Sulfamic-acid-catalyzed simple and efficient synthesis of 4-aryl-3-methyl-1-phenyl-1H-benzo[g]pyrazolo[3,4-b]quinoline-5,10-diones under solvent-free conditions

Article abstract of DOI:10.1007/s00706-010-0282-8

An efficient synthesis of 4-aryl-3-methyl-1-phenyl-1H-benzo[g]pyrazolo[3,4- b]quinoline-5,10-diones from the three-component condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine, aromatic aldehydes, and 2-hydroxy-1,4-naphthoquinone under solvent-

Full text of DOI:10.1007/s00706-010-0282-8

Monatsh Chem (2010) 141:565–568
DOI 10.1007/s00706-010-0282-8
ORIGINAL PAPER
Sulfamic-acid-catalyzed simple and efficient synthesis
of 4-aryl-3-methyl-1-phenyl-1H-benzo[g]pyrazolo[3,4-b]
quinoline-5,10-diones under solvent-free conditions
•
•
•
Liqiang Wu Suying Ma Fulin Yan
Chunguang Yang
Received: 26 September 2009 / Accepted: 23 February 2010 / Published online: 29 April 2010
Ó Springer-Verlag 2010
Abstract An efficient synthesis of 4-aryl-3-methyl-1-
phenyl-1H-benzo[g]pyrazolo[3,4-b]quinoline-5,10-diones
from the three-component condensation reaction of
3-methyl-1-phenyl-1H-pyrazol-5-amine, aromatic aldehydes,
and 2-hydroxy-1,4-naphthoquinone under solvent-free
conditions in good to excellent yields and short reaction
times using sulfamic acid as heterogeneous acid catalyst
has been investigated.
phenylpyrazole, and dimedone under thermal [7] or
microwave conditions [8].
In recent years, the use of solid acidic catalysts has
offered important advantages in organic synthesis. One of
those heterogeneous catalysts is sulfamic acid (SA). It
makes reaction processes convenient, more economic, and
environmentally benign. Owing to the numerous advanta-
ges associated with this cheap and nonhazardous catalyst,
SA has been explored as a powerful catalyst for various
organic transformations [9–12]. We report herein a highly
efficient procedure for the preparation of 4-aryl-3-methyl-
1-phenyl-1H-benzo[g]pyrazolo[3,4-b]quinoline-5,10-
diones using SA as an efficient and versatile catalyst under
solvent-free conditions (Scheme 1).
Keywords Pyrazolo[3,4-b]quinoline Á Sulfamic acid Á
One-pot synthesis Á Solvent-free
Introduction
Pyrazolo[3,4-b]quinoline derivatives are used as pharma-
ceutical agents [1], as inhibitors of oncogenic Ras [2], and
as a dopant in multilayer organic light-emitting diode
(OLED) fabrication [3]. In the past several decades, three
general strategies for the synthesis of pyrazolo[3,4-
b]quinolines have been developed: (1) by the Friedlander
condensation reaction of 2-aminobenzophenones and
pyrazolin-5-ones [4], although availability of 2-amino-
benzophenones limits the range of applicability of this
reaction; (2) by cyclization of 4-arylidenepyrazolin-5-ones
with anilines [5] or 5-(arylamino)pyrazoles with aromatic
aldehydes [6], although the method is complicated and has
a lower yield; and (3) by a three-component one-pot
reaction of aromatic aldehydes, 5-amino-3-methyl-1-
Results and discussion
To choose optimum conditions, first, the effect of tempera-
ture on the rate of the reaction was studied for the
preparation of 3-methyl-1,4-diphenyl-1H-benzo[g]pyrazolo-
[3,4-b]quinoline-5,10-dione from the three-component
condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-
amine (1 mmol), benzaldehyde (1 mmol), and 2-hydroxy-
1,4-naphthoquinone (1 mmol) under solvent-free conditions
(Table 1). At 90 °C, the reaction proceeded smoothly, and
almost complete conversion of product was observed.
Further increase in temperature to 100 and 110 °C increased
the rate of reaction. Therefore, we kept the reaction
temperature at 100 °C (giving short reaction time and high
yield).
L. Wu (&) Á S. Ma Á F. Yan Á C. Yang
School of Pharmacy,
Xinxiang Medical University, Xinxiang 453003, Henan,
People’s Republic of China
e-mail: wliq1974@sohu.com
Next, the study set out to determine the optimal amount
of SA, so the reaction was carried out by varying the
amount of catalyst (Table 1). Maximum yield was obtained
with 10 mol% of catalyst. Further increase in amount of
123

566
L. Wu et al.
Scheme 1
R
N
O
O
O
HO
N
N
N
SA
+
+
N
RCHO
heat, 100oC
O
NH2
1
2
3
4
Table 1 Optimization of the one-pot synthesis of 3-methyl-1,4-
diphenyl-1H-benzo[g]pyrazolo[3,4-b]quinoline-5,10-dione
Table 2 Synthesis of 4-aryl-3-methyl-1-phenyl-1H-benzo[g]pyraz-
olo[3,4-b]quinoline-5,10-diones
Yield (%)a
Entry
SA (mol%)
Time (h)
Temp. (°C)
Yield (%)a
Entry
R
Time (h)
Product
1
0
5
5
2
2
2
5
3
2
2
2
2
5
5
100
90
0
60
1
2
3
4
5
6
7
8
9
C6H5
2
4a
4b
4c
4d
4e
4f
88
91
85
87
93
90
89
86
85
2
4-Cl-C6H4
4-MeO-C6H4
4-Me-C6H4
4-NO2-C6H4
4-F-C6H4
1.5
2
3
5
100
110
r.t.
62
4
5
73
2
5
10
10
10
10
10
15
15
20
\10
59
1.5
1.5
3
6
50
7
90
79
3-NO2-C6H4
2-Cl-C6H4
3,4-Cl2-C6H3
4g
4h
4i
8
100
110
90
88
2
9
87
3
10
11
12
87
Reaction conditions: 3-methyl-1-phenyl-1H-pyrazol-5-amine (1 mmol),
aldehyde (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol), SA
(10 mol%); 100 °C; solvent-free
100
100
85
88
a
Isolated yield
Reaction conditions: 3-methyl-1-phenyl-1H-pyrazol-5-amine (1 mmol),
benzaldehyde (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol);
solvent-free
The formation of products 4a–4i can be rationalized by
initial formation of heterodiene 5 by standard Knoevenagel
condensation of 2-hydroxynaphthalene-1,4-dione 3 and
aromatic aldehyde 2 in the presence of a catalytic amount
of SA. Subsequent Michael-type addition of 3-methyl-1-
phenyl-1H-pyrazol-5-amine 1 to the heterodienes 5 fol-
lowed by cyclization, dehydration, and air oxidation afford
the corresponding products 4a–4i (Scheme 2).
a
Isolated yield
SA in the mentioned reaction did not have any significant
effect on product yield.
The generality of this reaction was examined using sev-
eral types of aldehydes. In all cases, the reactions gave the
corresponding products in good to excellent yield (Table 2).
This methodology offers significant improvements with
regard to the scope of this transformation, simplicity of
operation, and green aspects by avoiding expensive or cor-
rosive catalysts. In addition, we noticed also that, when this
reaction was carried out with aliphatic aldehydes such as
butanal or pentanal, thin-layer chromatography (TLC) and
1H nuclear magnetic resonance (NMR) spectra of the reac-
tion mixture showed a combination of starting materials and
numerous products, and the yield of the expected product
was very poor. There were two doublets at d = 8.77–
8.84 ppm for H-9 and 8.05–8.19 ppm for H-6, which prob-
ably arise from the protons peri to the quinone C=O. If the
target compounds were another possible structure, in which
the two carbonyl groups were in the ortho-position, they
would have two doublets or dd at d \ 8.3 ppm. The reso-
nances of two nonequivalent carbonyl groups in the 13C
NMR spectrum of 4 appeared at d = 179.8–180.8 ppm and
179.3–180.3 ppm.
In summary, an efficient protocol for one-pot prepara-
tion of 4-aryl-3-methyl-1-phenyl-1H-benzo[g]pyrazolo
[3,4-b]quinoline-5,10-diones from the three-component
condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-
amine, aldehyde, and 2-hydroxy-1,4-naphthoquinone using
commercially available, environmentally friendly SA as
catalyst was described. The reactions were carried out
under thermal solvent-free conditions with short reaction
time and produced the corresponding products in good to
excellent yield. The one-pot nature and the use of hetero-
geneous solid acid as an ecofriendly catalyst make it an
interesting alternative to multistep approaches.
Experimental
NMR spectra were determined on a Bruker AV-400
spectrometer at room temperature using TMS as internal
123

Sulfamic-acid-catalyzed synthesis
567
Scheme 2
O
O
O
O
OH
Ar
O
OH
OH
O
-H2O, H
H
3
Ar
H
Ar
Ar
H
OH
O
O
2
5
N
N
O
O
Ar
Ar
O
NH2
N
N
1
N
N
N
H
O
NH2
OH
O
Ar
O
O
Ar
O
O
Air
N
-H2O
N
N
N
N
N
H
4
1H), 7.64–7.52 (m, 6H), 7.43–7.39 (m, 1H), 7.32–7.30 (m,
2H), 1.95 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 180.5, 179.9, 153.7, 152.2, 150.5, 146.5, 138.6, 137.3,
136.0, 135.9, 131.7, 131.3, 129.2, 129.1, 128.4, 127.2,
127.0, 126.5, 121.3, 119.8, 117.0, 14.3 ppm.
standard. Elemental analyses were performed by a Vario-
III elemental analyzer, and results agreed with calculated
values. Melting points were determined on a XT-4 binoc-
ular microscope. Commercially available reagents were
used throughout without further purification unless other-
wise stated.
4-(4-Chlorophenyl)-3-methyl-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione
(4b, C27H16ClN3O2)
General procedure for the preparation of 4
1
Yellow crystals, m.p.: 243–245 °C; H NMR (400 MHz,
To a mixture of 3-methyl-1-phenyl-1H-pyrazol-5-amine
(1 mmol), aldehyde (1 mmol), and 2-hydroxynaphthalene-
1,4-dione (1 mmol), SA (0.1 mmol) was added. The mix-
ture was stirred at 100 °C for an appropriate time
(Table 2). After completion of the reaction (TLC), the
reaction mixture was treated with 10 cm3 water and
extracted with CH2Cl2 (2 9 10 cm3), filtered, and the
solvent evaporated in vacuo. Products were purified by
recrystallization from ethanol.
CDCl3): d = 8.80 (d, 1H, J = 8.0 Hz), 8.30 (d, 2H,
J = 8.0 Hz), 8.15 (d, 1H, J = 7.6 Hz), 7.87–7.83 (m,
1H), 7.64–7.51 (m, 5H), 7.43–7.40 (m, 1H), 7.28–7.24 (m,
2H), 2.00 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 180.3, 179.9, 153.8, 150.8, 150.5, 146.2, 138.5, 137.1,
136.0, 134.6, 134.3, 131.6, 131.4, 129.3, 129.2, 129.1,
128.7, 128.5, 127.2, 126.7, 121.4, 121.0, 119.7, 116.8,
14.5 ppm.
3-Methyl-1,4-diphenyl-1H-benzo[g]pyrazolo[3,4-b]-
quinoline-5,10-dione (4a, C27H17N3O2)
4-(4-Methoxyphenyl)-3-methyl-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione (4c, C28H19N3O3)
1
1
Yellow crystals, m.p.: 266–267 °C; H NMR (400 MHz,
Yellow crystals, m.p.: 274–275 °C; H NMR (400 MHz,
CDCl3): d = 8.82 (d, 1H, J = 8.0 Hz), 8.31 (d, 2H,
J = 7.6 Hz), 8.16 (d, 1H, J = 7.6 Hz), 7.88–7.84 (m,
CDCl3): d = 8.82 (d, 1H, J = 8.0 Hz), 8.32 (d, 2H,
J = 8.0 Hz), 8.16 (d, 1H, J = 8 Hz), 7.88–7.84 (m, 1H),
123

568
L. Wu et al.
7.64–7.60 (m, 3H), 7.43–7.39 (m, 1H), 7.23 (d, 2H,
J = 8.4 Hz), 7.06 (d, 2H, J = 8.4 Hz), 3.93 (s, 3H), 2.03
(s, 3H) ppm; 13C NMR (100 MHz, CDCl3): d = 180.8,
180.3, 159.8, 153.8, 152.4, 150.5, 146.6, 138.6, 137.4,
136.0, 131.6, 131.3, 129.2, 129.0, 128.6, 127.7, 127.2,
126.5, 121.4, 120.2, 117.3, 113.9, 55.3, 14.6 ppm.
136.2, 133.3, 131.7, 131.6, 129.6, 129.3, 129.2, 127.3,
126.9, 123.4, 122.4, 121.5, 119.4, 116.5, 14.6 ppm.
4-(2-Chlorophenyl)-3-methyl-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione
(4h, C27H16ClN3O2)
1
Yellow crystals, m.p.: 229–230 °C; H NMR (400 MHz,
3-Methyl-4-(4-methylphenyl)-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione (4d, C28H19N3O2)
CDCl3): d = 8.84 (d, 1H, J = 8.0 Hz), 8.33 (d, 2H,
J = 8.0 Hz), 8.19 (d, 1H, J = 7.6 Hz), 7.89–7.85 (m,
1H), 7.65–7.40 (m, 7H), 7.25–7.23 (m, 1H), 2.00 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): d = 179.9, 179.3,
153.8, 150.8, 148.5, 146.2, 138.6, 137.2, 136.0, 135.1,
131.7, 131.6, 131.4, 129.9, 129.5, 129.3, 129.2, 128.3,
127.2, 127.0, 126.6, 121.4, 119.6, 116.5, 13.6 ppm.
1
Yellow crystals, m.p. 276–277 °C; H NMR (400 MHz,
CDCl3): d = 8.82 (d, 1H, J = 8.0 Hz), 8.31 (d, 2H,
J = 8.0 Hz), 8.15 (d, 1H, J = 7.6 Hz), 7.87–7.83 (m,
1H), 7.63–7.60 (m, 3H), 7.43–7.39 (m, 1H), 7.33 (d, 2H,
J = 7.6 Hz), 7.18 (d, 2H, J = 7.6 Hz), 2.49 (s, 3H), 1.99
(s, 3H) ppm; 13C NMR (100 MHz, CDCl3): d = 180.7,
180.1, 153.7, 152.6, 150.5, 146.7, 138.6, 138.2, 137.4,
135.9, 132.8, 131.6, 131.3, 129.2, 129.1, 129.0, 127.2,
126.9, 126.5, 121.4, 120.0, 117.1, 21.5, 14.4 ppm.
4-(3,4-Dichlorophenyl)-3-methyl-1-phenyl-1H-
benzo[g]pyrazolo[3,4-b]quinoline-5,10-dione
(4i, C27H15Cl2N3O2)
1
Yellow crystals, m.p.: 269–270 °C; H NMR (400 MHz,
3-Methyl-4-(4-nitrophenyl)-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione (4e, C27H16N4O4)
CDCl3): d = 8.78 (d, 1H, J = 8.0 Hz), 8.28 (d, 2H,
J = 8.0 Hz), 8.15 (d, 1H, J = 7.6 Hz), 7.87–7.83 (m,
1H), 7.63–7.59 (m, 4H), 7.43–7.40 (m, 2H), 7.16 (d, 1H,
J = 8.0 Hz), 2.03 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 179.9, 179.5, 153.7, 150.4, 148.9, 145.9,
138.4, 136.9, 136.1, 135.7, 132.8, 131.5, 130.5, 129.2,
129.0, 127.2, 126.8, 126.6, 121.3, 119.4, 116.5, 14.7 ppm.
1
Yellow crystals, m.p.: 326–328 °C; H NMR (400 MHz,
CDCl3): d = 8.82 (d, 1H, J = 8.0 Hz), 8.42 (d, 2H,
J = 8.4 Hz), 8.30 (d, 2H, J = 8.0 Hz), 8.18 (d, 1H,
J = 7.6 Hz), 7.90–7.86 (m, 1H), 7.67–7.62 (m, 3H), 7.51
(d, 2H, J = 8.8 Hz), 7.46–7.42 (m, 1H), 1.97 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3): d = 179.8, 179.6, 153.9,
150.5, 149.2, 147.9, 145.7, 143.1, 138.4, 136.9, 136.2,
131.7, 131.6, 129.4, 129.3, 128.2, 127.3, 126.9, 123.8,
121.5, 119.2, 116.1, 14.5 ppm.
Acknowledgments We are pleased to acknowledge the financial
support from Xinxiang Medical University.
References
4-(4-Fluorophenyl)-3-methyl-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione (4f, C27H16FN3O2)
1
1. El-Sayed OA, Aboul-Enein HY (2001) Arch Pharm 334:117
2. Wolin R, Wang D, Kelly J, Afonso A, James L, Kirschmeier P,
McPhail AT (1996) Bioorg Med Chem Lett 6:195
3. He Z, Milburn GHW, Baldwin KJ, Smith DA, Danel A, Tomasik
P (2000) J Lumin 86:1
4. Tomasik P, Tomasik D, Abramovitch RA (1983) J Heterocycl
Chem 20:1539
5. Chaczatrian K, Chaczatrian G, Danel A, Tomasik P (2001)
Arkivoc vi:63
Yellow crystals, m.p.: 282–283 °C; H NMR (400 MHz,
DMSO-d6): d = 8.77 (d, 1H, J = 8.0 Hz), 8.30 (d, 2H,
J = 7.6 Hz), 8.05 (d, 1H, J = 7.2 Hz), 7.98–7.94 (m, 1H),
7.74–7.66 (m, 3H), 7.44–7.36 (m, 5H), 1.90 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3): d = 180.5, 180.0, 164.1,
161.6, 153.8, 151.1, 150.2, 146.3, 138.6, 137.2, 136.0,
131.7, 131.6, 131.4, 129.3, 129.2, 129.1, 129.0, 128.9,
127.2, 126.7, 121.4, 119.9, 117.0, 115.7, 115.5, 14.4 ppm.
6. Danel A, Chaczatrian K, Tomasik P (2000) Arkivoc i:51
7. Quiroga J, Insuasty B, Saitz C, Jullian C (1998) J Heterocycl
Chem 35:575
3-Methyl-4-(3-nitrophenyl)-1-phenyl-1H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10-dione (4g, C27H16N4O4)
8. Hua GP, Xu JN, Tu SJ, Wang Q, Zharlg JP, Zhu XT, Li TJ, Zhu
SL, Zhang X (2005) J Chin Org Chem 25:1610
9. Jin TS, Sun G, Li YW, Li TS (2002) Green Chem 4:255
10. Nagarajan R, Magesh CJ, Perumal PT (2004) Synthesis 69
11. Rajitha B, Sunil Kumar B, Thirupathi Reddy Y, Narsimha Reddy
P, Sreenivasulu N (2005) Tetrahedron Lett 46:8691
12. Venu Madhav J, Naveen Kumar Rajitha VB (2008) Synth
Commun 38:1799
1
Yellow crystals, m.p.: 288–289 °C; H NMR (400 MHz,
CDCl3): d = 8.83 (d, 1H, J = 8.0 Hz), 8.41 (d, 1H,
J = 8.4 Hz), 8.30 (d, 2H, J = 8.0 Hz), 8.24 (s, 1H), 8.18
(d, 1H, J = 7.6 Hz), 7.91–7.86 (m, 1H), 7.77–7.73 (m,
1H), 7.69–7.61 (m, 4H), 7.46–7.42 (m, 1H), 1.97 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): d = 179.9, 179.7,
153.9, 150.6, 148.7, 148.2, 145.6, 138.4, 137.7, 136.9,
123