Novel, efficient, and green procedure for the Knoevenagel condensation catalyzed by diammonium hydrogen phosphate in water

Article abstract of DOI:10.1080/10916460600946113

Knoevenagel condensation of various aromatic and heteroaromatic aldehydes with active methylene compounds such as methyl and ethyl cyanoacetate, malononitrile, and cyanoacetamide proceeds smoothly with stirring in water in the presence of 4 mol% of diammo

Full text of DOI:10.1080/10916460600946113

This article was downloaded by: [Colorado College]
On: 14 October 2014, At: 16:09
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Novel, Efficient, and Green Procedure for
the Knoevenagel Condensation Catalyzed by
Diammonium Hydrogen Phosphate in Water
a
a
b
Saeed Balalaie , Morteza Bararjanian , Shohreh Hekmat & Peyman
c
Salehi
a
Department of Chemistry , K. N. Toosi University of Technology , Tehran,
Iran
b
Department of Chemistry , Islamic Azad University , Tehran, Iran
c
Department of Phytochemistry , Medicinal Plants and Drugs Research
Institute, Shahid Beheshti University , Tehran, Iran
Published online: 01 Dec 2006.
To cite this article: Saeed Balalaie , Morteza Bararjanian , Shohreh Hekmat & Peyman Salehi (2006) Novel,
Efficient, and Green Procedure for the Knoevenagel Condensation Catalyzed by Diammonium Hydrogen
Phosphate in Water, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 36:24, 3703-3711, DOI: 10.1080/10916460600946113
To link to this article: http://dx.doi.org/10.1080/10916460600946113
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

w
Synthetic Communications , 36: 3703–3711, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/10916460600946113
Novel, Efficient, and Green Procedure for
the Knoevenagel Condensation Catalyzed by
Diammonium Hydrogen Phosphate
in Water
Saeed Balalaie and Morteza Bararjanian
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran
Shohreh Hekmat
Department of Chemistry, Islamic Azad University, Tehran, Iran
Peyman Salehi
Department of Phytochemistry, Medicinal Plants and
Drugs Research Institute, Shahid Beheshti University,
Tehran, Iran
Abstract: Knoevenagel condensation of various aromatic and heteroaromatic
aldehydes with active methylene compounds such as methyl and ethyl cyanoacetate,
malononitrile, and cyanoacetamide proceeds smoothly with stirring in water in the
presence of 4 mol% of diammonium hydrogen phosphate. The reactions were
carried out at room temperature in short periods with a very simple workup
procedure and good to high yields.
Keywords: Alkene, diamamonium hydrogen phosphate, Knoevenagel condensation,
water
Received in the U.K. January 14, 2006
Address correspondence to Saeed Balalaie, Department of Chemistry, K. N. Toosi
University of Technology, P.O. Box 15875-4416, Tehran, Iran. E-mail: balalaie@kntu.
ac.ir
3
703

3
704
S. Balalaie et al.
INTRODUCTION
The Knoevenagel condensation of aldehydes with active methylene
compounds is an important and widely employed method for carbon–
[1]
carbon bond formation in organic synthesis. The versatile Knoevenagel
reaction has numerous applications in the elegant synthesis of fine
[
chemicals, in the hetero Diels–Alder reaction, and in synthesis of carbo-
2]
[3]
[4]
cyclic and heterocyclic compounds of biological significance. The reaction
is usually catalyzed by bases such as amines or their ammonium salts,
[
5]
[6]
ammonia, and sodium ethoxide in organic solvents.
Lewis acids,
have also been employed to
catalyze the reaction. Recently, the solvent-free Knoevenagel condensation
[
7]
[8]
zeolites,
and heterogenous catalysts
[9]
[10]
on solid support promoted by infrared,
[
ultrasound,
and also in support-free stoichiometric molten condition
or microwave
[12]
11]
irradiation
has been a matter of interest. However, most of the reported procedures
were carried out in organic solvents with a notable amount of waste. It
should be emphasized that most solvent-free methods still require organic
solvents during workup, and this is so for the catalyst-free Knoevenagel
[
13]
[14]
reaction in water. Kaupp et al. reported a green method for the Knoeve-
nagel condensation by the molten catalyst and in the absence of solvent. Yet
high reaction temperatures (150–1708C) and long reaction times were
required for a complete reaction. There are also some new catalysts such as
[
15]
[16]
[17]
TPP (triphenylphosphane), urea, ionic liquids, and TBAH (tetrabuty-
[
18]
lammonium hydroxide)
that were used for the Knoevenagel condensation.
Nowadays, in the development of a new synthesis, ecological points of
view must also be taken into account. In this process the solvents are
especially important, because they are generally used in large quantities.
Many organic solvents are ecologically harmful, and their use should
therefore be minimized as far as possible or even avoided altogether. One
ideal alternative under investigation as solvent for organic reactions is
[
19]
water ; many biochemical processes occur in the presence of water, and
the diversity of the in vivo reactions has prompted chemists to rediscover
the potential of water as a solvent. Some efforts have been made to perform
the Knoevenagel condensation in aqueous medium as well as in the absence
[20]
of organic solvents. (Scheme 1)
RESULTS AND DISCUSSION
I continue our interest in the Knoevenagel condensation and its applications in
[21]
the synthesis of bioactive molecules, we hereby report a very simple, green,
and highly efficient method for the condensation of various aromatic and het-
eroaromatic aldehydes (1) with several active methylene compounds (2) such
as malononitrile, methyl- and ethyl cyanoacetate, and cyanoacetamide. The
reactions were carried out in water at room temperature in the presence of

Diammonium Hydrogen Phosphate in Water
3705
Scheme 1.
4 mol% of diammonium hydrogen phosphate. It was exciting to observe that,
except in a few cases, all reactions run rapidly and were completed in just a
few minutes, giving excellent yields of the Knoevenagel product 3.
It was also shown that natural phosphate,
[
22]
[23]
AlPO -Al O ,
natural
[25]
and phosphate complexes
4
2 3
[24]
phosphate doped with potassium fluoride,
are efficient catalysts for the Knoevenagel condensation, but all the reported
methods need extraction with organic solvents or advance preparation of
the catalyst. Diammonium hydrogen phosphate is a very cheap, nontoxic,
and commercially available compound that can be used in practice without
any special precaution. To the best of our knowledge, there is only one
report on the application of diammonium hydrogen phosphate in the
[26]
synthesis of some classes of heterocyclic compounds.
At first, the reaction of 4-chlorobenzaldeyde with malononitrlie was
selected as a model to examine the effects of catalyst ranging from 0–10%
at room temperature. The best yield was obtained when the reaction was
carried out in the presence of 4 mol% of diammonium hydrogen phosphate
in aqueous media. No other by-product was formed during the course of the
reaction. Electron-deficient aldehydes gave relatively higher yields than
electron-rich counterparts.
In conclusion, we have demonstrated that the Knoevenagel condensation
between aromatic and heteroaromatic aldehydes with active methylene
compounds can be effectively performed at room temperature in the
presence of a catalytic amount (4 mol%) of diammonium hydrogen
phosphate in aqueous media, which provides a simple route to the synthesis
of trisubstituted alkenes. The present method has many obvious advantages
compared to those reported in literature, including simplicity of the method-
ology, ease of product isolation (only simple filtration), good yields, short
reaction times, use of a very cheap catalyst, and being environmentally
benign (Table 1).
EXPERIMENTAL
Melting points were recorded on an Electrothermal 9100 melting-point
apparatus and are not corrected. IR spectra were recorded on a FT-IR
1
Perkin-Elmer GX spectrophotometer using KBr disks. H NMR spectra

3
706
S. Balalaie et al.
Table 1. Synthesis of alkenes catalyzed by diammonium hydrogen phosphate in
aqueous media
Mp (8C)
a
Yield
(%)
Product
Ar
4-Cl-C
4-Me N-C H
R
Found
Reported
[
27]
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
6
H
4
CN
70
80
85
90
75
90
87
92
92
90
90
85
80
82
83
95
90
80
90
70
161
162
179–180
[
23]
CN
CN
CO
179
160
2
6
4
[
18,27]
4-NO
2
-C
6
H
4
160
[
89
5a,21a]
C
4-Cl-C H
6
H
5
2
Me
89
122
CO Me
2
6
4
2,4-Cl
3-OH-C
4-Me N-C H
2
-C
6
H
3
CO
CO
2
Me
Me
78
145
79–80
g
h
i
6
H
4
2
[
[
[
18]
18]
18]
CO Me
2
146
135
146
135
178
2
6
4
3-NO -C H
CO Me
2
2
2
6
4
4
j
4-NO
-C
6
H
CO
CO
2
Me
Me
178
144
[
21a]
k
l
PhCH 55 CH-
2-Furyl
2-Thienyl
2
145
[
95
15,21a]
CO Me
2
94
m
n
o
p
q
r
s
CO
CO
2
Me
Et
113–114
91–92
125
[
23]
4-Cl-C
6
H
4
2
91
[
[
18]
4-Me N-C H
2
CO Et
2
125
139
6
4
18]
16]
3-NO
2-Furyl
2-Thienyl
2
-C
6
H
4
CO
CO
2
Et
Et
139
91–93
106
[
2
91–93
[
18]
CO Et
2
105–108
237–238
3-NO
4-NO
2
2
-C
-C
6
H
H
4
4
CONH
CONH
2
2
156–159
235–236
[
16]
t
6
a
In all cases, the yields are related to pure isolated compounds.
were recorded on Bruker DRX 500 (500 MHz) Avance spectrometer in CDCl3
using TMS as the internal standard.
General Procedure for the Preparation of Alkenes at Room
Temperature
To a stirred solution of malononitrile (2.2 mmol, 145 mg) in water (10 ml),
diammonium hydrogen phosphate (7 mg, 0.04 mmol) and benzaldehyde
(
212 mg, 2 mmol) were added. Progress of the reaction was monitored by
thin-layer chromatography (TLC) (eluent: petroleum ether–EtOAc, 3:1).
After 10 min, the solid material was isolated by simple filtration. Further puri-
fication for some samples was made by recrystallization from EtOH.
Selected Data for Compounds 3a–t
[
27]
3
a: 2-(4-Chlorophenylmethylene)malononitrile: mp: 1618C [lit.: 1628C]
;
IR (KBr, cm ): 3038, 2227, 1583, 1486; H NMR (d, CDCl ) 7.56
2
1
1
3

Diammonium Hydrogen Phosphate in Water
3707
(
d, 2H, J ¼ 8.4 Hz, H-Ar), 7.77 (s, 1H, H-C 55 C), 7.89 (d, 2H, J ¼ 8.4 Hz,
H-Ar).
3
1
b: 2-(4-N,N-dimethylphenylmethylene)malononitrile: mp: 1798C [lit.: 179–
[18,23] 21
80]
; IR (KBr, cm ): 3010, 2208, 15609.
[18,27]
3
IR (KBr, cm ): 3038, 2227, 1582, 1519; H NMR (d, CDCl ) 7.88 (s,
c: 2-(4-Nitrophenylmethylene)malononitrile: mp: 1608C [lit.: 160]
;
2
1
1
3
1H, H-C 55 C), 8.10 (d, 2H, J ¼ 7.20 Hz, H-Ar), 8.39 (d, 2H, J ¼ 7.2 Hz,
H-Ar).
[
5a,21a]
3
d: Methyl-(E)-2-cyano-3-phenyl-2-propenoate: mp: 898C [lit.: 89]
; IR
KBr, cm ): 3038, 2227, 1725, 1608, 1428; H NMR (d, CDCl ) 3.90 (s, 3H,
2
1
1
(
OMe), 7.70–8.15 (m, 5H, Ar), 8.25 (s, 1H, H-C 55 C).
3
3
(
e: Methyl-(E)-2-cyano-3-(4-chlorophenyl)-2-propenoate: mp: 1228C; IR
2
KBr, cm ): 3060, 2227, 1725, 1583; H NMR (d, CDCl ) 3.99 (s, 3H,
1
1
3
OMe), 7.53 (d, 2H, J ¼ 8.60 Hz, H-Ar), 7.98 (d, 2H, J ¼ 8.60 Hz, H-Ar),
8
.25 (s, 1H, H-C-C).
3
(
f: Methyl-(E)-2-cyano-3-(2,4-dichlorophenyl)-2-propenoate: mp: 788C; IR
2
1
1
KBr, cm ): 3050, 2250, 1731, 1577; H NMR (d, CDCl ) 4.00 (s, 3H,
3
OMe), 7.45 (dd, 1H, J ¼ 8.50, 1.70 Hz, H-Ar), 7.59 (d, 1H, J ¼ 1.70 Hz,
H-Ar), 8.25 (d, 1H, J ¼ 8.50, H-Ar), 8.65 (s, 1H, H-C 55 C).
3
g: Methyl-(E)-2-cyano-3-(3-hydroxyphenyl)-2-propenoate: mp: 1458C; IR
2
KBr, cm ): 3412, 3032, 2227, 1725, 1596; H NMR (d, CDCl ) 3.98
1
1
(
(
3
s, 3H, Me), 5.90 (brs, 1H, OH), 7.12 (m, 1H, Ar), 7.41 (t, 1H, J ¼ 7.80 Hz,
H-Ar), 7.47 (d, 1H, J ¼ 7.80 Hz, H-Ar), 8.25 (s, 1H, H-C 55 C).
3
[
h: Methyl-(E)-2-cyano-3-(4-N,N-dimethylphenyl)-2-propenoate: mp: 1468C
[18] 21 1
lit.: 146] ; IR (KBr), [cm ] 2907, 2215, 1715, 1610, 1575; H NMR (d,
CDCl ) 3.10 (s, 6H,-NMe), 3.90 (s, 3H, OMe), 6.70 (d, 2H, J ¼ 9 Hz,
3
H-Ar), 7.90 (d, 2H, J ¼ 9 Hz, H-Ar), 8.20 (s, 1H, 55 CH).
3
1
i: Methyl-(E)-2-cyano-3-(3-nitrophenyl)-2-propenoate: mp: 1358C [lit.:
[18] 21
358C] ; IR (KBr, cm ) 3080, 2226, 1720, 1609, 1536, 1359.
[18]
3
IR (KBr, cm ) 3119, 2847, 2225, 1731, 1613; H NMR (d, CDCl ) 4.0 (s, 3H,
j: Methyl-(E)-2-cyano-3-(4-nitrophenyl)-2-propenoate:1788C[lit.:1788C]
;
2
1
1
3
OMe), 8.15 (d, 2H, J ¼ 9 Hz, Ar), 8.34 (s, 1H, H 22 C 55 C), 8.38 (d, 2H,
J ¼ 9 Hz, Ar).
[
21a]
3
IR (KBr, cm ) 3031, 2220, 1611,1583; H NMR (d, CDCl ) 3.94 (s, 3H,
k: Methyl-(E)-2-cyano-5-phenyl-2,4-pentadieneoate: 1458C [lit.: 1458C]
;
2
1
1
3

3
708
S. Balalaie et al.
OMe), 7.33 (m, 2H, HC 55 C), 7.42–7.48 (m, 3H, H-Ar), 7.63 (m, 2H, H-Ar),
8
.06 (dd, 1H, J ¼ 11, 2.9 Hz, HC 55 C).
[
15,21a]
3
(
l: Methyl-(E)-2-cyano-3-(furyl)-2-propenoate: 948C [lit.: 958C]
; IR
KBr, cm ) 3135, 2961, 2221, 1725, 1538; H NMR (d, CDCl ) 3.95
2
1
1
3
(
s, 3H, OMe), 6.70 (dd, 1H, J ¼ 4.0, 1.9 Hz, H-Furyl), 7.45 (d, 1H,
J ¼ 4.0 Hz, H-Furyl), 7.78 (d, 1H, J ¼ 1.9 Hz, H-Furyl), 8.05 (s,1H,
H-C 55 C).
2
1
3
3
7
7
m: Methyl-(E)-2-cyano-3-(thienyl)-2-propenoate: 1138C IR (KBr, cm
)
090, 2961, 2220, 1719, 1596; H NMR (d, CDCl ) 3.96 (s, 3H, OMe),
1
3
.27 (d, 1H, J ¼ 4.50 Hz, H-thienyl), 7.83 (d, 1H, J ¼ 4.50 Hz, H-thienyl),
.89 (d, 1H, J ¼ 3, 50 Hz, H-thienyl), 8.39 (s, 1H, H-C 55 C).
3
9
n: Ethyl-(E)-2-cyano-3-(4-chlorophenyl)-2-propenoate: 91–928C [lit.:
18C] ; IR (KBr, cm ) 3050, 2950, 2220, 1725, 1608; H NMR (d,
[
23]
21
1
CDCl ) 1.45 (t, 3H, J ¼ 7.12 Hz), 4.43 (q, 2H, J ¼ 7.12 Hz, OCH ), 7.52
3
2
(
H-C 55 C).
d, 2H, J ¼ 8.56 Hz, H-Ar), 7.97 (d, 2H, J ¼ 8.56 Hz, H-Ar), 8.23 (s, 1H,
3
1
o: Ethyl-(E)-2-cyano-3-(4-N,N-dimethylphenyl)-2-propenoate: 1258C [lit.:
[18] 21 1
258C] ; IR (KBr, cm ) 2944, 2212, 1713, 1611, 1575; H NMR: (d,
CDCl ) 1.40 (t, 3H, J ¼ 8 Hz, CH ), 3.10 (s, 6H, 2NMe), 4.30 (q, 2H,
3
3
J ¼ 8 Hz, OCH ), 6.70 (d, 2H, J ¼ 9 Hz, H-Ar), 7.90 (d, 2H, J ¼ 9 Hz,
2
H-Ar), 8.10 (s, 1H, HC 55 C).
[
18]
3
p: Ethyl-(E)-2-cyano-3-(3-nitrophenyl)-2-propenoate: 1398C [lit.: 1398C]
;
IR (KBr, cm ) 3036, 2226, 1727, 1609, 1537; H NMR: (d, CDCl ):
2
1
1
3
d ¼ 1.50 (t, 3H, J ¼ 7.2 Hz, CH ), 4.40 (q, 2H, J ¼ 7.2 Hz, OCH ), 7.6–
3
2
8.80 (m, 4H, Ar), 8.32 (s, 1H, 55 CH).
[
16]
3
q: Ethyl-(E)-2-cyano-3-(furyl)-2-propenoate: 91–938C [lit.: 91–938C]
;
IR (KBr, cm ) 3130, 3040, 2223, 1716, 1621; H NMR (d, CDCl ) 1.42
2
1
1
3
(
t, 3H, J ¼ 7.2 Hz, Me), 4.40 (q, 2H, J ¼ 7.2 Hz, OCH ) 6.69 (dd, 1H,
2
J ¼ 3.6, 1.5 Hz, H-Furyl), 7.44 (d, 1H, J ¼ 3.6 Hz, H-Furyl), 7.75 (d, 1H,
J ¼ 1.5 Hz, H-Furyl), 8.05 (s,1H, H-C 55 C).
[
15,18]
3
r: Ethyl-(E)-2-cyano-3-(thienyl)-2-propenoate: 1068C [lit.: 105–1088C]
;
IR (KBr, cm ) 3086, 2219, 1717, 1599; H NMR: (d, CDCl ) 1.39 (t, 3H,
2
1
1
3
J ¼ 7.1 Hz, CH ), 4.36 (q, 2H, J ¼ 7.1 Hz, CH ), 7.26 (t, J ¼ 4.79 Hz, 1H,
3
2
H-Thienyl), 7.81 (d, J ¼ 4.90 Hz, 1H, H-Thienyl) 7.88 (d, J ¼ 3.70 Hz, 1H,
H-Thienyl), 8.37 (s, 1H, H-C 55 C).
2
1
3
3
s: 2-Cyano-3-(3-nitrophenyl)-2-propenamide: 156–1598C; IR (KBr, cm
)
3418, 3129, 2227, 1706, 1608; H NMR (d, CDCl ) 5.80 (brs, 1H, NH),
1
3

Diammonium Hydrogen Phosphate in Water
3709
6
.30 (brs, 1H, NH), 7.77 (t, 1H, J ¼ 8 Hz, H-Ar), 8.32 (d, 1H, J ¼ 7.7 Hz,
H-Ar), 8.43 (d, 1H, J ¼ 7.7 Hz, H-Ar), 8.45 (s, 1H, H-C 55 C), 8.77 (d, 1H,
J ¼ 1.67 Hz, H-Ar).
[
16]
3
t: 2-Cyano-3-(4-nitrophenyl)-2-propenamide: 235–2388C [lit.: 237–2388C]
;
IR (KBr, cm ) 3438, 3347, 2227, 1688, 1596; H NMR (d, CDCl ) 7.35 (brs,
2
1
1
3
1
H, NH), 7.45 (brs, 1H, NH), 8.12 (d, 2H, J ¼ 8.7 Hz, H-Ar), 8.39 (d, 2H,
J ¼ 8.7 Hz, H-Ar), 8.44 (s, 1H, H-C 55 C).
ACKNOWLEDGMENTS
Saeed Balalaie is grateful to the Alexander von Humboldt foundation for the
research fellowship and equipment donation. Partial support of this work by
the K. N. Toosi University of Technology Research Council is gratefully
acknowledged.
REFERENCES
1
. (a) Jones, G. The Knoevenagel condensation reaction. In Organic Reactions; John
Wiley: New York, 1967; Vol. 15, p. 204; (b) Tietze, L.; Beifuos, V. The Knoeve-
nagel condensation, In Comprehensive Organic Synthesis; B. M. Trost and I.
Fleming, Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp. 341–392 Chapter 1.11.
. Freeman, F. Properties and reactions of ylidene malononitriles. Chem Rev. 1981,
2
3
81, 329.
. (a) Borah, H. N.; Deb, M. L.; Boruah, R. C.; Bhuyan, P. J. Stereoselective intra-
molecular hetero Diels–Alder reaction of 1-oxa-1,3-butadienes: Synthesis of
novel annelated pyrrolo[1,2-a]indoles. Tetrahedron Lett. 2005, 46, 3391.
4
5
. Tietze, L. F. Domino reactions in organic synthesis. Chem. Rev. 1996, 96, 115.
. (a) Ayoubi, S. A.; Texier-Boullet, F.; Hamelin, J. Minute synthesis of electrophilic
alkenes under microwave irradiations. Synthesis 1994, 258, and references therein;
(
b) Ayoubi, S. A.; Texier-Boullet, F. Clay-mediated synthesis of gem-bis(alkoxy-
carbonyl)alkenes under microwave irradiation. J. Chem. Res. Synop. 1995, 208;
c) Choudary, B. M.; Kantam, M. L.; Neeraja, V.; Rao, K. K.; Figueras, F.;
(
Delmotte, L. Layered double hydroxide fluoride: A novel solid base catalyst for
C-C bond formation. Green Chem. 2001, 3, 257; (d) Narasaiha, A. V.;
Basak, A. K.; Visali, B.; Nagaiah, K. An eco-friendly synthesis of electrophilic
alkenes catalyzed by dimethyl aminopyridine under solvent-free conditions.
Synth. Commun. 2004, 34, 2893.
6
. (a) Prajapati, D.; Lekhok, K. C.; Sandhu, J. S.; Ghosh, A. C. Lithium bromide as a
new catalyst for carbon–carbon bond formation in solid state. J. Chem. Soc. Perkin
Trans. 1 1996, 959; (b) Rao, P. S.; Ratnam, R. V. Zinc chloride as a new catalyst
for Knoevenagel condensation. Tetrahedron Lett. 1991, 32, 5821;
(
catalyzed by LaCl
c) Narsaiah, A. V.; Nagaiah, K. An efficient Knoevenagel condensation
.
3 2
7H O in hetergenous medium. Synth. Commun. 2003, 33,
3825.

3
710
S. Balalaie et al.
7
. (a) Wang, Q. L.; Ma, Y.; Zuo, B. Knoevenagel condensation catalyzed by USY
zeolite. Synth. Commun. 1997, 27, 4107; (b) Reddy, T. I.; Varma, R. S. Rare-
earth (RE) exchanged NaY zeolite promoted Knoevenagel condensation. Tetrahe-
dron Lett. 1997, 38, 1721.
8
. Lu, Y.; Ren, Z.; Cao, W.; Tong, W.; Gao, M. Solent-free synthesis of ethyl a-cya-
nocinnamate in the presence of CaO. Synth. Commun. 2004, 34, 2047.
. Obrador, E.; Castro, M.; Tamariz, J.; Zepeda, G.; Miranda, R.; Delgado, F. Knoe-
venagel condensation in heterogeneous phase catalyzed by IR radiation and tonsil
actisil FF. Synth. Commun. 1998, 28, 4649.
9
1
0. Li, J. T.; Chen, G. F.; Wang, S. X.; He, L.; Li, T. S. Synthesis of arylmethylene-
malononitrile catalyzed by KF-Al under ultrasound. Aus. J. Chem. 2005, 58,
31.
2 3
O
2
11. (a) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacqualt, P.; Mathe, F.
New solvent-free organic synthesis using focused microwave. Synthesis 1998,
1213; (b) Hayes, B. L. Recent advances in microwave assisted synthesis. Aldrichi-
mica Acta 2004, 73, 66.
1
1
1
1
1
1
2. Ren, Z.; Cao, W.; Tong, W. The Knoevenagel condensation reaction of aromatic
aldehydes with malononitrile by grinding in the absence of solvents and catalyst.
Synth. Commun. 2002, 32, 3475.
3. Bigi, F.; Carloni, S.; Ferrari, L.; Maggi, R.; Mazzacani, A.; Sartori, G. Clean
synthesis in water, part 2: Uncatalyzed condensation reaction of Meldrum’s acid
and aldehydes. Tetrahedron Lett. 2001, 42, 5203.
4. Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J. Solvent-free Knoevenagel conden-
sation and Michael additions in the solid state and in the melt with quantitative
yield. Tetrahedron 2003, 59, 3753.
5. Yadav, J. S.; Reddy, B. S.; Basak, A. K.; Visali, B.; Narsaiah, A. V.; Nagaiah, K.
Phosphane-catalyzed Knoevenagel condensation: A facile synthesis of a-cyano-
acrylates and a-cyanoacrylonitriles. Eur. J. Org. Chem. 2004, 546.
6. Sun, Q.; Shi, L. X.; Ge, Z. M.; Cheng, T. M.; Li, R. T. An efficient and green
procedure for the Knoevenagel condensation catalyzed by urea. Chin. J. Chem.
2
005, 23, 745.
7. (a) Harjani, J. R.; Nara, S. J.; Salunkhe, M. M. Lewis acidic ionic liquids for the
synthesis of electrophilic alkenes via the Knoevenagel condensation. Tetrahedron
Lett. 2002, 43, 1127; (b) Chen, Z. C.; Zheng, Q. G. Organic reactions in ionic
liquids: Knoevenagel condensation catalyzed by ethylenediammonium diacetate.
Synthesis 2003, 555.
1
8. Balalaie, S.; Barajanian, M. Tetra-butylammonium hydroxide (TBAH) catalyzed
Knoevenagel condensation: A facile synthesis of a-cyanoacrylates, a-cyanoacry-
lonitriles, and a-cyanoacrylamides. Synth. Commun. 2006, 36, 533–539.
9. (a) Grieco, P. A. In Organic Synthesis in Water; Thomson Science: London, 1998;
pp. 1–304; (b) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media; John
Wiely and Sons: New York, 1997; pp. 1–189; (c) Lindstrom, U. M. Stereoselec-
tive organic reaction in water. Chem. Rev. 2002, 102, 2751.
1
2
0. (a) Hangarge, R. V.; Sonwane, S. A.; Jarikote, D. V.; Shingare, M. S. Water
mediated uncatalyzed facile synthesis of ylidenenitriles of 4-oxo-4H-1-benzo-
pyran-3-carbaldehyde. Green Chem. 2001, 3, 310; (b) Wang, S.; Ren, Z.;
Cao, W.; Tong, W. The Knoevenagel condensation of aromatic aldehydes with
malonitrile or ethylcyanoacetate in the presence of CTMAB in water. Synth.
Commun. 2001, 31, 673; (c) Deb, M. L.; Bhuyan, P. J. Uncatalyzed Knoevenagel
condensation in aqueous medium at room temperature. Tetrahedron Lett. 2005, 46,
6
453.

Diammonium Hydrogen Phosphate in Water
3711
21. (a) Balalaie, S.; Nemati, N. Ammonium acetate–basic alumina catalyzed
Knoevenagel condensation under microwave irradiation and solvent-free
condition. Synth. Commun. 2000, 30, 869; (b) Balalaie, S.; Nemati, N. One-pot
preparation of coumarins by Knoevenagel conditions under solvent-free
condition and microwave irradiation. Heterocycl. Commun. 2001, 7, 67.
2. (a) Sebti, S.; Saber, A.; Rhihil, A. Phosphate naturel et phosphate trisodique;
nouveaux catalyseurs solides de la condensation de Knoevenagel en milieu hetero-
gene. Tetrahedron Lett. 1994, 35, 9399; (b) Sebti, S.; Nazih, R.; Tahir, R.;
Saber, A. Fluorapatite/sodium nitrate as a solid support for the Knoevenagel
reaction. Synth. Commun. 2001, 31, 993.
2
2
2
2
2
3. Cabello, J. A.; Campelo, J. M.; Garcia, A.; Luna, D.; Marians, J. M. Knoevenagel
4 2 3
condensation in the heterogenous phase using AlPO -Al O as a new catalyst.
J. Org. Chem. 1984, 49, 5195.
4. Sebti, S.; Smahli, A.; Solhy. A. Natural phosphate doped with potassium flouride
and modified with sodium nitrate: Efficient catalysts for the Knoevenagel conden-
sation. Tetrahedron Lett. 2002, 43, 1813.
5. Bennazha, J.; Zahouilly, M.; Boukhari, A.; Hole, E. A. Investigation of catalytic
activity of solid state phosphate complexes in the Knoevenagel condensation.
J. Mol. Catal. A. 2003, 202, 247.
6. Salehi, P.; Dabiri, M.; Khosropour, A. R.; Roozbehniya, P. Diammonium
hydrogen phosphate: A versatile and cheap reagent for one-pot synthesis of dihy-
dropyrimidinones, quinazolinones, and azalactones under solvent-free conditions.
J. Iran. Chem. Soc. 2006, 3, 98–104.
27. Moison, H.; Texier-Boullet, F.; Foucaud, A. Knoevenagel, Wittig and Wittig–
Horner reactions in the presence of magnesium oxide or zinc oxide. Tetrahedron
1987, 43, 537.