Zirconium oxide nanoparticles as an efficient catalyst for three-component synthesis of pyrazolo [1,2-a][1,2,4]triazole-1,3-diones derivatives

Article abstract of DOI:10.13005/ojc/320339

An efficient and green protocol for the synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones derivatives by one pot, three component coupling reaction of aromatic aldehyde, malononitrile, and 4-phenylurazole has been developed using ZrO₂ nanoparticles (NPs) as the catalyst. The procedure is formed in high yields, short reaction time and an environmentally friendly specificity.

Full text of DOI:10.13005/ojc/320339

ISSN: 0970-020 X
CODEN: OJCHEG
2016, Vol. 32, No. (3):
Pg. 1625-1629
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Zirconium Oxide Nanoparticles as an Efficient Catalyst
for three-component Synthesis of Pyrazolo
[1,2-a][1,2,4]triazole-1,3-diones Derivatives
HOSSEIN ANARAkI-ARDAkANI* and TAYEbE HEIDARI-RAkATI
Department of Chemistry, Mahshahr Branch, Islamic Azad University, Mahshahr, Iran
*Corresponding author E-mail: hosseinanaraki@yahoo.com
http://dx.doi.org/10.13005/ojc/320339
(Received: April 22, 2016; Accepted: June 13, 2016)
AbSTRACT
An efficient and green protocol for the synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
derivatives by one pot, three component coupling reaction of aromatic aldehyde, malononitrile, and
4-phenylurazole has been developed using ZrO2 nanoparticles (NPs) as the catalyst.The procedure
is formed in high yields, short reaction time and an environmentally friendly specificity.
keywords: multicomponent reaction, ZrO2 nanoparticles (NPs), solvent-free, Malononitrile.
INTRODUCTION
catalysts are highly preferred as they offer high
surface area and low-coordinated sites, which are
responsible for the higher catalytic activity, 2-4 having
the advantage of easy product purification and
reusability of the catalyst.
Multi-component reactions have been
attracting much interest from synthetic chemists
because they provide simple one-pot routs for the
synthesis of complex molecules from simple and
easily available starting materials.These processes
are single-step and don’t require separation and
purification of intermediates and so save time,
energy and raw materials.1
N-Heterocycles receive considerable
attention in the literature as a consequence of
their exciting biological properties and their role
as pharmacophores.5 Among a large variety of
N-containing heterocyclic compounds, those
containing Pyrazoles or urazole (1,2,4-triazolidine-
3,5-dione) moiety have received considerable
attention because of their pharmacological properties
and clinical applications.6-9
Recently, heterogeneous catalysts have
attracted the attention of researchers due to their
economic and industrial significance and published
reports indicate that they scored over homogeneous
catalysts. Among these, nanoscale heterogeneous

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ANARAkI-ARDAkANI et al., Orient. J. Chem., Vol. 32(3), 1625-1629 (2016)
Considering the above reports and in of metal oxides exhibit both Lewis acid and Lewis
continuation of our research on multi-component base character18,19and according to the literature
reactions10-14, Herein we have researched for three- survey15-17, the suggested mechanism for the
component coupling of aldehydes1, malononitrile formation of the products is shown in Scheme 2.First,
2, and 4-phenylurazole 3 in the presence of ZrO2 via a knoevenagel condensation of malononitrile 1
nanoparticles to the synthesis of pyrazolo[1,2-a] and arylaldehydes 2 in the presence of ZrO2 NPs as
[1,2,4]triazole-1,3-diones derivatives 4 (Scheme 1). the catalyst was afforded benzylidenemalononitrile
5 Then, Michael addition of 4-phenylurazole 3 to
RESULTS AND DISCUSSION
benzylidenemalononitrile 5 formed intermediate 6
that underwent cyclization and tautomerism affords
To choose optimum conditions, first, the corresponding products 4.
the effect of temperature on the rate of the
reaction was studied for the preparation of
The reusability of the catalyst was tested in
7-amino-5-(4-chlorophenyl)-1, 2,3, 5-tetrahydro-1, the synthesis of 7-amino-5-(4-chlorophenyl)-1,2,3,5-
3-dioxo-2-phenylpyrazolo [1,2-a][1,2,4]triazole-6- tetrahydro-1,3-dioxo-2-phenylpyrazolo[1,2-a][1,2,4]
carbonitrile from the three-component condensation triazole-6-carbonitrile, as shown in Figure 1. The
reaction of 4-phenylurazole, malononitrile, and catalyst was recovered after each run, washed with
4-chlorobenzaldehyde under solvent-free conditions ethanol, dried in an oven at 100oC for 15 min. prior
(Table 1). At 80oC, the reaction proceeded smoothly to use and tested for its activity in the subsequent
and almost complete conversion of product was run. The catalyst was tested for 4 runs. It was seen
observed. Further increase in temperature to, 100 that the catalyst displayed very good reusability
and 120oC increased the rate of reaction.Therefore, (Figure 1).
we kept the reaction temperature as 100oC (giving
short reaction time and high yield). Next, the study
set out to determine optimal amount of nano-ZrO2,
the reaction was carried out by varying amount of the
ExPERIMENTAL
Melting points were determined with
catalyst (Table 1). Maximum yield was obtained with an Electrothermal 9100 apparatus. Elemental
0.02 g (0.2 mmol) of the catalyst.Further increase in analyses were performed using a Heraeus CHN-O-
amount of nano-ZrO2 , in the mentioned reaction did Rapid analyzer. Mass spectra were recorded on a
not has any significant effect on the product yield.
FINNIGAN-MAT 8430 mass spectrometer operating
at an ionization potential of 70 eV. IR spectra were
1
To study the scope of the reaction, a recorded on a Shimadzu IR-470 spectrometer. H
series of aldehydes were employed.The results are and 13C NMR spectra were recorded on Bruker
shown in Table 2. In all cases, aromatic aldehydes DRX-500 Avance spectrometer at solution in
substituted with either electron-donating or electron- DMSO-d6 using TMS as internal standard. The
withdrawing groups underwent the reaction smoothly chemicals used in this work were purchased from
and gave the products in good yields. When this Fluka (Buchs, Switzerland) and were used without
reaction was carried out with aliphatic aldehyde such further purification. In all experiments, ZrO2 (5–25
as butanal or pentanal, TLC and 1H NMR spectra of nm, Plasma Chem GmbH) was used.
the reaction mixture showed a combination of starting
materials and numerous products, the yield of the
expected product was very poor.
95
90
88
90
85
80
75
70
82
The compounds 4a–j were known
compounds and their identity was confirmed by a
comparison of their m.p. (Table 2) and their spectral
properties with literature data.15-17
78
1
2
3
4
Although it is not clear how ZrO2 acts as a
Run No.
catalyst for the reaction, on the basis of the surface
Fig. 1: Reusability of the catalyst

ANARAkI-ARDAkANI et al., Orient. J. Chem., Vol. 32(3), 1625-1629 (2016)
1627
Table 1: Optimization amount of ZrO2 nanoparticles and reaction
temperature for preparation 7-amino-5-(4-chlorophenyl)-1,2,3,5-tetrahydro-
1,3-dioxo-2- phenylpyrazolo[1,2-a][1,2,4]triazole-6-carbonitrile under
solvent-free conditionsa
Temp (oC) Time (min)
Yield(%)b
Catalyst (g,mmol)
Entry
0.01g,0.1 mmol
0.02g,0.2 mmol
100
100
72
91
30
30
1
2
0.03g,0.3 mmol
0.04g,0.4 mmol
0.02g,0.2 mmol
100
100
120
30
30
25
88
88
89
3
4
5
6
0.02g,0.2 mmol
90
40
88
80
0.02g,0.2 mmol
80
40
7
a Reaction conditions: 4-Phenylurazole (1.0 mmol),
malononitrile (1.0 mmol), 4-chlorobenzaldehyde (1.0 mmol).
b Isolated yield
Table 2:Three-component reaction of aromatic
aldehydes, malononitrile and 4-phenylurazole
catalyzed by ZrO2 NPs under solvent-free conditionsa
Yieldb (%)
Entry
4a
Ar
Time (min)
mp (oC)(lit)
>220(>221)15-17
233(>218)15-17
>224(>224)15-17
30
35
90
88
85
4-Cl-C6H4
2-Cl-C6H4
4-Br-C6H4
4-F-C6H4
2-NO2-C6H4
4b
35
35
35
4c
4d
89
87
90
>223(>222)15-17
233(>221)15-17
4e
4f
4-NO2-C6H4
C6H5
30
40
220(>218)15-17
>210(>210)15-17
226(>225)15-17
>200(>200)15-17
>217(>217)15-17
86
4g
4h
3-CN-C6H4
35
30
40
40
87
82
80
--
2,4-Cl-C6H3
4-CH3-C6H4
n-C5H11
4i
4j
4k
a Reaction conditions: 4-Phenylurazole (1.0 mmol),
malononitrile (1.0 mmol), aromatic aldehyde (1.0 mmol) under
thermal solvent-free condition at 100 oC.
bIsolated Yield

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ANARAkI-ARDAkANI et al., Orient. J. Chem., Vol. 32(3), 1625-1629 (2016)
NH2
Ar
O
O
O
CN
nano - ZrO2
HN
HN
N
N
+
CN
+
Ph
N
N
Ph
Solvent-free,100 oC
Ar
H
CN
O
O
1
2
4
3
(Scheme 1)
CN
H
N
H
CN
N
N
Ar
O
2
C
Ar
HN
O
O
NC
CN
ZrO2 NPs
N
H
N
N
NC
NC
N
N
Ar
H
Ph
ZrO2 NPs
+
4
O
O
O
N
N
O
ZrO2 NPs
Ph
5
Ph
Ar
H
6
7
1
Scheme 2:The proposed mechanism for the synthesis of pyrazolo[1,2-a][1,2,4]
triazole-1,3-diones in solvent-free conditions catalyzed by ZrO2 NPs (20%)
General procedure
126.7, 128.4, 128.8, 129.2, 129.7, 130.3, 131.0,
A mixture of malononitrile (1.0 mmol), 131.8, 146.3, 148.0, 150. 7,154. Analyses: Calcd.
aromatic aldehyde (1.0 mmol), 4-arylurazole for C18H12ClN5O2: C, 59.11; H, 3.31;N, 19.15 Found:
(1.0 mmol), and nano-ZrO2 (20 mol %) was heated at C, 59.34; H, 3.12;N, 19.36 %.
100°C for 30-40 min.After completion of the reaction
as indicated by TLC, the reaction mixture was
cooled to room temperature. The solid residue was
dissolved in hot ethanol and centrifuged to separate
CONCLUSIONS
We have developed a simple, efficient,
the catalyst. By recrystallization from ethanol, pure one-pot and green protocol for the synthesis of
products were obtained.
pyrazolo[1,2-a][1,2,4]triazole-1,3-diones derivatives
using nano-ZrO2 as a reusable heterogeneous
7-amino-5-(4-chlorophenyl)-1,2,3,5- catalyst under solvent-free conditions.The simplicity,
tetrahydro-1,3-dioxo-2-phenylpyrazolo[1,2-a][1,2,4] easy workup, as well as safety and reusability of
triazole-6-carbonitrile 4a:
catalyst are advantages of this method.
White powder mp >220 ºC, yield 90%,
ACkNOwLEDGEMENTS
1
IR (kBr) (nmax, cm-1):1731, 1712 ( CO ester), H
NMR (500 MHZ, DMSO-d6): d = 6.03 (1H, s, CH),
We gratefully acknowledge financial support
7.35-8.35 (11H, m, H-Ar and NH2).13C NMR (125.8 from the Research Council of Islamic Azad University,
MHZ, DMSO-d6): d = 61.7, 63.6, ,116.4, 124.2, Mahshahr branch.

ANARAkI-ARDAkANI et al., Orient. J. Chem., Vol. 32(3), 1625-1629 (2016)
1629
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