Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine- 5,10-diones

Article abstract of DOI:10.1016/j.tetlet.2011.10.136

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b] phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehy

Full text of DOI:10.1016/j.tetlet.2011.10.136

Tetrahedron Letters 52 (2011) 7195–7198
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Solvent-free sonochemical one-pot three-component synthesis
of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-
pyrazolo[1,2-b]phthalazine-5,10-diones
⇑
Gaurav Shukla, Rajiv K. Verma, Girijesh K. Verma, Maya Shankar Singh
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthal-
azine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino
coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well
as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 10 September 2011
Revised 20 October 2011
Accepted 23 October 2011
Available online 29 October 2011
Keywords:
Ultrasound irradiation
Solvent-free conditions
Indazolo[2,1-b]phthalazine-1,6,11-triones
Pyrazolo[1,2-b]phthalazine-5,10-diones
(S)-Camphorsulfonic acid
One-pot three-component reaction
The continual upsurge in facile and non-polluting synthetic pro-
cedures urges synthetic chemists to increase tools of their arsenal,
because of the increasing concern for the harmful effects of organic
solvents on the environment. Ultrasound-promoted syntheses1
have attracted much attention during the last few years, and exten-
sively utilized to accelerate a number of organic transformations.2
Simple experimental procedure, clean reaction, short reaction time,
high yields, and improved selectivity of many ultrasound induced
organic transformations offer additional convenience in the field
of synthetic organic chemistry.3 Recently, numerous important het-
erocycles have been synthesized under solvent-free conditions
accelerated by ultrasound irradiation.4
important N-heterocycles possessing multiple biological activi-
ties12 such as anticonvulsant,13 cardiotonic,14 vasorelaxant,15 anti-
microbial,16a antifungal,16b anticancer,16c and anti-inflammatory17
along with unique electrical and optical properties.18
Despite many methods being available for the synthesis of
phthalazine derivatives,19 their broad utility has accentuated the
need to develop eco-compatible and clean synthetic routes. Re-
cently, several elegant multicomponent strategies for the synthesis
of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones by the cyclo-
condensation of phthalhydrazide, aldehydes, and 1,3-diketones uti-
lizing different types of catalysts have been reported.20,21 The
reported methods show varying degrees of successes as well as lim-
itations such as harsh reaction conditions, expensive catalyst/re-
agent, toxic organic solvents, low product yields, long reaction
times, and co-occurrence of several side products. Therefore, there
still remains a high demand for the development of more general,
efficient, economically viable, and eco-compatible protocol to
assemble such scaffolds. Camphorsulfonic acid (CSA) has emerged
as a highly efficient and effective potential organic acid catalyst
imparting high stereoselectivity in various chemical transforma-
tions.22 We therefore became interested in devising more general
and green methods for the synthesis of indazolo[2,1-b]phthal-
azine-1,6,11-triones and pyrazolo[1,2-b]phthalazine-5,10-diones
under solvent-free ultrasound irradiation utilizing (S)-CSA as the
catalyst.
Over the years, multicomponent reactions5 (MCRs) have become
increasingly popular tools to ensure sufficient molecular diversity
and complexity. They have gained significant popularity in recent
years due to their atom-economy and straightforward reaction de-
sign due to substantial minimization of waste, labor, time, and
cost.6 MCRs leading to interesting heterocyclic scaffolds are partic-
ularly useful for the construction of diverse chemical libraries of
‘drug like’ molecules.7,8 Many organic reactions have been reported
to proceed efficiently under solvent-free conditions9–11 showing
enhanced selectivities and excellent yields. 2H-indazolo[2,1-
b]phthalazine-1,6,11-triones constitute a key structural motif in a
number of natural and synthetic bioactive molecules. They are
Our literature survey at this stage revealed that there are no re-
ports on the synthesis of indazolo[2,1-b]phthalazine-1,6,11-triones
⇑
Corresponding author. Fax: +91 542 2368127.
E-mail address: mssinghbhu@yahoo.co.in (M.S. Singh).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.136

7196
G. Shukla et al. / Tetrahedron Letters 52 (2011) 7195–7198
R2
and pyrazolo[1,2-b]phthalazine-5,10-diones under solvent-free
ultrasound irradiation at room temperature mediated by (S)-cam-
phorsulfonic acid. Our main strategy is to develop a green organic
reaction enhancement methodology, which is relatively faster and
cleaner than the conventional reactions. As part of our ongoing re-
search program on the development of clean protocols under sol-
vent-free conditions23 herein, we report a facile one-pot synthesis
of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazol-
o[1,2-b]phthalazine-5,10-diones 6 via the three-component cou-
pling of phthalhydrazide 1, 1,3-diketones 2, and aldehydes 3
under solvent-free conditions at 80 °C as well as under solvent-free
ultrasound irradiation at room temperature (Scheme 1).24
O
O
O
O
N
N
R
R
R
O
O
O
R
4
2a
or
O
R = H, CH3
I or II
NH
NH
+
+
R2CHO
or
R2
One-pot
3
O
O
R1
1
R1
N
N
R1
O
R1
2b
6
No chromatographic
separation
O
Initial study was carried out utilizing phthalhydrazide
1
R1 = CH3, Ph
(1.0 mmol), dimedone 2 (1.1 mmol), and 4-nitrobenzaldehyde 3a
(1.1 mmol) under solvent-free conventional heating (method I)
and under ultrasound irradiation at room temperature separately,
in the absence of a catalyst. We did not observe a trace of the de-
sired product even after 12 h under the above two conditions (Ta-
ble 1, entries 1 and 14). To explore suitable reaction conditions, the
above model reaction was performed in the presence of various
catalysts such as L-proline, P2O5, InCl3, NH2HSO3, BF3.OEt2, and
(S)-CSA separately, under solvent-free conditions at 80 °C as well
as under ultrasound irradiation at room temperature. The results
are summarized in Table 1. L-proline could not trigger the reaction
even after 12 h of heating, whereas P2O5, InCl3, NH2HSO3, and
BF3.OEt2 were found to catalyze the reaction to give the desired
2H-indazolo[2,1-b]phthalazine-1,6,11-trione 4a in moderate yields
along with Knoevenagel condensation product 5 in 15–25% yields
as a side product. To our delight (S)-CSA provided the desired com-
pound 4a in a 94% yield as an exclusive product under solvent-free
conditions at 80 °C. Subsequently, catalyst loading was optimized
and 20 mol % loading of the (S)-CSA provided the maximum yield
Scheme 1. Synthesis of indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyr-
azolo[1,2-b]phthalazine-5,10-diones 6. Reagents and conditions: (I) (S)-CSA
(20 mol %),80 °C, solvent-free; (II) (S)-CSA (20 mol %), rt,)))), solvent-free.
in minimum time (Table 1, entry 11). A further increase in the
amount of (S)-CSA did not have any significant effect on the prod-
uct yield or reaction time, whereas the yield was reduced by
decreasing the amount of (S)-CSA (Table 1, entries 12 and 13).
Recently, organic synthesis involving multicomponent reaction
under ultrasonic irradiation has attracted much attention. There-
fore, we explored the possibility of obtaining the target compounds
under ultrasonic irradiation. We performed the above test reaction
in the presence of 20 mol % of (S)-CSA under ultrasound irradiation
at room temperature. The desired product 4a was obtained exclu-
sively in a 92% yield within 20 min (Table 1, entry 15). Thus,
20 mol % of (S)-CSA was found to be optimum for both conditions
I and II. Although, the yields are found to be almost parallel under
Table 1
Optimization of reaction conditions for the synthesis of 4a
NO2
NO2
CHO
O
O
O
O
O
O
O
O
NH
NH
+
+
N
N
+
O
NO2
O
2
1
4a
3
5
Entry
Catalyst
None
-proline
Loading (mol %)
Method I and II
Time
Yieldb (%) 4a
Yield (%) 5
1
2
—
20
80 °C
80 °C
12 h
12 h
—
—
—
—
L
3
4
5
6
7
P2O5
P2O5
InCl3
InCl3
20
30
20
30
20
30
20
30
20
30
10
—
20
10
30
20
20
20
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
)))), rt
)))), rt
)))), rt
)))), rt
)))), rt
)))), rt
)))), rt
50 min
40 min
40 min
25 min
30 min
20 min
30 min
25 min
15 min
14 min
35 min
12 h
20 min
40 min
20 min
50 min
35 min
40 min
40
55
50
55
65
70
60
65
94
92
78
—
92
75
90
45
60
55
25
20
20
15
15
12
15
20
—
—
Trace
—
—
Trace
—
H2NHSO3
H2NHSO3
BF3.OEt2
BF3.OEt2
(S)-CSA
(S)-CSA
(S)-CSA
None
(S)-CSA
(S)-CSA
(S)-CSA
InCl3
8
9
10
11
12
13
14
15
16
17
18
19
20
20
20
15
H2NHSO3
BF3.OEt2
a
Reaction of phthalhydrazide (1.0 mmol), dimedone (1.1 mmol), and 4-nitrobenzaldehyde (1.1 mmol).
Isolated pure yields.
b

G. Shukla et al. / Tetrahedron Letters 52 (2011) 7195–7198
7197
Table 2
Synthesis of 2H-indazolo[2,1-b]phthalazinetriones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6.
Entry
R
R1
R2
Time I/II (min)
Yielda I/II (%)
mp (°C)Lit.
4a
4b
4c
4d
4e
4f
4g
4h
4i
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
Me
Me
Me
Me
H
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
4-NO2C6H4
3-NO2C6H4
C6H5
4-OMeC6H4
4-ClC6H4
15/20
20/25
15/20
20/25
15/20
20/25
15/20
20/30
20/25
25/35
25/30
25/30
20/25
20/30
35/40
30/40
35/40
40/45
60/70
65/70
94/92
88/85
90/87
82/80
92/90
85/83
92/90
90/88
94/92
92/90
92/88
85/80
68/65
62/60
52/50
90/85
85/82
82/80
52/50
50/45
(224–225)21a,b
(268–267)20a
(206–208)20a
(218–220)21b
(260–262)20b
(205–207)21b
(265–267)20b
(274–276)20b
(263–265)21b
(248–250)20b
(265–268)20b
260–262
217–219
230–232
88–90
214–216
217–218
233–234
Viscous oil
Viscous oil
3-ClC6H4
4-BrC6H4
2,4-Cl2C6H3
4-NO2C6H4
4-CH3C6H4
3-OHC6H4
4-CHOC6H4
2-Thienyl
2-Pyridyl
n-C7H15
Cyclohexyl
4-NO2C6H4
4-CH3C6H4
Isopropyl
Cyclohexyl
4j
4k
4l
4m
4n
4o
4p
6a
6b
6c
6d
—
—
—
—
Me
Ph
Me
Ph
a
Isolated pure yields under both conditions I and II.
both conditions, ultrasound irradiation appears milder than the
conventional heating, and offers significant improvements in terms
of simplicity and green aspects by avoiding high temperature.
Subsequently, with optimal conditions in hand, the generality
and synthetic scope of this coupling protocol were demonstrated
by synthesizing a series of 2H-indazolo[2,1-b]phthalazine-1,6,11-
triones 4a–p and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6a–
d (Table 2). Gratifyingly, a wide range of aldehydes (aromatic,
heteroaromatic, and aliphatic), and cyclic and acyclic 1,3-diketones
were well tolerated under the optimized reaction conditions. How-
ever, in comparison to aromatic aldehydes, aliphatic aldehydes
gave lower yields (Table 2, entries 4o, 6c, and 6d). Moreover, when
cyclic 1,3-diketones such as indane-1,3-dione, 1,3-dimethylbarbi-
turic acid, and 4-hydroxycoumarin were treated with phthalhyd-
razide and aldehyde under the optimized reaction conditions
failed to give the expected product and furnished the Knoevenagel
condensation product exclusively, thus limiting the scope of this
reaction to some extent. The time taken for complete conversion
(monitored by TLC) and the isolated yields are recorded in Table
2. All new compounds were characterized by their satisfactory ele-
mental analyses and spectral (IR, 1H, 13C NMR and mass) studies,
and known compounds by comparison of their physical and spec-
tral data with those of the reported ones.20,21
In summary, we have devised a simple and efficient one-pot
approach to construct the structurally diverse 2H-indazolo
[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthal-
azine-5,10-diones 6 via three-component coupling of phthalhydraz-
ide, 1,3-diketones, and aldehydes under solvent-free conditions at
80 °C as well as under solvent-free ultrasound irradiation at room
temperature promoted by (S)-camphorsulfonic acid through dom-
ino Knoevenagel condensation/Michael addition/intramolecular
cyclodehydration sequence. The advantages of operational simplic-
ity, economic viability, high atom-economy together with ecologi-
cally benign nature make this protocol a very efficient alternative
to the literature methods, which could be directly used for biological
assays. The economical factors (time, money, waste etc.) for these
three-component reactions hold promise for the future of organic
synthesis.
of Science and Technology (DST), New Delhi. G.S. and G.K.V. are
grateful to CSIR and UGC, New Delhi, respectively for their junior
research fellowship. R.K.V. thanks the CSIR, New Delhi for his se-
nior research fellowship.
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We gratefully acknowledge financial support from the Council
of Scientific and Industrial Research (CSIR) and the Department

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M.; Atack, J. R.; Wafford, K. A.; Thompson, S. A.; Dawson, G. R.; Ferris, P.; Castro,
J. L. J. Med. Chem. 2004, 47, 1807.
22. (a) Gorityala, B. K.; Cai, S.; Ma, J.; Liu, X.-W. Bioorg. Med. Chem. Lett. 2009, 19,
3093; (b) Wu, Y. S.; Cai, J.; Hu, Z. Y.; Lin, G. X. Tetrahedron Lett. 2004, 45, 8949;
(c) Gayet, A.; Bolea, C.; Andersson, P. G. Org. Biomol. Chem. 2004, 2, 1887; (d)
Oh, S.; Kim, G.; Ko, N.; Shim, S. E.; Choe, S. Macromol. Res. 2005, 13, 187; (e)
Kellogg, R. M.; Nieuwenhuijzen, J. W.; Pouwer, K.; Vries, T. R. Synthesis 2003,
1626.
23. (a) Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S. Tetrahedron 2009, 65, 7129;
(b) Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S. Tetrahedron Lett. 2009, 50,
7220; (c) Samai, S.; Nandi, G. C.; Kumar, R.; Singh, M. S. Tetrahedron Lett. 2009,
50, 7096; (d) Kumar, R.; Raghuvanshi, K.; Verma, R. K.; Singh, M. S. Tetrahedron
Lett. 2010, 51, 5933; (e) Nandi, G. C.; Samai, S.; Singh, M. S. Synlett 2010, 1133;
(f) Verma, R. K.; Verma, G. K.; Raghuvanshi, K.; Singh, M. S. Tetrahedron 2011,
67, 584; (g) Verma, G. K.; Raghuvanshi, K.; Verma, R. K.; Dwivedi, P.; Singh, M.
S. Tetrahedron 2011, 67, 3698; (h) Chowdhury, S.; Nandi, G. C.; Samai, S.; Singh,
M. S. Org. Lett. 2011, 13, 3762.
24. General procedure for the synthesis of compounds 4 and 6: (I) Conventional
Method: To
(1.0 mmol), cyclic/acyclic 1,3-diketone
a
thoroughly homogenated mixture of phthalhydrazide
(1.1 mmol), and aldehyde
1
3
2
(1.1 mmol), (S)-CSA (0.046 g, 0.2 mmol) was added. The reaction mixture was
heated at 80 °C for a stipulated period of time (Table 2). After completion of the
reaction (monitored by TLC), the reaction mixture was cooled to room
temperature and washed twice with water. The product obtained was
purified by crystallization from ethyl acetate-n-hexane (1:3) or by column
chromatography (in case of acyclic 1,3-diketones) over silica gel (Merck, 60–
120 mesh, ethyl acetate-n-hexane, 1:3). (II) Ultrasound Irradiation: To
thoroughly homogenated mixture of (1.0 mmol), (1.1 mmol), and
a
3
1
2
(1.1 mmol), (S)-CSA (0.046 g, 0.2 mmol) was added. The reaction mixture
(solid paste using drop of acetonitrile was prepared in case of solid
a
aldehydes) was subjected to ultrasound irradiation (Qualigen ultrasonic
cleaner with power of 200 W) under solvent-free conditions at room
temperature until completion of the reaction (monitored by TLC). The
desired product obtained was purified as mentioned above. Analytical and
spectral data for the selected products: Compound 4m: 3,3-Dimethyl-13-
thiophen-2-yl-2,3,4,13-tetrahydro-indazolo[2,1-b]phthalazine-1,6,11-trione: 1H
NMR (CDCl3, 300 MHz): d 8.34–8.29 (m, 2H, ArH), 7.86–7.83 (m, 2H, ArH),
7.33 (s, 1H, ArH), 7.23–7.22 (m, 1H, ArH), 6.99–6.96 (m, 1H, ArH), 6.82 (s, 1H,
CH), 3.44 and 3.19 (d, J = 18.9 Hz, 2H, CH2), 2.39 (s, 2H, CH2), 1.29 and 1.22 (s,
6H, 2 Â CH3).13C NMR (75 MHz, CDCl3): d 192.0, 154.1, 151.5, 138.6, 134.4,
133.4, 128.7, 128.2, 127.9, 127.5, 126.9, 125.8, 117.0, 59.2, 50.7, 37.8, 34.3,
13. (a) Grasso, S.; De Sarro, G.; De Sarro, A.; Micale, N.; Zappala, M.; Puia, G.;
Baraldi, M.; De Micheli, C. J. Med. Chem. 2000, 43, 2851; (b) Zhang, L.; Guan, L.
P.; Sun, X. Y.; Wei, C. X.; Chai, K. Y.; Quan, Z. S. Chem. Bio. Drug Design 2009, 73,
313.
14. Nomoto, Y.; Obase, H.; Takai, H.; Teranishi, M.; Nakamura, J.; Kubo, K. Chem.
Pharm. Bull. 1990, 38, 2179.
28.8, 28.1. IR (KBr):
m
= 2945, 1669, 1374, 1301, 1257, 800 cmÀ1. ESI MS (m/z):
379 [M+1]+. Anal. Calcd for C21H18N2O3S (378.4): C, 66.65; H, 4.79; N 7.40%.
Found C, 66.75; H, 4.89; N, 7.31%. Compound 4p: 13-Cyclohexyl-2,3,4,13-
tetrahydroindazolo[2,1-b]phthalazine-1,6,11-trione: 1H NMR (CDCl3, 300 MHz):
d 8.36–8.30 (m, 2H, ArH), 7.91–7.81 (m, 2H, ArH), 5.58 (s, 1H, CH), 3.35–3.50
and 3.18–3.09 (m, 2H, CH2), 2.63–2.20 (m, 5H, CH2), 2.04–1.92 (m, 1H, CH),
1.74–1.58 (m, 6H, CH2), 1.21–1.10 (m, 3H, CH2). 13C NMR (75 MHz, CDCl3): d
192.5, 155.2, 154.4, 153.0, 133.8, 132.7, 131.6, 128.2, 128.0, 127.1, 126.7, 124.8,
15. Watanabe, N.; Kabasawa, Y.; Takase, Y.; Matsukura, M.; Miyazaki, K.; Ishihara,
H.; Kodama, K.; Adachi, H. J. Med. Chem. 1998, 41, 3367.
16. (a) El-Sakka, S. S.; Soliman, A. H.; Imam, A. M. Afinidad 2009, 66, 167; (b) Ryu,
C.-K.; Park, R.-E.; Ma, M.-Y.; Nho, J.-H. Bioorg. Med. Chem. Lett. 2007, 17, 2577;
(c) Li, J.; Zhao, Y. F.; Yuan, X. Y.; Xu, J. X.; Gong, P. Molecules 2006, 11, 574.
17. Sinkkonen, J.; Ovcharenko, V.; Zelenin, K. N.; Bezhan, I. P.; Chakchir, B. A.; Al-
Assar, F.; Pihlaja, K. Eur. J. Org. Chem. 2002, 2046.
117.3, 65.6, 40.5, 36.3, 27.5, 25.6, 25.4, 23.7, 21.3. IR (KBr):
m = 2962, 1667,
1365, 1294, 1243 cmÀ1. ESI MS (m/z): 351 [M+1]+. Anal. Calcd for C21H22N2O3
(350.4): C, 71.98; H, 6.33; N 7.99%. Found C, 71.75; H, 6.52; N, 7.71%. Compund
18. (a) Lichtenthaler, F. W. Acc. Chem. Res. 2002, 35, 728; (b) Litvinov, V. P. Russ.
Chem. Rev. 2003, 72, 69; (c) Xu, Y.; Guo, Q.-X. Heterocycles 2004, 63, 903.
19. (a) Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. J. Org. Chem. 2002, 67, 3169; (b)
Csampai, A.; Kormendy, K.; Ruff, F. Tetrahedron 1991, 47, 4457; (c)
Ghahremanzadeh, R.; Shakibaei, G. I.; Bazgir, A. Synlett 2008, 1129; (d) Nabid,
M. R.; Rezaei, S. J. T.; Ghahremanzadeh, R.; Bazgir, A. Ultrason. Sonochem. 2010,
17, 159; (e) Ghahremanzadeh, R.; Ahadi, S.; Sayyafi, M.; Bazgir, A. Tetrahedron
Lett. 2008, 49, 4479; (f) Liu, L. P.; Lu, J. M.; Shi, M. Org. Lett. 2007, 9, 1303.
20. (a) Sayyafi, M.; Seyyedhamzeh, M.; Khavasi, H. R.; Bazgir, A. Tetrahedron 2008,
64, 2375; (b) Khurana, J. M.; Devanshi, M. Tetrahedron Lett. 2009, 50, 7300; (c)
Nagarapu, L.; Bantu, R.; Mereyala, H. B. J. Heterocycl. Chem. 2009, 46, 728; (d)
Shaterian, H. R.; Ghashang, M.; Feyzi, M. Appl. Catal. A: Gen. 2008, 345, 128; (e)
Shaterian, H. R.; Hosseinian, A.; Ghashang, M. Arkivoc 2009, ii, 59; (f)
Mosaddegh, E.; Hassankhani, A. Tetrahedron Lett. 2011, 52, 488.
21. (a) Shaterian, H. R.; Khorami, F.; Amirzadeh, A.; Doostmohammadi, R.;
Ghashang, M. J. Iran. Chem. Res. 2009, 2, 57; (b) Fazaeli, R.; Aliyan, H.; Fazaeli,
N. Open Catal. J. 2010, 3, 14; (c) Sabitha, G.; Srinivas, C.; Raghavendar, A.; Yadav,
J. S. Helv. Chim. Acta 2010, 93, 1375; (d) Ghorbani-Vaghei, R.; Karimi-Nami, R.;
Toghraei-Semiromi, Z.; Amiri, M.; Ghavidel, M. Tetrahedron 2011, 67, 1930; (e)
Wang, X.; Ma, W.-W.; Wu, L.-Q.; Yan, F.-L. J. Chin. Chem. Soc. 2010, 57, 1341.
6a:
2-Acetyl-3-methyl-1-(4-nitrophenyl)-1H-pyrazolo[1,2-b]phthalazine-5,10-
dione: 1H NMR (CDCl3, 300 MHz):
d
8.38–8.35 (m, 1H, ArH), 8.21 (d,
J = 8.7 Hz, 3H, ArH), 7.86–7.83 (m, 2H, ArH), 7.65 (d, J = 8.7 Hz, 2H, ArH), 6.55
(s, 1H, CH), 3.09 (s, 3H, COCH3), 2.23 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): d
192.0, 156.0, 153.9, 147.6, 146.0, 143.6, 134.3, 133.6, 129.1, 128.8, 128.0, 127.9,
127.0, 123.7, 119.1, 65.0, 30.5, 14.6. IR (KBr):
m = 2924, 1662, 1616, 1521, 1351,
1310 cmÀ1. ESI MS (m/z): 378 [M++1]. Anal. Calcd for C20H15N3O5 (377.3): C,
63.66; H, 4.01; N 11.14%. Found: C, 63.78; H, 4.12; N, 11.01%. Compound 6b: 2-
Benzoyl-3-phenyl-1-p-tolyl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione: 1H NMR
(CDCl3, 300 MHz): d 8.28–8.22 (m, 2H, ArH), 7.84–7.75 (m, 2H, ArH), 7.44 (d,
J = 7.8 Hz, 2H, ArH), 7.35–7.31 (m, 4H, ArH), 7.21–7.13 (m, 6H, ArH), 7.07–7.02
(m, 2H, ArH), 6.83 (s, 1H, CH), 2.27 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): d
192.8, 154.7, 142.4, 138.6, 137.2, 134.0, 133.5, 133.4, 132.0, 130.0, 129.8, 129.6,
128.8, 128.5, 127.9, 127.7, 127.5, 127.4, 127.0, 123.2, 68.1, 21.2. IR (KBr):
m
= 3046, 2925, 2856, 1739, 1662, 1412, 1339 cmÀ1. ESI MS (m/z): 471 [M++1].
Anal. Calcd for C31H22N2O3 (470.5): C, 79.13; H, 4.71; N 5.95%. Found: C, 79.24;
H, 4.82; N, 6.01%.