One-pot, three-component synthesis of polyfunctionalized benzo[h]pyrazolo[3,4-b][1,6]naphthyridine and benzo[g]pyrazolo[3,4-b]quinoline derivatives in the presence of silver nanoparticles (AgNPs)

Article abstract of DOI:10.1002/jhet.4105

An efficient and straightforward protocol for one-pot, three-component reaction of aryl glyoxal monohydrates 1a-h, 5-amino-1-aryl-3-methylpyrazoles 2a,b and 4-hydroxyquinoline-2(1H)-one (3) or 2-hydroxy-1,4-naphthoquinone (4) using silver nanoparticles (AgNPs) as a high performance nanocatalyst in H₂O/EtOH at 60°C afforded the corresponding polyfunctionalized benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h and benzo[g]pyrazolo[3,4-b]quinolines 6a-i, respectively. Excellent catalytic activity, high yields, employing green media and green nanocatalyst, cost-effective and simple procedure are some notable advantages of using AgNPs as a noble metal nanocatalyst in this synthetic strategy. The structures of fused heterocycles were confirmed by their Fourier transform infrared, proton nuclear magnetic resonance (¹H-NMR), and ¹³C-NMR spectral data and microanalysis.

Full text of DOI:10.1002/jhet.4105

One-pot, three-component synthesis of polyfunctionalized
benzo[h]pyrazolo[3,4-b][1,6]naphthyridine and benzo[g]pyrazolo[3,4-
b]quinoline derivatives in the presence of silver nanoparticles (AgNPs)
Jabbar Khalafy, Fatemeh Majidi Arlan*, Ahmad Poursattar Marjani, and Vahid Sarchami
Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, Irancorre
Email: majiidi@yahoo.com
Abstract
An efficient and straightforward protocol for one-pot, three-component reaction of aryl glyoxal
monohydrates 1a-h, 5-amino-1-aryl-3-methylpyrazoles 2a,b and 4-hydroxyquinoline-2(1H)-
one 3 or 2-hydroxy-1,4-naphthoquinone 4 using AgNPs as a high performance nanocatalyst in
o
H2O/EtOH at 60 C afforded the corresponding polyfunctionalized benzo[h]pyrazolo[3,4-
b][1,6]naphthyridines 5a-h and benzo[g]pyrazolo[3,4-b]quinolines 6a-i, respectively. Excellent
catalytic activity, high yields, employing green media and green nanocatalyst, cost-effective and
simple procedure are some notable advantages of using AgNPs as a noble metal nanocatalyst in
this synthetic strategy. The structures of fused heterocycles were confirmed by their FT-IR, 1H-
NMR, and 13C-NMR spectral data and microanalysis.
1. INTRODUCTION
According to researchers, the heterocycles containing at least one nitrogen atom generally, have
exhibited biological and pharmaceutical properties. Hence, contriving and synthesis of such aza-
heterocycles and aza-aromatic compounds have been recognized worthwhile, and have become a
major challenge in organic synthesis. Among these, polyfunctionalized heterocycles have
considered as magic structures due to appearance of several hetero rings with wide medicinal and
clinical applications. Polyfunctionalized fused heterocyclic scaffolds due to the appearance of
diverse N containing rings simultaneously, have supposed to create a versatile bioactive
compound so we faced an increasing prevalence of research in this field.[1-3] As mentioned,
pyrazoloquinoline derivatives are highly regarded due to their pharmaceutical and biological
properties.[4-8]
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One of the most prominent and facile strategies in organic synthesis and specially, synthesis of
heterocyclic compounds and natural products is multicomponent reactions (MCRs); which
undoubtedly, has provided a compatible path in the synthesis by breaking or making multiple
bonds through environmentally and economically useful one-pot procedures avoiding separation
of intermediates or changing the solvent.[9-16]
During recent years, chemists have organized sustainable MCRs, using green solvents alongside
novel nanocatalysts have altered this strategy to a conspicuous tool. High catalytic activity,
selectivity, stability, reusability and moving along green chemistry are notable features of
nanocatalysts. Among them, noble metal nanocatalyst such as AgNPs due to superior
physicochemical, and biological properties, environmentally benign, and low-cost have
extensively investigated.[17]
Afterwards, synthesis of heterocycles containing bioactive core framework with diverse
biological and pharmaceutical activities is noteworthy and contriving economical, simple and
efficient methods to achieve such compounds is much more various. Aryl glyoxals are known as
an important synthon in the preparation of complex hetero scaffolds due to the presence of two
active sites that has made it as 1,2-biacceptor which could be attacked by nucleophilic
reagents.[18-21]
In continuation of our previous studies on the application of aryl glyoxals in the synthesis of
heterocyclic compounds,[22-29] herein, we report a one-pot, three-component reaction of aryl
glyoxal monohydrates, 5-amino-1-aryl-3-methylpyrazoles and 4-hydroxyquinoline-2(1H)-one or
2-hydroxy-1,4-naphthoquinone (lawsone) using AgNPs as nanocatalyst in H2O/EtOH under mild
conditions to afford the corresponding pyrazolonaphthyridines and pyrazoloquinolines
respectively in good to high yields.
2. RESULTS AND DISCUSSION
It was found that the reaction of aryl glyoxal monohydrates 1a-h, 5-amino-1-aryl-3-
methylpyrazoles 2a,b and 4-hydroxyquinoline-2(1H)-one (3) or 2-hydroxy-1,4-naphthoquinone
(4) using AgNPs as nanocatalyst in H2O/EtOH (1:1) at 60 oC gave the desired
benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h and benzo[g]pyrazolo[3,4-b]quinolines 6a-i in
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1
good to high yields (Scheme 1). The products were fully characterized by their FT-IR and H-
NMR and 13C-NMR spectral data and microanalysis.
SCHEME 1 Synthesis of benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h and
benzo[g]pyrazolo[3,4-b]quinolines 6a-i
In our initial studies, we evaluated one-pot, three-component reaction of pheyl glyoxal
monohydrates 1a, 5-amino-1-phenyl-3-methylpyrazole 2a, and 4-hydroxyquinoline-2(1H)-one 3.
The equimolar mixture, of 1a, 2a, and 3, was tested under various conditions. The effects of
solvent, catalyst and temperature were appraised for model reaction, and the results are
summarized in Table 1.
Firstly, the reaction was carried out under catalyst-free conditions at room temperature but, no
product was observed even after 24 h (Table 1, entry 1). Increasing the temperature of reaction
up to 60 oC under catalyst-free condition in H2O/EtOH (1:1) for 1 h, also did not give any
product (Table 1, entry 2). Using 5 and 10 ppm of AgNPs as nanocatalyst, the desired products
achieved in good yields (Table 1, entries 11-12). The best result was obtained in terms of yield
87% and reaction time 1 h, while 10 ppm of AgNPs were utilized (Table 1, entry 13). Employing
20 ppm of AgNPs, the yield of reaction was not improved so much (Table 1, entry 14). The
model reaction was carried out using various solvents such as ethanol, acetic acid, and water to
find the best solvent system. Among these solvents, H2O/EtOH (1:1) evaluated as the best
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solvent system (Table 1, entry 13). Based on achieved results, we shifted our attention toward
using various ordinary catalysts for the same model reaction in H2O/EtOH (1:1) at 60 oC. Other
catalysts such as DBU, Et3N, p-TSA, and L-proline were tested under similar reaction conditions
to obtain the maximum yield and minimum reaction time. The results are mentioned in (Table 1,
entries 7-10). In conclusion, the reaction was performed in the presence of catalytic amount of
AgNPs in H2O/EtOH at 60 oC, the smooth progress of reaction was clear, by monitoring the
reaction completion via TLC. High yield of 7-benzoyl-8-methyl-10-phenyl-5,10-dihydro-6H-
benzo[h]pyrazolo[3,4-b][1,6]naphthyridin-6-one was obtained within 1 h.
TABLE 1 Optimization of the reaction conditions for synthesis of 5a
Entry Catalyst (mol%)
Solvent
Temperature (oC) Time (h) Yield (%)
H2O/EtOH (1:1)
H2O/EtOH (1:1)
H2O/EtOH (2:1)
H2O
1
2
3
-
-
-
r.t.
60
60
24
1
-
-
-
1
4
5
6
7
8
9
-
60
60
60
60
60
60
1
1
1
1
1
1
-
-
-
-
-
EtOH
AcOH
H2O/EtOH (1:1)
H2O/EtOH (1:1)
H2O/EtOH (1:1)
(10 mol%)
(10 mol%)
35
31
32
DBU
Et3N
p-TSA (10 mol%)
L-proline (10
mol%)
H2O/EtOH (1:1)
10
60
1
40
(1:1)
H2O/EtOH
11
12
13
14
Ag bulk
60
60
60
60
1
1
1
1
37
68
87
87
H2O/EtOH (1:1)
AgNPs (5 ppm)
AgNPs (10 ppm)
AgNPs (20 ppm)
(1:1)
H2O/EtOH
(1:1)
H2O/EtOH
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(1:2)
H2O/EtOH
H2O
15
AgNPs (10 ppm)
60
1
68
16
17
18
AgNPs (10 ppm)
AgNPs (10 ppm)
AgNPs (10 ppm)
60
60
60
1
1
1
56
64
70
EtOH
AcOH
The optimized conditions are shown in bold text.
The reaction conditions were then applied to a range of different aryl glyoxal monohydrates, to
synthesize a series of products. The reaction times, melting points, and yields of the synthesized
polyfunctional benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h are shown in Table 2.
TABLE 2 The yields, reaction times and melting points of compounds 5a-h
Entry Products
R1
R2
Time (h)
Mp (°C)
Yielda (%)
1
H
H
1
310-311
87
5a
2
3
4
5
6
7
8
4-Br
4-Cl
4-F
H
H
H
H
H
H
H
2
2
300-302
305-307
298-300
304-306
303-305
268-270
298-300
68
86
75
77
79
81
65
5b
5c
5d
5e
5f
1.5
1.5
1.5
1.5
2
4-Me
4-MeO
3,4-(MeO)2
4-NO2
5g
5h
aIsolated yield.
Further investigations, we tried to extend the scope of reactions so, 2-hydroxy-1,4-
naphthoquinone 4 as dicarbonyl compound (active methylene) was employed. Interestingly, 2-
hydroxy-1,4-naphthoquinone 4 in combination with aryl glyoxal monohydrates 1a-h and 5-
amino-1-aryl-3-methylpyrazoles 2a,b provided the corresponding fused products 6a-i in high
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yields under the optimized reaction conditions as shown in Table 3. The reaction times, melting
points, and yields of the synthesized benzo[g]pyrazolo[3,4-b]quinoline-5,10-diones 6a-i are
listed in Table 3.
TABLE 3 The yields, reaction times and melting points of compounds 6a-i
Entry Products
R1
R2
Time (h)
Mp (°C)
Yielda (%)
1
2
3
4
5
6
7
8
H
4-Cl
4-F
4-MeO
4-NO2
4-Cl
4-F
4-MeO
4-NO2
H
H
H
H
H
3-Cl
3-Cl
3-Cl
3-Cl
1
2
1.5
1.5
2
1.5
2
1
283-285
279-282
272-274
284-286
275-277
295-298
272-274
263-265
248-251
89
85
88
90
93
89
88
93
87
6a
6b
6c
6d
6e
6f
6g
6h
6i
9
1.5
aIsolated yield.
The proposed mechanism for this reaction, involves the Knoevenagel condensation of aryl
glyoxals 1a-h with 4-hydroxyquinolin-2(1H)-one 3 or 2-hydroxy-1,4-naphthoquinone 4 by loss
of a water molecule to form the corresponding intermediate 7. Following Michael addition of 3-
methyl-1-aryl-1H-pyrazol-5-one
2a,b
to
this
intermediate
will
form
the
final products benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h and benzo[g]pyrazolo[3,4-
b]quinoline-5,10-diones 6a-i, through protonation to 9, loss of a water molecule by
intramolecular cyclization to 10, followed by tautomerization to 11, and final oxidation along
with aromatization. (Scheme 2)
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SCHEME 2 The proposed mechanism for synthesis of final products 5a-h and 6a-i
In the 1H NMR spectra of products 5a-h and 6a-i, the characteristic broad singlets at around δ =
11.66-11.75 ppm, ascribed to the NH groups, and singlets at δ = 2.11-2.23 ppm are attributed to
13
the methyl groups of pyrazole ring, which were present in all new products. In the C NMR
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spectra, signals located around δ = 160.8-194.2 were attributed to three different carbonyl
groups. In the FT-IR (KBr) spectra, the characteristic absorptions bands at 3327-3411 cm-1 and
1565-1680 cm-1 could be assigned to the vibrations of NH and different carbonyl groups,
respectively.
3. CONCLUSIONS
We have reported an efficient method for the synthesis of pyrazolonaphthyridines and
pyrazoloquinolines through one-pot, three-component condensation reaction of aryl glyoxals, 5-
amino-1-aryl-3-methylpyrazoles and 4-hydroxyquinoline-2(1H)-one or 2-hydroxy-1,4-
naphthoquinone (lawsone) in the presence of AgNPs as a nobel metal nanocatalyst in EtOH/H2O
o
at 60 C. The products 5a-h, 6a, 6d, 6f, 6h and 6i have been fully characterized by FT-IR, 1H-
NMR, and 13C-NMR spectral data and microanalysis, products 6b, 6c and 6e have been
confirmed by FT-IR and 1H-NMR spectral data and microanalysis and also compound 6g,
characterized by FT-IR spectrum and microanalysis. The simplicity of the method, ease of
product isolation, green reaction condition, and short reaction times are the advantages of this
procedure. The synthesized pyrazolonaphthyridines and pyrazoloquinolines may have biological
and pharmacological activities.
Experimental Section
The chemicals used in this work were purchased from Acros and Merck companies and were
used without purification. Melting points were measured on an Electrothermal 9200 apparatus
and are uncorrected. FT-IR (KBr) spectra were recorded on a Thermo-Nicolet (Nexus 670)
spectrometer using KBr discs. 1H (300 MHz) and 13C (75.5 MHz) NMR spectra were recorded
on a Bruker DRX-300 Avance spectrometer in DMSO-d6 with TMS as the internal reference.
Elemental analyses were performed using a Leco Analyzer 932. The aryl glyoxals were prepared
as their hydrates by oxidation of the corresponding acetophenones with SeO2.[30] The AgNPs as
nanocatalyst was prepared according to the literature.[31, 32]
General procedure for synthesis of benzo[h]pyrazolo[3,4-b][1,6]naphthyridines 5a-h and
benzo[g]pyrazolo[3,4-b]quinoline-5,10-diones 6a-i
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A mixture of 5-amino-1-aryl-3-methylpyrazoles (1 mmol), 4-hydroxyquinoline-2(1H)-one (1
mmol) or 2-hydroxy-1,4-naphthoquinone (1 mmol) and various aryl glyoxal monohydrates (1
mmol), in the presence of AgNPs (10 ppm) in H2O/EtOH (1:1) (5 mL) was heated at 60oC for
the appropriate time. The progress of the reaction was monitored by TLC (chloroform:n-hexane /
1:2). Upon the completion of the reaction, the mixture was cooled, and the precipitate was easily
isolated by simple filtration and then rinsed with distilled cold water and ethanol. The pure
products were obtained by recrystallization from EtOH.
The physical and spectral data for all new products as well as their elemental analyses are
reported.
7-Benzoyl-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-b][1,6]naphthyridin-
6-one (5a)
Yellow powder; mp: 310-312 ºC; yield: 87% (375 mg). IR (KBr)νmax: 3327, 3036, 2984, 2863,
1
1667, 1570, 1498, 1433, 1350, 128, 1169, 1125, 750 cm-1. H-NMR (300 MHz, DMSO-d6) δ:
11.71 (s, exchanged by D2O addition, 1H, NH), 8.76 (d, J = 7.8 Hz, 1H, Ar), 8.39 (d, J = 7.8 Hz,
2H, Ar), 7.81 (d, J = 7.2 Hz, 2H, Ar), 7.72-7.54 (m, 4H, Ar), 7.51 (t, J = 7.5 Hz, 2H, Ar), 7.40
(t, J = 7.5 Hz, 3H, Ar), 2.19 (s, 3H, CH3) ppm. 13C-NMR (75.5 MHz, DMSO-d6) δ: 193.2, 160.9,
151.9, 151.6, 146.2, 143.5, 139.1, 139.1, 137.1, 130.1, 129.8, 129.4, 129.0, 128.7, 122.0, 121.7,
120.1, 119.3, 114.7, 114.3, 14.2 ppm. Anal. Calcd for C27H18N4O2: C, 75.34; H, 4.21; N, 13.02.
Found: C, 75.40; H, 4.15; N, 13.12.
7-(4-Bromobenzoyl)-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5b)
Yellow powder; mp: 300-301 ºC; yield: 68% (347 mg). IR (KBr) νmax: 3339, 2981, 2859, 1666,
1
1571, 1351, 1261, 1223, 1168, 1123, 1068, 756 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 11.75
(s, exchanged by D2O addition, 1H, NH), 8.74 (d, J = 7.8 Hz, 1H, Ar), 8.39 (d, J = 8.1 Hz, 2H,
Ar), 7.70-7.55 (m, 7H, Ar), 7.43-7.30 (m, 3H, Ar), 2.21 (s, 3H, CH3) ppm. 13C-NMR (75.5 MHz,
DMSO-d6) δ: 193.1, 160.9, 151.9, 151.6, 145.4, 143.5, 139.1, 139.0, 136.1, 132.5, 131.1, 129.8,
128.3, 127.1, 122.6, 122.0, 120.1, 119.3, 114.7, 114.3, 14.2 ppm. Anal. Calcd for C27H17BrN4O2:
C, 63.67; H, 3.36; N, 11.00. Found: C, 63.72; H, 3.42; N, 10.92.
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7-(4-Chlorobenzoyl)-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5c)
White powder; mp: 305-306 ºC; yield: 86% (400 mg). IR (KBr) νmax: 3311, 2982, 2860, 1666,
1566, 1348, 1224, 1096, 1021, 758 cm-1. 1H-NMR (300 MHz, DMSO-d6) δ: 11.75 (s, exchanged
by D2O addition, 1H, NH), 8.74 (d, J = 7.8 Hz, 1H, Ar), 8.39 (d, J = 7.8 Hz, 2H, Ar), 7.83 (d, J
= 8.1 Hz, 2H, Ar), 7.75-7.60 (m, 3H, Ar), 7.56 (d, J = 8.1 Hz, 2H, Ar), 7.44-7.30 (m, 3H, Ar),
13
2.21 (s, 3H, CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ: 192.9, 160.9, 151.9, 151.6, 145.5,
143.5, 139.1, 139.0, 135.8, 131.0, 129.9, 129.6, 128.5, 122.1, 121.9, 120.1, 119.9, 119.2, 114.7,
114.3, 14.2 ppm. Anal. Calcd for C27H17ClN4O2: C, 69.75; H, 3.69; N, 12.05. Found: C, 69.70;
H, 3.72; N, 12.02.
7-(4-Fluorobenzoyl)-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5d)
Yellow powder; mp: 298-299 ºC; yield: 75% (336 mg). IR (KBr) νmax: 3313, 3178, 3032, 2978,
1
2856, 1664, 1564, 1502, 1430, 1350, 1232, 1151, 1025, 853, 760 cm-1. H-NMR (300 MHz,
DMSO-d6) δ: 11.73 (s, exchanged by D2O addition, 1H, NH), 8.75 (d, J = 6.9 Hz, 1H, Ar), 8.39
(d, J = 6.6 Hz, 2H, Ar), 7.90 (bs, 2H, Ar), 7.65 (bs, 3H, Ar), 7.45-7.30 (m, 5H, Ar), 2.20 (s, 3H,
13
CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ: 192.5, 160.9, 151.9, 151.6, 145.8, 143.5, 139.0,
133.9, 133.2, 131.0, 129.8, 128.7, 122.1, 121.9, 120.4, 120.0, 119.2, 116.6, 114.6, 114.3, 14.2
ppm. Anal. Calcd for C27H17FN4O2: C, 72.31; H, 3.82; N, 12.49. Found: C, 72.40; H, 3.72; N,
12.52.
8-Methyl-7-(4-methylbenzoyl)-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5e)
White powder; mp: 304-306 ºC; yield: 77% (342 mg). IR (KBr) νmax: 3327, 3037, 2982, 2861,
1
1666, 1568, 1499, 1428, 1351, 1262, 1170, 1124, 1027, 760 cm-1. H-NMR (300 MHz, DMSO-
d6) δ: 11.69 (s, exchanged by D2O addition, 1H, NH), 8.75 (d, J = 7.8 Hz, 1H, Ar), 8.39 (d, J =
8.1 Hz, 2H, Ar), 7.72-7.60 (m, 5H, Ar), 7.41 (d, J = 7.8 Hz, 2H, Ar), 7.40 (t, J = 6.9 Hz, 1H,
13
Ar), 7.31 (d, J = 8.1 Hz, 2H, Ar), 2.38 (s, 3H, CH3), 2.23 (s, 3H, CH3) ppm. C-NMR (75.5
MHz, DMSO-d6) δ: 193.5, 160.9, 151.9, 151.6, 146.5, 144.6, 143.6, 139.1, 139.1, 134.8, 130.6,
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130.3, 129.8, 129.4, 129.1, 128.8, 122.0, 120.1, 119.2, 114.6, 114.4, 21.9, 14.2 ppm. Anal. Calcd
for C28H20N4O2: C, 75.66; H, 4.54; N, 12.60. Found: C, 75.60; H, 4.62; N, 12.65.
7-(4-Methoxybenzoyl)-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5f)
Yellow powder; mp: 303-304 ºC; yield: 79% (364 mg). IR (KBr) νmax: 3411, 2980, 2857, 1670,
1
1566, 1502, 1358, 1255, 1168, 1023, 756 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 11.69 (s,
exchanged by D2O addition, 1H, NH), 8.75 (d, J = 7.8 Hz, 1H, Ar), 8.39 (d, J = 7.8 Hz, 2H, Ar),
7.76 (d, J = 8.4 Hz, 2H, Ar), 7.66 (bt, J = 7.8 Hz, 3H, Ar), 7.45-7.32 (m, 3H, Ar), 7.02 (d, J =
8.7 Hz, 2H, Ar), 3.83 (s, 3H, OCH3), 2.20 (s, 3H, CH3) ppm. 13C-NMR (75.5 MHz, DMSO-d6) δ:
192.4, 163.9, 160.8, 151.9, 151.5, 146.7, 143.7, 139.1, 132.6, 131.4, 131.0, 130.3, 122.1, 121.9,
121.7, 120.1, 119.9, 119.2, 114.7, 114.5, 114.3, 56.6, 14.2 ppm. Anal. Calcd for C28H20N4O3: C,
73.01; H, 4.38; N, 12.17. Found: C, 73.10; H, 4.42; N, 12.12.
7-(3,4-Dimethoxybenzoyl)-8-methyl-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5g)
Yellow powder; mp: 263-265 ºC; yield: 81% (397 mg). IR (KBr) νmax: 3330, 2987, 2917, 1667,
1
1589, 1504, 1430, 1349, 1267, 1131, 1024, 758 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 11.66
(s, exchanged by D2O addition, 1H, NH), 8.75 (d, J = 7.5 Hz, 1H, Ar), 8.40 (d, J = 7.8 Hz, 2H,
Ar), 7.75-7.30 (m, 7H, Ar), 7.12 (bd, J = 6.9 Hz, 1H, Ar), 6.92 (d, J = 8.1 Hz, 1H, Ar), 3.85 (s,
13
3H, OCH3), 3.81 (s, 3H, OCH3), 2.21 (s, 3H, CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ:
192.4, 163.8, 160.8, 154.0, 151.9, 151.5, 149.5, 146.7, 143.7, 139.2, 131.0, 130.3, 129.8, 128.6,
125.2, 121.9, 120.1, 119.2, 114.5, 56.8, 56.3, 14.2 ppm. Anal. Calcd for C29H22N4O4: C, 71.01;
H, 4.52; N, 11.42. Found: C, 71.10; H, 4.52; N, 11.38.
8-Methyl-7-(4-nitrobenzoyl)-10-phenyl-5,10-dihydro-6H-benzo[h]pyrazolo[3,4-
b][1,6]naphthyridin-6-one (5h)
Yellow powder; mp: 298-300 ºC; yield: 65% (309 mg). IR (KBr) νmax: 3366, 3040, 2993, 2916,
1
1663, 1569, 1498, 1433, 1346, 1225, 756 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 11.81 (s,
exchanged by D2O addition, 1H, NH), 8.76 (d, J = 7.8 Hz, 1H, Ar), 8.40 (d, J = 7.8 Hz, 2H, Ar),
8.30 (d, J = 7.8 Hz, 2H, Ar), 8.08 (d, J = 8.4 Hz, 2H, Ar), 7.67 (t, J = 7.2 Hz, 3H, Ar), 7.45-7.30
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13
(m, 3H, Ar), 2.23 (s, 3H, CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ: 192.8, 161.1, 151.9,
151.7, 150.6, 144.7, 143.4, 141.3, 139.0, 139.0, 131.1, 129.9, 129.6, 125.7, 125.5, 123.7, 122.0,
120.2, 119.3, 114.8, 114.3, 14.3 ppm. Anal. Calcd for C27H17N5O4: C, 68.21; H, 3.60; N, 14.73.
Found: C, 68.15; H, 3.65; N, 14.62.
7-Benzoyl-8-methyl-10-phenyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-5,6(10H)-dione (6a)
Orange powder; mp: 283-286 °C; yield: 89% (396 mg). IR (KBr) νmax: 3064, 1675, 1566, 1446,
1282, 1221, 753, 383 cm-1. 1H-NMR (300 MHz, DMSO-d6) δ: 8.71 (d, J = 7.5 Hz, 1H, Ar), 8.27
(d, J = 7.8 Hz, 2H, Ar), 8.06 (d, J = 7.2 Hz, 1H, Ar), 7.92-7.73 (m, 3H, Ar), 7.70 (t, J = 7.5 Hz,
2H, Ar), 7.65 (t, J = 7.8 Hz, 2H, Ar), 7.54 (t, J = 7.5 Hz, 2H, Ar), 7.42 (t, J = 7.5 Hz, 1H, Ar),
2.13 (s, 3H, CH3) ppm. 13C-NMR (75.5 MHz, DMSO-d6) δ: 194.2, 178.2, 177.5, 162.3, 153.8,
151.0, 147.2, 144.4, 138.6, 136.4, 135.9, 135.7, 134.7, 133.2, 132.1, 129.9, 129.5, 129.3, 128.8,
127.2, 121.4, 120.7, 113.9, 13.8 ppm. Anal. Calcd for C28H17N3O3: C, 75.84; H, 3.86; N, 9.48.
Found: C, 75.75; H, 3.82; N, 9.35.
7-(4-Chlorobenzoyl)-8-methyl-10-phenyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-5,6(10H)-
dione (6b)
Yellow powder; mp: 279-282 °C; yield: 85% (391 mg). IR (KBr) νmax: 3078, 1673, 1565, 1493,
1
1426, 1283, 1220, 1090, 759 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 8.71 (d, J = 8.1 Hz, 1H,
Ar), 8.28 (d, J = 7.8 Hz, 2H, Ar), 8.07 (d, J = 7.5 Hz, 1H, Ar), 7.99 (t, J = 7.8 Hz, 1H, Ar), 7.91
(d, J = 7.8 Hz, 2H, Ar), 7.71 (t, J = 7.8 Hz, 1H, Ar), 7.65 (t, J = 7.5 Hz, 2H, Ar), 7.60 (d, J = 8.1
Hz, 2H, Ar), 7.43 (t, J = 6.9 Hz, 1H, Ar), 2.15 (s, 3H, CH3) ppm. Anal. Calcd for C28H16ClN3O3:
C, 70.37; H, 3.37; N, 8.79. Found: C, 70.30; H, 3.32; N, 8.85.
7-(4-Fluorobenzoyl)-8-methyl-10-phenyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-5,6(10H)-
dione (6c)
Yellow powder; mp: 272-274 °C; yield: 88% (408 mg). IR (KBr) νmax: 3076, 2926, 1680, 1576,
1498, 1426, 1285, 1230, 1156, 761 cm-1. 1H-NMR (300 MHz, DMSO-d6) δ: 8.72 (d, J = 7.8 Hz,
1H, Ar), 8.28 (d, J = 8.4 Hz, 2H, Ar), 8.07 (d, J = 7.5 Hz, 1H, Ar), 7.99 (t, J = 6.9 Hz, 1H, Ar),
7.90 (d, J = 7.8 Hz, 2H, Ar), 7.71 (t, J = 8.1 Hz, 1H, Ar), 7.66 (t, J = 8.1 Hz, 2H, Ar), 7.44 (d, J =
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7.5 Hz, 2H, Ar), 7.36 (t, J = 8.4 Hz, 1H, Ar), 2.15 (s, 3H, CH3) ppm. Anal. Calcd for
C28H16FN3O3: C, 72.88; H, 3.50; N, 9.11. Found: C, 72.75; H, 3.60; N, 9.15.
7-(4-Methoxybenzoyl)-8-methyl-10-phenyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-5,6(10H)-
dione (6d)
Yellow powder; mp: 284-286 °C; yield: 90% (428 mg). IR (KBr) νmax: 3068, 2932, 1672, 1586,
1
1497, 1450, 1266, 1162, 762 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 8.71 (d, J = 7.8 Hz, 1H,
Ar), 8.27 (d, J = 7.8 Hz, 2H, Ar), 8.05 (t, J = 7.5 Hz, 1H, Ar), 7.92 (d, J = 7.5 Hz, 1H, Ar), 7.85
(t, J = 7.8 Hz, 2H, Ar), 7.70 (t, J = 7.5 Hz, 1H, Ar), 7.65 (t, J = 7.5 Hz, 2H, Ar), 7.42 (d, J = 7.2
Hz, 1H, Ar), 7.04 (d, J = 9 Hz, 2H, Ar), 3.84 (s, 3H, OCH3), 2.14 (s, 3H, CH3) ppm. 13C-NMR
(75.5 MHz, DMSO-d6) δ: 192.5, 178.3, 177.5, 164.3, 159.2, 158.1, 153.8, 147.5, 144.6, 138.6,
137.6, 136.5, 135.7, 133.1, 132.0, 131.7, 129.9, 129.0, 128.7, 127.1, 121.4, 120.5, 114.8, 56.1,
13.8 ppm. Anal. Calcd for C29H19N3O4: C, 73.56; H, 4.04; N, 8.87. Found: C, 73.65; H, 4.02; N,
8.80.
8-Methyl-7-(4-nitrobenzoyl)-10-phenyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-5,6(10H)-
dione (6e)
Yellow powder; mp: 275-277 °C; yield: 93% (456 mg). IR (KBr) νmax: 3071, 2926, 1678, 1530,
1431, 1346, 1284, 1218, 757, 687 cm-1. 1H-NMR (300 MHz, DMSO-d6) δ: 8.74 (d, J = 6 Hz, 1H,
Ar), 8.32 (d, J = 9 Hz, 2H, Ar), 8.29 (d, J = 8.1 Hz, 2H, Ar), 8.15 (d, J = 8.7 Hz, 2H, Ar), 8.08
(d, J = 8.4 Hz, 1H, Ar), 7.94 (bt, J = 8.4 Hz, 1H, Ar), 7.72 (t, J = 7.5 Hz, 1H, Ar), 7.67 (t, J = 7.5
Hz, 2H, Ar), 7.45 (bt, J = 7.8 Hz, 1H, Ar), 2.17 (s, 3H, CH3) ppm. Anal. Calcd for C28H16N4O5:
C, 68.85; H, 3.30; N, 11.47. Found: C, 68.93; H, 3.32; N, 11.52.
7-(4-Chlorobenzoyl)-10-(3-chlorophenyl)-8-methyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-
5,6(10H)-dione (6f)
Yellow powder; mp: 295-298 °C; yield: 89% (458 mg). IR (KBr) νmax: 3081, 2926, 1678, 1575,
1
1477, 1455, 1277, 1223, 1162, 1091, 772 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 8.62 (d, J =
7.8 Hz, 1H, Ar), 8.32 (t, J = 8.7 Hz, 1H, Ar), 8.24 (d, J = 7.8 Hz, 1H, Ar), 8.05 (d, J = 7.8 Hz,
1H, Ar), 7.89 (bd, J = 7.8 Hz, 2H, Ar), 7.70 (t, J = 7.5 Hz, 1H, Ar), 7.64 (d, J = 8.4 Hz, 1H, Ar),
7.64 (t, J = 8.4 Hz, 1H, Ar), 7.60 (d, J = 8.4 Hz, 2H, Ar), 7.43 (bd, J = 8.1 Hz, 1H, Ar), 2.12 (s,
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13
3H, CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ: 192.9, 177.9, 177.4, 162.3, 153.9, 151.2,
146.3, 145.0, 139.7, 136.1, 135.6, 134.5, 134.1, 133.1, 132.2, 131.6, 131.1, 129.8, 129.7, 128.8,
126.6, 126.4, 120.9, 120.5, 114.2, 13.8 ppm. Anal. Calcd for C28H15Cl2N3O3: C, 65.64; H, 2.95;
N, 8.20. Found: C, 65.68; H, 2.90; N, 8.25.
10-(3-Chlorophenyl)-7-(4-fluorobenzoyl)-8-methyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-
5,6(10H)-dione (6g)
Yellow powder; mp: 288-290 °C; yield: 88% (438 mg). IR (KBr) νmax: 3109, 2927, 1675, 1564,
1477, 1443, 1279, 1226, 774 cm-1. Anal. Calcd for C28H15ClFN3O3: C, 67.82; H, 3.05; N, 8.47.
Found: C, 67.87; H, 3.02; N, 7.35.
10-(3-Chlorophenyl)-7-(4-methoxybenzoyl)-8-methyl-5H-benzo[h]pyrazolo[3,4-b]quinoline-
5,6(10H)-dione (6h)
Yellow powder; mp: 263-265 °C; yield: 93% (474 mg). IR (KBr) νmax: 3058, 2929, 1670, 1583,
1
1448, 1258, 1165, 1022, 770 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 8.63 (d, J = 7.8 Hz, 1H,
Ar), 8.32 (d, J = 8.1 Hz, 1H, Ar), 8.29 (s, 1H, Ar), 8.04 (d, J = 7.8 Hz, 1H, Ar), 7.90 (t, J = 7.5
Hz, 1H, Ar), 7.84 (d, J = 8.7 Hz, 2H, Ar), 7.69 (t, J = 7.5 Hz, 1H, Ar), 7.64 (t, J = 8.1 Hz, 1H,
Ar), 7.43 (d, J = 8.7 Hz, 1H, Ar), 7.03 (d, J = 8.7 Hz, 2H, Ar), 3.32 (s, 3H, OCH3), 2.11 (s, 3H,
13
CH3) ppm. C-NMR (75.5 MHz, DMSO-d6) δ: 192.3, 178.1, 177.4, 164.4, 162.3, 153.9, 151.2,
147.5, 145.1, 139.7, 136.3, 135.7, 134.1, 133.1, 132.1, 131.6, 129.0, 128.8, 126.6, 126.4, 120.6,
120.4, 119.2, 114.8, 114.3, 56.1, 13.7 ppm. Anal. Calcd for C29H18ClN3O4: C, 68.58; H, 3.57; N,
8.27. Found: C, 68.65; H, 3.62; N, 8.25.
10-(3-Chlorophenyl)-8-methyl-7-(4-nitrobenzoyl)-5H-benzo[h]pyrazolo[3,4-b]quinoline-
5,6(10H)-dione (6i)
Yellow powder; mp: 248-251 °C; yield: 87% (457 mg). IR (KBr) νmax: 3093, 1675, 1571, 1531,
1
1452, 1344, 1218, 771 cm-1. H-NMR (300 MHz, DMSO-d6) δ: 8.67 (d, J = 7.8 Hz, 1H, Ar),
8.63 (s, 1H, Ar), 8.32 (bd, J = 8.4 Hz, 3H, Ar), 8.14 (t, J = 8.7 Hz, 2H, Ar), 7.93 (t, J = 8.1 Hz,
1H, Ar), 7.92 (d, J = 7.8 Hz, 1H, Ar), 7.72 (t, J = 7.5 Hz, 1H, Ar), 7.67 (d, J = 7.8 Hz, 1H, Ar),
7.47 (d, J = 7.2 Hz, 1H, Ar), 2.15 (s, 3H, CH3) ppm. 13C-NMR (75.5 MHz, DMSO-d6) δ: 192.9,
177.8, 177.5, 162.3, 154.0, 151.0, 145.6, 144.9, 139.9, 136.0, 135.7, 134.1, 133.2, 132.3, 131.7,
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130.6, 128.8, 126.8, 124.7, 121.1, 120.6, 120.6, 119.3, 114.1, 13.91 ppm. Anal. Calcd for
C28H15ClN4O5: C, 64.32; H, 2.89; N, 10.71. Found: C, 64.29; H, 2.82; N, 10.75.
1
13
The compounds 6b, 6c, 6e and 6g did not show either H-NMR and C-NMR or both due to
very low solubilities in DMSO-d6.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the financial assistance from Urmia University.
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