydroxyethylammonium
acetate as catalyst. The workup is simple, and 2-hydroxyethylammo-
nium acetate can be used at least four runs without noticeable loss of
catalytic activity.
EXPERIMENTAL
Melting points were uncorrected. Fourier transform–infrared (FT-IR)
spectra were obtained on a Nexus 470 spectrophotometer. 1H NMR spec-
tra were recorded on a Varian Mercury 300 spectrometer.
In a round-bottomed flask, 2-hydroxyethylammonium acetate
(3 mmol) was added to a stirring mixture of 4-methylbenzaldehyde
(15 mmol) and ethyl cyanoacetate (15 mmol) at room temperature. After
completion of the reaction, the crude product was purified by recrys-
tallization from 95% ethanol to give pure ethyl (E)-2-cyano-3-(4-methyl-
phenyl)-2-propenoate (3.1 g, 95%) as white crystals, mp 89–91ꢀC (lit.[32]
88–89ꢀC). The mother liquor was concentrated under reduced pressure
to give the ionic liquid. The ionic liquid was washed with a small amount
of ethyl acetate and dried under vacuum. A second run using the recov-
ered ionic liquid was performed under the identical conditions.
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