CeO2 nanoparticles: an efficient and robust catalyst for the synthesis of 2-amino-4,6-diarylbenzene-1,3-dicarbonitriles

Article abstract of DOI:10.1007/s00706-016-1693-y

CeO₂ nanoparticles as an efficient catalyst have been used for the preparation of 2-amino-4,6-diarylbenzene-1,3-dicarbonitriles by the multi-component condensation reaction of aldehydes, acetophenones, and malononitrile in good to excellent yields, short reaction times, mild reaction conditions, and the employment of a cost-effective catalyst. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1693-y

Monatsh Chem
DOI 10.1007/s00706-016-1693-y
ORIGINAL PAPER
CeO2 nanoparticles: an efficient and robust catalyst
for the synthesis of 2-amino-4,6-diarylbenzene-1,3-dicarbonitriles
Javad Safaei-Ghomi1 Hossein Shahbazi-Alavi1 Sima Kalhor2,3
•
•
Received: 30 October 2015 / Accepted: 7 February 2016
Ó Springer-Verlag Wien 2016
Abstract CeO2 nanoparticles as an efficient catalyst have
been used for the preparation of 2-amino-4,6-diarylben-
physicochemical and spectral properties than other aniline
derivatives. The molecular geometry and electron distri-
bution in 2,6-DCA are favorable for intramolecular
hydrogen bond formation between the amino and cyano
groups in the ground state [1]. 2-Amino-4-methyl-6-
(methylsulfanyl)isophthalonitrile scaffolds functionalized
with an amino functionality flanked between two nitrile
substituents showed antileishmanial activity and has
opened a new avenue for further exploration [2]. Recently,
K2CO3 [3] and NaOH [4, 5] were reported for the synthesis
of 2-amino-4,6-diarylbenzene-1,3-dicarbonitrile deriva-
tives. To improve the synthesis of these compounds, we
developed a practical three-component reaction that sig-
nificantly increases the yields, and make the protocol to be
attractive, greener, and economic.
zene-1,3-dicarbonitriles
by
the
multi-component
condensation reaction of aldehydes, acetophenones, and
malononitrile in good to excellent yields, short reaction
times, mild reaction conditions, and the employment of a
cost-effective catalyst.
Graphical abstract
R1
R2
O
O
H
CN
CN
3
CH3
+
CeO2 NPs
R1
R2
+
2
NC
4
CN
NH2
1
2
Multi-component reactions (MCRs) supply a practical
method for the synthesis of various compounds with
pharmaceutical and biological activities. MCRs enhance
the efficiency by combining several operational steps
without isolation of intermediates or changing the reaction
conditions [6–11]. MCRs are environmentally friendly, and
play a prominent role in green chemistry. Green chemistry
emphasizes the need for environmentally clean synthesis,
which involves reduction or elimination the use or gener-
ation of hazardous chemicals and simple separation with
recovery and reuse of reagents [12]. Solvent-free organic
synthesis is the best eco-friendly methodology to overcome
the problems from green chemistry viewpoint. Solvent-free
reactions have many advantages, such as reduced pollution,
low costs, and simplicity in the process and handling.
The possibility of performing multicomponent reactions
under solvent-free conditions with a heterogeneous catalyst
could enhance their effectiveness from cost-effective and
ecological points of view. Nano-catalysts should present
higher surface areas which are mainly responsible for their
Keywords CeO2 nanoparticles Á Heterogeneous catalyst Á
2-Amino-4,6-diarylbenzene-1,3-dicarbonitrile Á One-pot
Introduction
2,6-Dicyanoaniline scaffolds are core building blocks for
the structure of highly functionalized organic compounds.
2,6-Dicyanoaniline (DCA) reveals remarkably different
& Javad Safaei-Ghomi
safaei@kashanu.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry,
University of Kashan, Kashan, P.O. Box 87317-51167,
Islamic Republic of Iran
2
Department of Chemistry, Qom Branch, Islamic Azad
University, Qom, Islamic Republic of Iran
3
Young Researchers and Elite Club, Qom Branch, Islamic
Azad University, Qom, Islamic Republic of Iran
123

J. Safaei-Ghomi et al.
Scheme 1
R1
R2
O
O
H
CN
CN
CH3
+
R1
CeO2
NPs
R2
+
2
NC
CN
NH2
1
2
3
4
catalytic activity. Separation of the catalyst and final pro-
duct from the reaction mixture is one of the most essential
aspects of synthetic protocols. Nanoparticles decrease
reaction times, impart greater selectivity and they can be
simply recovered from the reaction mixture by easy fil-
tration [13–20]. We reported herein the synthesis of
2-amino-4,6-diarylbenzene-1,3-dicarbonitrile derivatives
using a three-component one-pot protocol under solvent-
free conditions in the presence of CeO2 nanoparticles
(Scheme 1).
microscopy (SEM) as shown in Fig. 2. The SEM images
show particles with diameters in the range of nanometers.
To optimize the reaction conditions a series of experi-
ments were carried out in the presence of different catalysts
for a representative reaction of 4-chlorobenzaldehyde,
malononitrile, and acetophenone (Table 1). The results
showed that the best reaction conditions for the synthesis of
2,6-dicyanoanilines were CeO2 nanoparticles as the cata-
lyst at 3 mol% under solvent-free conditions with an
isolated product with good yield. Performing the reaction
with a higher catalyst loading (5 mol%) had no significant
effect on yield.
Results and discussion
Using the optimized reaction conditions, the scope of
the reaction was tested by extending the reaction to dif-
ferent aldehydes and acetophenones and it was found, that
all the aldehydes and acetophenones displayed high reac-
tivity and generated the products in good to excellent yields
(Table 2).
The catalyst was prepared by the co-precipitation method
using aqueous ammonia solution as the precipitating agent.
The XRD patterns for CeO2 nanoparticles are shown in
Fig. 1. The pattern agrees well with the reported pattern for
CeO2 nanoparticles (JCPDS No. 43-1002). The crystalline
size was calculated from FWHM using Scherrer’s formula
and was observed to be 11 nm. The morphology and particle
size of CeO2 NPs were investigated by scanning electron
The influence of electron-withdrawing and electron-
donating substituents on the aromatic ring of aldehydes
upon the reaction yields was investigated. The results in
Table 2 show that the aromatic aldehydes bearing both
Fig. 1 The XRD pattern of CeO2 NPs
123

CeO2 nanoparticles: an efficient and robust catalyst for the synthesis of 2-amino-4,6-…
electron-donating and electron-withdrawing groups gave
excellent yield of the desired products.
A plausible mechanism for the preparation of 2-amino-4,6-
diarylbenzene-1,3-dicarbonitriles by CeO2 NPs is shown in
Scheme 2. The mechanism was supported by the literatures
[3, 4]. Firstly, we assumed that the reaction occurs via a
Knoevenagel condensation between aldehyde and acetophe-
none to form the intermediate I. Then, Michael addition of
malononitrile 3 to the chalcone I leads to the formation of
adduct II, which undergoes a Knoevenagel condensation with
anothermoleculeofmalononitrile3 toaffordintermediateIII.
In the presence of CeO2 NPs, deprotonation of III and sub-
sequent intramolecular cycloaddition take place to generate
intermediate IV, which undergoes an elimination of hydrogen
cyanide and aromatization to give substituted 2-amino-4,6-
diarylbenzene-1,3-dicarbonitriles.
Fig. 2 SEM image of CeO2 nanoparticles
In this article, we have developed a new and efficient
method for the synthesis of 2-amino-4,6-diarylbenzene-1,3-
dicarbonitriles using CeO2 NPs. We also investigated recy-
cling of the CeO2 NPs as catalyst. After completion of the
reaction, the reaction mixture was centrifuged at
2000–4000 rpm for 4 min, until the catalyst was deposited
at the bottom of the centrifuge tube. The deposited catalyst
was washed with ethanol 3–4 times to confirm the complete
removal of any organic residuals; the catalyst was reused for
further catalytic reaction cycles. The results showed that
CeO2 NPs can be reused several times without noticeable
loss of catalytic activity (yields 87–84 %; Fig. 3).
Table 1 The model reaction was carried out by various catalysts
Entry
Catalyst
mol%
Time/min
Yielda/%
1
2
ZrO2
3
3
4
2
2
3
2
1
3
5
66
55
35
40
40
40
50
14
10
10
21
31
45
43
45
50
43
83
87
87
InCl3
3
CuO
4
CuI
5
CAN
6
Ce(NO3)3
Nd2O3
CeO2 NPs
CeO2 NPs
CeO2 NPs
7
8
9
10
Conclusion
4-Chlorobenzaldehyde (2 mmol), malononitrile (4 mmol), and ace-
tophenone (2 mmol)
In conclusion, we have developed a straight forward and
efficient approach for the synthesis of 2-amino-4,6-diaryl-
benzene-1,3-dicarbonitriles by a simple one-pot three-
Conditions for the best results are indicated in bold
a
Isolated yield
Table 2 Synthesis of polysubstituted 2,6-dicyanoanilines
Entry
Product
R1
R2
Time/
min
Yielda/
%
M.p./°C
Found
M.p./°C
Literature
[Ref.]
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
4-Cl
H
10
12
14
16
14
12
15
87
84
83
80
83
85
80
242–244
240–242
250–252
203–205
192–194
345–347
207–209
244–246 [4]
240–241 [22]
251–253 [4]
201–202 [4]
191–192 [4]
349–351 [23]
–
4-NO2
4-Br
H
H
4-Me
4-Me
4-NO2
2-Me
H
4-Cl
4-NO2
H
4g
Aromatic aldehyde (2 mmol), acetophenones (2 mmol), malononitrile (4 mmol), and CeO2 (3 mol%)
a
Isolated yield
123

J. Safaei-Ghomi et al.
Scheme 2
O
O
O
NC CN
R2
O
H
+
R1
NC CN
3
1
2
I
II
CN
CN
NH
NH
H
CN
CN
CN
CN
CN
CN
NC
NC
-HCN
H H
H
V
IV
III
=
CeO2 NPs
NH2
CN
NC
R1
R2
reaction times, good yields, solvent-free conditions, room
temperature and a recyclable catalyst with a very easy
operation.
Experimental
All organic materials were purchased commercially from
Sigma-Aldrich and Merck and were used without further
purification. Flash-column chromatography was performed
by using Merck silica gel 60 with freshly distilled solvents.
All melting points were determined in capillary tube on
Boetius melting point microscope.1H NMR and 13C NMR
spectra were obtained on Bruker 400 MHz spectrometer
with DMSO-d6 as solvent using tetramethylsilane (TMS)
as an internal standard, the chemical shift values are in d.
FT-IR spectrum was recorded on Magna-IR, spectrometer
Fig. 3 Reusability of CeO2 NPs for the preparation of 4a
component reaction of aldehydes, acetophenones, and
malononitrile in the presence of CeO2 nanoparticles as
catalyst under solvent-free conditions. The present
methodology offers several advantages, such as short
550 Nicolet in KBr pellets in the range of 400–4000 cm-1
.
The elemental analysis (C, H, N) were obtained from a
123

CeO2 nanoparticles: an efficient and robust catalyst for the synthesis of 2-amino-4,6-…
125.7, 126.5, 127.4, 128.5, 128.6, 129.3, 130.5, 130.8,
Carlo ERBA Model EA 1108 analyzer. Powder X-ray
diffraction (XRD) was carried out on a Philips diffrac-
tometer of X’pert Company with mono chromatized Cu Ka
radiation (k = 1.5406 A). Microscopic morphology of
products was visualized by SEM (MIRA 3 TESCAN).
137.3, 146.5, 153.2 ppm.
Acknowledgments The authors acknowledge a reviewer who pro-
vided helpful insights. The authors are grateful to University of
Kashan for supporting this work by Grant No: 159196/XXI.
˚
Preparation of CeO2 nanoparticles
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Afterwards, the solid was treated at 700 °C for 2 h to
obtain the CeO2 nanoparticles.
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123