Regioselective synthesis of fused azo-linked pyrazolo[4,3-e]pyridines using nano-Fe3O4

Article abstract of DOI:10.1002/cjoc.201100181

A multicomponent reaction for the synthesis of fused azo-linked pyrazolo[4,3-e]pyridines from 3-amino-5-methylpyrazole, indan-1,3-dione and synthesized azo-linked aldehydes using nano-Fe₃O₄ as an effective and reusable catalyst is re

Full text of DOI:10.1002/cjoc.201100181

FULL PAPER
DOI: 10.1002/cjoc.201100181
Regioselective Synthesis of Fused Azo-linked
Pyrazolo[4,3-e]pyridines Using Nano-Fe3O4
Nikpassand, Mohammad*,a
Zare, Leilab
Shafaati, Tamilaa
Shariati, Shahaba
a Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
b Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
A
multicomponent reaction for the synthesis of fused azo-linked pyrazolo[4,3-e]pyridines from
3-amino-5-methylpyrazole, indan-1,3-dione and synthesized azo-linked aldehydes using nano-Fe3O4 as an effective
and reusable catalyst is reported. The present methodology offers several advantages, such as a simple procedure
with an easy work-up, short reaction times, high yields, and the absence of any volatile and hazardous organic sol-
vents.
Keywords multicomponent, pyrazolo[4,3-e]pyridines, 3-amino-5-methylpyrazole, indan-1,3-dione
Introduction
through multicomponent reactions of 3-amino-5-
methylpyrazole, azo-linked aldehydes and active me-
thylene compounds using nano-Fe3O4 (Scheme 1).
Pyrazolopyridines have received more and more at-
tention in the recent years. Pharmaceutical researches of
this kind of compounds have been reported, such as a
potent cyclin dependent kinase 1 (CDK1) inhibitor,[1]
HIV reverse transcriptase inhibitors,[2] CCR1 antago-
nists,[3] protein kinase inhibitors[4] and inhibitors of
cGMP degradation, together with several herbicidal and
fungicidal activities.[5] Some derivatives exhibit poten-
tial antimalarial[6] and antiviral properties.[7,8] Others
show intense fluorescence in the bluegreen region and
have been considered for applications as fluorescence
standards and luminophores in organic light emitting
experimental diodes.[9] Numerous methods for the syn-
thesis of pyrazolopyridines in the last twenty years have
been reported with respect to their different struc-
tures.[10]
Scheme 1 Multicomponent synthesis of pyrazolopyridine
O
Me
nano-Fe3O4
N N
OH
+
Ar
Ar
+
N
NH2
N
H
CHO
1a - 1j
O
3
2
Ar
N
N
O
OH
Me
N
N
OH
Me
O
N
N
or
NH
NH
N
N
H
The main disadvantages of most of these procedures
are harsh reaction condition, tedious workup, low yield,
high reaction time, multi-step reaction, use of large
quantity of volatile organic solvents and low regioselec-
tivity. Due to these problems, development of an effi-
cient and versatile method for the preparation of novel
derivatives of pyrazolopyridines is an important aspect
and there is a scope for the further improvement to-
wards milder reaction conditions, improved yields and
green procedure.
Recent development in the pyrazolopyridines chem-
istry and our continued interest in the development of
efficient and environmentally friendly procedure for the
synthesis of pharmaceutical compound[11-14] triggered us
to describe here an efficient method for the regioselec-
tive synthesis of new derivatives of pyrazolopyridines
5g - 5j
4a - 4f
Experimental
Melting points were measured on an Electrothermal
9100 apparatus. IR spectra were determined on a Shi-
madzo IR-470 spectrometer. H NMR spectra were re-
1
corded on a 500 MHz Bruker DRX-500 and 13C NMR
spectra were recorded on a 250 MHz Bruker DRX-500
in DMSO-d6 as solvent. Chemicals were purchased
from Merck and Fluka. Elemental analyses were done
on a Carlo-Erba EA1110CNNO-S analyser and agreed
with the calculated values. All solvents used were dried
and distilled according to standard procedures.
*
E-mail: Nikpassand@iaurasht.ac.ir; Tel.: 0098-1314223152; Fax: 0098-1314223152
Received July 29, 2011; accepted September 14, 2011.
604
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 604—608

Regioselective Synthesis of Fused Azo-linked Pyrazolo[4,3-e]pyridines Using Nano-Fe3O4
General procedure for the synthesis of azo linked
pyrazolopyridines using nano-Fe3O4
carbons), 121.64, 122.86, 126.94, 128.49, 130.90,
131.83, 135.90, 137.06, 137.44, 138.12, 138.60, 148.04,
148.26, 154.56, 158.71, 159.44, 190.23; FT-IR (KBr) ν:
3398, 3064, 2925, 1712, 1668, 1614, 1554, 1512, 1427,
A solution of 3-amino-5-methylpyrazole 3 (1 mmol,
0.097 g), indan-1,3-dione 2 (1 mmol, 0.146 g), synthe-
sized aldehyde 1 (1 mmol) and 0.05 g nano-Fe3O4 in
H2O (10 mL) was refluxed for the required reaction
times (Table 4). The progress of the reaction was moni-
tored by TLC (EtOAc∶petroleum ether, 1∶4). After
completion of the reaction, the mixture was filtered in
the presence of an efficient magnetic bar. The crude
product was recrystallized from ethanol to produce
pyrazolopyridine derivatives 4a—4f and 5g—5i as pure
crystalline product.
－
1
1361, 1224, 1087 cm . Anal. calcd for C27H20N6O4: C
65.85, H 4.09, N 17.06; found C 65.58, H 4.09, N 17.45.
4-(2-Hydroxy-5-((2-chlorophenyl)diazenyl)phen-
yl)-3-methyl-4,10-dihydroindeno[1,2-b]pyrazolo[4,3-
e]pyridin-5(1H)-one (4d) Dark brown solid, decom-
position 200 ℃; 1H NMR (DMSO-d6, 500 MHz) δ: 1.9
(s, 3H), 5.3 (s, 1H), 6.98 (d, J＝9.0 Hz, 1H), 7.18 (d,
J＝6.9 Hz, 1H), 7.29—7.33 (m, 1H), 7.36 (d, J＝7.6 Hz,
1H), 7.38—7.44 (m, 2H), 7.54 (d, J＝7.7 Hz, 1H), 7.59
(d, J＝5.7Hz, 3H), 7.67 (d, J＝7.1Hz, 1H), 10.5 (s, 1H),
11.2 (s, 1H), 12.06 (s, 1H); 13C NMR (DMSO-d6, 125
MHz) δ: 10.20, 56.01, 105.37, 105.79, 117.00, 118.41,
119.76, 120.40, 122.03, 127.36, 128.75, 129.54, 130.89,
131.31, 131.83, 132.30, 133.88, 135.91,137.06, 137.47,
138.56, 146.71, 148.03, 148.85, 158.70, 190.23; FT-IR
(KBr) ν: 3384, 3255, 2927, 1728, 1660, 1614, 1548,
1496, 1465, 1280, 1062 cm － 1. Anal. calcd for
C26H18ClN5O2: C 66.74, H 3.88, N 14.97; found C
66.73, H 3.46, N 14.71.
4-(2-Hydroxy-5-((4-iodophenyl)diazenyl)phenyl)-
3-methyl-4,10-dihydroindeno[1,2-b]pyrazolo[4,3-e]-
pyridine-5(1H)-one (4a) Red solid, decomposition
1
190 ℃; H NMR (DMSO-d6, 500 MHz) δ: 1.9 (s, 3H),
5.3 (s, 1H), 6.97 (d, J＝8.5 Hz, 1H), 7.17 (d, J＝6.8 Hz,
1H), 7.30 (t, J＝7.3 Hz, 1H), 7.39 (t, J＝7.3 Hz, 1H),
7.50 (d, J＝8.2 Hz, 2H), 7.54 (s, 1H), 7.58 (d, J＝8.5
Hz, 1H), 7.67 (d, J＝7.1 Hz, 1H), 7.81 (d, J＝8.2 Hz,
2H), 10.4 (s, 1H), 11.2 (s, 1H), 12.06 (s, 1H); 13C NMR
(DMSO-d6, 125 MHz) δ: 10.17, 56.30, 98.01, 105.37,
105.79, 116.91, 120.41 (two carbons), 122.45, 124.89,
126.32, 130.90, 131.83 (two carbons), 135.89, 137.11,
138.96, 139.56, 146.17, 148.03, 152.31, 158.63, 158.73,
190.23; FT-IR (KBr) ν: 3450, 3193, 3056, 2896, 1695,
4-(2-Hydroxy-5-((3-chlorophenyl)diazenyl)phen-
yl)-3-methyl-4,10-dihydroindeno[1,2-b]pyrazolo[4,3-
e]pyridin-5(1H)-one (4e) Brown solid, decomposi-
tion 125 ℃; 1H NMR (DMSO-d6, 500 MHz) δ: 2.06 (s,
3H), 5.2 (s, 1H), 7.20 (d, J＝8.7 Hz, 1H), 7.46—7.52
(m, 3H), 7.56 (d, J＝7.1 Hz, 1H), 7.67 (t, J＝7.3 Hz,
1H), 7.75 (br, 2H), 7.88 (br, 2H), 7.95 (dd, J＝2.2, 8.7
Hz, 1H), 10.5 (br, 1H), 11.2 (br, 1H), 13.8 (s, 1H); 13C
NMR (DMSO-d6, 125 MHz) δ: 12.28, 56.94, 91.30,
114.04, 117.06, 120.28, 121.45, 121.78, 122.17, 122.91,
123.92, 126.16, 127.77, 130.86, 131.82, 132.45, 134.91,
135.99, 137.71, 141.19, 141.74, 142.85, 145.30, 153.86,
159.70, 164.70, 190.15; FT-IR (KBr) ν: 3332, 3215,
－
1
1660, 1614, 1554, 1485, 1433, 1280, 1080 cm . Anal.
calcd for C26H18IN5O2: C 55.83, H 3.24, N 12.52; found
C 55.72, H 3.47, N 12.40.
4-(2-Hydroxy-5-((4-nitrophenyl)diazenyl)phenyl)-
3-methyl-4,10-dihydroindeno[1,2-b]pyrazolo[4,3-e]-
pyridin-5(1H)-one (4b) Red solid, decomposition
1
245 ℃; H NMR (DMSO-d6, 500 MHz) δ: 1.9 (s, 3H),
5.3 (s, 1H), 7.00 (d, J＝8.2 Hz, 1H), 7.17 (d, J＝6.4 Hz,
1H), 7.30 (t, J＝7.1 Hz, 1H), 7.39 (t, J＝7.0 Hz, 1H),
7.62 (s, 1H), 7.67 (t, J＝7.6 Hz, 2H), 7.90 (d, J＝8.2 Hz,
2H), 8.28 (d, J＝8.2 Hz, 2H), 10.6 (s, 1H), 11.2 (s, 1H),
12.06 (s, 1H); 13C NMR (DMSO-d6, 125 MHz) δ: 10.16,
56.23, 105.27, 105.67, 117.05, 119.82, 120.42, 123.28,
123.86, 125.67, 126.95, 130.91, 131.83, 135.87, 136.07,
137.11, 137.44, 146.45, 148.02, 148.46, 156.44, 158.64,
159.81, 190.19; FT-IR (KBr) ν: 3407, 3191, 3058, 2896,
1649, 1612, 1550, 1487, 1427, 1338, 1234, 1188, 1139
－
1
2925, 1704, 1600, 1568, 1452, 1292, 1085 cm . Anal.
calcd for C26H18ClN5O2: C 66.74, H 3.88, N 14.97;
found C 66.79, H 3.44, N 14.96.
4-(2-Hydroxy-5-((4-chlorophenyl)diazenyl)phen-
yl)-3-methyl-4,10-dihydroindeno[1,2-b]pyrazolo[4,3-
e]pyridin-5(1H)-one (4f) Dark yellow solid, decom-
position 185 ℃; 1H NMR (DMSO-d6, 500 MHz) δ: 2.0
(s, 3H), 5.1 (s, 1H), 7.21 (d, J＝8.7 Hz, 1H), 7.54 (t, J＝
7.2 Hz, 1H), 7.58 (d, J＝5.7 Hz, 1H), 7.60 (d, J＝8.7 Hz,
2H), 7.73 (t, J＝7.4 Hz, 1H), 7.82 (d, J＝8.7 Hz, 2H),
7.84 (d, J＝2.4 Hz, 1H), 7.92 (d, J＝7.4 Hz, 1H), 7.97
(dd, J＝2.4, 8.7Hz, 1H), 10.8 (s, 1H), 13.7 (s, 1H);13C
NMR (DMSO-d6, 125 MHz) δ: 12.29, 56.90, 91.23,
117.07, 120.30, 121.83, 122.15, 124.00, 124.67, 125.83,
126.65, 130.31, 132.57, 135.89, 136.13, 137.73, 139.20,
142.85, 145.36, 151.48, 152.15, 159.32, 164.73, 190.18;
FT-IR (KBr) ν: 3350, 3213, 2925, 1706, 1641, 1566,
1496, 1427, 1292, 1085 cm － 1. Anal. calcd for
C26H18ClN5O2: C 66.74, H 3.88, N 14.97; found C
66.57, H 3.82, N 14.43.
－
1
cm . Anal. calcd for C26H18N6O4: C 65.27, H 3.79, N
17.56; found C 65.52, H 3.67, N 17.85.
4-(2-Hydroxy-5-((2-methyl-4-nitrophenyl)di-
azenyl)phenyl)-3-methyl-4,10-dihydroindeno[1,2-b]-
pyrazolo[4,3-e]pyridin-5(1H)-one (4c)
Red solid,
decomposition 221 ℃; 1H NMR (DMSO-d6, 500 MHz)
δ: 1.9 (s, 3H), 2.5 (s, 3H), 5.3 (s, 1H), 6.98 (d, J＝8.3
Hz, 1H), 7.17 (d, J＝7.0 Hz, 1H), 7.30 (t, J＝7.4 Hz,
1H), 7.39 (t, J＝7.3 Hz, 1H), 7.56 (d, J＝8.8 Hz, 1H),
7.61 (d, J＝2.4 Hz, 1H), 7.63 (s, 1H), 7.67 (d, J＝7.2
Hz, 1H), 8.01 (dd, J＝2.3, 8.9 Hz, 1H), 8.20 (d, J＝2.1
Hz, 1H), 10.6 (s, 1H), 11.2 (s, 1H), 12.06 (s, 1H); 13C
NMR (DMSO-d6,125 MHz) δ: 10.20, 17.70, 56.07,
105.31, 105.75, 117.16, 117.46, 119.78, 120.40 (two
4-(2-Hydroxy-5-(phenyldiazenyl)phenyl)-3-
methylineno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one
Chin. J. Chem. 2012, 30, 604—608
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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605

Nikpassand et al.
FULL PAPER
(5g) Red solid, decomposition 305 ℃; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.02 (s, 3H), 7.20 (d, J＝8.7
Hz, 1H), 7.46 (d, J＝7.1 Hz, 1H), 7.52 (t, J＝7.5 Hz,
3H), 7.57 (d, J＝7.2 Hz, 1H), 7.69 (t, J＝7.4 Hz, 1H),
7.80 (d, J＝7.6 Hz, 2H), 7.85 (d, J＝2.2 Hz, 1H), 7.91
(d, J＝7.4 Hz, 1H), 7.97 (dd, J＝2.3, 8.7 Hz, 1H), 10.6
(s, 1H), 13.7 (s, 1H); 13C NMR (DMSO-d6, 125 MHz) δ:
14.46, 114.00, 117.00, 120.34, 121.81, 122.07, 123.03,
123.97, 125.72, 126.46, 130.17, 131.48, 132.52, 136.06,
137.73, 141.90, 142.86, 145.24, 145.52, 152.89, 155.49,
158.94, 164.75, 190.19; FT-IR (KBr) ν: 3450, 3195,
Table 1 Effect of amount of nano-Fe3O4 on synthesizing 5g
Entry Catalyst
Catalyst amount Time/min Yielda/%
1
2
3
4
5
6
—
—
240
60
2
70
77
86
81
86
87
Fe3O4
0.05 g
0.05 g
0.01 g
0.03 g
0.1 g
Nano-Fe3O4
Nano-Fe3O4
Nano-Fe3O4
Nano-Fe3O4
15
10
2
a Isolated yield.
－
1
2995, 1704, 1660, 1564, 1487, 1431, 1315, 1153 cm .
Anal. calcd for C26H17N5O2: C 72.38, H 3.97, N 16.23;
found C 72.17, H 3.45, N 16.83.
to push the reaction forward completion and 10 or 30
mg of catalyst was not enough. Higher amount of cata-
lyst did not lead to significant change in the reaction
yields.
Furthermore, the reaction was carried out in different
solvents. As shown in Table 2, the yields of the reaction
in H2O were greater and the reaction times were gener-
ally shorter than the conventional methods.
4-(2-Hydroxy-5-(p-tolyldiazenyl)phenyl)-3-meth-
ylindeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one (5h)
Drown solid, decomposition 260 ℃; 1H NMR (DMSO-
d6, 500 MHz) δ: 2.01 (s, 3H), 2.35 (s, 3H), 7.18 (d, J＝
8.7 Hz, 1H), 7.31 (d, J＝8.1 Hz, 2H), 7.50 (t, J＝7.6 Hz,
1H), 7.53 (d, J＝7.3 Hz, 1H), 7.70 (d, J＝8.1 Hz, 3H),
7.92 (t, J＝7.8 Hz, 2H), 10.5 (s, 1H), 11.5 (br, 1H), 13.7
(s, 1H); 13C NMR (DMSO-d6, 125 MHz) δ: 14.37,
21.81, 114.00, 114.90, 116.97, 120.31, 121.81, 122.01,
123.03, 123.97, 125.49, 126.00, 126.27, 130.69, 132.54,
136.09, 137.74, 141.57, 142.00, 142.87, 145.47, 150.95,
158.70, 164.74, 190.18; FT-IR (KBr) ν: 3452, 1708,
1647, 1554, 1427, 1298 cm － 1. Anal. calcd for
C27H19N5O2: C 72.80, H 4.30, N 15.72; found C 72.55,
H 4.47, N 15.15.
Table 2 Synthesis of pyrazolopyridine 5g in the presence of
nano-Fe3O4 (0.05 g) in different solvents
Entry
Solvent
MeOH
EtOH
Time/min
Yielda/%
1
2
3
4
5
25
15
35
75
2
66
78
56
53
86
CH3CN
toluene
H2O
4-(2-Hydroxy-5-((4-methoxyphenyl)diazenyl)-
phenyl)-3-methylindeno[1,2-b]pyrazolo[4,3-e]pyri-
din-5(1H)-one (5i) Brown solid, decomposition 163
a Isolated yields.
1
The same model reaction in the presence of 0.05 g of
the catalyst was carried out at different temperatures in
H2O to assess the effect of temperatures on the reaction
yield. It was observed that yield is a function of tem-
perature since the yield was increased as the reaction
temperature was raised (Table 3).
℃; H NMR (DMSO-d6, 500 MHz) δ: 2.01 (s, 3H), 3.8
(s, 3H), 7.03 (d, J＝8.05 Hz, 2H), 7.16 (d, J＝8.35 Hz,
1H), 7.50 (d, J＝6.77 Hz, 1H), 7.56 (d, J＝6.52 Hz, 1H),
7.68 (br, 1H), 7.79 (br, 3H), 7.89 (d, J＝7.07 Hz, 2H),
10.47 (s, 1H), 13.71 (s, 1H); 13C NMR (DMSO-d6, 125
MHz) δ: 25.96, 67.86, 114.00, 115.29, 116.90, 120.31,
121.78, 121.97, 123.93, 124.85, 125.23, 126.02, 132.47,
132.80, 136.02, 137.74, 142.30, 142.87, 145.20, 145.53,
147.05, 158.26, 162.17, 164.74, 190.17; FT-IR (KBr) ν:
3191, 3110, 2935, 1706, 1593, 1568, 1498, 1460, 1253
Table 3 Synthesis of pyrazolopyridine 5g in the presence of
nano-Fe3O4 (0.05 g) at different temperatures in water
Entry
Temperature
Time/min
Yielda/%
－
1
cm . Anal. calcd for C27H19N5O3: C 70.27, H 4.15, N
1
2
3
r.t.
60
45
10
2
75
79
86
15.18; found C 70.52, H 4.74, N 15.49.
100
Results and Discussion
a Isolated yield.
Initially, the condensation reaction of 2-hydroxy-5-
(phenyldiazenyl)benzaldehyde (1g), indan-1,3-dione (2)
and 3-methyl-5-aminopyrazole (3) (i) in a catalyst free
reaction and (ii) in the presence of Fe3O4 and (iii) in the
presence of nano-Fe3O4 was done and the results are
listed in Table 1.
As depicted, nano-Fe3O4 proved to be better catalyst
than Fe3O4 for the synthesis of pyrazolopyridines. With
the best catalyst in hand, we moved to study the effects
of catalyst amount on the model reaction and the results
are listed in Table 1. 50 mg of nano-Fe3O4 is sufficient
With the best optimized condition in hand, we were
interested in synthesis of several pyrazolopyridines re-
fluxing at 100 ℃ using nano-Fe3O4 in H2O. The results
are summarized in Table 4.
It is important to point out the fact that when
3-amino-5-methylpyrazole (3), indan-1,3-dione (2) and
azo-linked benzaldehyde containing electron releasing
substituents 1g—1i were refluxed for required reaction
time, the reaction leads to the formation of the aroma-
tized pyrazolopyridine 5, which were isolated and char-
606
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 604—608

Regioselective Synthesis of Fused Azo-linked Pyrazolo[4,3-e]pyridines Using Nano-Fe3O4
Table 4 Synthesis of pyrazolopyridine using catalytic amount
produced as an intermediate. The addition of 7 to
of nano-Fe3O4
3-amino-5-methyl-pyrazole (3) then could furnish the
intermediate product 8, which upon intermolecular cy-
clization and dehydration would give rise to 4. Com-
pounds 4 were oxidized to aromatized pyrazolopyridine
5 with electron donating substituted aldehydes.
Entry Product
Ar
Time/min
Yield/%
75
1
2
3
4
5
6
7
8
9
4-I-C6H4-
4-NO2-C6H4
5
8
4a
4b
4c
4d
4e
4f
83
2-Me-4-NO2-C6H3-8
75
Scheme 2 Proposed mechanism for the synthesis of pyrazolo
pyridine
2-Cl-C6H4-
3-Cl-C6H4-
4-Cl-C6H4-
C6H5-
5
5
5
2
1
1
83
95
O
+O nano-Fe3O4
O
84
Ar
H
86
5g
5h
5i
Ar
H
O
5
2
1
4-Me-C6H4-
4-MeO-C6H4-
79
nano-Fe3O4
O
O
87
nano-Fe3O4
acterized, but in the case of using azo-linked aldehydes
containing electron withdrawing substituents 1a—1f,
just pyrazolopyridine 4 were observed.
Ar
H
O
6
O
H
All of compounds summarized in Table 1 were char-
1
acterized by spectroscopic methods (IR, H NMR, 13C
7
Ar
1
O
NMR) and elemental analysis. In the H NMR spectra
of azo-linked pyrazolopyridines 4a—4f, benzilic C-H
proton resonated at δ 5.1—5.3 and in their 13C NMR
spectra, the benzilic C—H carbon resonated at δ 56.
Apart from the simplicity of the process and its ex-
cellent results, the simplicity of product isolation, re-
placement of carcinogenic solvent with H2O and the
possibility to recycle nano-Fe3O4 offer a significant ad-
vantage. After the reaction was completed, the catalyst
could be easily attracted by an efficient magnetic bar.
After further treatments including washing with CHCl3
O
Ar
H3C
Me
N
N
NH2
N
H
N
H
O
NH2
Me
8
3
Ar
O
N
NH
Me
Ar
N
H
O
N
◦
4
NH
and activation at 80 C, the recycled catalyst has been
N
examined in next run. Studies on the synthesis of 5g as a
model substrate showed that the recovered catalyst
could be successively recycled in subsequent reactions
without any decrease of yields (Figure 1).
5
Conclusions
In conclusion, this one-pot three component protocol
using nano-Fe3O4 in water provides a regioselective,
fast and practical method for the preparation of fused
pyrazolo pyridines from 5-amino-3-methylpyrazole,
indan-1,3-dione and various azo-linked aldehydes in
short reaction times and excellent yields. The simplicity,
high atom economy, easy execution and work up, pro-
ductivity, together with the use of inexpensive material
and environmentally friendly procedure are the remark-
able features of this procedure.
Figure 1 Reusability of nano-Fe3O4 in the synthesis of 5g.
Acknowledgements
We propose
a
possible mechanism for the
nano-Fe3O4 catalyzed synthesis of fused pyrazolopyri-
dine derivatives (Scheme 2). We suggest that,
nano-Fe3O4 catalyzes the formation of iminium ion 5 in
a reversible reaction with the aldehyde 1. The higher
reactivity of the iminium ion compared to the carbonyl
species could facilitate Knoevenagel condensation be-
tween aldehyde 1 and indandione 2, via intermediate 6
and after the elimination of nano-Fe3O4, 7 might be
We thank the Research Committee of Islamic Azad
University of Rasht Branch for partial support given to
this study.
References
[1] Huang, S.; Lin, R.; Yu, Y.; Lu, Y.; Connolly, P. J.; Chiu, G.; Li, S.;
Emanuel, S. L.; Middleton, S. A. Bioorg. Med. Chem. Lett. 2007, 17,
Chin. J. Chem. 2012, 30, 604—608
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
607

Nikpassand et al.
FULL PAPER
1243.
[8] Crenshaw, R.; Luke, G. M.; Smirnoff, P. CA 1032538, 1978 [Chem.
Abstr. 1978, 89, 179995r].
[9] Kendre, D. B.; Toche, R. B.; Jachak, M. N. Tetrahedron 2007, 63,
11000.
[10] (a) Diaz-Ortiz, A.; De la Hoz, A.; Langa, F. Green Chem. 2000, 2,
165; (b) Krygowski, T. M.; Anulewicz, R.; Cyranski, M. K.; Puchala,
A.; Rasala, D. Tetrahedron 1998, 54, 12295.
[11] Nikpassand, M.; Mamaghani, M.; Tabatabaeian, K.; Kupaei Abiazi,
M. Mol. Diversity 2009, 389.
[2] Saggar, S. A.; Sisko, J. T.; Tucker, T. J.; Tynebor, R. M.; Su, D. S.;
Anthony, N. J. US 2007021442, 2007.
[3] Zhang, P.; Pennell, A. M. K.; Wright, J. J. K.; Chen, W.; Leleti, M.
R.; Li, Y.; Li, L.; Xu, Y. WO 2007002293, 2007 [Chem. Abstr. 2007,
146, 121980].
[4] Chiu, G.; Li, S.; Connolly, P. J.; Middleton, S. A.; Emanuel, S. L.;
Huang, R.; Lu, Y. WO 2006130673, 2006 [Chem. Abstr. 2006, 146,
45513]
[5] Feurer, A.; Luithle, J.; Wirtz, S.; Koenig, G.; Stasch, J.; Stahl, E.;
Schreiber, R.; Wunder, F.; Lang, D. WO 2004009589, 2004 [Chem.
Abstr. 2004, 140, 146157].
[6] Stein, R. G.; Biel, J. H.; Singh, T. J. Med. Chem. 1970, 13, 153.
[7] Crenshaw, R. R.; Luke, G. M.; Smirnoff, P. J. Med. Chem. 1976, 19,
262.
[12] Nikpassand, M.; Mamaghani, M.; Tabatabaeian, K. Molecules 2009,
14, 1468.
[13] Nikpassand, M.; Mamaghani, M.; Zanjanchi, M. A.; Mahmoodi, N.
O.; Mirzaeinejad, M. Chin. Chem. Lett. 2010, 21, 5.
[14] Nikpassand, M.; Mamaghani, M.; Shirini, F.; Tabatabaeian, K. Ul-
trason. Sonochem. 2010, 17, 301.
(Lu, Y.)
608
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 604—608