Organic reactions in ionic liquids: Ionic liquid ethylammonium nitrate-promoted knoevenagel condensation of meldrum's acid with aromatic aldehydes

Article abstract of DOI:10.1080/00397910500278362

The Knoevenagel condensation of Meldrum's acid with aromatic aldehydes proceeded efficiently in a reusable ionic liquid, ethylammonium nitrate, at room temperature in the absence of any catalyst with high yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500278362

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Organic Reactions in
Ionic Liquids: Ionic
Liquid Ethylammonium
Nitrate–Promoted Knoevenagel
Condensation of Meldrum's
Acid With Aromatic Aldehydes
Yi Hu a b , Ping Wei a , He Huang a , Zhang‐Gao Le c &
Zhen‐Chu Chen b
a College of Life Science and Pharmaceutical
Engineering, Nanjing University of Technology,
Nanjing, China
b Department of Chemistry, Zhejiang University (Xi
Xi Campus), Hangzhou, China
c Department of Applied Chemistry, East China
Institute of Technology, Fuzhou, China
Published online: 21 Aug 2006.
To cite this article: Yi Hu , Ping Wei , He Huang , Zhang‐Gao Le & Zhen‐Chu
Chen (2005) Organic Reactions in Ionic Liquids: Ionic Liquid Ethylammonium
Nitrate–Promoted Knoevenagel Condensation of Meldrum's Acid With Aromatic
Aldehydes, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:23, 2955-2960
To link to this article: http://dx.doi.org/10.1080/00397910500278362

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Synthetic Communicationsw, 35: 2955–2960, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500278362
Organic Reactions in Ionic Liquids: Ionic
Liquid Ethylammonium Nitrate–Promoted
Knoevenagel Condensation of Meldrum’s
Acid With Aromatic Aldehydes
Yi Hu
College of Life Science and Pharmaceutical Engineering,
Nanjing University of Technology, Nanjing, China and Department
of Chemistry, Zhejiang University (Xi Xi Campus), Hangzhou, China
Ping Wei and He Huang
College of Life Science and Pharmaceutical Engineering,
Nanjing University of Technology, Nanjing, China
Zhang-Gao Le
Department of Applied Chemistry, East China Institute of Technology,
Fuzhou, China
Zhen-Chu Chen
Department of Chemistry, Zhejiang University (Xi Xi Campus),
Hangzhou, China
Abstract: The Knoevenagel condensation of Meldrum’s acid with aromatic aldehydes
proceeded efficiently in a reusable ionic liquid, ethylammonium nitrate, at room
temperature in the absence of any catalyst with high yields.
Keywords: Aromatic aldehydes, ionic liquids, Knoevenagel condensation,
Meldrum’s acid
Received in Japan March 27, 2005
Address correspondence to Yi Hu, Department of Chemistry, Zhejiang University
(Xi Xi Campus), Hangzhou, 310028, China. E-mail: amit-129@hotmail.com
2955

2956
Y. Hu et al.
The reactivity of the Meldrum’s acid (2,2-dimethyl-1,3-dioxan-4,6-dione) as a
methylene active compound was explored about 40 years after its preparation,
when the structure was correctly attributed by Davidson et al.,[1] who assigned
the acidic proton to the central carbon. Its high acidity is still a subject of
study.[2] It is known that Meldrum’s acid undergoes standard Knoevenagel
condensation with aromatic aldehydes to furnish the corresponding arylidene
derivatives, which are important intermediates in organic synthetic chemistry
and used as versatile substrates for different kinds of reactions.[3,4] The
Knoevenagel condensation of Meldrum’s acid with aromatic aldehydes is
generally catalyzed by bases, such as pyridine,[1,5] or by piperdine/glacial
acetic acid in benzene with water removal,[6] often using an excess of
aldehyde to minimize the undesired formation of a bis adduct resulting
from Michael addition with a second molecular of the methylene compo-
nent.[3c,6a,7] Uncatalyzed reactions were reported in the literature[8] using
DMF or DMSO as solvents, which are toxic, teratogenic, suspected carcino-
gens, and difficult to reuse. After long reaction times at room temperature,
these gave mixtures of one (mono) condensation product and a Michael
addition product for some aromatic aldehydes. Recently, Shi et al.[9] and
Bigi et al.[4] reported this uncatalyzed condensation reaction performed in
DMF and water respectively. The reactions need energy supply and
sometimes only moderate yields were obtained. Besides, Lewis acid
catalysts,[10] microwave irradiation,[11] ultrasound irradiation,[6] and melt
reaction[12] were applied to facilitate this condensation reaction. Considering
the importance of the product, arylmethylene isopropylidene malonate, we
think it is still significant to develop more facile and efficient methods with
environmentally sound technologies to prepare these compounds.
In recent years ionic liquids are emerging as potential “greener” alterna-
tives to volatile organic solvents[13] and they have been used as environmen-
tally benign media for many important organic reactions.[14] To date, some
reports have shown the Knoevenagel condensation could be performed
more efficiently using various catalysts in ionic liquids than the traditional
methods.[15] Previously, we have also reported an effective Knoevenagel con-
densation catalyzed by ethylenediammonium diacetate in ionic liquids
[Bmim]BF4 or [Bmim]PF6.[16] In continuation of our interest in using ionic
liquids as a recyclable, ecofriendly reaction medium in the Knoevenagel con-
densation, we found that Knoevenagel reaction of Meldrum’s acid with
aromatic aldehydes occurred in ionic liquid ethylammonium nitrate (EAN)
without any added catalyst. Shingare et al. reported a reaction of pyrazolone
with aromatic aldehydes in ethylammonium nitrate.[17]
First, we investigated the efficacy of EAN compared to the most
commonly used ionic liquids, [Bmim]PF6 and [Bmim]BF4 ([Bmim] ¼
1-butyl-3-methylimidazolium); some organic solvents; and water by the
model condensation between p-N,N-dimethylaminobenzaldehyde and
Meldrum’s acid. The experimental results summarized in Table 1 showed
that the ionic liquid, EAN, was truly comparable with the other traditional

Organic Reactions in Ionic Liquids
Table 1. Condensation of p-N,N-dimethylamino-
2957
benzaldehyde with Meldrum’s acid in different
solvents
Entrya
Solvent
Yields (%)b
1
2
3
4
5
6
7
EAN
95
41
[Bmim]PF6
[Bmim]BF4
Water
35
33
Ethanol
Benzene
DMF
18
65.2c
81d
aAll reactions were run with p-N,N-dimethyl-
aminobenzaldehyde (2mmol) and Meldrum’s acid
(2mmol) in 2 ml of solvent at room temperature for
half an hour.
bIsolated yield.
cLiterature[5b] reported yield obtained in refluxing
benzene catalyzed by piperdine/glacial acetic acid.
dLiterature[8] reported yield obtained after 1 h at
808C in DMF.
solvents, [Bmim]PF6 and [Bmim]BF4, with the advantage of rate acceleration
and increase of yield. Obviously, EAN played a dual role as solvent and
promoter in this reaction.
Next, the scope of the Knoevenagel condensation of Meldrum’s acid with
various aromatic aldehydes in the ionic liquid EAN was investigated
(Scheme 1). The results are summarized in Table 2. The products were charac-
1
terized by melting points, H NMR, and IR, which were consistent with the
literature data.
As can be seen from Table 2, this procedure was found to be general and
applicable to the aromatic aldehydes bearing various substituents such as
choloro, nitro, methoxyl, hydroxyl, N,N0-dimethylamino, and so forth. It is
noteworthy that aromatic aldehydes bearing electron-donating groups
reacted more easily compared with those containing electron-withdrawing
groups, which is different from the previous literature.[6,8,9] The reaction of
Scheme 1.

2958
Y. Hu et al.
Table 2. Condensation of Meldrum’s acid with aromatic aldehydes in EAN
Time
(h)
Yieldb
(%)
Mpc
Lit. mp
(8C)
Entrya
R
Product
(8C)
1
2
C6H5
1
3a
3b
3c
3d
3e
3f
90
97
96
95
92
92
94
93
80
91
95d
97e
83–84
163–164
82–83[6]
p-Me2NC6H4
p-MeOC6H4
p-OHC6H4
0.5
1
162–164[8]
3
124–125 126[5b]
4
1
194–195
166–167
161–162 162[10]
214–215 217[5b]
117–118 119[5b]
192–194[8]
167–169[8]
5
3,4-(OCH2)C6H3
p-ClC6H4
1
6
2
7
p-NO2C6H4
o-NO2C6H4
2-Furyl
2
3g
3h
3i
8
2
9
2
90–91
92[5b]
10
11
12
C6H5CH55CH
p-Me2NC6H4
p-Me2NC6H4
1
3j
108–109 108[5b]
163–164
163–164
0.5
0.5
3b
3b
aAll reactions were run with Meldrum’s acid (2 mmol) and aromatic aldehyde
(2 mmol) in 2 ml of EAN at room temperature.
bIsolated yields.
cMelting points are uncorrected.
d,eSecond and third recycling of EAN, respectively.
2-furancarboxaldehyde (Entry 9) and the aromatic a,b-unsaturated aldehyde,
cinnamic aldehyde (Entry 10), with Meldrum’s acid also could be completed
with high yields. Unfortunately, as simple as this reaction is, we could not
obtain satisfactory results when it was applied to aliphatic aldehydes and
ketones under the same reaction conditions. In addition, the ionic liquid
could be typically recovered and reused with no appreciable decrease in
yields and reaction rates (Entries 11 and 12).
In conclusion, we have demonstrated that the Knoevenagel condensation
of Meldrum’s acid with aromatic aldehydes can be effectively performed at
room temperature in the ionic liquid EAN. The present method has many
obvious advantages compared to previous methods, including no need for
any catalyst, being environmentally more benign, the easy of product
isolation, the simplicity of methodology, the higher yield, the generality,
and the potential for recycling of ionic liquid. We have shown the ionic
liquids play a dual role as solvent and promoter in this reaction and gives a
simpler system—a good example of green chemistry.
EXPERIMENTAL
Melting points were determined on digital melting-point apparatus and are
1
uncorrected. Infrared spectra were recorded on a Vector22 (Brucker), and H
NMR spectra were recorded on a Bruker 400-MHz spectrometer using CDCl3

Organic Reactions in Ionic Liquids
2959
asthe solvent withTMSasaninternalstandard. Theionic liquids[Bmim]PF6 and
[Bmim]BF4 weresynthesized accordingtotheliterature,[18] andethylammonium
nitrate (EAN) was synthesized according to the literature.[19]
General Procedure for the Knoevenagel of Meldrum’s Acid with
Aromatic Aldehydes
Meldrum’s acid 1 (2 mmol) and aromatic aldehyde 2 (2 mmol) were dissolved
in ionic liquid EAN (2 ml). The reaction mixture was stirred at room tempera-
ture for 0.5 to 2 h, and the reaction was monitored by TLC. Upon completion
of the reaction, all the insoluble material in the reaction mixture was filtered
and washed with water to give the desired products 3 in high yields with
essential purity. After isolation of the product, the remainder of the ionic
liquids ENA was dried for 4 h under vacuum at 508C. The next run was
performed under identical reaction conditions.
ACKNOWLEDGMENTS
This work is supported by the Natural Sciences Foundation of China (No:
20336010), and the State Key Basic Research and Development Project of
China (No: 2003CB7160004).
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