An efficient approach for the synthesis of pyrazolo [1,2,a] [1,2,4]triazole-1,3-diones using an electrochemical cell

Article abstract of DOI:10.13005/ojc/320252

A mild and efficient method was applied for the one-pot three-component synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones from the condensation between arylaldehydes, malononitrile and 4-phenylurazole using electrolysis in an undivided cell in the presence of sodium bromide as an electrolyte. This procedure has many advantages such as : no need to catalyst, clean work-up, short reaction time and high yield. The products were obtained just with the simple filtration.

Full text of DOI:10.13005/ojc/320252

ISSN: 0970-020 X
CODEN: OJCHEG
2016, Vol. 32, No. (2):
Pg. 1255-1260
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
An Efficient Approach for the Synthesis of Pyrazolo [1,2,a]
[1,2,4]Triazole-1,3-Diones Using an Electrochemical Cell
KHATEREH KHANDAN-BARANI1*, MOHAMMAD DODANgEH2,
MEHRNOOSH KANgANI2 and MALEK-TAHER MAgHSOODLOU2*
1Department of Chemistry, Islamic Azad University, Zahedan Branch,
PO Box 98135-978, Zahedan, Iran.
2Department of Chemistry, Faculty of Science, University of Sistan and Baluchistan,
P. O. Box: 98135-674, Zahedan, Iran.
http://dx.doi.org/10.13005/ojc/320252
(Received: December 08, 2015; Accepted: January 15, 2016)
ABSTRACT
A mild and efficient method was applied for the one-pot three-component synthesis of
pyrazolo[1,2-a][1,2,4]triazole-1,3-diones from the condensation between arylaldehydes, malononitrile
and 4-phenylurazole using electrolysis in an undivided cell in the presence of sodium bromide as
an electrolyte. This procedure has many advantages such as : no need to catalyst, clean work-up,
short reaction time and high yield. The products were obtained just with the simple filtration.
Keywords: Pyrazolo[1,2-a][1,2,4]triazole-1,3-dione; 4-phenylurazole; Malononitrile; Electrolysis.
INTRODUCTION
of new approaches for their synthesis seems to be
interesting challenge.
Manyofheterocycliccompoundscontaining
nitrogen have significant synthetic and biological
importance, which act as polyfunctionalized
fragments, agrochemicals, and pharmaceuticals1–10.
Pyrazolourazoles as their fused derivatives with
diverse structures have attracted much interest
because of their wide range of biological properties
such as analgesic, antibacterial, anti-inflammatory,
antidiabetic, and psychoanaleptic activities11–16
(Figure 1). Many methods have been reported for
their synthesis in recent years17–26, and development
Forpreparingbiologicallyactivecompounds
in organic, combinatorial, and medicinal chemistry
the electrosynthetically multicomponent reactions
(EMCRs) have been used widely27. Due to the
electron transfer between an electrode and the
substrate molecules, the formation of highly reactive
intermediates is achieved under mild conditions,
avoiding reductive or oxidant agents as well as acids,
bases and related waste by-products so that it can
be one of the various fields in green chemistry28.

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KHANDAN-BARANI et al., Orient. J. Chem., Vol. 32(2), 1255-1260 (2016)
General procedure for the synthesis of
In continue of our research on multi-component
reactions29-32, Herein, we report an efficient and 7-amino-1,3-dioxo-2-phenyl-2,3-dihydro-1H,5H-
green synthesis of pyrazolo[1,2-a][1,2,4]triazole- pyrazolo(1,2-a)(1,2,4)triazole-6-carbonitrile
1,3-dione derivatives using an electrochemical cell
(scheme 1).
A mixture of arylaldehyde (1 mmol),
malononitrile (1mmol), 4-phenylurazole (1mmol )
and NaBr (0.05 g, 0.5 mmol ) in EtOH (20 mL) was
stirred with a magnetic stirrer and electrolyzed in
MATERIALS AND METHOD
All reagents and solvents were obtained an undivided cell equipped with a graphite anode,
from Fluka and Merck and used without further and an iron cathode at ambient temperature under
purification. TLC was performed on Silica–gel a constant current density of 10mA/cm2 ( electrodes
Polygram SILG/UV 254 plates. Melting points and square 5 cm2), until the catalytic quantity of 0.1 F/mol
IR spectra were measured on an Electro thermal of electricity was passed. After electrolysis process,
9100 apparatus and a JASCO FT-IR-460 plus the mixture was filtered, then it was rinsed twice with
spectrometer. Controlled-current coulometer and cold ethanol to obtained corresponding product.
preparative electrolysis were performed using a
SAMA potentiostate/galvanostate (Zahedan, Iran), Analytical data for the selected compounds
respectively. The1H NMR spectra were obtained on 7-amino-5-(3-nitrophenyl)-1,3-dioxo-2-phenyl-2,3-
Bruker DRX-400 Advance instruments with DMSO. dihydro-1H,5H-pyrazolo(1,2-a)(1,2,4)triazole-6-
Ph
O
OH
H
N
O
N
antimicrobial agent
O
O
O
Ph
N
N
O
N
O
Ph
N
H
OH
O
Cintazone
anti-inflammatory agent
Inhibitor of HSP induction
Fig. 1: pyrazolourazoles with diverse structures
H2N
N
Electrolysis
0.1 F mol-1
O
CN
O
CN
CN
O
HN
HN
+
+
N Ph
H
N
NaBr, EtOH
N
R
Ph
O
R
O
4a-l
1
2
3
Scheme 1: Synthesis of pyrazolo [1,2-a][1,2,4]triazole-1,3-dione derivatives
with an electrochemical cell

KHANDAN-BARANI et al., Orient. J. Chem., Vol. 32(2), 1255-1260 (2016)
1257
carbonitrile (4b)
White powder, m.p:(>300°C).; IR (KBr) (nmax/cm-1):
3450, 3338, 2200, 1778, 1715.1H NMR (400 MHz,
DMSO-d6) dH 6.09 (1H, s, CH), 7.47-8.37 (11H, m,
H-Ar and NH2)
7-amino-5-(2-chlorophenyl)-1,3-dioxo-2-phenyl-
2,3-dihydro-1H,5H-pyrazolo(1,2-a)(1,2,4)triazole-
6-carbonitrile (4l)
White powder, m.p:(>300°C).; IR (KBr) (nmax/cm-1):
White powder, m.p: (>300°C).; IR (KBr) (nmax/cm-1):
3430, 3314, 2189, 1766, 1715. 1H NMR (400 MHz,
DMSO-d6) dH 6.094 (1H, s, CH), 7.47-8.37 (11H, m,
H-Ar and NH2).
7-amino-5-(3-chlorophenyl)-1,3-dioxo-2-phenyl-
2,3-dihydro-1H,5H-pyrazolo(1,2-a)(1,2,4)triazole-
6-carbonitrile (4c)
Table 1: Optimization of Reaction Conditions for the Synthesis of 7-Amino-
1,2,3,5-Tetrahydro-1,3-Dioxo-2,5-Diphenylpyrazolo[1,2-A][1,2,4]Triazole-6-
Carbonitrile
Entry
I (mA)
Current
density
(mA/cm2)
Time
(min)
catalyst
passed
(F/mol)
Electricity
(%)
Yields
1
2
3
4
5
5
1
2
4
10
15
250
160
50
33
23
-
-
-
-
-
0.1
0.1
0.1
0.1
0.1
50
65
80
93
80
10
20
50
75
+ 1/2H2
EtO
Cathode:
EtOH + 1e
In solution:
EtO
+
NC
CN
EtOH
NC
CN +
2
O
O
Ar
H
1
NH
NH
Ph N
O
N
N
CN
H
N
N
Ar
3
O
H
CN
Ph
N
A
H
Ar
H
O
B
O
NH2
H
O
NH
H
N
N
N
N
H
CN
Ph N
CN
Ph N
O
C
Ar
4
O
Ar
Scheme 2: Proposed mechanism for the synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-dione
derivatives using electrolysis in the presence of sodium bromide as an electrolyte

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KHANDAN-BARANI et al., Orient. J. Chem., Vol. 32(2), 1255-1260 (2016)
Table 2: Synthesis Of Pyrazolo[1,2-A][1,2,4]Triazole-1,3-Dione Derivatives
Entry
Aldehyde
CHO
Product
Yield(%)
m.p(°C) Reference [24]
1
4a
93
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
CHO
2
4b
4c
4d
4e
4f
93
85
90
85
90
90
89
83
87
90
93
NO2
CHO
CHO
3
Cl
4
Br
5
CHO
Br
CHO
6
O2N
7
4g
4h
4i
CHO
Cl
8
CHO
F
9
CHO
H3C
Cl
10
11
12
4j
CHO
Cl
NO2
4k
4l
CHO
CHO
Cl

KHANDAN-BARANI et al., Orient. J. Chem., Vol. 32(2), 1255-1260 (2016)
1259
3400, 3319, 1778, 1725.1H NMR (400 MHz, DMSO-
d6) dH 6.27 (1H, s, CH), 7.44-7.69 (11H, m, H-Ar
and NH2).
at the cathode leads to the formation of the alkoxide
anion33. It’s subsequent reaction in solution with
malononitrile gives rise to the malononitrile anion.
Then, Knoevenagel condensation of aldehyde 1, with
the malononitrile anion takes place in the solution
with the elimination of water and the formation of the
corresponding a-cyanocinnamo-nitrile derivatives
A. The subsequent hydroxide-promoted Michael
addition of 4-phenylurazole 3 to the electron-deficient
Knoevenagel adduct A followed by intramolecular
cyclization results in the corresponding products
4, with regeneration of the alkoxide anion as the
last step, which continues the catalytic chain
process by the interaction with the next molecule of
malononitrile.
RESULTS AND DISCUSSION
To optimized the reaction conditions, the
condensation between benzaldehyde, malononitrile
and 4-phenylurazole was chosen as model reaction.
The reactive mixture was stirred at room temperature,
and this progress was monitored by TLC. The
reaction is performed in alcoholic solvents in the
presence of sodium bromide as an electrolyte.
Various current quantities were applied under the
mentioned conditions. As can be seen in Table 1,
excellent conversions of the starting materials were
obtained under 10 mA/cm2 current densities after
0.1 F/mol of electricity had passed. The current
density of 10 mA/cm2, I = 50 mA, electrode surface
Scheme 1.
CONCLUSION
The pyrazolo[1,2-a][1,2,4]triazole-1,3-dione
derivatives were synthesised in the presence of
sodium bromide as an electrolyte under neutral and
mild conditions.The main advantages of this method
are the very short reaction time, high yields, simple
work-up, use of non- hazardous organic solvent and
catalyst.
Using mentioned optimized reaction, the
reaction were explored for the synthesis of a wide
variety of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
using aromatic aldehydes, malononitriles and
4-phenylurazol.The results are summarized inTable
2. As shown in Table 2, the products were obtained
in excellent yields.
ACKNOwLEDgMENT
We gratefully acknowledge financial
support from the Research Council of the University
of Sistan and Baluchestan.
We proposed mechanism for the
preparation of pyrazolo[1,2-a][1,2,4]triazole-1,3-
dione derivatives. First, deprotonation of an alcohol
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