1314
Chemistry Letters Vol.35, No.11 (2006)
An Efficient and Facile Synthesis of 2-Amino-4,6-diarylbenzene-1,3-dicarbonitrile
and 1,2-Dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile
under Solvent-free Conditions
Liangce Rong,ꢀ Xiaoyue Li, Haiying Wang, Daqing Shi, and Shujiang Tu
Department of Chemisty, Xuzhou Normal University, Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu 221116, P. R. China
(Received September 5, 2006; CL-061027)
A one-pot three-component condensation of aromatic alde-
ence of 1.5 equivalents NaOH. The mixture was ground with a
pestle and the reaction could be completed within 3–5 min with
high yields. The results of reaction are listed in Table 1.
In order to investigate the reactions conditions of synthesis
of polysubstituted 2,6-dicyanoanilines derivatives, we put the
4-chlorobenzaldehyde, acetophenone, malononitrile and 1.5
equivalents of NaOH in a reaction flask and let them keep under
70 ꢁC, however, we could not get the anticipated target com-
pound 4e. Surprisingly, we gained another new compound: 4-(4-
chlorophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-3-carbo-
nitrile. This prompted us to extend our studies toward the incor-
poration of different aldehydes and ketones (Scheme 2). A series
of 1,2-dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile deriva-
tives13 5 could be obtained via the reaction of aromatic aldehyde,
aromatic ketone, and malononitrile under heating conditions in
good yields. The structure of compound 5 was confirmed by
X-ray diffraction analysis.14 The results are summarized in
Table 2.
hyde, aromatic ketone, and malononitrile leading to an efficient
synthesis of 2-amino-4,6-diarylbenzene-1,3-dicarbonitrile and
1,2-dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile has been
carried out in a mortar just by grinding or heating under
solvent-free conditions. Compared with the classical reaction
conditions, these new synthetic methods have the advantages
of excellent yields, shorter reaction time, and mild reaction
conditions.
Over the past several years, chemists have been aware of the
environmental implications of their chemistry. Nowadays, they
are trying to develop new synthetic methods, reaction condi-
tions, and uses of chemicals that reduce risks to humans and
the environment. Organic solvents are high on the list of damag-
ing chemicals because they are employed in huge amounts and
are usually volatile liquids that are difficult to store. In recent
years the dramatic increases in the investigation of the solvent-
free reactions have been seen, such as the Grignard reaction,1
Knoevenagel condensation,2 Aldol condensation,3 Dieckmann
condensation,4 Reformatsky reaction,5 reduction,6 and other
reactions.7 The advantages of these processes are higher efficien-
cy, milder conditions, easier workup, and environmental accept-
ability. Some solvent-free reactions could be carried out just by
grinding.8
Under the different reaction conditions, two types of prod-
ucts 4 and 5 could be gained. When grinding aromatic aldehyde
1, aromatic ketone 2, and malononitrile (3) at room temperature
(Scheme 1), the compound 4 was only obtained. However, when
heating the starting materials (Scheme 2), the compound 5 could
be obtained, accompanied with a trace amount of byproduct 4.
Ar1
The polysubstituted 2,6-dicyanoanilines are the very import-
ment compounds of their optical properties.9 Synthesis of these
compounds have brought the much attention of chemists.
Though various methods for the synthesis of them are reported,10
many of these procedures are not fully satisfactory with regard to
operational simplicity, cost of the reagent and isolated yield,
moreover, the majority of those synthetic methods were carried
out in nocuous organic solvent. For example, Pedro et al.10a have
reported that polysubstituted 2,6-dicyanoanilines could be syn-
thesized by the reaction between malononitrile and ꢀ,ꢁ-
unsaturated ketones in the sodium methoxide/methanol solu-
tion. However, this method suffered from several disadvantages
such as longer reaction times, excess of organic solvents, harsh
refluxing conditions, especially, the poor yields (5–20%). In
continuation to our ongoing endeavour on the application of sol-
vent-free conditions for the synthesis of organic compounds,11
herein, we wish to report a practical and simple method to
prepare polysubstituted 2,6-dicyanoaniline derivatives 4 by
grinding the starting materials under dry conditions at room
temperatures. The synthetic procedure12 of polysubstituted
2,6-dicyanoanilines derivatives 4 was operated as follows
(Scheme 1): The aromatic aldehyde 1, aromatic ketone 2, and
malononitrile (3) were mixed together in a mortar in the pres-
CN
NaOH
Grinding r. t.
Ar1CHO Ar2COCH3
+
2 NCCH2CN
+
Ar2
NH2
CN
4
1
2
3
Scheme 1.
Table 1. Synthesis of product 4 by the grinding method
Time
/min
Yields
/%
Entry
Ar1
Ar2
Product
1
2
4-CH3C6H4 C6H5
3,4-Cl2C6H3 C6H5
3
3
3
3
4
3
3
3
5
3
4a
4b
4c
4d
4e
4f
4g
4h
4i
79
70
71
73
76
73
70
69
70
72
3
4
5
6
7
8
9
10
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-FC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
4-ClC6H4
4-BrC6H4
4-CH3OC6H4
3-ClC6H4
4j
Copyright Ó 2006 The Chemical Society of Japan