Nano-ZnO: An efficient and reusable catalyst for one-pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and pyrazolo[1,2-a][1,2,4]triazole-1, 3-diones

Article abstract of DOI:10.1007/s13738-012-0159-3

The catalytic activity of nano-structured ZnO has been explored in the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione and pyrazolo[1,2-a][1,2,4] triazole-1,3-dione derivatives via a three-component coupling reaction between aromatic aldehydes, malononitrile, and phthalhydrazides or 4-arylurazoles, respectively. High yield, low reaction times, non-toxicity and recyclability of the catalyst, and easy work-up are the main merits of this protocol. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-012-0159-3

J IRAN CHEM SOC (2013) 10:297–306
DOI 10.1007/s13738-012-0159-3
ORIGINAL PAPER
Nano-ZnO: an efficient and reusable catalyst for one-pot
synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones
and pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
•
Ali Azarifar Razieh Nejat-Yami Davood Azarifar
•
Received: 8 June 2012 / Accepted: 18 August 2012 / Published online: 5 September 2012
Ó Iranian Chemical Society 2012
Abstract The catalytic activity of nano-structured ZnO has
been explored in the synthesis of 1H-pyrazolo[1,2-b]phthal-
azine-5,10-dione and pyrazolo[1,2-a][1,2,4]triazole-1,3-
dione derivatives via a three-component coupling reaction
between aromatic aldehydes, malononitrile, and phthalhyd-
razides or 4-arylurazoles, respectively. High yield, low
reaction times, non-toxicity and recyclability of the catalyst,
and easy work-up are the main merits of this protocol.
zinc oxide exhibit versatile applications as active adsorbents
for gases or destruction of hazardous chemicals [21–23], and
alsoascatalystsinvariousorganic transformations [8, 24–29].
On the other hand, one-pot multi-component reactions
(MCRs) are known to be superior to conventional linear-
type processes that usually suffer from complex isolation
procedures and produce significant amounts of waste
materials [30–32]. In addition, multi-component processes
provide rapid and efficient approach to organic transfor-
mations including diverse synthesis of polyfunctionalized
heterocycles [33–35]. Such heterocycles are of significant
biological and pharmaceutical importance and play vital
roles in drug discovery process. Among these, the multi-
component synthesis of polyfunctionalized heterocyclic
compounds has become more challenging in organic and
medicinal chemistry [33–35]. Pyrazolo-fused 1,2,4-triaz-
olidine-3,5-dione derivatives exhibit a wide range of bio-
logical activities as anti-convulsant and fungicidal agents,
[36, 37]. Also, pyrazolo-fused phthalazine derivatives
constituting a bridgehead hydrazine are reported to possess
multiple biological and pharmacological properties
including anti-convulsant [38], vasorelaxant [39], cardio-
tonic [40], anti-pyretic, anti-inflammatory and anti-bacte-
rial activities [41–43]. Raghuvanshi and co-worker have
recently reported a highly efficient green synthesis of
1H-pyrazolo[1,2-b]phthalazine-5,10-diones of photophysi-
cal importance [44].
Keywords ZnO nanoparticles Á Nano-catalyst Á
Pyrazolo[1,2-b]phthalazine-5 Á 10-Dione Á Pyrazolo[1,2-a]
[1,2,4]triazole-1 Á 3-Dione Á 4-Arylurazoles
Introduction
Heterogeneous catalysts have emerged as economically via-
ble because of their high potent of recyclability [1–4]. In
particular, nano-particles as heterogeneous catalysts have
received considerable attraction in recent years owing to
their interesting structures and outstanding catalytic activities
[5–10]. Currently, use of nano-metal oxides has appeared as
interesting challenge in synthetic organic chemistry due to
their extraordinary physical and chemical properties [11–15].
The advantages allocated to these nano-metal oxides are high
activity, strong oxidizing power, recyclability, and long-term
stability [16–20]. Nano-crystalline metal oxides such as nano
A. Azarifar
School of Applied Sciences, Royal Melbourne Institute
of Technology, Melbourne, VA 3001, Australia
Experimental
Chemicals
R. Nejat-Yami Á D. Azarifar (&)
Faculty of Chemistry, Bu-Ali Sina University,
Zip Code 65178 Hamedan, Islamic Republic of Iran
e-mail: dazarifar@gmail.com; azarifar@basu.ac.ir
Chemicals used in this work were purchased from Fluka
and Merk chemical companies and used without
123

298
J IRAN CHEM SOC (2013) 10:297–306
Table 1 Optimization of the model reaction between malonitrile, phthalhydrazide and benzaldehydea
O
O
NH2
N
N
HN
nano-ZnO
+
+
CN
CHO
NC
CN
HN
O
Ph
O
5
1
2a
4a
Entry
Temperature (°C)
Solvent
Catalyst (mol %)
Time (min)
Yield (%)b
1
rt
EtOH
MeCN
H2O
Nano-ZnO (15)
Nano-ZnO (15)
Nano-ZnO (15)
None
120
120
120
120
14
Trace
Trace
Trace
Trace
53
2
rt
3
rt
4
100
100
100
100
100
100
80
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
H2O/reflux
5
Nano-ZnO (5)
Nano-ZnO (10)
Nano-ZnO (15)
Nano-ZnO (20)
Nano-ZnO (15)
Nano-ZnO (15)
Nano-ZnO (15)
6
14
72
7
14
90
8
14
91
9
40
48
10
11
a
EtOH/reflux
CH3CN/reflux
40
61
80
40
53
Conditions: malononitrile (1 mmol), phthalhydrazide (1 mmol), benzaldehyde (1 mmol)
b
Isolated yield
(1.0 mmol), or 4-arylurazole 5 (1.0 mmol), and nano-ZnO
(15 mol %) are placed in a mortar. The reaction mixture was
then heated at 80–100 °C for an appropriate time (Table 2)
until the completion of the reaction was achieved as monitored
by TLC. Then, the reaction mixture was cooled, washed with
ethanol (2 9 3 mL) and evaporated under vacuum to give the
products 5 and 6. The structures of the products were fully
purification. IR spectra were recorded on a Shimadzu
1
435-U-04 FT spectrophotometer from KBr pellets. H and
13C NMR spectra were measured for samples in DMSO-d6
using a BRUKER DRX-300 AVANCE instrument at
300.13 and 75.47 MHz, respectively, using Me4Si as
internal standard. Mass spectra were recorded with a
spectrometer FINNIGAN-MAT 8430 operating at an ion-
ization potential of 70 eV. Melting points were measured
on a SMPI apparatus. Elemental analysis for C, H and N
atoms were performed using a Perkin–Elmer 2400 series
analyzer. Urazoles were synthesized according to the
reported procedures [45–48].
1
established on the basis of their H NMR, 13C NMR and IR
spectra as well as the elemental and MS spectral analysis for the
new compounds as given below.
Physical and spectroscopic data
3-Amino-1-(2-bromophenyl)-5,10-dihydro-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4 g) Yellow
powder. M.p. 248–250 °C. 1H-NMR (DMSO-d6, 300 MHz):
d 6.30 (s, 1H, CH), 7.63–8.37 (m, 10H, Ar–H and NH2) ppm.
13C-NMR (DMSO-d6, 75 MHz): d 60.7, 62.6, 116.4, 122.3,
123.9, 127.1, 127.7, 128.7, 129.3, 130.7, 134.2, 134.3, 135.1,
141.0, 148.4, 151.5, 154.4, 157.2. IR (KBr, cm-1): 3363,
3259, 2193, 1681, 1655 ppm. MS (70 eV) m/z: 394 [M?].
Anal. Calcd. for C18H11BrN4O2: C 54.69, H 2.78, N 14.18;
Found: C 54.56, H 2.73, N 14.12.
Synthesis of ZnO nanoparticles
ZnO Nanorods are prepared according to the literature
method developed by Pacholski and co-workers with some
modification [49]. In a flask containing methanol (50 mL)
was added Zn(OAc)2 (2.195 g). The solution was heated to
60 °C under magnetic stirring. Then, in a separate flask,
85 % pure potassium hydroxide (0.953 g) was dissolved in
methanol (50 mL) and the solution was added dropwise to
the stirring solution of zinc acetate during 10–15 min. At
the constant temperature of 60 °C, it takes 135 min until
ZnO nanospheres with 6 nm diameter is obtained.
3-Amino-5,10-dihydro-1-(3-methoxyphenyl)-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4 h) Yel-
low powder. M.p. 232–234 °C. 1H-NMR (DMSO-d6,
300 MHz): d 3.72 (s, 3H, OCH3), 6.04 (s, 1H, CH), 6.84–8.19
(m, 10H, Ar–H and NH2) ppm. 13C-NMR (DMSO-d6,
75 MHz): d 55.5, 61.7, 63.3, 113.1, 113.7, 116.5, 119.1,
General procedure for the synthesis of 1H-pyrazolo[1,2-b]
phthalazine-5,10-diones
4a–n
and
pyrazolo[1,2-a]
[1,2,4]triazole-1,3-diones 6a–o A mixture of malononitrile
1 (1.0 mmol), aldehyde 2 (1.0 mmol), phthalhydrazide 3
123

J IRAN CHEM SOC (2013) 10:297–306
299
Table 2 Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–n catalyzed by nano-ZnOa
Entry
Ar1
Product 4
Time (min)
Yield (%)b
M.p. (°C)
Found
Reported
251–253
a
C6H5
14
90
249–251
O
N
N
CN
NH2
O
O
b
c
2-ClC6H4
11
89
91
256–258
257–259
265–267
Cl
CN
N
N
NH2
O
3-ClC6H4
8
265–267
264–266
Cl
O
N
CN
N
NH2
O
NO2
d
4-NO2C6H4
9
87
266–267
O
N
CN
N
NH2
O
F
e
4-FC6H4
8
93
265–267
264–265
O
N
CN
N
NH2
O
f
4-MeC6H4
20
86
253–255
255–256
CH3
O
N
CN
N
NH2
O
O
g
2-BrC6H4
10
18
90
87
248–250
232–234
–
–
Br
N
N
CN
NH2
O
h
3-MeOC6H4
OMe
O
O
N
N
CN
NH2
i
4-Pyridyl
15
86
260–262
–
N
O
O
N
N
CN
NH2
123

300
J IRAN CHEM SOC (2013) 10:297–306
Table 2 continued
Entry
Ar1
Product 4
Time (min)
12
Yield (%)b
M.p. (°C)
Found
Reported
–
j
3-Pyridyl
90
91
267–270
N
O
O
N
N
CN
NH2
k
2-Naphthyl
18
267–269
–
O
N
CN
NH2
N
O
NC
l
3-CHOC6H4
45
88
271–273
–
NH2
N
O
N
O
N
N
O
CN
NH2
O
Cl
m
2,4-Cl2C6H3
11
14
92
91
231–232
261–263
–
–
O
Cl
N
CN
N
NH2
O
n
2,3-Cl2C6H3
Cl
O
O
Cl
CN
N
N
NH2
a
Conditions: aldehyde (1 mmol), malononitrile (1 mmol), phthalhydrazide (1 mmol), nano-ZnO catalyst (15 mol %), solvent free at 100 °C
Isolated yield
b
127.1, 127.7, 128.8, 129.1, 130.3, 134.3, 135.2, 140.3, 151.0,
powder. M.p. 268–270 °C. 1H-NMR (DMSO-d6,
300 MHz): d 6.21 (s, 1H, CH), 7.37–8.72 (m, 10H, Ar–H
and NH2) ppm. 13C-NMR (75 MHz, DMSO-d6): d 60.7,
62.1, 116.5, 128.9, 129.4, 133.5, 134.4, 149.0, 149.1,
150.0, 151.3, 151.4, 154.2, 157.1 ppm. IR (KBr, cm-1):
3368, 3265, 2193, 1681, 1654. MS (70 eV) m/z: 317 [M?].
Anal. Calcd. for C17H11N5O2: C 64.35, H 3.47, N 22.08;
Found: C 64.23, H 3.37, N 21.96.
154.1, 157.1, 159.8 ppm. IR (KBr, cm-1): 3373, 3267, 2192,
1665, 1603. MS (70 eV) m/z: 346 [M?]. Anal. Calcd. for
C19H14N4O3: C 65.89, H 4.04, N 16.18; Found: C 65.76, H
3.98, N 16.13.
3-Amino-5,10-dihydro-5,10-dioxo-1-(pyridin-4-yl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4i) Yellow
powder. M.p. 260–262 °C. 1H-NMR (DMSO-d6, 300 MHz):
d 6.19 (s, 1H, CH), 7.40–8.72 (m, 10H, Ar–H and NH2) ppm.
13C-NMR (DMSO-d6, 75 MHz): d 60.0, 61.8, 116.1, 128.3,
128.9, 134.5, 135.4, 150.5, 151.6, 154.0, 157.1 ppm. IR
(KBr, cm-1):3367, 3246, 2201, 1684, 1667. MS(70 eV)m/z:
317 [M?]. Anal. Calcd. for C17H11N5O2: C 64.35, H 3.47, N
22.08; Found: C 64.28, H 3.45, N 22.04.
3-Amino-5,10-dihydro-1-(naphthalen-2-yl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4k) Yellow
powder. M.p. 267–269 °C. 1H-NMR (DMSO-d6, 300 MH,): d
6.28 (s, 1H, CH), 7.50–8.26 (m, 13H, Ar–H and NH2) ppm.
13C-NMR (DMSO-d6, 75 MHz): d 61.8, 63.7, 116.6, 124.8,
126.5,126.8, 126.9, 127.1, 127.7, 128.3, 128.9, 129.1, 129.3,
133.2, 133.3, 134.2, 135.1, 136.4, 151.1, 154.2, 157.1 ppm. IR
(KBr, cm-1): 3368, 3265, 2192, 1681, 1658. MS (70 eV) m/z:
3-Amino-5,10-dihydro-5,10-dioxo-1-(pyridin-3-yl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile
(4j) Yellow
123

J IRAN CHEM SOC (2013) 10:297–306
301
Table 3 Synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones 6a–o catalyzed by nano-ZnOa
Entryb
Ar1
Ar2
Product 6
Time (min)
25
Yield (%)c
90
a
C6H5
C6H5
O
NH2
CN
N
N
N
H
O
O
b
4-ClC6H4
C6H5
25
88
NH2
N
N
CN
H
N
O
Cl
c
C6H5
4-ClC6H4
4-ClC6H4
18
20
91
91
O
NH2
CN
N
N
Cl
N
H
O
d
4-ClC6H4
O
NH2
N
N
CN
H
Cl
N
O
Cl
e
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-ClC6H4
30
20
25
90
86
71
O
NH2
N
CN
H
Cl
Cl
N
N
O
NO2
f
2,4-Cl2C6H3
O
NH2
CN
N
N
N
H
Cl
O
NO2
NH2
g
4-NO2C6H4
O
N
CN
H
N
O2N
N
O
NO2
h
C6H5
4-MeOC6H4
30
84
O
NH2
CN
N
N
MeO
N
H
O
123

302
J IRAN CHEM SOC (2013) 10:297–306
Table 3 continued
Entryb
Ar1
Ar2
Product 6
Time (min)
25
Yield (%)c
81
i
4-NO2C6H4
4-MeOC6H4
O
NH2
CN
N
N
MeO
N
H
O
NO2
j
C6H5
4-Me3CC6H4
25
30
80
75
O
NH2
CN
N
Me3C
Me3C
N
N
H
O
k
4-NO2C6H4
4-Me3CC6H4
O
NH2
CN
N
N
N
H
O
NO2
l
(4-Cl-3-NO2)C6H3
C6H5
25
86
O
NH2
CN
N
N
N
H
O
NO2
Cl
m
2,4,6-(OMe)3C6H2
C6H5
30
78
O
NH2
CN
N
N
N
H OMe
O
MeO
O
OMe
n
2,3-Cl2C6H3
C6H5
15
91
NH2
CN
N
N
N
H
Cl
Cl
O
o
C2H5
C6H5
120
–
O
NH2
N
N
CN
N
H
O
C2H5
a
Conditions: aldehyde (1 mmol), malononitrile (1 mmol), 4-arylurazole (1 mmol), nano-ZnO catalyst (15 mol %), solvent-free at 80 °C
All the products decompose ([300 °C) prior to melting as reported [53, 54]
Isolated yield
b
c
366 [M?]. Anal. Calcd. for C22H14N4O2: C 72.13, H 3.82, N
13C-NMR (DMSO-d6, 75 MHz): d 61.2, 82.6, 113.6, 114.5,
116.3,128.9,129.2, 132.2, 151.2, 154.1, 157.1 ppm. IR
(KBr, cm-1): 3363, 3262, 2228, 2190, 1651, 1604.
MS (70 eV) m/z: 554 [M?]. Anal. Calcd. for C30H18N8O4:
C 64.98, H 3.25, N 20.21; Found: C 64.84, H 3.22, N
20.16.
15.30; Found: C 72.05, H 3.78, N 15.26.
1,3-Bis{3-amino-2-cyano-5,10-dihydro-5,10-dioxo-1H-py-
razolo[1,2-b]phthalazin-2- yl}benzene (4l) Yellow pow-
1
der. M.p. 271–273 °C. H-NMR (DMSO-d6, 300 MHz): d
6.20 (s, 1H, CH), 7.63–8.46 (m, 16H, Ar–H and NH2) ppm.
123

J IRAN CHEM SOC (2013) 10:297–306
303
3-Amino-1-(2,4-dichlorophenyl)-5,10-dihydro-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4m) Yel-
low powder. M.p. 231–232 °C. 1H-NMR (DMSO-d6,
300 MHz): d 6.43 (s, 1H, CH), 7.39–8.25 (m, 9H, Ar–H
and NH2) ppm. 13C-NMR (75 MHz, DMSO-d6): d 61.2,
62.5, 116.5, 127.1, 127.9, 128.6, 128.9, 129.2, 130.3,
130.5, 131.5, 134.4, 138.2, 138.9, 151.6, 154.1, 157.0 ppm.
IR (KBr, cm-1): 3364, 3262, 2197, 1681, 1660. MS
(70 eV) m/z: 384 [M?]. Anal. Calcd. for C18H10Cl2N4O2:
C 56.10, H 2.59, N 14.54; Found: C 56.03, H 2.54, N
14.43.
(70 eV) m/z: 400 [M?]. Anal. Calcd. for C18H11Cl2N5O2:
C 54.00, H 2.75, N 17.50; Found: C 53.92, H 2.70, N
17.56.
Results and discussion
In continuation of our ongoing efforts to develop newer
and more benign approaches to the synthesis of various
heterocyclic compounds [50–54], and also owing to the
numerous advantages associated with participation of
nano-catalysts in organic transformations, we were
encouraged to examine the use of hitherto unexplored ZnO
nanoparticles as efficient and reusable catalyst in the one-
pot synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-di-
ones 4a–n and pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
6a–n (Scheme 1).
3-Amino-1-(2,3-dichlorophenyl)-5,10-dihydro-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4n) Yel-
low powder. M.p. 261–263 °C. 1H-NMR (DMSO-d6,
300 MHz): d 6.51 (s, 1H, CH), 7.33–8.27 (m, 9H, Ar–H
and NH2) ppm. 13C-NMR (DMSO-d6, 75 MHz): d 60.7,
61.8, 116.6, 124.9, 125.9, 126.2, 126.5, 127.1, 127.8,
128.1, 128.3, 129.0, 129.2, 138.8, 138.9, 151.1, 154.0,
157.1 ppm. IR (KBr, cm-1): 3372, 3236, 2211, 1686, 1661.
MS (70 eV) m/z: 384 [M?]. Anal. Calcd. for
C18H10Cl2N4O2: C 56.10, H 2.59, N 14.54; Found: C
55.97, H 2.53, N 14.58.
In order to establish the conditions of the titled reac-
tions, we preliminary examined the model condensation
reaction between malononitrile 1 (1 mmol), benzaldehyde
2a (1 mmol) and phthalhydrazide 3 (1 mmol) as test
compounds. Screening of the reaction parameters was
studied by using different solvents such as EtOH, MeCN,
and H2O. The results are summarized in Table 1. As seen
in this Table, it was noticed that, the reaction worked out
best at 100 °C under solvent-free conditions with
15 mol % nano-ZnO catalyst loading (entry 7). To sub-
stantiate the important role of the catalyst, the reaction was
carried out at 100 °C in the absence of the catalyst under
solvent-free conditions. As a result, only trace amounts of
the product was formed and the starting materials remained
almost intact (entry 4). Also the reaction was conducted
under conventional heating at reflux point using various
solvents such as EtOH, MeCN, and H2O that resulted in
the formation of only trace amounts of the product (entries
9–11).
7-Amino-5-(4-chloro-3-nitrophenyl)-1,3-dihydro-1,3-dioxo-
2-phenyl-2H,5H-pyrazolo[1,2-a][1,2,4]triazole-6-carboni-
trile (6l) White powder. M.p.[300 °C. 1H-NMR (DMSO-
d6, 300 MHz): d 6.03 (s, 1H, CH), 7.45–8.27 (m, 10H, Ar–H
and NH2) ppm. 13C-NMR (DMSO-d6, 75 MHz): d 61.1,
62.9, 116.8, 124.4, 125.5, 127.3, 129.2, 129.9, 131.4, 140.9,
145.9, 148.4, 150.7, 150.9, 154.1 ppm. IR (KBr, cm-1):
3422, 3302, 2179, 1781, 1721. MS (70 eV) m/z: 410 [M?].
Anal. Calcd. for C18H11ClN6O4: C 52.61, H 2.67, N 20.46;
Found: C 52.56, H 2.64, N 20.38.
7-Amino-1,3-dihydro-1,3-dioxo-2-phenyl-5-(2,4,6-trime-
thoxyphenyl)-2H,5H-pyrazolo[1,2-a][1,2,4]triazole-6-car-
1
bonitrile (6m) White powder. M.p. [300 °C. H-NMR
To develop the scope of these reactions, various other
aromatic aldehydes 2a–n were subjected to condensation
with malononitrile 1 under the optimized conditions (sol-
vent-free/100 °C, 15 mol % nano-ZnO catalyst). Almost
all the reactions proceeded smoothly in relatively short
reaction times (8–20 min) to afford the respective 1H-
pyrazolo[1,2-b]phthalazine-5,10-diones 4a–n in high
yields (86–93 %). The experimental results are summa-
rized in Table 2.
(DMSO-d6, 300 MHz): d 3.69 (s, 3H, OCH3), 3.81(s, 6H,
2OCH3), 5.82 (s, 1H, CH), 6.76–7.63 (m, 9H, Ar–H and
NH2) ppm. 13C-NMR (DMSO-d6, 75 MHz): d 56.4, 60.5,
60.8, 104.5, 127.3, 129.1, 129.5, 129.9, 130.1, 130.39,
131.5, 145.9, 153.6, 154.1 ppm. IR (KBr, cm-1): 3361,
3283, 2186, 1756, 1716. MS (70 eV) m/z: 421 [M?]. Anal.
Calcd. for C21H19N5O5: C 59.85, H 4.51, N 16.62; Found:
C 59.82, H 4.48, N 16.56.
7-Amino-5-(2,3-dichlorophenyl)-1,3-dihydro-1,3-dioxo-2-
phenyl-2H,5H-pyrazolo[1,2-a][1,2,4]triazole-6-carbonitrile
(6n) White powder. M.p.[300 °C. 1H-NMR (DMSO-d6,
300 MHz): d 6.30 (s, 1H, CH), 7.45–7.75 (m, 10H, Ar–H
and NH2) ppm. 13C-NMR (DMSO-d6, 75 MHz): d 60.9,
62.5, 116.6, 127.3, 128.7, 129.5, 129.9, 130.1, 130.4,
131.3, 131.4, 132.7, 139.2, 145.9, 150.7, 151.1, 154.2 ppm.
IR (KBr, cm-1): 3417, 3298, 2167, 1782, 1689. MS
Also, the reaction between malononitrile 1, benzalde-
hyde 2a and 4-phenylurazole 5a as test compounds for the
synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones
worked out best at 80 °C under solvent-free conditions
catalyzed with nano-crystalline ZnO catalyst (15 mol %)
as shown in Table 3 (entry a). Similarly, this reaction was
successfully extended to various other 4-arylurazoles to
furnish the corresponding products 6a–n in high yields as
123

304
J IRAN CHEM SOC (2013) 10:297–306
18000
16000
14000
12000
10000
8000
6000
4000
2000
0
20
30
40
50
60
70
80
90
2θ (degree)
Fig. 3 EDAX spectrum of the prepared ZnO nanoparticles
Fig. 1 X-ray diffraction (XRD) patterns of the prepared ZnO
nanoparticles
diffraction peaks other than ZnO crystal in the synthesized
sample suggests that the nanocrystals have preferential
orientation. All the XRD peaks are indexed by hexagonal
Wurtzite phase of ZnO (JCPDS Card No. 80-0075). Pow-
der XRD patterns were recorded on a Burker D4
ENDEAVOR X-ray diffractometer with Cu Ka radiation.
The specific surface area (SSABET) of ZnO samples has
been measured using Brunauer–Emmett–Teller (BET)
analysis. The average BET equivalent particle diameter
(dBET) were calculated using the average of the density of
ZnO nanoparticles. The BET specific surface areas of the
ZnO nanoparticles were determined using an accelerated
surface area and porosimetry system (ASAP 2010)
Micrometrics Instrument Corporation. Sample was degas-
sed overnight at 373 K and surface area was measured by
N2 adsorption/desorption at 77 K. The measured BET
given in Table 3. However, this method appears to be
unsuitable for aliphatic aldehydes (entry o). The known
products 4a–f [43] and 6a–k [53, 54] were characterized
1
based on their physical and spectral (IR, H NMR, 13C
NMR, MS) data which were in accord with the reported
data. The new products 4g–n and 6l–n were characterized
1
by their elemental and spectral (IR, H NMR, 13C NMR,
MS) analysis as reported below.
Structural analysis of ZnO nanoparticles
The X-ray diffraction (XRD) spectrum of ZnO nanoparti-
cles is shown in Fig. 1. Single phase formation has been
observed and hardly appearance of any significant extra
(a)
(b)
25
20
15
10
5
0
2
3
4
5
6
7
8
9
10
Particle size(nm)
Fig. 2 Transmission electron micrographs (TEM) picture of ZnO is shown in (a) and the particle size distribution as obtained from TEM
micrograph is shown in (b)
123

J IRAN CHEM SOC (2013) 10:297–306
305
Scheme 1 Nano-ZnO-
catalyzed synthesis of
1H-pyrazole[1,2-b]phthalazine-
5,10-diones 4a–n and
pyrazolo[1,2-a]triazole-1,3-
diones 6a–n
O
O
HN
HN
NH2
O
O
N
N
CN
3
Ar1
4a-n
NC
nano-ZnO
O
Ar1CHO
+
NH
NH
NC
solvent free/
80-100 oC
NH2
Ar2
N
O
1
2a-i
N
N
Ar2
N
O
CN
5
Ar1
O
6a-n
Ar1
O
O
O
H
CN
NC
CN
O
O
NH
Zn
O
HN
N
H
H
Ar1
H
Ar1
N
HC
H
N
N
H
CN
H
1
C
N
H
(A)
O
3
O
2
N
NC
(B)
N
Ar1
(C)
H
O Zn
O
Zn
O
Zn
Ar1
O
Zn
O
Zn
Zn
N
nano-ZnO:
:
CN
NH2
O
N
O
4
Scheme 2 A putative mechanism for the formation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4
surface area of the ZnO nanoparticles catalyst was found to
be 29.06 m2/g. Also using the same instrument almost no
surface porosity was found on the surface of the
nanopraticles.
methanol and then directly deposited on a copper grid
coated with a carbon film.
ZnO Nanoparticles possess an amphoteric structure
creating both Lewis acid and base properties. Accordingly,
a possible mechanism to explain the formation of 1H-
pyrazolo[1,2-b]phthalazine-5,10-diones 4a–n is depicted in
Scheme 2. As shown in this Scheme, the reaction is likely
initiated by a Knoevenagel-type condensation reaction
between malononitrile 1 and aromatic aldehyde 2 under the
catalytic effect of nano-ZnO followed by dehydration to
provide the malononitrile derivative (A). This occurs
through the activation of C–H bond in malononitrile by
basic oxygen in the catalyst from the one hand, and the
activation of the carbonyl group in aldehyde by the acidic
part (Zn) of the catalyst on the other hand. Subsequently, a
Michael-type addition of intermediate (A) to phthalhyd-
razide 3 under the catalytic effect of nano-ZnO occurs to
yield a second intermediate (B) which successively
undergoes cyclization to (C) and nano-ZnO-promoted
tautomerization to afford the expected product 4.
TEM and EDX
The transmission electron microscopy (TEM) image deter-
mined for the pure ZnO nanoparticles is given in Fig. 2a. It is
indicated that, the average size is ca 8 nm which approxi-
mately matches with the particle size calculated using Sher-
rer’s formula. Figure 2b shows the particle size (diameter)
distribution which is in the range of 3–9 nm.
The corresponding energy-dispersive X-ray (EDAX)
spectrum of ZnO in Fig. 3 indicates the high purity of ZnO
nanoparticles. In addition to the Zn peaks, the cupper peaks
are also detected which are due to the used copper grid.
The TEM image and EDAX spectrum were obtained on a
Jeol 2010 microscope operated at 200 kV with Link Si(Li)
X-ray detector. Sample powders were suspended in
123

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J IRAN CHEM SOC (2013) 10:297–306
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(2004)
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In conclusion, we have developed a convenient one-pot
three component cyclocondensation reaction between aro-
matic aldehydes, malononitrile and phthalhydrazide or
4-arylurazoles for the synthesis of 1H-pyrazolo[1,
2-b]phthalazine-5,10-diones and pyrazolo[1,2-a][1,2,4]tri-
azole-1,3-diones, respectively. High surface area and
recyclability of the nano-crystalline ZnO catalyst, solvent-
free conditions, easy preparation of the catalyst, low
reaction times and high yields products are the main
advantages of this method.
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Acknowledgments This work was supported by the Research
Council of the Bu-Ali Sina University (Iran). The School of Applied
Sciences, Royal Melbourne Institute of Technology in Melbourne is
also gratefully acknowledged for preparation and instrumental anal-
ysis of the nano-catalyst ZnO.
¨
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