Green approach for Knoevenagel condensation of aromatic aldehydes with active methylene group

Article abstract of DOI:10.1080/00397911.2010.537423

An ecofriendly and economical method of Knoevenagel condensation of aromatic aldehydes with malononitrile catalyzed by lemon juice, a natural catalyst, in the absence of any solvent is described. Copyright Taylor & Francis Group, LLC.

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Green Approach for Knoevenagel
Condensation of Aromatic Aldehydes
with Active Methylene Group
M. B. Deshmukh a , Suresh S. Patil b , S. D. Jadhav b & P. B. Pawar b
a Department of Chemistry, Shivaji University, Kolhapur, India
b Department of Chemistry, PDVP College, Sangli, India
Accepted author version posted online: 07 Oct 2011. Version of
record first published: 22 Dec 2011
To cite this article: M. B. Deshmukh, Suresh S. Patil, S. D. Jadhav & P. B. Pawar (2012): Green
Approach for Knoevenagel Condensation of Aromatic Aldehydes with Active Methylene Group,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:8, 1177-1183
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Synthetic Communications1, 42: 1177–1183, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.537423
GREEN APPROACH FOR KNOEVENAGEL
CONDENSATION OF AROMATIC ALDEHYDES
WITH ACTIVE METHYLENE GROUP
M. B. Deshmukh,1 Suresh S. Patil,2 S. D. Jadhav,2 and
P. B. Pawar2
1Department of Chemistry, Shivaji University, Kolhapur, India
2Department of Chemistry, PDVP College, Sangli, India
GRAPHICAL ABSTRACT
Abstract An ecofriendly and economical method of Knoevenagel condensation of aromatic
aldehydes with malononitrile catalyzed by lemon juice, a natural catalyst, in the absence of
any solvent is described.
Keywords Knoevenagel condensation; lemon juice; malononitrile
INTRODUCTION
Concern for the environment demands the development of ecofriendly and
economical processes wherein even slightly hazardous by-products are not desirable.
In the development of new syntheses, ecological points of view must be taken into
account. A number of organic reactions employing natural catalysts such as clay[1,2]
and phosphates[3–5] are reported in literature. In accordance with this, we report the
Knoevenagel condensation of active methylene compound with aromatic aldehydes
in the presence of lemon juice, a natural catalyst, without any solvent (Scheme 1).
Citrus limonium, Citrus aurantium, and Citrus indica are some important spe-
cies of citrus family, commonly known as the lemon. The lemon is indigenous to
the northwestern regions of India and is also cultivated in Asia and Europe. It is
now widely grown in all tropical and subtropical countries. In India, it is also
cultivated in home gardens.
For the present work, we used the extract of Citrus limonium as a natural cata-
lyst. The main ingredients of this extract are moisture (85%), citric acid (5–7%),
carbohydrates (11.1%), vitamin C (0.4%), protein (1%), fat (0.9%), minerals
Received August 22, 2010.
Address correspondence to Suresh S. Patil, Department of Chemisty, PDVP College, Tasgaon
District, Sangli 416312, India. E-mail: sanyujapatil@yahoo.com
1177

1178
M. B. DESHMUKH ET AL.
Scheme 1. Knoevenagel condensation of aromatic aldehydes with malononitrile.
Scheme 2. Mechanism for acid catalyzed Knoevenagel condensation.
(0.3%), fibers (1.7%), and some free and combined organic acids. As lemon juice is
acidic in nature (pH about 2–3) and the percentage of citric acid is 5–7%, it will
be worked as acid catalyst for condensation (Scheme 2).
The Knoevenagel condensation of aldehydes with active methylene compounds
is an important method used for the synthesis of different pharmaceutically impor-
tant organic compounds.[6] The Knoevenagel condensation reaction is mostly cata-
lyzed by bases such as amines or their ammonium salts, ammonia in organic
solvents, and dimethylaminopyridine.[7]
The importance of Knoevenagel condensation for carbon–carbon bond forma-
tion in organic synthesis has attracted renewed attention. A number of improved
Table 1. Comparison of different catalysts used for synthesis of 2-(phenyl)methylenemalononitrile
(R ¼ C6H4)
Sr. no.
Catalyst
Solvent
Time
Condition
Yield (%) Reference
1
2
USY Zeolite
Benzene
12 hr. Reflux
92
80
95
80
90.6
90
80
91
96
98
91
8
10
11
14
15
16
17
18
20
22
–
AlPO4-Al2O3
LaCl3 ꢀ 7H2O
I2=K2CO3
–
–
14 hr.
1 hr.
Stirred at RT
Heated at 80 ꢁC
3
4
EtOH=DMF 12 min RT
Water
5
CTMAB
TEBA
1.5 hr. Stirred at RT
6
–
10 min Ground at RT
6 min MW (850 Watt)
15 min Refluxed
7
NH4OAc & Basic Alumina
H3PW12O40
NaF & LiCl
MgBr2 ꢀ OEt2
Lemon Juice
–
Water
–
8
9
1 min MW
10
11
TEA, THF 1–2 hr. Stirred at RT
2 hr. Stirred at RT
–

GREEN KNOEVENAGEL CONDENSATION
1179
Table 2. Lemon juice catalyzed Knoevengel condensation of aromatic aldehydes and malononitrile
M.P. ꢁC
Product
1
R
Color
Time (min)
120
Yield (%)
91
Found
82
Reported
84[25]
Light brown crystals
2
3
4
5
6
Yellow crystals
Yellow crystals
Light Yellow crystals
Orange crystals
Yellow crystals
15
05
90
86
91
85
88
118
158
182
142
129
115[25]
160[25]
188[25]
138[25]
128[17]
15
120
05
7
8
Colourless solid
Colourless solid
60
10
87
95
164
158
163[25]
155[16]
9
Yellow crystals
05
92
124
127[25]
10
11
Orange crystals
30
82
82
179
74
182[16]
Faint brown crystals
120
72[17]
12
Lemon yellow solid
20
92
132
135[25]
procedures have been reported for the Knoevenagel condensation. Some green meth-
ods have been reported using catalysts in the absence of solvent. However, high reac-
tion temperatures and long reaction times were required for complete reactions. There
are also some new reported methods employing catalysts, such as USY zeolites,[8] cal-
cium hydroxyapatite,[9] AlPO4 ꢀ Al2O3,[10] and LaCl3 ꢀ 7H2O.[11] The reaction is also
carried out by using catalysts such as the methane sulfonic acid (MSA)=morphine
system,[12] basic alumina,[13] I2=K2CO3,[14] cetyltrimethylammoniumbromide

1180
M. B. DESHMUKH ET AL.
Figure 1. IR spectrum of 2.
(CTMAB),[15] triethylbenzylammonium (TEBA),[16] ammonium acetate–basic alu-
mina,[17] 12-tungstophosphoric acid,[18] (NH4)2HPO4,[19] NaF and LiCl,[20] ZnCl2,[21]
MgBr2 ꢀ OEt2, and triethylamine (TEA),[22] and ionic liquids.[23] The condensation is
also carried out in presence of various solvents.[24] These methods have various draw-
backs such as prolonged reaction time, toxicity, poor recovery, and use of harmful
organic solvents (Table 1). Therefore, introduction of clean procedures and eco-
friendly green catalysts have attracted attention of workers.
RESULTS AND DISCUSSION
We herein report a Knoevenagel condensation of aromatic aldehydes with
active methylene groups using a catalytic amount of lemon juice under solvent-free
conditions. In addition to its simplicity, this catalyst resulted in better yields for the
products (Table 2) in the Knoevenagel condensation. A stoichiometric amount of
catalyst was sufficient to obtain good yields.
The synthesis of 2-(p-methoxyphenyl)methylenemalononitrile (2) is described
as a representative example: A mixture of 10 mmol (1.36 g) of p-methoxy-
benzaldehyde, 10 mmol (0.66 g) of malononitrile, and 1 ml lemon juice was stirred
at room temperature for 15 min with monitoring by thin-layer chromatography
(TLC). Then the reaction mixture was filtered, and the pure yellow crystalline pro-
duct was recovered by crystallization with ethanol. Its identity was confirmed by
infrared (IR) spectrum (Fig. 1), NMR spectrum (Fig. 2), and its melting point.

GREEN KNOEVENAGEL CONDENSATION
1181
Figure 2. NMR spectrum of 2.
Compound 2 is a yellow crystalline product, yield 90%, mp 118 ꢁC; IR (KBr):
1
2220, 1665, 1318, 1276, 936, 833 cmꢂ1; H NMR (CDCl3): 3.9 (3H, s, ꢂOCH3), 7.0
=
(2H, d, Ar-H), 7.6 (1H, s, CH), 7.9 (2H, d, Ar-H).
The experimental procedure is followed for the appropriate time to synthesize
all the products listed in Table 2.
CONCLUSION
We have developed an ecofriendly and economical method for the Knoevenagel
condensation by lemon juice catalyst with good yields. This solvent-free approach is
nonpolluting and does not employ any toxic materials, quantifying it as a green
approach to Knoevenagel condensation. In addition to this, it involved mild reaction
conditions and simple workup.
ACKNOWLEDGMENT
S. S. P. and S. D. J. thank the University Grants Commission, New Delhi, for
sanctioning Minor Research Project (MRP).
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