Multicomponent synthesis of 3,5-diaryl-2,6-dicyanoanilines under thermal solvent-free conditions

Article abstract of DOI:10.1007/s00706-010-0302-8

A facile parallel synthesis of 3,5-diaryl-2,6-dicyanoanilines via three-component reaction of aryl aldehydes, acetophenone derivatives, and malononitrile under thermal green solvent-free conditions in the presence of potassium carbonate and also potassium bicarbonate without using any hazardous materials is described.

Full text of DOI:10.1007/s00706-010-0302-8

Monatsh Chem (2010) 141:557–560
DOI 10.1007/s00706-010-0302-8
ORIGINAL PAPER
Multicomponent synthesis of 3,5-diaryl-2,6-dicyanoanilines
under thermal solvent-free conditions
•
Hamid Reza Shaterian Moones Honarmand
•
Ali Reza Oveisi
Received: 19 January 2010 / Accepted: 16 March 2010 / Published online: 9 April 2010
Ó Springer-Verlag 2010
Abstract A facile parallel synthesis of 3,5-diaryl-2,6-
dicyanoanilines via three-component reaction of aryl
aldehydes, acetophenone derivatives, and malononitrile
under thermal green solvent-free conditions in the presence
of potassium carbonate and also potassium bicarbonate
without using any hazardous materials is described.
large molecular cavity [11] and host–guest complexes [12].
Some of these molecular systems are the basis for artificial
photosynthetic systems [13, 14], materials presenting
semiconducting or nonlinear optical properties [15–18],
and molecular electronic devices [19]. These compounds
have been prepared from arylidenemalonodinitriles and
1-arylethylidenemalonodinitriles in the presence of piper-
idine [20]. The reaction between malononitrile and
a,b-unsaturated ketones can also give 3,5-diaryl-2,6-dicy-
anoanilines, but the yields were very poor (5–20%) [21,
22]. A literature survey showed that several methods have
been reported for the synthesis of 3,5-diaryl-2,6-dicyano-
anilines [23–27], but they suffer from several drawbacks,
such as multistep reactions, long reaction times, an excess
of volatile organic solvents, harsh refluxing conditions, and
especially lower product yields. To improve the synthesis
of 3,5-diaryl-2,6-dicyanoanilines, we developed a practical
three-component reaction that significantly reduces the
reaction time and increases the yields. In addition,
according to the reported literature, some of these prod-
ucts show fluorescent properties [25]. The a,b-unsaturated
ketones are generated in situ from the corresponding aryl
aldehydes and aromatic enolizable acetophenone deriva-
tives in the presence of potassium carbonate and also
potassium bicarbonate, the desired products are captured
one-pot by two equivalents (eq) of malononitrile under the
same experimental conditions, forming the corresponding
3,5-diaryl-2,6-dicyanoaniline derivatives under thermal
green solvent-free conditions (Scheme 1).
Keywords Multicomponent Á Aryl aldehydes Á
Acetophenones Á Malononitrile Á Carbonate salts
Introduction
Combinatorial chemistry techniques have evolved very
rapidly and are playing significant roles in the development
of modern synthetic organic chemistry [1–3]. This meth-
odology allows molecular complexity and diversity to be
created by the facile formation of several new covalent
bonds in a one-pot transformation quite closely approach-
ing the concept of an ideal synthesis and is particularly well
adapted for combinatorial synthesis [4, 5]. Combinatorial
chemistry has been successfully applied to development
and improvement of novel pharmaceutics [6], materials,
and catalysts by using rapid parallel syntheses in solvent-
free systems [7] and also on polymer supports [8]. Com-
binatorial synthesis on the solid phase can generate very
large numbers of products, using a method described as
mix and split synthesis [9].
3,5-Diaryl-2,6-dicyanoanilines are useful intermediates
and act as building blocks for cyclophanes [10] to create a
Results and discussion
H. R. Shaterian (&) Á M. Honarmand Á A. R. Oveisi
Department of Chemistry, Faculty of Sciences,
University of Sistan and Baluchestan, Zahedan, Iran
e-mail: hrshaterian@hamoon.usb.ac.ir
First, a mixture of 1 eq benzaldehyde, 1 eq acetophenone,
and 2.5 eq malononitrile was reacted in the presence of
123

558
H. R. Shaterian et al.
R2
R1
O
O
CH3
H
K2CO3
Solvent-Free, 60 oC
R2
R1
+
+ 2 CH2(CN)2
NC
CN
NH2
R1 = R2 = H, Cl, F,Br, CH3, OCH3
Scheme 1
0.5 g potassium carbonate under thermal solvent-free
conditions in an oil bath (60 °C) and also at room tem-
perature. The reaction proceeded at 60 °C, whereas
the starting materials remained unchanged at room tem-
perature. Next, we synthesized some 3,5-diaryl-2,6-
dicyanoaniline derivatives via three-component reaction of
aryl aldehydes, acetophenone derivatives, and malononit-
rile under thermal solvent-free conditions in the presence
of K2CO3 at 60 °C (Table 1). As shown in Table 1, the
reaction completed within only a few minutes and
the yields were extensively increased as compared with the
published methods. When potassium bicarbonate was used
instead of potassium carbonate, the yields decreased dra-
matically despite much longer reaction times.
materials. Use of potassium carbonate as catalyst has
inherent advantages including operational simplicity, low
cost, and suitability in industrial applications.
Experimental
All reagents were purchased from Merck and Aldrich and
used without further purification. All yields refer to isolated
products after purification. Products were characterized by
comparison with authentic samples and by spectroscopic
data (IR, 1H NMR spectra). The NMR spectra were
recorded on a Bruker Avance 400-MHz instrument. The
spectra were measured in DMSO-d6 and CDCl3 relative to
TMS (0.00 ppm). IR spectra were recorded on a JASCO
460 Plus spectrophotometer. Melting points were deter-
mined in open capillaries with a BUCHI 510 melting point
apparatus. TLC was performed on silica gel polygram SIL
G/UV 254 plates.
A mechanistic rationale for the three-component reac-
tion is shown in Scheme 2.
We studied the products of the reactions and found
3,5-diaryl-2,6-dicyanoaniline derivatives, accompanied by
a small quantity of the a,b-unsaturated ketones I and
nitriles II as by-products. In this methodology, the products
were purified by recrystallization in ethanol.
General procedure for preparation of 3,5-diaryl-2,
6-dicyanoanilines
In conclusion, we have demonstrated a facile method for
the preparation of 3,5-diaryl-2,6-dicyanoanilines via a
three-component reaction of aryl aldehydes, acetophenone,
and malononitrile under thermal green solvent-free condi-
tions at short reaction times without using any hazardous
To a mixture of 1 mmol aryl aldehyde, 1 mmol acetophe-
none, and 2.5 mmol malononitrile, 0.5 g K2CO3 (3.5 mmol)
was added. The mixture was stirred at 60 °C in an oil bath.
Table 1 Synthesis of 3,5-diaryl-2,6-dicyanoaniline derivatives using K2CO3 as base
Entry
Aldehyde
Ketone
Time (min)/yield (%)a
M.p. (°C)
Found
Literature [Ref.]
1
2
3
4
5
6
7
8
9
10
a
4-CH3–C6H4
4-CH3–C6H4
4-F–C6H4
C6H5
2/72
15/75
6/68
15/70
8/67
8/69
10/74
3/65
4/70
4/72
200–202
191–193
222–224
246–247
209–211
220–221
253–254
278–279
185–187
271–273
201–202 [26]
191–192 [27]
221–223 [27]
244–246 [27]
208–210 [27]
221–223 [27]
251–254 [27]
278–280 [27]
188–191 [27]
271–273 [27]
4-Cl–C6H4
C6H5
4-Cl–C6H4
2-Cl–C6H4
3-Cl–C6H4
4-Br–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
C6H5
C6H5
C6H5
C6H5
4-Br–C6H4
4-CH3O–C6H4
4-Cl–C6H4
Yields refer to pure isolated products. All known products have been reported previously in the literature and were characterized by
comparison of melting points, IR, and NMR spectra with authentic samples
123

Multicomponent synthesis of 3,5-diaryl-2,6-dicyanoanilines
559
R1
O
O
O
CH2(CN)2
K2CO3
R1
K2CO3
CH3
H
H
R2
R1
R2
+
O
I
NC
NC
O
R2
R1
O
CH3
R2
K2CO3
CH2(CN)2
R1
K2CO3
+
NC
II
CN
K2CO3
CH2(CN)2
R1
R1
R1
R1
H
H
NC
NC
HN
NC
NC
NC
NC
K2CO3
H
NC
R2
R2
NC
NC
R2
R2
N
C
NC
H2N
CN
NC
CN
-HCN
R1
NC
R2
H2N
CN
III
Scheme 2
3. Kappe O, Stadler A (2005) Microwaves in organic and medicinal
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4. Pirrung MC (2004) Molecular diversity and combinatorial
chemistry: principles and applications. Wiley-VCH, Germany
The completion of the reaction was monitored by TLC
(Table 1). For work-up the mixture was cooled to 25 °C,
ethyl acetate added, and the mixture stirred for 5 min. Then
water was added to the solutions, and the organic phase was
extracted twice with 10 cm3 of ethyl acetate. The organic
solution was separated and concentrated; the solid so
obtained was filtered and recrystallized from ethanol.
The desired pure products were characterized by compari-
son of their physical data with those of known compounds
[26, 27].
ˇ´
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¨
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Baluchestan Research Council for the partial support of this research.
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