Synthesis of arylidene propanedioic acids by Knoevenagel condensation for use in ceramic sols

Article abstract of DOI:10.14233/ajchem.2014.17949

This paper is primarily concerned with the synthesis of arylidene propanedioic acids by Knoevenagel condensation. Generally organic bases pyridine and piperidine are used as catalyst in Knoevenagel condensation which are costly and health hazard. In this research work, Knoevenagel condensation of various aromatic aldehydes (benzaldehyde, salicylaldehyde and p-chlorobenzaldehyde) and active methylenes (malonic acid and ethyl acetoacetate) was carried out in the presence of amino acids (glycine, lysine, hippuric acid, methionine and leucine) as catalyst. Using salicylaldehyde gave coumarin-3-carboxylic acid, a solvent free synthesis. These products were isolated and purified and were characterized through melting points, TLC, IR, mass and ¹H NMR. These acids are synthesized for eventual development of organically modified ceramic nano powders.

Full text of DOI:10.14233/ajchem.2014.17949

Asian Journal of Chemistry; Vol. 26, No. 24 (2014), 8463-8466
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17949
Synthesis of Arylidene Propanedioic Acids by Knoevenagel Condensation for use in Ceramic Sols
1
2,3
4
SYED SALMAN SHAFQAT , MISBAHUL AIN KHAN , AZHAM ZULKHARNAIN ,
1
1
1,*
SININ HAMDAN , ANDREW RAGAI HENRY RIGIT and AMIR AZAM KHAN
1Department of Mechanical and Manufacturing Engineering, Faculty of Engineering, Universiti Malaysia Sarawak, 94300 Kota Samarahan,
Sarawak, Malaysia
2Institute of Chemistry, University of the Punjab, Lahore, Pakistan
3Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
4Department of Molecular Biology, Faculty of Resource Science & Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak,
Malaysia
*Corresponding author: E-mail: akamir@feng.unimas.my
Received: 5 May 2014;
Accepted: 26 August 2014;
Published online: 1 December 2014;
AJC-16382
This paper is primarily concerned with the synthesis of arylidene propanedioic acids by Knoevenagel condensation. Generally organic
bases pyridine and piperidine are used as catalyst in Knoevenagel condensation which are costly and health hazard. In this research work,
Knoevenagel condensation of various aromatic aldehydes (benzaldehyde, salicylaldehyde and p-chlorobenzaldehyde) and active methylenes
(malonic acid and ethyl acetoacetate) was carried out in the presence of amino acids (glycine, lysine, hippuric acid, methionine and
leucine) as catalyst. Using salicylaldehyde gave coumarin-3-carboxylic acid, a solvent free synthesis. These products were isolated and
purified and were characterized through melting points, TLC, IR, mass and 1H NMR. These acids are synthesized for eventual development
of organically modified ceramic nano powders.
Keywords: Knoevenagel condensation, Amino acid catalysis, Ceramic sols.
and as such economically very important material5. Many aryl
and hetaryl acrylic acids are reported in the literature, such as
INTRODUCTION
cinnamic acid, furylacrylic acid6, pyrrole acrylic acid7-10 and
Knoevenagel condensation reaction is a versatile method
pyridine acrylic acid11. Some of these acids are being coupled as
for the formation of new carbon-carbon bonds by reaction
between a carbonyl compound and an "active methylene" subs-
trate. Among various classes of compounds produced through
this reaction, acrylic acids are produced by the reaction of
aldehydes and malonic acid. This reaction needs base catalysis
and organic bases such as piperidine and pyridine are generally
employed at a waterbath temperature. The reaction is accompa-
nied by a decarboxylation. The intermediate dicarboxylic acid
is seldom isolated1. During the course of our work on pyrazole
carbaldehydes where we had utilized the reaction of 1-aryl-
pyrazole-4-carbaldehydes, using ethanol as a solvent, we were
surprised to find that the reaction with malonic acid as substrate
did not undergo decarboxylation and a dioic acid product was
obtained2. In our other area of research on the synthesis of
triarylimidazoles3 and Biginelli synthesis4, we have found amino
acids as efficient catalysts in these reactions. This led us to extend
our work for efficacy of amino acids as catalysts in other organic
reactions. Acrylic acid is an important molecule which has its
main utility as the starting material in various polymer reactions
monomers which are later on used in polymer synthesis.
Knoevenagel condensation provides this material but
utilizes pyridine or piperidine bases which are environmental
hazards.As such there is a need to explore other catalysts which
are environmentally benign. Amino acids thus seem to be of
choice. Literature search shows that there are few references
for the use of amino acids for catalyzing Knoevenagel conden-
sation12. Amino acids and their derivatives have been investi-
gated in the catalysis of reduction, oxidation, electrophilic α-
fluorination and amination, carbon-carbon bond forming reac-
tions13-16, transamidation of carboxamide17 as well as promoter
of some of the reaction.
We are now extending our work of this eco-friendly catalyst
in this condensation. Besides being non toxic these are well
tolerated by physiological systems and are readily available.
In this preliminary note we would like to report the findings
of our work in the synthesis of organic-inorganic polymeric
hybrid materials.

8464 Shafqat et al.
Asian J. Chem.
Organic-inorganic polymeric hybrid materials are
recrystallized from hot water. The results are presented in the
Table-2 (Scheme-II).
synthesized by sol-gel processing of organofunctional metal
alkoxides. These hybrid materials were initially termed as
“ormosil” (organically modified silane) and latter “oromocers”
(organically modified ceramis). Ormocers based on acrylic
acids will be synthesized to explore their utility as multipurpose
coatings. Acrylic co-polymers and acrylic acids modified
terpolymer-silica hybrinano composite18 as well as poly-
(oxyethylenemethacrylate) (POEM) modified silica nano-
particles19 with improved properties have been synthesized and
characterized.Acrylics were first made commercially available
in the 1950. The worldwide production of acrylic acid in 1994
was estimated to be approximately 2 million tonnes5.
O
O
OH
HO
Amino acid
H
OH
+
O
O
HO
(3)
O
(1)
(2)
Scheme-I
O
O
OH
HO
Amino acid
H
OH
+
O
O
Cl
Cl
O
OH
(4)
(2)
(5)
EXPERIMENTAL
Scheme-II
Most of the chemicals used during this research work were
of commercial quality and were purified through normal tech-
niques. Commercial TLC plates were used and UV light was
used as a spot locating agent. Infrared spectra (IR) were recorded
on Perkins Elmer FTIR (spectrum RXI) spectrometer. Mass
spectra were recorded on mass spectrometer (MAT 312 Model).
1H NMR spectra were recorded on Bruker NMRAM-400 MHz
and 300 MHz.
Coumarin-3-carboxylic acid (7): Following the general
procedure, from salicylaldehyde (6) malonic acid (2) and an
amino acid gave coumarin-3-carboxylic acid (7) which was
recrystallized from hot water. The results are given in the Table-3
(Scheme-III).
O
O
Preparation of arylidene propanedioic acids:A mixture
consisting of 0.2 mol of benzaldehyde (1), 0.2 mol of malonic
acid (2) and 0.01 g of an amino acid in a 50 mL round bottomed
flask was heated on a water bath for 2 h. The reaction mixture
was cooled to room temperature and poured into 20 mL cold
water. After 15 min standing it was filtered, washed with water,
dried and recrystallized from ethanol to give benzylidene
propanedioic acid (3) (Scheme-I).
OH
HO
Amino acid
H
OH
+
O
O
OH
O
O
(6)
(2)
(7)
Scheme-III
Ethyl-2-(4-chlorobenzylidene)-3-oxobutanoate (9): A
reaction of p-chlorobenzaldehyde (4) ethyl acetoacetate (8)
and an amino acid gave ethyl-2-(4-chlorobenzylidene)-3-
oxobutanoate (9). It was recrystallized thrice from hot water.
The results are presented in Table-4 (Scheme-IV).
p-Chlorobenzylidene propanedioic acid (5): From p-
chlorobenzaldehyde (4) and malonic acid (2) in 5 mL ethanol,
p-chlorobenzylidene propanedioic (5) was isolated which was
TABLE-1
YIELD OF COMPOUND 3 EMPLOYING VARIOUS AMINO ACID
CATALYSTS TOGETHER WITH THE 1H NMR, FTIR AND MASS SPECTRA
Catalyst
Glycine
Colour
Pale yellow
Yellow
Yield (%) m.p. (°C)
Lit. m.p.20
191°C
IR (cm-1)
Mass (m/z)
192(25 %)M+; 174(100
%);
1H NMR
65
56
68
65
64
185
188
186
190
182
Lysine
(CDCl3, 300 MHz)
δ: 7.24–.11(5H, m,
Ar-H, H-2-H-6)
1677cm-1 (C=O);
1628cm-1(C=C)
146(52 %); 129(26 %);
118(50 %); 102(51 %);
77(98 %).
Methionine
Hippuric acid
Leucine
White
White
Pale yellow
TABLE-2
SUMMARY OF CONDENSATION OF p-CHLOROBENZALDEHYDE WITH MALONIC ACID
Catalyst
Glycine
Lysine
Methionine
Hippuric acid
Leucine
Colour
White
White
Yellow
White
Light yellow
Yield (%) m.p. (°C)
Lit. m.p.21
IR (cm-1)
Mass (m/z)
58
76
55
65
70
210
205
198
207
202
226 (45 %) M+; 228 (16 %) M+; 180 (100
%); 173 (72 %); 165 (24 %); 152 (19 %);
136 (27 %); 101 (39 %); 75 (28 %).
1677 cm- 1 (C=O);
1623 cm-1 (C=C)
215 °C
TABLE-3
COMPOUND (7) FROM THE CONDENSATION OF SALICYLDEHYDE WITH MALONIC ACID
Catalyst
Glycine
Lysine
Methionine
Hippuric acid White
Leucine White
Colour Yield (%) m.p. (°C)
Lit. m.p.22
IR
Mass (m/z)
1H NMR
White
White
White
66
75
68
73
76
181
182
180
184
189
CDCl3, 300 MHz 9.97 (1H, 5, H-4), 8.03
(1H, dd, J = 8.5, 2.0 H2, H-5). 7.24 (1H,
ddd, J = 8.5, 2.0, 2.0 H2, H-6), 7.80 (1H,
ddd, J = 8.0, 7.5 2.0 Hz, H-7) 7.44 (1H,
dd, J = 8.0, 2.5 H2, H-8)
190 (31 %) M+; 146
(100 %); 118 (67 %);
89 (60 %); 63 (64 %).
1704 cm-1
(C=O)
189-192 °C

Vol. 26, No. 24 (2014)
Synthesis of Arylidene Propanedioic Acids by Knoevenagel Condensation for use in Ceramic Sols 8465
TABLE-4
COMPOUND (9) FROM THE CONDENSATION OF p-CHLOROBENZALDEHYE WITH ETHYL ACETOACETATE
Catalyst
Glycine
Lysine
Methionine
Hippuric acid White
Physical appearance
Pale yellow
White
Yield (%)
m.p. (°C)
154
155
158
155
IR (cm-1)
Mass (m/z)
63
65
55
50
68
252 (100 %) M+; (254 (30 %) M+; 237 (66 %); 217
(%); 207 (46 %); 178 (27 %); 165 (77 %); 141 (29
%); 101 (28 %); 83 (58 %);
1739 cm-1 (C=O);
1623 cm-1 (C=C)
Yellow
Leucine
White
156
O
O
It was expected that the use of amino acids will not only
catalyze the condensation but also help decarboxylation during
the course of the reaction since it was conducted at the water
bath (100 °C). But to our surprise in all the three reactions
and with all the amino acid catalysts (Tables 1-3) dioic acids
(3 and 5) and coumarin-3-carboxylic acid (7) were isolated.
There was no indication of corresponding decarboxylated
product.
O
O
Amino acid
H
+
CH
CH
3
3
O
CH
3
H C
3
Cl
Cl
O
O
(4)
(8)
(9)
Scheme-IV
These dioic acids3,5 could easily be decarboxylated to yield
the corresponding acrylic acids10,11 and the product also could
easily be selectively converted to compounds 10, 11 and 13
(Scheme-V).
RESULTS AND DISCUSSION
Benzylidene propanedioic acid: Condensation of
benzaldehyde (1) with malonic acid (2) was carried out in the
presence of glycine as catalyst. This reaction gave good yield
of benzylidene propanedioic acid (3).With a successful reaction
it was then carried out in the presence of some other amino
acids (Table-1). The product in each case was characterized
through its TLC, m.p., IR, mass spectrum and 1H NMR and
were found to be identical with the product obtained with
glycine (m.p., mixed m.p., TLC, IR 1677 cm-1 (C=O); mass
(m/z 192 (25 %) M+) and 1H NMR: δ 7.24-8.11 (5H, m, Ar-H,
H-2-H-6).
O
OH
O H
O
-CO
2
Heat
HO
O
(10)
(3)
O
O
OH
OH
-CO 2
Heat
p-Chlorobenzylidene propanedioic acid: A similar
condensation of p-chlorobenzaldehyde (4) with malonic acid
(2) with different amino acids as catalyst gave 4-chloro-benzy-
lidene propanedioic acid (5) characterized through its TLC,
m.p., IR and mass spectra (Table-2). All the products were
similar as characterized through IR and mass.
Cl
Cl
HO
O
(11)
(5)
O
O
O
CH3
Hydrolysis
CH3
Coumarin-3-carboxylic acid: Condensation of salicylal-
dehyde (6) with malonic acid (2) was carried out in the presence
of amino acids as catalyst (Table-3). The most important
characteristic of this reaction is that it is a solvent free synthesis
of coumarin derivatives. The product, coumarin-3-caboxylic
acid (7) was fully characterized through its TLC, m.p., IR,
mass and 1H NMR. The characteristic features of the spectra
are as follows; IR (KBr, νmax, cm-1): 1704 (C=O); mass (m/z):
190 (31 %) M+; 146 (100 %); 118 (67 %); 89 (60 %); 63
(64 %). 1H NMR: (CDCl3, 300 MHz): 9.97 (1H, 5, H-4), 8.03
(1H, dd, J = 8.5, 2.0, H2, H- 5). 7.24 (1H, ddd, J = 8.5, 2.0,
2.0 H2, H-6), 7.80 (1H, ddd, J = 8, 7.5 2.0 Hz, H-7) 7.44 (1H,
dd, J = 8.0, 2.5 H2, H-8).
Cl
O
Cl
O
OH
(9)
CH
3
(12)
O
-CO
2
CH
3
Heat
Cl
(13)
Scheme-V
In this preliminary note amino acids are shown to be
efficient catalysts in the Knoevenagel condensation. Further
work is in progress in our laboratories.
Conclusion
Ethyl-2-(4-chlorobenzylidene)-3-oxobutanoate: Con-
densation of p-chlrobenzyldehyde (4) with ethyl acetoacetate
(8) was carried out in the presence of amino acids as catalyst.
The product, ethyl-2-(4-chlorobenzylidene)-3-oxobutanoate
(9) in each case was characterized through its TLC, m.p., IR
and mass. All the products were similar as characterized
through IR, mass and 1H-NMR (Table-4). The salient features
of these spectra are as follows; IR (KBr, νmax, cm-1): 1739
(C=O); 1623 (C=C). Mass (m/z): 252 (100 %) M+; (254 (30 %)
M+; 237 (66 %); 217 (45 %); 207 (46 %); 178 (27%); 165
(77 %); 141 (29 %); 101 (28 %); 83 (58 %).
In conclusion, we have described a general and highly
efficient procedure for the preparation of some arylidene
propanedioic acids. It is concluded from this work that amino
acids in addition to be used in the synthesis employed as
catalyst in other Knoevenagel condensations as well as other
C-C bond forming reactions. In the present work the procedure
for the synthesis of coumarin involved a solvent less system
which is also environmentally benign. These acids have a
potential use for applications in synthesis of organometallic
sols for ceramic nano powders.

8466 Shafqat et al.
Asian J. Chem.
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materials. The applications of these composite materials can
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The authors are grateful to the Department of Mechanical
and Manufacturing Engineering, Faculty of Engineering,
Universiti Malaysia Sarawak (UNIMAS), 94300 Kota Samarahan,
Sarawak, Malaysia for supporting this work under the DPI
grant No 02(DPI08)/824/2011(08). The authors would also
like to thank the Institute of Chemistry, University of the
Punjab, Lahore, Pakistan, for their valuable help in conducting
experiments.
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