The Knoevenagel condensation reaction of aromatic aldehydes with malononitrile by grinding in the absence of solvents and catalysts

Article abstract of DOI:10.1081/SCC-120014780

An improved Knoevenagel condensation reaction of aldehydes and malononitrile can be achieved by grinding at room temperature in the absence of solvents and catalysts. This process is simple, efficient, economical, and environmentally benign. Compared to r

Full text of DOI:10.1081/SCC-120014780

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THE KNOEVENAGEL CONDENSATION REACTION
OF AROMATIC ALDEHYDES WITH MALONONITRILE
BY GRINDING IN THE ABSENCE OF SOLVENTS AND
CATALYSTS
Zhongjiao Ren a , Weigud Cao b & Weiqi Tong a
a Department of Chemistry, Shanghai University, Shanghai, 200436, P.R. China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai, 200032, P.R. China
Version of record first published: 22 May 2009.
To cite this article: Zhongjiao Ren, Weigud Cao & Weiqi Tong (2002): THE KNOEVENAGEL CONDENSATION REACTION OF
AROMATIC ALDEHYDES WITH MALONONITRILE BY GRINDING IN THE ABSENCE OF SOLVENTS AND CATALYSTS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:22, 3475-3479
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 22, pp. 3475–3479, 2002
THE KNOEVENAGEL CONDENSATION
REACTION OF AROMATIC ALDEHYDES
WITH MALONONITRILE BY GRINDING
IN THE ABSENCE OF SOLVENTS
AND CATALYSTS
Zhongjiao Ren,1, Weigud Cao,1,2 and Weiqi Tong1
*
1Department of Chemistry, Shanghai University,
Shanghai 200436, P.R. China
2State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, P.R. China
ABSTRACT
An improved Knoevenagel condensation reaction of alde-
hydes and malononitrile can be achieved by grinding at
room temperature in the absence of solvents and catalysts.
This process is simple, efficient, economical, and environ-
mentally benign. Compared to reactions carried out by micro-
wave irradiation, this procedure is completely free from
organic solvents during both the reaction and separation of
the product.
*Corresponding author.
3475
DOI: 10.1081/SCC-120014780
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3476
REN, CAO, AND TONG
With the increasing public concern over environmental degradation,
one of the challenges for chemists is to come up with new approaches that
are less hazardous to human health and the environment. The solvents used
in organic synthesis are high on the list of environmental pollutants, because
they are employed in large amounts and usually are volatile liquids. We are
interested in seeking new processes involving solvent-free reactions, for these
methods have many advantages such as reduced pollution, lower cost, and
simplicity in processing. These factors are beneficial to industry as well as to
the environment.[1]
In the conventional view, it is very important for a successful reaction
that the molecules move freely and collide with each other at the most
suitable orientation. As a result, most of the organic reactions are accom-
plished in a solvent serving as the medium. In recent years, significant
articles have appeared reporting solid-state reactions by grinding, such as
Grignard Reaction,[2] Reformatsky Reaction,[3] Aldol Condensation,[4]
Dieckhmann Condensation,[5] Phenol Coupling Reaction,[6] Reduciton,[7]
and other reactions.[8] These works show the great potential of this method-
ology, but are just a beginning. Most of the reactions are carried out at
room temperature, are absolutely solvent-free and use only a mortar and
pestle, and therefore the common merit of these processes is that they are
efficient, economical, and environmentally friendly. We focus on developing
this novel procedure involving a solid-state reaction performed by grinding.
The Knoevenagel reaction is one of the most common synthetic
methods of effecting carbon–carbon bond formation.[9] The reaction is
catalyzed by various amines, their corresponding ammonium salts[9] or
Lewis acids, such as TiCl4/base,[10] ZnCl2,[11] BiCl3,[12] and CdI2.[13]
Recently, the Knoevenagel reaction carried out by microwave irradiation
in the absence of solvents has rapidly increased.[14] Herein, we will report a
new process of Knoevenagel reaction at room temperature by grinding in
the absence of solvents and catalysts.
Evidence of the condensation and dehydration reaction of aromatic
aldehydes with malononitrile performed by grinding is obvious. First, the
mixture of aldehydes, either solid or liquid and malononitrile turned into a
liquid or a colloid in several minutes. About 15 min later, the mixture
became a muddy colloid and the color of the ground substance changed.

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AROMATIC ALDEHYDES AND MALONONITRILE
3477
After 45 min of grinding with the glass mortar and pestle, the colloid was
transformed into powdered solid compounds.
The Knoevenagel reaction is strongly solvent-dependent. The first step
the aldol addition, is facilitated in a solvent of high polarity and the second
step, 1,2-eliminaiton is inhibited by protic solvents.[9] The result of our
experiment indicates that the grinding can cause condensation and a dehy-
dration reaction with a glass mortar and pestle as effectively as with an
organic solvent. To our knowledge, this is the first report that the
Knoevenagel condensation can occur by grinding at room temperature in
the absence of solvents and catalysts.
In order to verify the role of grinding, we have examined the model
reaction of 4-methyl-benzaldehyde (1b) with malononitrile (2) stirred or left
standing in the glassware at room temperature for 24 h. The mixture of
starting materials was still liquid and the solid product was not obtained.
To keep this method economical, we chose a glass mortar and pestle. But
when we used a china mortar and pestle to repeat this experiment under the
same conditions, it was very surprising that the mixture of 4-methyl-benzal-
dehyde and malononitrile was still liquid after grinding for 1 h, whereas with
a glass mortar and pestle the yield of the condensation reaction of the same
starting material was 96%. So far we cannot exactly explain this result, but
it will stimulate further research.
This process results in an excellent yield of condensate from
liquidaromatic aldehydes, with the exception of benzaldehyde (Table 1).
The reason for the low yield from benzaldehyde is that it is volatilized
during grinding, as indicated by the fact that the weight of the condensation
mixture before separation 72% of the starting material.
In the microwave irradiation process, organic solvents are finally
necessary for isolation of the product by extraction. However, the
Knoevenagel reaction carried out by grinding is completely free from
organic solvents during both the reaction and separation of the
product.[14a,14b]
Table 1. Knoevenagel Reaction of 1 and 2 in the Absence of Solvent
Entry
Ar
Yield (%) Entry
Ar
Yield (%)
3a
3b
3c
3d
3e
3f
C6H5
68
96
94
95
83
87
3g
3h
3I
3J
3k
3l
3-CH3O-4-HO-C6H3
3,4-CH2O2-C6H3
4-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
4-(CH3)2N-C6H4
80
80
85
88
91
92
4-CH3-C6H4
4-CH3O-C6H4
2-Cl-C6H4
4-HO-C6H4
3-HO-C6H4

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3478
REN, CAO, AND TONG
In conclusion, we have found a simple, efficient, economical, and
environmentally benign Knoevenagel reaction by grinding.
EXPERIMENTAL SECTION
General Procedure for the Knoevenagel Reaction in the
Absence of Solvents and Catalysts
A mixture of aromatic aldehydes (2.5 mmol) and malononitrile
(3 mmol) is ground at room temperature in the glass mortar and pestle for
1 h and the mixture is allowed to stand over night. The reaction product is
stirred in 15 mLof water for 15 min collected by suction filtration and dried
at room temperature.
3a: M.p. 82.0–83.0ꢀC, (lit.[15a] m.p. 83.5–84.0ꢀC), IR (KBr, ꢀ/cmÀ1):
CN, 2222.
3b: M.p. 134.5–135.0ꢀC, (lit.[15b] m.p. 134.0ꢀC), IR (KBr, ꢀ/cmÀ1): CN,
2221.
3c: M.p. 113.5–114.0ꢀC, (lit.[15a] m.p. 114.5–115.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2221.
3d: M.p. 94.0–95.0ꢀC, (lit.[15a] m.p. 95.0–96.0ꢀC), IR (KBr, ꢀ/cmÀ1):
CN, 2224.
3e: M.p. 187.5–188.0ꢀC, (lit.[15a] m.p. 188.0–189.5ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2228.
3f: M.p. 155.0–156.0ꢀC, (lit.[15c] m.p. 151.5–153.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2224.
3g: M.p. 137.0–138.0ꢀC, (lit.[15d] m.p. 136.5–139.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2227.
3h: M.p. 201.0–202.0ꢀC, (lit.[15a] m.p. 198.0–200.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2223.
3I: M.p. 162.0–163.0ꢀC, (lit.[15c] m.p. 162.0–163.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2225.
3j: M.p. 103.0–104.0ꢀC, (lit.[15a] m.p. 104.0–105.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2253.
3k: M.p. 161.5–162.0ꢀC, (lit.[15c] m.p. 159.0–160.0ꢀC), IR (KBr,
ꢀ/cmÀ1): CN, 2230.
3l: M.p. 180.0–181.0ꢀC, IR (KBr, ꢀ /cmÀ1): CN, 2220.
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AROMATIC ALDEHYDES AND MALONONITRILE
3479
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Received in Japan July 10, 2001

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