L-proline catalyzed multicomponent reactions: Facile access to 2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10(4H,11H)-dione derivatives

Article abstract of DOI:10.1039/c4ra00876f

A series of 2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10(4H,11H)-dione derivatives has been synthesized from the three component reactions of 2-hydroxy-1,4-naphthoquinone, aldehydes, and aminopyrazoles in the presence of a catalytic amount of l-proline. This domino reaction proceeds smoothly in good to excellent yields and offers several advantages including no column chromatography, a simple reaction procedure, metal-free reaction conditions and being applicable to a broad range of aldehydes. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra00876f

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L-proline catalyzed multicomponent reactions:
facile access to 2H-benzo[g]pyrazolo[3,4-b]-
quinoline-5,10(4H,11H)-dione derivatives†
Cite this: RSC Adv., 2014, 4, 15319
a
a
b
a
*
Shaik Karamthulla, Suman Pal, Tasneem Parvin and Lokman H. Choudhury
A series of 2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10(4H,11H)-dione derivatives has been synthesized
from the three component reactions of 2-hydroxy-1,4-naphthoquinone, aldehydes, and aminopyrazoles
in the presence of a catalytic amount of L-proline. This domino reaction proceeds smoothly in good to
excellent yields and offers several advantages including no column chromatography, a simple reaction
procedure, metal-free reaction conditions and being applicable to a broad range of aldehydes.
Received 30th January 2014
Accepted 14th March 2014
DOI: 10.1039/c4ra00876f
www.rsc.org/advances
1,4-naphthoquinone and aldehyde using readily available
organocatalyst for the synthesis of polycyclic N-heterocycles as
Introduction
shown in Scheme 1.
Synthesis of diverse polycyclic heterocycles from readily avail-
able starting materials in a cost and time effective manner has
remained useful in organic synthesis owing to their widespread
applications in pharmaceuticals, agrochemicals and in mate-
rials sciences.1 Multicomponent reactions (MCRs), where three
or more reactants are mixed in a single pot to generate a product
incorporating most of the atoms of the starting materials,2 are
considered as one of the best tools for the easy access to diverse
heterocycles under Pot Atom and Step Economic (PASE)3
conditions. Organocatalysis in multicomponent reactions
makes the process greener as it works under the metal-free
conditions and avoids the toxicity associated with metals.
Considering this fact, in recent times, organo catalyzed MCRs
have become very popular in organic synthesis.4
Recently we have, reported the virtue of imidazole as orga-
nocatalyst in MCRs for the synthesis of diverse carbo and
heterocycles.5 We also have demonstrated a three component
reaction of 4-hydroxycoumarin, aldehyde and aminopyrazole
for the construction of a series of fused dihydroypyridines.6
MCRs using amino pyrazoles have become very popular strategy
for the construction of functionalized polycyclic heterocycles.7
Similar to aminopyrazoles, 2-hydroxy-1,4-naphthoquinone is
also a widely used starting material in MCRs.8 Considering their
usefulness and potent bioactivities we wanted to explore further
these two substrates in our MCRs. In continuation of our
ongoing research on MCRs,9 we wished to develop a simple and
useful three component reaction of aminopyrazole, 2-hydroxy-
L-proline is one of the cheap, readily available and most
explored organocatalyst both in two and multicomponent
reactions.10 Due to the presence of a basic secondary amine and
an acidic carboxylic group, proline can catalyze a wide range of
reactions. Thus, we envisioned that L-proline will also act as an
efficient organocatalyst in our proposed MCRs.
Pyrazolo[3,4-b]quinoline derivatives (A) posses a wide range
of medicinal properties such as antiviral,11 antibacterial,12
antimicrobial,13 oncogenic Ras inhibiting,14 and cyclooxygenase
inhibiting activities.15 In addition, these compounds exhibit
luminescence16 and uorescence17 properties. Considering
their wide spread applications, development of new and effi-
cient methods for the access of these classes of compounds
have lot of signicance. Recently Li et al.18 have reported a
microwave assisted methodology for the synthesis of benzo[h]-
pyrazolo[3,4-b]quinolines in acetic acid. They have successfully
converted the resulting benzoquinoline products into qui-
noxaline-fused benzo[h]isoxazolo[5,4-b]quinolines by reacting
with benzene-1,2-diamine under microwave irradiation. On the
other hand, a few methods employing various catalysts such as
molecular iodine,19 diammonium hydrogen phosphate20 and
InCl321 are also known in the literature for synthesis of 4-aryl-3-
methyl-1-phenyl-1H-benzo[h]pyrazolo[3,4-b]quinoline-5,10-dio-
nes (a 1,4-diketone derivative) by the three component
aDepartment of Chemistry, Indian Institute of Technology Patna, Patna-800013, India.
E-mail: lokman@iitp.ac.in; Fax: +91 612 227 7383; Tel: +91 612 2552038
bDepartment of Chemistry, National Institute of Technology Patna, Ashok Rajpath,
Patna-800 005, India
† Electronic supplementary information (ESI) available: 1H NMR and 13C NMR
Scheme
1 Synthesis of polycyclic N-heterocycles using three
spectra for all the products are available. See DOI: 10.1039/c4ra00876f
component reactions.
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three component product 1c was obtained in 15% only (Table 1,
entry 2). The compound 1c was fully characterized by IR, 1H, 13
C
NMR and elemental analysis. Encouraged by this result, we
shied our attention towards optimization of the reaction
conditions using various catalysts for the same model reaction
in ethanol as solvent under reux conditions. Basic organo-
catalysts such as DBN, Et3N, and DABCO were screened under
the similar reaction conditions to nd the optimum yield and
reaction time. The results are summarized in Table 1 (entries 3–
5). Interestingly, L-proline (20 mol%) showed the best result
among all the screened catalysts. Next, to nd the best solvent
for this transformation the same reaction was also screened in
various solvents such as EtOH, CH3CN, DMF, CH2Cl2 and THF
(Table 1, entries 6 and 9–12) in the presence of 20 mol%
L-proline. Among all these solvents, EtOH was found to be the
best solvent for this transformation.
To check the generality and versatility of this method, a study
on the substrate scope was carried out under the optimized
reaction conditions and the results are summarized in Table 2.
It can be found from the results that a wide range of aldehydes
are suitable for this multicomponent reaction. Aromatic alde-
hydes tethered with both electron-donating and electron-
Fig. 1 Structural correlation of A and B.
condensation of 3-methyl-1-phenyl-1H-pyrazol-5-amine, alde-
hydes and 2-hydroxynaphthalene-1,4-dione. Nageswar et al.22
have recently synthesized pyrazolo[3,4-b]quinoline derivatives
by one pot three component reaction of aldehyde, amino-
pyrazole, and 1,3-cyclohexanedione using polyethylene glycol
(PEG)-400 as reaction medium. Interestingly, all the above
mentioned reported protocols describe the synthesis of Pyr-
azolo[3,4-b]quinoline derivatives with a fused pyridine ring (A),
and our objective is to access 2H-benzo[g]pyrazolo[3,4-b]quino-
line-5,10(4H,11H)-dione derivatives (B) with a fused dihy-
dropyridine ring from the three component reaction of
2-hydroxy-1,4-naphthoquinone, aldehyde, and aminopyrazole
using metal-free environmentally benign reaction conditions
(Fig. 1).
Table
5,10(4H,11H)-diones
2 Synthesis of 2H-benzo[g]pyrazolo[3,4-b]quinoline-
Result and discussion
Initially the reaction of 4-chlorobenzaldehyde (1.0 mmol), 2-
hydroxy-1,4-naphthoquinone (1.0 mmol) and 3-amino-5-meth-
ylpyrazole (1.0 mmol) was studied without using any catalyst in
ethanol. At room temperature, the above combination did not
provide the expected three component product even aer 24 h
stirring. Interestingly, when the same set of reactants in ethanol
was reuxed in absence of any catalyst for 9 hours, the desired
Table 1 Optimisation of reaction conditions
Entry
Catalyst
Mole%
Solvent
Time (h)
Yielda
1
2
3
4
5
6
7
8
—
—
DBN
DABCO
Et3N
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
—
—
20
20
20
20
10
30
20
20
20
20
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
DMF
24
9
12
9
9
9
9
9
9
9
NRb
15
28
35
80
88
75
89
68
9
10
11
12
64
Trace
60
CH2Cl2
THF
9
9
a
Isolated yield. b Reaction performed at room temperature.
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by recording melting point without correction, 1H NMR, 13C
NMR and elemental analysis.
Typical experimental procedure for the synthesis of 1c. To a
stirred mixture of 4-chlorobenzaldehyde (1 mmol) and 2-
hydroxy-1,4-naphthoquinone (1 mmol) in ethanol (5 ml), was
added L-proline (0.2 mmol) and the reaction mixture was stirred
under reux conditions for 30 minutes. Then 3-amino-5-methy-
lpyrazole (1 mmol) was added to it. The resulting mixture was
stirred until the reaction was completed as indicated by TLC.
The resulting solid was collected by ltration and washed with
ethanol to afford the product. The resulting product was pure
enough for characterization.
Scheme 2 Proposed mechanism for the synthesis of 2H-benzo[g]-
pyrazolo[3,4-b]quinoline-5,10(4H,11H)-diones.
3-Methyl-4-phenyl-2H-benzo[g]pyrazolo[3,4-b]quinoline-
5,10(4H,11H)-dione (1a). Yield: 71%. Brown solid. m.p. 292–
294ꢀ C. IR (KBr): 3421, 3411, 3071, 2909, 1667, 1607, 1550, 1510,
withdrawing substituents like F, Cl, Br, Me, NO2, OMe, OH,
CH(Me)2 afforded the desired products (1b–1n) in very good
yields with both 3-amino-5-methylpyrazole and 3-amino-
pyrazole. To extend the utility of this method, aliphatic alde-
hyde such as butanal and heteroaromatic aldehyde i.e.
furfuraldehyde were also tested and the corresponding prod-
ucts (1o and 1p) were obtained in good yields (Table 2).
The plausible mechanism of this reaction is shown in Scheme
2. We believe the mechanism goes via domino Aldol reaction–
Michael addition–N-cyclization–tautomerism sequence to give
the nal product 1 regioselectively. Interestingly, we have not
isolated the ortho isomer as mentioned by Li et al.18 It is evident
from the fact that no reaction was observed when the product
obtained from the above reaction was treated with o-phenylene-
diamine. This presumably can be an indirect evidence for the
regioselectivity observed in this reaction.
1429, 1384, 1319, 1273, 1207, 1154, 1051, 957, 742 cmꢁ1 1H
.
NMR (300 MHz, DMSO-d6): d ¼ 12.10 (s, 1H, NH), 10.20 (s, 1H,
NH), 8.05–7.70 (m, 5H, ArH), 7.50–7.30 (m, 4H, ArH), 5.40 (s, 1H,
CH), 2.01 (s, 3H, CH3) ppm. 13C NMR (75 MHz, DMSO-d6): d ¼
181.7, 181.3, 147.1, 146.9, 142.0, 137.0, 135.6, 133.5, 131.2,
130.3, 128.9, 126.6, 126.3, 114.7, 103.5, 80.1, 36.4, 10.3 ppm.
Anal. calcd for C21H15N3O2 (341.36): C, 73.89; H, 4.43; N, 12.31;
found: C, 73.93. H, 4.45; N, 12.38%.
4-(4-Fluorophenyl)-3-methyl-1H-benzo[g]pyrazolo[3,4-b]-
quinoline-5,10(4H,11H)-dione (1b). Yield: 75%. Dark purple
ꢀ
solid. m.p. 299–301 C. IR (KBr): 3435, 3419, 3024, 2950, 2867,
1670, 1611, 1551, 1344, 1224, 1156, 957, 793, 607 cmꢁ1. 1H NMR
(400 MHz, DMSO-d6): 12.10 (s, 1H, NH), 10.20 (s, 1H, NH), 8.0
(d, J ¼ 7.6 Hz, 1H, ArH), 7.84 (d, J ¼ 7.6 Hz, 1H, ArH), 7.83–7.70
(m, 2H, ArH), 7.29–7.25 (m, 2H, ArH), 7.0 (t, J ¼ 7.6 Hz, 2H, ArH),
5.36 (s, 1H, CH), 1.94 (s, 3H, CH3) ppm. 13C NMR (75 MHz,
DMSO-d6): d ¼ 180.8, 180.5, 145.2, 143.5, 141.0, 135.5, 134.7,
132.6, 130.3, 129.3, 129.2, 125.7, 125.4, 114.9, 114.6, 102.9, 35.2,
9.4 ppm. Anal. calcd for C21H14FN3O2 (359.35): C, 70.19; H, 3.93;
N, 11.69. Found: C, 70.14; H, 3.96; N, 11.75%.
Conclusion
We have developed a facile and efficient one-pot, three
component reaction for the synthesis of functionalized poly-
cyclic N-heterocycles using readily available L-proline as organo
catalyst. This domino reaction proceeded smoothly in good to
excellent yields and offered several advantages including short
reaction time, simple experimental procedure, no column
chromatography, and no toxic by-product. Due to the presence
of NH and C]O functionality in these molecules they can serve
as organic ligands for the formation of metal complexes as well
as further functionalization of these molecules is feasible, and
work in this direction is ongoing in our laboratory and will be
reported in due course.
4-(4-Chlorophenyl)-3-methyl-2H-benzo[g]pyrazolo[3,4-b]-
quinoline-5,10(4H,11H)-dione (1c). Yield: 88%. Reddish brown
ꢀ
solid. m.p. 298–300 C. IR (KBr): 3455, 3420, 3024, 1670, 1609,
1561, 1352, 1250, 1170, 957, 785 cmꢁ1 1H NMR (300 MHz,
.
DMSO-d6): d ¼ 12.10 (s, 1H, NH), 10.25 (s, 1H, NH), 8.0 (d, J ¼
7.6 Hz, 1H, ArH), 7.88–7.71 (m, 3H, ArH), 7.40 (d, J ¼ 9.0 Hz, 2H,
ArH), 7.20 (d, J ¼ 7.5 Hz, 2H, ArH), 5.45 (s, 1H, CH), 1.93 (s, 3H,
CH3) ppm. 13C NMR (125 MHz, DMSO-d6): d ¼ 181.2, 180.9,
146.9, 145.7, 141.5, 136.0, 135.2, 133.0, 132.9, 131.4, 130.8,
130.2, 126.2, 125.9, 119.3, 114.1, 103.0, 36.1, 9.9 ppm. Anal.
calcd for C21H14ClN3O2 (375.81): C, 67.12; H, 3.75; N, 11.18.
Found: C, 67.16; H, 3.72; N, 11.26%.
Experimental
General information
4-(4-Bromophenyl)-3-methyl-2H-benzo[g]pyrazolo[3,4-b]-
quinoline-5,10(4H,11H)-dione (1d). Yield: 75%. Purple solid.
ꢀ
All reagents and chemicals required for the reactions were m.p. 305–307 C. IR (KBr): 3302, 3290, 3059, 2972, 1662, 1613,
procured from commercial sources and used without further 1556, 1516, 1432, 1384, 1344, 1273, 1204, 1147, 1085, 1051, 904,
purication. IR spectra were recorded in Shimadzu FTIR spec- 760 cmꢁ1. 1H NMR (400 MHz, DMSO-d6): d ¼ 12.10 (s, 1H, NH),
trophotometer. 1H NMR spectra and 13C NMR spectra were 10.23 (s, 1H, NH), 8.02 (d, J ¼ 7.2 Hz, 1H, ArH), 7.99–7.73 (m,
recorded on 500, 400 and 300 MHz spectrometer in DMSO-d6 3H, ArH), 7.40 (d, J ¼ 8.4 Hz, 2H, ArH), 7.21 (d, J ¼ 8.0 Hz, 2H,
using TMS as internal reference. Elemental analyses were ArH), 5.34 (s, 1H, CH), 1.96 (s, 3H, CH3) ppm. 13C NMR (100
carried out in a Perkin Elmer 2400 automatic CHN analyzer or MHz, DMSO-d6): d ¼ 181.7, 181.3, 147.4, 145.5, 142.0, 135.6,
Elementer Vario EL III. All new compounds were characterized 133.5, 133.4, 131.9, 131.2, 130.7, 126.6, 126.3, 119.7, 114.5,
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103.4, 36.5, 10.3 ppm. Anal. calcd for C21H14BrN3O2 (420.26): C, 157.7, 153.1, 151.7, 137.6, 135.9, 135.1, 132.9, 132.1, 129.3,
60.02; H, 3.36; N, 10.00. Found: C, 60.08; H, 3.32; N, 10.09%. 128.8, 128.4, 127.5, 126.7, 120.3, 115.2, 35.9, 14.8 ppm. Anal.
3-Methyl-4-p-tolyl-2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10- calcd for C21H15N3O3 (357.36): C, 70.58; H, 4.23; N, 11.76.
(4H,11H)-dione (1e). Yield: 81%. Purple solid. m.p. 289–291 ꢀC. Found: C, 70.64; H, 4.20; N, 11.85%.
IR (KBr): 3450, 3432, 3012, 1665, 1610, 1512, 1355, 1260, 1180,
3-Methyl-4-(3-nitrophenyl)-1H-benzo [g] pyrazolo [3,4-b]-
958 cmꢁ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 12.03 (s, 1H, NH), quinoline-5,10(4H,11H)-dione (1j). Yield: 52%. Reddish brown
ꢀ
10.12 (s, 1H, NH), 8.10–7.70 (m, 4H, ArH), 7.11 (d, J ¼ 8.1 Hz, solid. m.p. 265–267 C. IR (KBr): 3436, 3420, 3100, 3031, 1663,
2H, ArH), 7.00 (d, J ¼ 7.8 Hz, 2H, ArH), 5.35 (s, 1H, CH), 2.25 (s, 1609, 1510, 1467, 1345, 1272, 1149, 1101, 956, 849, 790, 601
3H, CH3), 1.93 (s, 3H, CH3) ppm. 13C NMR (125 MHz, DMSO-d6): cmꢁ1. H NMR (400 MHz, DMSO-d6): d ¼ 12.14 (bs, 1H, NH),
1
d ¼ 181.2, 181.0, 144.8, 141.3, 136.0, 135.2, 135.1, 133.0, 132.9, 10.31 (bs, 1H, NH) 8.10 (s, 1H, ArH), 8.0 (d, J ¼ 7.6 Hz, 1H, ArH),
130.7, 129.1, 127.8, 126.1, 125.9, 114.9, 103.6, 35.9, 21.0, 9.9 7.97 (d, J ¼ 8.0 Hz, 1H, ArH), 7.83 (d, J ¼ 7.6 Hz, 1H, ArH) 7.79–
ppm. Anal. calcd for C22H17N3O2 (355.39): C, 74.35; H, 4.82; N, 7.72 (m, 3H, ArH), 7.51 (t, J ¼ 7.6 Hz, 1H, ArH), 5.55 (s, 1H, CH),
11.82. Found: C, 74.42; H, 4.79; N, 11.90%.
1.93 (s, 3H, CH3) ppm. 13C NMR (100 MHz, DMSO-d6): d ¼ 180.7,
3-Methyl-4-(4-nitrophenyl)-2H-benzo[g]pyrazolo[3,4-b]quin- 180.3, 149.1, 147.6, 141.4, 135.9, 134.7, 134.4, 132.5, 132.4,
oline-5,10(4H,11H)-dione (1f). Yield: 59%. Dark purple solid. 130.3, 129.6, 125.7, 125.4, 121.9, 120.9, 112.9, 102.1, 35.9, 9.4
ꢀ
m.p. 277–279 C. IR (KBr): 3215, 3210, 3025, 2965, 1678, 1611, ppm. Anal. calcd for C21H14N4O4 (386.36): C, 65.28; H, 3.65; N,
1
1592, 1518, 1345, 1249, 988 cmꢁ1. H NMR (300 MHz, DMSO- 14.50. Found: C, 65.22; H, 3.68; N, 14.60%.
d6): d 12.10 (s, 1H, NH), 10.30 (s, 1H, NH), 8.40 (d, J ¼ 8.4 Hz, 2H,
4-(4-Isopropylphenyl)-2H-benzo[g]pyrazolo[3,4-b]quinoline-
ArH), 8.11 (d, J ¼ 9.0 Hz, 1H, ArH), 8.02 (d, J ¼ 9.0 Hz, 1H, ArH), 5,10(4H,11H)-dione (1k). Yield: 88%. Dark brown solid. m.p.
7.85–7.66 (m, 2H, ArH), 7.56 (d, J ¼ 9.0 Hz, 2H, ArH), 5.50 (s, 1H, 266–268 ꢀC. IR (KBr): 3420, 3405, 3090, 2953, 1662, 1609, 1563,
CH), 1.98 (s, 3H, CH3) ppm. 13C NMR (75 MHz, DMSO-d6): d ¼ 1525, 1507, 1410, 1351, 1204, 1101, 1060, 954, 829, 760 cmꢁ1. 1H
180.7, 180.3, 154.4, 145.6, 141.5, 134.8, 132.4, 132.4, 130.3, NMR (400 MHz, DMSO-d6): d ¼ 12.20 (bs, 1H, NH), 10.20 (bs,
128.8, 128.3, 125.8, 125.4, 123.5, 112.9, 101.8, 36.3, 9.4 ppm. 1H, NH), 8.0 (d, J ¼ 6.8 Hz, 1H, ArH), 7.85 (d, J ¼ 6.4 Hz, 1H,
Anal. calcd for C21H14N4O4 (386.36): C, 65.28; H, 3.65; N, 14.50. ArH), 7.78–7.70 (m, 1H, ArH), 7.41 (s, 1H, ArH), 7.18–7.01 (m,
Found: C, 65.34; H, 3.62; N, 14.59%.
5H, ArH), 5.20 (s, 1H, CH), 2.76–2.74 (m, 1H, CH), 1.10 (d, J ¼ 6.8
4-(4-Methoxyphenyl)-3-methyl-2H-benzo[g]pyrazolo[3,4-b]- Hz, 6H, CH3) ppm. 13C NMR (100 MHz, DMSO-d6): d ¼ 181.8,
quinoline-5,10(4H,11H)-dione (1g). Yield: 86%. Purple solid. 181.3, 146.6, 146.3, 142.2, 135.6, 133.5, 133.4, 131.2, 127.8,
ꢀ
m.p. 269–271 C. IR (KBr): 3435, 3419, 3024, 2956, 1670, 1609, 127.3, 127.0, 126.6, 126.4, 114.7, 106.8, 36.3, 33.9, 24.8 ppm.
1570, 1528, 1326, 1214, 957, 785 cmꢁ1 1H NMR (300 MHz, Anal. calcd for C23H19N3O2 (369.42): C, 74.78; H, 5.18; N, 11.37.
.
DMSO-d6): d ¼ 12.10 (s, 1H, NH), 10.25 (s, 1H, NH), 8.0 (d, J ¼ Found: C, 74.72; H, 5.20; N, 11.46%.
7.2 Hz, 1H, ArH), 7.90–7.70 (m, 3H, ArH), 7.14 (d, J ¼ 8.4 Hz, 2H,
4-(4-Isopropylphenyl)-3-methyl-2H-benzo[g]pyrazolo[3,4-b]-
ArH), 6.76 (d, J ¼ 8.4 Hz, 2H, ArH), 5.25 (s, 1H, CH), 3.75 (s, 3H, quinoline-5,10(4H,11H)-dione (1l). Yield: 86%. White solid.
OCH3), 1.95 (s, 3H, CH3) ppm. 13C NMR (75 MHz, DMSO-d6): d ¼ m.p. 291–293 C. IR (KBr): 3447, 3421, 3051, 2958, 1665, 1534,
ꢀ
180.8, 180.5, 157.3, 145.3, 140.6, 139.4, 135.2, 134.6, 132.5, 1342, 1267, 1151, 959, 788, 724, 613 cmꢁ1. H NMR (300 MHz,
1
132.4, 130.2, 128.4, 125.6, 125.3, 114.6, 113.4, 103.2, 54.8, 34.9, DMSO-d6): d ¼ 12.04 (bs, 1H, NH), 10.13 (bs, 1H, NH), 8.0 (d, J ¼
9.3 ppm. Anal. calcd for C22H17N3O3 (371.39): C, 71.15; H, 4.61; 6.9 Hz, 1H, ArH), 7.85 (d, J ¼ 7.2 Hz, 1H, ArH), 7.80–7.70 (m, 2H,
N, 11.31. Found: C, 71.10; H, 4.63; N, 11.40%.
ArH), 7.15 (d, J ¼ 7.8 Hz, 2H, ArH), 7.07 (d, J ¼ 8.1 Hz, 2H, ArH)
4-(4-Chlorophenyl)-2H-benzo[g]pyrazolo[3,4-b]quinoline 5.31 (s, 1H, CH), 2.70 (m, 1H, CH), 1.98 (s, 3H, CH3), 1.12 (d, J ¼
5,10(4H,11H)-dione (1h). Yield: 72%. Reddish brown solid. m.p. 6.9 Hz, 6H) ppm. 13C NMR (100 MHz, DMSO-d6): d ¼ 180.7,
282–284 ꢀC. IR (KBr): 3246, 3202, 3078, 2909, 1672, 1609, 1553, 180.5, 145.6, 145.3, 144.6, 140.9, 135.2, 134.6, 132.5, 130.3,
1510, 1432, 1384, 1326, 1238, 1207, 1172, 1113, 1038, 960, 760 127.2, 125.9, 125.6, 125.4, 114.4, 103.2, 35.3, 32.9, 23.8, 9.4 ppm.
cmꢁ1
.
1H NMR (400 MHz, DMSO-d6): d ¼ 12.20 (s, 1H, NH), Anal. calcd for C24H21N3O2 (383.44): C, 75.18; H, 5.52; N, 10.96.
10.20 (s, 1H, NH), 8.05 (d, J ¼ 7.2 Hz, 1H, ArH), 7.89–7.71 (m, Found: C, 75.12; H, 5.55; N, 10.06%.
3H, ArH), 7.48 (s, 1H, ArH), 7.20 (d, J ¼ 8.8 Hz, 2H, ArH), 7.12 (d,
4-(2,4-Dichlorophenyl)-3-methyl-1H-benzo[g]pyrazolo[3,4-b]-
J ¼ 8.4 Hz, 2H, ArH), 5.50 (s, 1H, CH) ppm. 13C NMR (100 MHz, quinoline-5,10(4H,11H)-dione (1m). Yield: 64%. White solid.
DMSO-d6): d ¼ 181.8, 181.2, 147.8, 142.4, 135.6, 133.5, 133.4, m.p. 313–315 ꢀC. IR (KBr): 3277, 3183, 3091, 2965, 1672, 1613,
131.3, 131.2, 129.8, 129.0, 126.7, 126.3, 113.9, 106.2, 80.7, 36.4 1560, 1538, 1510, 1437, 1338, 1275, 1213, 1083, 1038, 1013,
ppm. Anal. calcd for C20H12ClN3O2 (361.78): C, 66.40; H, 3.34; N, 920, 848, 783 cmꢁ1. H NMR (500 MHz, DMSO-d6): d ¼ 12.10
1
11.61. Found: C, 66.34; H, 3.37; N, 11.71%.
(bs, 1H, ArH), 10.25 (bs, 1H, ArH), 8.0 (d, J ¼ 7.2 Hz, 1H, ArH),
4-(4-Hydroxyphenyl)-3-methyl-2H-benzo[g]pyrazolo[3,4-b]- 7.80–7.72 (m, 3H, ArH), 7.48 (s, 1H, ArH), 7.26 (d, J ¼ 8.4 Hz,
quinoline-5,10(4H,11H)-dione (1i). Yield: 85%. Blue solid. m.p. 1H, ArH), 7.23 (d, J ¼ 8.0 Hz, 1H, ArH), 5.71 (s, 1H, CH), 1.93
276–278 ꢀC. IR (KBr): 3440, 3430, 3031, 2956, 1668, 1608, 1509, (s, 3H, CH3) ppm. 13C NMR (125 MHz, DMSO-d6): d ¼ 181.1,
1464, 1371, 1287, 955 cmꢁ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 180.8, 145.6, 144.1, 142.1, 136.2, 135.2, 133.0, 132.9, 132.6,
12.10 (s, 1H, NH), 10.10 (s, 1H, NH), 9.12 (bs, 1H, OH), 8.0 (d, J ¼ 132.3, 131.4, 130.7, 128.6, 128.2, 126.2, 125.9, 113.6, 102.3,
7.5 Hz, 1H, ArH), 7.90–7.70 (m, 3H, ArH), 7.01 (d, J ¼ 8.4 Hz, 2H, 33.7, 9.9 ppm. Anal. calcd for C21H13Cl2N3O2 (410.25):
ArH), 6.58 (d, J ¼ 8.4 Hz, 2H, ArH), 5.35 (s, 1H, CH), 1.93 (s, 3H, C, 61.48; H, 3.19; N, 10.24. Found: C, 61.41; H, 3.21;
CH3) ppm. 13C NMR (100 MHz, DMSO-d6): d ¼ 180.6, 179.9, N, 10.35%.
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4-(4-Methoxyphenyl)-2H-benzo[g]pyrazolo[3,4-b]quinoline-
RSC Advances
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5,10(4H,11H)-dione (1n). Yield, 80%. Brown solid. m.p. 232–
234 ꢀC. IR (KBr): 3283, 3254, 2972, 1672, 1613, 1560, 1541, 1510,
1437, 1338, 1275, 1213, 1088, 1041, 923, 836, 780 cmꢁ1. 1H NMR
(500 MHz, DMSO-d6): d ¼ 12.30 (s, 1H, NH), 10.20 (s, 1H, NH),
8.0 (d, J ¼ 9.0 Hz, 1H, ArH), 7.84 (d, J ¼ 8.0 Hz, 1H, ArH), 7.70–
7.60 (m, 2H, ArH), 7.41 (s, 1H, ArH), 7.12 (d, J ¼ 8.5 Hz, 2H, ArH),
6.74 (d, J ¼ 8.5 Hz, 2H, ArH), 5.39 (s, 1H, CH), 3.63 (s, 3H, OCH3)
ppm. 13C NMR (125 MHz, DMSO-d6): d ¼ 181.4, 180.9, 157.8,
141.5, 140.8, 135.1, 135.1, 132.9, 130.8, 130.5, 128.5, 126.1,
125.9, 114.5, 114.0, 106.4, 55.4, 35.5 ppm. Anal. calcd for
C
21H15N3O3 (357.36): C, 70.58; H, 4.23; N, 11.76. Found: C,
70.52; H, 4.26; N, 11.86%.
3-Methyl-4-propyl-2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10-
(4H,11H)-dione (1o). Yield: 64%. White solid. m.p. 218–220 ꢀC.
IR (KBr): 3210, 3188, 2961, 1683, 1653, 1573, 1453, 1340, 1262,
726, 619 cmꢁ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 12.10 (s, 1H,
NH), 10.23 (s, 1H, NH), 8.0 (d, J ¼ 6.9 Hz, 1H, ArH), 7.96 (d, J ¼
6.3 Hz, 1H, ArH), 7.80–7.70 (m, 2H, ArH), 5.35 (s, 1H, CH), 1.95
(s, 3H, CH3), 1.30–0.80 (m, 7H, 2CH2, and CH3) ppm. 13C NMR
(100 MHz, DMSO-d6): d ¼ 181.9, 181.2, 147.4, 142.8, 135.5,
133.5, 133.3, 131.1, 126.5, 126.4, 115.2, 102.7, 80.1, 30.0, 18.9,
15.0, 10.6 ppm. Anal. calcd for C18H17N3O2 (307.35): C, 70.34; H,
5.58; N, 13.67. Found: C, 70.41; H, 5.61; N, 13.77%.
¨
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3-Methyl-4-(furan-2-yl)-2H-benzo[g]pyrazolo[3,4-b]quinoline-
5,10(4H,11H)-dione (1p). Yield: 71%. White solid. m.p. 246–248
ꢀC. IR (KBr): 3258, 3170, 3023, 2962, 2902, 1663, 1616, 1600,
1543, 1502, 1424, 1371, 1213, 1145, 1061, 964, 842, 813, 752
cmꢁ1
.
1H NMR (300 MHz, DMSO-d6): d ¼ 12.15 (s, 1H, NH),
10.25 (s, 1H, NH), 8.02 (d, J ¼ 7.5 Hz, 1H, ArH), 7.93 (d, J ¼ 7.2
Hz, 1H, ArH), 7.86–7.74 (m, 2H, ArH), 7.74 (d, J ¼ 7.2 Hz, 1H,
ArH), 6.26 (dd, J ¼ 3.0, 1.8 Hz, 1H, ArH), 6.04 (d, J ¼ 3.0 Hz, 1H,
ArH), 5.45 (s, 1H, CH), 2.10 (s, 3H, CH3) ppm. 13C NMR (100
MHz, DMSO-d6): d ¼ 180.7, 180.4, 157.6, 141.5, 141.1, 134.8,
134.1, 132.6, 132.5, 130.3, 126.8, 125.8, 125.5, 111.4, 110.3,
104.4, 100.4, 29.4, 9.4 ppm. Anal. calcd for C19H13N3O3 (331.32):
C, 68.88; H, 3.95; N, 12.68. Found: C, 68.82; H, 3.98; N, 12.79%.
6 S. Pal, M. N. Khan, S. Karamthulla and L. H. Choudhury, RSC
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Acknowledgements
L.H.C and T.P gratefully acknowledge nancial support from
the Department of Science and Technology India, with Sanction
No. SR/FT/CS-042/2009 and SR/FT/CS-08/2010 respectively for
carrying out this work. S.K and S.P are grateful to CSIR and UGC
respectively for their research fellowships (SRF). Authors are
also grateful to IIT Guwahati, Bose Institute, Kolkata and SAIF,
Panjab University for providing analytical facilities for charac-
terization of compounds.
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