A rapid and an efficient route to the one-pot, multicomponent synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione ring systems

Article abstract of DOI:10.1002/jhet.1809

CAN is found to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives via one-pot coupling reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate in PEG as solvent. The major attributes of this synthetic protocol are the use of nontoxic, inexpensive, and readily available catalyst, mild conditions, easy work up, improved yields, and the PEG 400 as solvent that is environmentally benign as well as recyclable.

Full text of DOI:10.1002/jhet.1809

Month 2014 A Rapid and an Efficient Route to the One-pot, Multicomponent Synthesis
of 1H-Pyrazolo[1,2-b]phthalazine-5,10-dione Ring Systems
*
Mazaahir Kidwai and Ritika Chauhan
Green Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India
*
E-mail: kidwai.chemistry@gmail.com
Received January 28, 2012
DOI 10.1002/jhet.1809
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
O
O
O
O
NH2
Ar
NH2
N
N
N
N
N
NC
H
COOEt
NC
CN
3b
3a
COOEt
CN
ArCHO
+
N H
CAN (5 mol%)
PEG 400
CAN (5 mol%)
PEG 400
1
2a-2u
Ar
O
O
5a-5t
4a-4t
CAN is found to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
derivatives via one-pot coupling reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl
cyanoacetate in PEG as solvent. The major attributes of this synthetic protocol are the use of nontoxic,
inexpensive, and readily available catalyst, mild conditions, easy work up, improved yields, and the PEG
400 as solvent that is environmentally benign as well as recyclable.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
compound, CAN has been explored as a powerful catalyst
for a variety of organic reactions [23].
The rapid assembly of molecular diversity utilizing
multicomponent reaction (MCRs) has received a great deal
of attention, most notably for the construction of heterocyclic
“drug-like” libraries [1–3]. These methodologies prove
useful particularly when they lead to the formation of
privileged medicinal heterocyclic scaffolds. Nitrogen-
containing heterocyclic compounds are widespread in
nature, and their applications to biologically active pharma-
ceuticals, agrochemicals, and functional materials are gaining
prominence these days [4–6]. The development of new
efficient methods to synthesize N-heterocycles with structural
diversity is one of the major interests of modern synthetic
chemists [7–9]. Among a large variety of nitrogen-containing
heterocyclic compounds, heterocycles containing bridgehead
hydrazine have attracted immense attention because of
their pharmacological properties and clinical applications
[10–15]. Similarly, pyrazole ring is a key fragment in numer-
ous biologically active compounds [16–19]. Pyrazolo[1,2-b]
phthalazine derivatives are known to possess a wide range of
biological activities such as antihyperglycemic, antibacterial,
antiviral, anti-inflammatory, analgesic, antihypoxic, and
antipyretic activities [20,21]. So far, only a few methods
have been reported for the synthesis of 1H-pyrazolo[1,2-b]
phthalazine-diones [22]. Despite the available methods,
there is still a need to develop a green as well as a convenient
protocol for the efficient preparation of heterocycles
containing a phthalazine ring fragment.
The search for alternative reaction media to replace volatile
and often toxic solvents commonly used in organic
synthetic procedures is an important objective of significant
environmental consequence. With the aim of improving the
eco-sustainability of the fundamental organic trans-
formations, recently, PEG has attracted great interest as a
green and novel solvent for catalytic processes because it is
relatively inexpensive, essentially nontoxic, readily available,
and biodegradable material (PEG is approved for use in
beverages) [24]. Various kinds of research have been
reported involving PEG as a solvent or medium for
organic synthesis [25].
Because pyrazolo[1,2-b]phthalazine-dione derivatives are
important biologically active compounds, which have poten-
tial medical applications, improvement and the development
of a preparation of this type of compound by using CAN as a
catalyst in reusable solvent PEG 400 were worthy of study.
RESULTS AND DISCUSSION
In continuation of our interest towards the exploration of
the catalytic potential of CAN in organic synthesis [26], and
development of new greener synthetic methodologies [27],
herein, we wish to report a one-pot, multicomponent
synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
derivatives utilizing CAN as catalyst in PEG 400 as an
eco-safe and recyclable solvent (Scheme 1).
We carried out an initial study in search for the optimal
amount of CAN for the proposed transformation by using a
model reaction involving phthalhydrazide 1, benzaldehyde
2a, and malononitrile 3a, and the most significant data
The use of CAN has recently received considerable
attention as an inexpensive, nontoxic, commercially available
catalyst for various organic transformations to afford the
corresponding products in excellent yields. Because of the
numerous advantages associated with this eco-friendly
© 2014 HeteroCorporation

M. Kidwai and R. Chauhan
Vol 000
Scheme 1. CAN-mediated synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones.
O
NH2
O
N
N
N
H
CAN (5 mol%)
Y
+
ArCHO +
NC
Y
PEG 400, 50-80 min
N H
1
2a-2u
3a-3b
3a Y = CN
3b Y = COOEt
Ar
O
O
4a-4t
5a-5t
Y = CN
Y = COOEt
obtained is summarized in Fig. 1. It was observed that the
yield of the final product increased with increasing amount
of catalyst in the reaction mixture. The best result was
obtained with 5 mol% of CAN, which gave the desired
product in 92% yield after 50 min at 45ꢀC. Further increase
in the amount of CAN to 10 mol% decreased the product
yield to 74%. A possible explanation for the low product
yields is that the starting material or the product may have
been destroyed during the reaction when excess amount
(10 mol%) of CAN was used in the reaction [26].
We also investigated the role of solvents on the synthesis
of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives by
using CAN as a catalyst. Among the various solvents, PEG
400 was found out to be the most appropriate solvent for this
transformation and gave excellent yields (Table 1, entry 8).
To study the effect of temperature on this reaction, we also
screened a range of temperatures for the model reaction, and
the results are summarized in Table 2. Faster reactions
occurred on increasing the reaction temperature, but the
product yield decreased at high temperature because one of
the reactants got oxidized at high temperature in the presence
of CAN [26]. We found out that the reaction proceeded
smoothly, and almost complete conversion of the product
was observed at 45ꢀC, affording 4a in 92% yield within
shorter time (Table 2, entry 2).
To explore the scope and limitation of this reaction, we
applied the optimized conditions and extended the reaction
of phthalhydrazide 1 with a range of aromatic aldehydes
2a–2u and malononitrile 3a and ethyl cyanoacetate 3b
(Scheme 1) furnishing the respective 1H-pyrazolo[1,2-b]
phthalazine-5,10-diones (4a–4t, 5a–5t) in good to excellent
yields (Table 3). The results were excellent in terms of yields
and product purity by using aromatic aldehydes carrying
electron-donating or electron-withdrawing substituents in
the presence of CAN. Moreover, heterocyclic carbaldehydes
were also well tolerated in the reaction and gave good results
(Table 3, entries 18, 19, 20, 38, 39, and 40). Aliphatic
Table 1
Effect of various solvents on the synthesis of 1H-pyrazolo[1,2-b]phthalazine-
5,10-dione derivatives.a
Entry
Solvent (x)
MeOH
EtOH
THF
Toluene
MeCN
Ethylene glycol
PEG 200
PEG 400
PEG 600
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
100
90
82
84
62
46
78
67
90
92
92
450
480
150
300
60
50
50
aReaction conditions: phthalhydrazide 1 (1 mmol), benzaldehyde 2a
(1 mmol), malononitrile 3a (1 mmol); catalyst: CAN (5 mol%); tempera-
ture: 45ꢀC; solvent: x (2 mL).
bIsolated yields.
Table 2
Effect of temperature.a
Entry
Temp (ꢀC)
Time (min)
Yield (%)b
1
2
3
4
25
45
60
80
540
50
40
54
92
80
72
40
aReaction conditions: phthalhydrazide 1 (1 mmol), benzaldehyde 2a
(1 mmol), malononitrile 3a (1 mmol); catalyst: CAN (5 mol%); tempera-
ture: (ꢀC); solvent: PEG 400 (2 mL).
Figure 1. Catalytic activity evaluation of CAN for synthesis of 1H-pyrazolo
[1,2-b]phthalazine-diones. Reaction conditions: phthalhydrazide 1 (1 mmol),
benzaldehyde 2a (1 mmol), malononitrile 3a (1 mmol); catalyst: CAN
a
(mol%); temperature: 45ꢀC; solvent: PEG 400 (2mL). Isolated yields.
bIsolated yields.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Rapid and an Efficient Route to the One-Pot, Multicomponent Synthesis
of 1H-Pyrazolo[1,2-b]phthalazine-5,10-dione Ring Systems
Table 3
CAN promoted synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones.a
S. No.
Ar
Y
Product
Time (min)
mp (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
C6H5 (2a)
CN (3a)
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
4a
4b
4c
4d
4e
4f
4g
4h
4i
50
50
60
60
60
50
70
75
70
65
65
60
50
60
55
50
65
60
70
75
50
60
60
70
60
60
80
75
70
70
60
55
60
65
60
60
60
50
65
65
274–276 [22b]
190–194 [22b]
120–124 [22b]
258–262 [22b]
266–268 [22e]
266–270 [22b]
256–260 [22e]
264–266 [22e]
160–164 [22b]
130–134 [22b]
172–174
232–236
292–296
294–296
120–124
152–154
182–184
192–194
>300
254–258 [22d]
112–116 [22e]
202–206 [22b]
146–150
236–240 [22b]
210–214 [22e]
166–170 [22e]
198–202 [22e]
234–238 [22e]
236–238 [22b]
244–246 [22b]
166–170
222–226
>300
5198–202
182–186
286–290
134–138
246–250
272–274
92
92
90
87
89
90
86
85
86
88
87
90
91
88
86
84
85
88
86
86
92
92
87
86
89
90
88
85
87
89
86
91
90
88
85
85
87
86
88
90
4-Me-C6H4 (2b)
4-MeO-C6H4 (2c)
2-Cl-C6H4 (2d)
3-Cl-C6H4 (2e)
4-Cl-C6H4 (2f)
4-Br-C6H4 (2g)
2-NO2-C6H4 (2h)
3-NO2-C6H4 (2i)
4-NO2-C6H4 (2j)
2-HO-C6H4 (2k)
3-HO-C6H4 (2l)
4-HO-C6H4 (2m)
4-Me2N-C6H4 (2n)
C6H5-CH═CH (2o)
2-HO-3-MeO-C6H3 (2p)
1-Naphthyl (2q)
Piperonyl (2r)
2-Furanyl (2s)
2-Thienyl (2t)
C6H5
4-Me-C6H4
4-MeO-C6H4
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-Br-C6H4
2-NO2-C6H4
3-NO2-C6H4
4-NO2-C6H4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
CN
CN
CN
COOEt (3b)
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
2-HO-C6H4
3-HO-C6H4
4-HO-C6H4
4-Me2N-C6H4
C6H5-CH═CH
4-HO-3-MeO-C6H3 (2u)
1-Naphthyl
Piperonyl
2-Furanyl
5m
5n
5o
5p
5q
5r
5s
5t
2-Thienyl
>300 [22d]
aReaction conditions: phthalhydrazide 1 (1 mmol), aromatic aldehyde 2a–2u (1 mmol), malononitrile 3a or ethyl cyanoacetate 3b (1 mmol); catalyst: CAN
(5 mol%); temperature: 45ꢀC; solvent: PEG 400 (2 mL).
bIsolated yields.
aldehydes were also utilized for the synthesis of 1H-pyrazolo
[1,2-b]phthalazine-5,10-diones. Unfortunately, the catalyst
was inactive for aliphatic substrates under the same reaction
conditions, whereas without CAN, the reaction took longer
time to complete (14 h) and gave only 38% of the desired
product. (Fig. 1, Entry 1)
All the products (4a–4t, 5a–5t) are stable solids and
whose structures have been successfully deduced from
their IR, 1H NMR, 13C NMR, and elemental analysis data.
The mechanistic aspect of the reaction involves the initial
formation of intermediate (6) by standard Knoevenagel
condensation of the malononitrile 3a or ethyl cyanoacetate
3b and aldehyde 2a–2u, which is followed by subsequent
Michael-type addition of the phthalhydrazide (1) to the
intermediate (6), which then undergoes cyclization and
tautomerization to afford the corresponding products 4a–4t,
5a–5t (Scheme 2). To prove the reaction mechanism, a
separate reaction of the Knoevenagel condensation product
(6) and phthalhydrazide (1) was also run in parallel to the
present model reaction. Both reactions gave the same
product under the same reaction conditions, so both reaction
pathways gave the same product.
Recycling experiments were also performed for the model
reaction to establish the economic viability of solvent PEG
400, and the results are illustrated in Fig. 2. After completion
of the reaction, the reaction mixture was kept in dry ice
acetone bath to freeze the PEG and was extracted with
ether (PEG being insoluble in ether). PEG 400 could be
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Kidwai and R. Chauhan
Vol 000
Scheme 2. Suitable mechanism for the formation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones.
O
N
N
H
H
O
O
N
Y
H
CN
Y
N
N
H
(1)
-H2O
O
Ar
+
Y
H
CN
Ar
(6)
2a-2u
3a-3b
O
O
Ar
O
NH2
NH
Ar
N
N
N
N
Tautomerization
Y
Y
Ar
O
O
4a-4t, 5a-5t
be successfully recycled for at least three runs with consistent
results. This method is quite simple, high yielding, time
saving, and most importantly an eco-friendly process.
EXPERIMENTAL
Materials and methods.
All chemicals were purchased
from Sigma-Aldrich (St. Louis, MO) and were used as such
without further purification. All reactions and purity of 1H-
pyrazolo[1,2-b]phthalazine-5,10-dione derivatives were monitored
by TLC using aluminium plates coated with silica gel F254 plates
(Merck) (Darmstadt, Germany) using 40% ethyl acetate and 60%
hexane as an eluent. The spots were detected either under UV
light or by placing in iodine chamber. Melting points were
determined using a Thomas Hoover melting point apparatus
(SECOR India Laboratory instruments, Delhi, India) and are
uncorrected. IR spectra were recorded on a Perkin-Elmer FTIR-
Figure 2. Recyclability of the solvent PEG 400. Reaction conditions:
phthalhydrazide 1 (1 mmol), benzaldehyde 2a (1 mmol), malononitrile
3a (1 mmol); catalyst: CAN (5 mol%); temperature: 45ꢀC; solvent: PEG
400 (2mL).aIsolated yields.
1
1710 spectrophotometer using KBr pellets/nujol film. H and 13C
NMR spectra were recorded on a JEOL JNM-ECX 400P FT
NMR spectrometer using TMS as an internal standard, and the
value of chemical shifts are recorded on the d scale, and coupling
constants (J) values are in hertz (Hz). Elemental analysis was
performed on a Hereaus CHN rapid analyzer. The temperature of
the reaction mixture was measured through a noncontact infrared
minigun thermometer (AZ minigun type, model 8868) (Shenzhen
Laesent Technology Co. Ltd., Guangdong, China).
successfully recycled up to three runs, and the yields of the
products were also comparable. Although a weight loss of
~4%–5% was observed from cycle to cycle because of me-
chanical loss, the percentages of PEG 400 recycled in each
run were 100%, 97%, 92%, and 88% for fresh, Run 1, Run
2, and Run 3, respectively.
General procedure for the synthesis of 1H-pyrazolo[1,2-b]
phthalazine-5,10-dione derivatives. In a 50 mL round-bottom
flask, 1 equiv. each of phthalhydrazide 1, aromatic aldehyde
(ArCHO) 2a–2u, and malononitrile 3a or ethyl cyanoacetate 3b in
PEG 400 (2 mL) were mixed and stirred at 45ꢀC. To this, CAN
(5 mol%) was added and stirred for the appropriate time as
indicated in Table 3. The progress of the reaction was monitored
by TLC. To recycle PEG 400, after completion of the reaction, the
reaction mixture was cooled with a dry ice–acetone bath to
precipitate the PEG 400 and was extracted with ether (PEG being
insoluble in ether). Thus, the PEG 400 remained as such and
CONCLUSION
In summary, we have developed an expedient and a
clean protocol for the synthesis of 1H-pyrazolo[1,2-b]
phthalazine-5,10-dione derivatives via cyclocondensation
of aldehyde, malononitrile, or ethyl cyanoacetate and
phthalhydrazide The one-pot nature and the use of CAN
as an eco-friendly catalyst make it an interesting alternative
to multistep approaches. Also, the solvent PEG 400 could
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Rapid and an Efficient Route to the One-Pot, Multicomponent Synthesis
of 1H-Pyrazolo[1,2-b]phthalazine-5,10-dione Ring Systems
which was then used for the subsequent reactions. The ether layer
was decanted, dried, and concentrated under reduced pressure. The
crude product thus obtained was subjected to purification by
column chromatography on silica gel (100–200 mesh size) using
hexane/ethyl acetate in varying proportions as eluent, which
afforded the respective 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
derivatives, 4a–4t, 5a–5t. The recovered PEG 400 was reused for
the consecutive runs. All the synthesized products were stable
solids, and their structures were established on the basis of their
spectral analysis (IR, 1H NMR, and 13C NMR) and elemental
analysis data and melting point determination. The spectral data for
synthesized compounds are listed in the following.
7.35–7.71 (m, 4H, Ar–H), 7.82–7.85 (m, 2H), 8.23–8.33 (m, 2H);
13C NMR (CDCl3, 100 MHz) d: 54.9, 81.8, 113.1, 126.9, 128.7,
128.9, 131.4, 131.7, 133.3, 140.0, 149.9, 158.5, 163.4, 165.5;
Anal. Calcd for C18H11ClN4O2: C, 61.64; H, 3.16; N, 15.97;
found: C, 61.50; H, 2.97; N, 15.68.
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-bromophenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4g).
Light brown
solid, IR (nmax, nujol) 3367, 3312, 2921, 2190, 1694, 1581 cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 6.19 (s, 1H, Ar–CH), 6.75
(br s, 2H, NH2), 7.35–7.72 (m, 4H, Ar–H), 8.05–8.09 (m, 2H),
8.25–8.36 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 52.7, 69.7,
119.2, 121.2, 125.7, 129.3, 130.0, 131.4, 132.4, 142.4, 158.7,
162.7, 165.8; Anal. Calcd for C18H11BrN4O2: C, 54.70; H, 2.81;
N, 14.18; found: C, 54.57; H, 2.74; N, 13.84.
Spectral data for the synthesized compounds. 3-Amino-5,
10-dihydro-5,10-dioxo-1-phenyl-1H-pyrazolo[1,2-b]phthalazine-2-
carbonitrile (4a). Light yellow solid, IR (nmax, KBr) 3361, 3165,
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-nitrophenyl)-1H-
1
3014, 2198, 1661, 1492 cmÀ1; H NMR (CDCl3, 400 MHz, TMS)
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4h).
Yellow solid,
IR (nmax, KBr) 3385, 3188, 2915, 2213, 1698, 1658 cmÀ1
;
1H
d: 6.22 (s, 1H, Ar–CH), 6.66 (br s, 2H, NH2), 7.35–7.77
(m, 5H, Ar–H), 7.89–7.91 (m, 2H), 8.26–8.33 (m, 2H); 13C NMR
(CDCl3, 100 MHz) d: 57.4, 82.9, 113.5, 126.6, 127.4, 129.6,
130.7, 130.9, 134.6, 142.6, 159.9, 162.3, 166.0; Anal. Calcd for
C18H12N4O2: C, 68.35; H, 3.82; N, 17.71; found: C, 68.20; H,
3.60; N, 17.58.
NMR (CDCl3, 400 MHz, TMS) d: 6.52 (s, 1H, Ar–CH), 6.95
(br s, 2H, NH2), 7.53–7.91 (m, 4H, Ar–H), 7.94–7.96 (m, 2H),
8.20–8.30 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 51.6, 78.8,
114.4, 122.8, 126.2, 126.7, 128.3, 129.4, 130.1, 132.4, 136.6,
142.8, 150.7, 158.8, 161.2; Anal. Calcd for C18H11N5O4:
C, 59.84; H, 3.07; N, 19.38; found: C, 59.72; H, 2.92; N, 19.24.
3-Amino-5,10-dihydro-5,10-dioxo-1-(3-nitrophenyl)-1H-
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-methylphenyl)-1H-pyrazolo
[1,2-b]phthalazine-2-carbonitrile (4b).
Light yellow solid, IR
(nmax, KBr) 3368, 3035, 2919, 2225, 1674, 1652cmÀ1; H NMR
(CDCl3, 400 MHz, TMS) d: 2.43 (s, 3H, CH3), 6.17 (s, 1H, Ar–CH),
6.67 (br s, 2H, NH2), 7.30–7.70 (m, 4H, Ar–H), 7.77–7.80
(m, 2H), 8.23–8.32 (m, 2H); 13C NMR (CDCl3, 100MHz) d: 22,
57.2, 81.2, 114, 127, 127.4, 128.4, 130.4, 130.9, 136.5, 146.4,
159.7, 162.7, 166.1; Anal. Calcd for C19H14N4O2: C, 69.08;
H, 4.27; N, 16.96; found: C, 68.98; H, 4.14; N, 16.80.
1
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4i).
Yellow solid, IR
(nmax, nujol) 3348, 3221, 2920, 2232, 1702, 1617, 1533, 1351 cmÀ1
;
1H NMR (CDCl3, 400 MHz, TMS) d: 6.74 (s, 1H, Ar–CH),
7.53–7.72 (m, 4H, Ar–H), 8.09 (br s, 2H, NH2), 8.59–8.61
(m, 2H), 8.64–8.71 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 52.3, 62.5, 114.2, 121.6, 122.5, 127.7, 128.6, 131.6, 132.3,
133.5, 137.5, 148.5, 157.1, 162.0, 164.3; Anal. Calcd for
C18H11N5O4: C, 59.84; H, 3.07; N, 19.38; found: C, 59.74; H,
2.95; N, 19.24.
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-methoxyphenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4c). Yellow solid,
IR (nmax, KBr) 3372, 3264, 2898, 2224, 1660, 1605cmÀ1 1H
;
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-nitrophenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4j). Yellow solid, IR
(nmax, nujol) 3403, 3238, 2915, 2193, 1718, 1658, 1522 cmÀ1; 1H
NMR (CDCl3, 400 MHz, TMS) d: 6.39 (s, 1H, Ar–CH), 6.65
(br s, 2H, NH2), 7.56–7.88 (m, 4H, Ar–H), 7.96–7.99 (m, 2H),
8.16–8.27 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 52.6, 60.1,
117.2, 122.7, 126.4, 128.3, 131.4, 132.9, 145.3, 147.5, 155.2,
162.3, 164.5; Anal. Calcd for C18H11N5O4: C, 59.84; H, 3.07;
N, 19.38; found: C, 59.75; H, 3.10; N, 19.32.
NMR (CDCl3, 400 MHz, TMS) d: 3.91 (s, 3H, OCH3), 6.21
(s, 1H, Ar–CH), 6.91 (br s, 2H, NH2), 7.00–7.65 (m, 4H, Ar–H),
7.90–7.92 (m, 2H), 8.25–8.34 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 54.3, 62.6, 86.4, 113.9, 114.4, 127.1, 128.0, 132.0, 132.9,
134.1, 158.9, 160.0, 161.9, 164.3; Anal. Calcd for C19H14N4O3:
C, 65.89; H, 4.07; N, 16.18; found: C, 65.72; H, 3.95; N, 16.10.
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-chlorophenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4d).
Yellow
solid, IR (nmax, KBr) 3372, 3160, 2224, 1678, 1634 cmÀ1; H
NMR (CDCl3, 400 MHz, TMS) d: 6.41 (s, 1H, Ar–CH), 6.84
(br s, 2H, NH2), 7.31–7.65 (m, 4H, Ar–H), 7.85–7.88 (m, 2H),
8.20–8.32 (m, 2H); 13C NMR (CDCl3, 100MHz) d: 54.6, 79.6,
114.2, 126.8, 127.3, 127.8, 128.6, 129.2, 131.8, 132.4, 133.6,
143.6, 151.6, 162.7, 165.5; Anal. Calcd for C18H11ClN4O2: C,
61.64; H, 3.16; N, 15.97; found: C, 61.47; H, 3.00; N, 15.72.
3-Amino-5,10-dihydro-5,10-dioxo-1-(3-chlorophenyl)-1H-
1
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-hydroxyphenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4k).
Brown solid,
IR (nmax, KBr) 3427, 3306, 2903, 2210, 1656, 1612 cmÀ1; H
NMR (CDCl3, 400 MHz, TMS) d: 6.14 (s, 1H, Ar–CH), 6.62–6.97
(m, 4H, Ar–H), 7.75 (br s, 2H, NH2), 7.86–7.90 (m, 2H), 8.22–8.30
(m, 2H), 10.86 (br s, 1H, OH); 13C NMR (CDCl3,
100 MHz) d: 51.3, 82.6, 115.6, 118.7, 119.2, 126.5, 127.2,
127.8, 131.8, 132.3, 134.6, 148.4, 158.8, 160.7; Anal. Calcd
for C18H12N4O3: C, 65.06; H, 3.64; N, 16.86; found: C,
64.93; H, 3.51; N, 16.74.
1
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4e).
Yellow solid,
;
IR (nmax, KBr) 3366, 3190, 2217, 1674, 1646cmÀ1
1H NMR
3-Amino-5,10-dihydro-5,10-dioxo-1-(3-hydroxyphenyl)-1H-
(CDCl3, 400MHz, TMS) d: 6.24 (s, 1H, Ar–CH), 6.72 (br s, 2H,
NH2), 7.36–7.70 (m, 4H, Ar–H), 7.83–7.86 (m, 2H), 8.22–8.32
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 54.3, 81.4, 114.6,
124.8, 125.5, 126.9, 127.2, 128.8, 130.8, 131.6, 132.7, 141.6,
149.8, 159.3, 163.5; Anal. Calcd for C18H11ClN4O2: C, 61.64;
H, 3.16; N, 15.97; found: C, 61.46; H, 2.95; N, 15.75.
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-chlorophenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4f). Yellow solid, IR
(nmax, KBr) 3376, 3094, 2229, 1652, 1586 cmÀ1; 1H NMR (CDCl3,
400 MHz, TMS) d: 6.18 (s, 1H, Ar–CH), 6.69 (br s, 2H, NH2),
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4l).
Light brown
solid, IR (nmax, KBr) 3371, 3267, 2897, 2193, 1661, 1603 cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 3.64 (br s, 1H, OH), 6.17
(s, 1H, Ar–CH), 6.68–7.02 (m, 4H, Ar–H), 7.72 (br s, 2H, NH2),
7.87–7.91 (m, 2H), 8.27À8.36 (m, 2H); 13C NMR (CDCl3,
100 MHz) d: 61.6, 63.1, 113.5, 115.7, 117.3, 119.6, 125.2, 127.5,
129.5, 132.2, 133.6, 143, 156.5, 157.5, 160.1, 163.7; Anal. Calcd
for C18H12N4O3: C, 65.06; H, 3.64; N, 16.86; found: C, 64.97;
H, 3.43; N, 16.77.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Kidwai and R. Chauhan
Vol 000
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-hydroxyphenyl)-1H-
pyrazolo[1,2-b]phthalazine-2-carbonitrile (4m). Off white solid,
IR (nmax, KBr) 3418, 3284, 2868, 2187, 1643, 1593 cmÀ1; 1H NMR
(DMSO-d6, 400 MHz, TMS) d: 6.18 (s, 1H, Ar–CH), 6.70–7.08 (m,
4H, Ar–H), 7.67 (br s, 2H, NH2), 7.84–7.86 (m, 2H), 8.23–8.32 (m,
2H), 10.60 (br s, 1H, OH); 13C NMR (DMSO-d6, 100 MHz) d: 54.2,
81.8, 116.7, 119.2, 126.7, 128.4, 129.6, 129.9, 132.4, 146.5, 157.3,
160.2, 164.8; Anal. Calcd for C18H12N4O3: C, 65.06; H, 3.64; N,
16.86; found: C, 64.91; H, 3.48; N, 16.75.
Ar–H), 7.46 (br s, 2H, NH2), 7.80–7.84 (m, 2H), 8.14–8.23
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 58.1, 82.3, 107.6,
113.7, 118.2, 127.2, 128.6, 129.7, 137.6, 143.5, 151.4, 158.2,
162.3; Anal. Calcd for C16H10N4O3: C, 62.74; H, 3.29; N,
18.29; found: C, 62.62; H, 3.16; N, 18.18.
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-thienyl)-1H-pyrazolo
[1,2-b]phthalazine-2-carbonitrile (4t). Green solid, IR (nmax, KBr)
3423, 3164, 2890, 2210, 1654, 1587 cmÀ1 1H NMR (CDCl3,
;
400 MHz, TMS) d: 6.10 (s, 1H, Ar–CH), 6.77–6.95 (m, 3H, Ar–H),
3-Amino-5,10-dihydro-5,10-dioxo-1-(4-dimethylaminophenyl)-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4n). Orange
7.54 (br s, 2H, NH2), 7.78–7.84 (m, 2H), 8.20–8.32 (m, 2H); 13
C
NMR (CDCl3, 100 MHz) d: 56.7, 83.2, 113.8, 122.8, 124.1,
125.7, 127.7, 129.6, 131.3, 136.5, 144.8, 153.9, 158.0; Anal.
Calcd for C16H10N4O2S: C, 59.62; H, 3.13; N, 17.38; found: C,
59.50; H, 3.06; N, 17.31.
solid, IR (nmax, KBr) 3329, 3186, 2896, 2211, 1661, 1615cmÀ1
;
1H NMR (CDCl3, 400 MHz, TMS) d: 3.06 (s, 6H, 2 Â CH3), 6.24
(s, 1H, Ar–CH), 6.63–6.96 (m, 4H, Ar–H), 7.60 (br s, 2H, NH2),
7.82–7.86 (m, 2H), 8.25–8.33 (m, 2H); 13C NMR
(CDCl3, 100 MHz) d: 49.3, 54.8, 81.4, 114.2, 116.3, 127.8,
128.6, 129.4, 131.6, 133.7, 139.1, 147.6, 158.3, 162.7; Anal.
Calcd for C20H17N5O2: C, 66.84; H, 4.77; N, 19.49; found: C,
66.75; H, 4.70; N, 19.37.
Ethyl-3-amino-5,10-dihydro-1-phenyl-5,10-dioxo-1H-pyrazolo
[1,2-b]phthalazine-2-carboxylate (5a). Yellow solid, IR (nmax, nujol)
3449, 3020, 2917, 2227, 1727, 1673, 1655, 1598 cmÀ1; 1H NMR
3
(CDCl3, 400MHz, TMS) d: 1.38 (t, 3H, JHH = 7.30 Hz, CH3),
3
4.37 (q, 2H, JHH = 7.30Hz, OCH2), 6.24 (s, 1H, Ar–CH), 6.84
3-Amino-5,10-dihydro-5,10-dioxo-1-(styryl)-1H-pyrazolo[1,2-
b]phthalazine-2-carbonitrile (4o). Brown solid, IR (nmax, nujol)
3327, 3170, 2918, 2226, 2197, 1684, 1606, 1577cmÀ1; 1H NMR
(CDCl3, 400 MHz, TMS) d: 6.22 (m, 1H, Ar–CH), 6.92 (m, 1H),
7.03 (d, 1 H, J = 15.2 Hz), 7.36–7.62 (m, 5H, Ar–H), 7.76 (br s,
2H, NH2), 7.86–7.91 (m, 2H), 8.26–8.37 (m, 2H); 13C NMR
(CDCl3, 100 MHz) d: 60.3, 69.7, 113.1, 121.7, 126.6, 127.7,
128.4, 128.7, 131.5, 132.3, 133.4, 160.0, 162.6, 164.7; Anal.
Calcd for C20H14N4O2: C, 70.17; H, 4.12; N, 16.37; found: C,
70.06; H, 4.02; N, 16.22.
(br s, 2H, NH2), 7.33–7.56 (m, 5H, Ar–H), 7.96–7.98 (m, 2H),
8.23–8.28 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 12.9, 59.2,
61.3, 69.0, 124.1, 127.1, 128.0, 129.6, 131.0, 132.1, 142.4, 149.5,
160.8, 165.0, 165.4; Anal. Calcd for C20H17N3O4: C, 66.11;
H, 4.72; N, 11.56; found: C, 66.03; H, 4.63; N, 11.40.
Ethyl-3-amino-5,10-dihydro-1-(4-methylphenyl)-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5b).
Yellow
solid, IR (nmax, nujol) 3442, 3310, 3284, 2919, 2219, 1722,
1667, 1632 cmÀ1
;
1H NMR (CDCl3, 400 MHz, TMS) d: 1.39
3
(t, 3H, JHH = 7.30 Hz, CH3), 2.43 (s, 3H, CH3), 4.38 (q, 2H,
3JHH = 7.30 Hz, OCH2), 6.25 (s, 1H, Ar–CH), 7.30–7.54
(m, 4H, Ar–H), 7.89–7.91 (m, 2H), 8.04 (br s, 2H, NH2), 8.22–8.30
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 13.8, 21.5, 62.2, 70.0,
101.1, 127.2, 128.4, 128.6, 129.7, 130.8, 135.7, 144.3, 154.6,
162.3, 164.7, 165.8; Anal. Calcd for C21H19N3O4: C, 66.83;
H, 5.07; N, 11.13; found: C, 66.59; H, 4.90; N, 10.91.
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-hydroxy-3-methoxyphenyl)-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4p). Dark green
solid, IR (nmax, nujol) 3333, 3171, 2897, 2202, 1735, 1654, 1567 cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 6.07 (s, 1H, Ar–CH), 3.65
(s, 3H, OCH3), 7.04 (br s, 2H, NH2), 7.15–7.35 (m, 3H, Ar–H),
7.76–7.83 (m, 2H), 8.24 (br s, 1H, OH), 8.40–8.44 (m, 2H);
13C NMR (CDCl3, 100 MHz) d: 47.5, 55.6, 60.5, 116.0, 119.7,
119.9, 120.2, 127.5, 131.0, 131.7, 132.2, 141.5, 147.3, 158.3,
160.2, 165.4; Anal. Calcd for C19H14N4O4: C, 62.98; H, 3.89;
N, 15.46; found: C, 62.84; H, 3.76; N, 15.32.
Ethyl-3-amino-5,10-dihydro-1-(4-methoxyphenyl)-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5c). Yellow solid,
IR (nmax, nujol) 3387, 3156, 2916, 2254, 1774, 1723, 1594 cmÀ1; 1H
NMR (CDCl3, 400 MHz, TMS) d: 1.36 (t, 3H, 3JHH =7.30Hz, CH3),
3
3-Amino-5,10-dihydro-5,10-dioxo-1-(1-naphthyl)-1H-pyrazolo
[1,2-b]phthalazine-2-carbonitrile (4q). Yellow solid, IR (nmax, nujol)
3.86 (s, 3H, OCH3), 4.34 (q, 2H, JHH = 7.30 Hz, OCH2), 6.26
(s, 1H, Ar–CH), 6.89–7.74 (m, 4H, Ar–H), 7.80–7.84 (m, 2H),
8.14 (br s, 2H, NH2), 8.24–8.34 (m, 2H); 13C NMR
(CDCl3, 100MHz) d: 13.4, 54.8, 60.3, 98.3, 114.0, 122.2, 123.4,
131.1, 133.1, 153.5, 162.1, 163.0, 163.7, 168.6; Anal. Calcd for
C21H19N3O5: C, 64.12; H, 4.87; N, 10.68; found: C, 64.17;
H, 4.79; N, 10.62.
3432, 3110, 2925, 2227, 1667, 1566 cmÀ1 1H NMR (CDCl3,
;
400 MHz, TMS) d: 6.15 (s, 1H, Ar–CH), 7.65 (br s, 2H, NH2),
7.32–7.94 (m, 7H, Ar–H), 7.98–8.02 (m, 2H), 8.18–8.26
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 54.6, 85.3, 115.2,
122.4, 124.6, 124.9, 125.3, 125.8, 126.2, 127.4, 128.5, 130.8,
131.3, 132.6, 135.8, 137.6, 154.7, 158.4, 163.4; Anal. Calcd
for C22H14N4O2: C, 72.12; H, 3.85; N, 15.29; found: C, 72.04;
H, 3.72; N, 15.20.
Ethyl-3-amino-5,10-dihydro-1-(2-chlorophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5d). Yellow solid, IR
(nmax, KBr) 3430, 3310, 3126, 2930, 2253, 1778, 1732, 1695,
1654, 1633 cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 1.36
3-Amino-5,10-dihydro-5,10-dioxo-1-(1-benzo[1,3]-dioxol-5-yl)-
1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4r). Yellow solid,
3
3
(t, 3H, JHH = 7.30 Hz, CH3), 4.35 (q, 2H, JHH = 7.32 Hz,
OCH2), 6.18 (s, 1H, Ar–CH), 6.84–7.42 (m, 4H, Ar–H), 7.81
(br s, 2H, NH2), 7.88–7.92 (m, 2H), 8.18–8.26 (m, 2H); 13C
NMR (CDCl3, 100 MHz) d: 13.5, 46.2, 61.3, 72.5, 125.8,
126.2, 126.9, 128.2, 128.8, 129.1, 130.3, 132.6, 140.4, 147.4,
155.3, 159.7, 162.8; Anal. Calcd for C20H16ClN3O4: C, 60.38;
H, 4.05; N, 10.56; found: C, 60.22; H, 3.91; N, 10.41.
IR (nmax, KBr) 3448, 2923, 2227, 1654, 1571 cmÀ1 1H NMR
;
(CDCl3, 400 MHz, TMS) d: 5.98 (s, 2H), 6.24 (s, 1H, Ar–CH),
6.76–6.92 (m, 3H, Ar–H), 7.82–7.85 (m, 2H), 8.14 (br s, 2H, NH2),
8.22–8.32 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 59.9, 81.8,
100.2, 109.3, 112.8, 115.6, 119.8, 125.4, 128.7, 129.6, 133.2,
137.8, 140.2, 147.6, 156.1, 160.2; Anal. Calcd for C19H12N4O4:
C, 63.33; H, 3.36; N, 15.55; found: C, 63.24; H, 3.26; N, 15.42.
3-Amino-5,10-dihydro-5,10-dioxo-1-(2-furanyl)-1H-pyrazolo
[1,2-b]phthalazine-2-carbonitrile (4s). Gray solid, IR (nmax, KBr)
Ethyl-3-amino-5,10-dihydro-1-(3-chlorophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5e). Yellow solid, IR
(nmax, nujol) 3453, 3342, 3066, 2926, 2244, 1704, 1669, 1648 cmÀ1
;
3352, 3165, 2896, 2224, 1661, 1560 cmÀ1
;
1H NMR (CDCl3,
1H NMR (CDCl3, 400 MHz, TMS) d: 1.32 (t, 3H, JHH =7.32Hz,
3
3
400 MHz, TMS) d: 6.17 (s, 1H, Ar–CH), 6.64–6.92 (m, 3H,
CH3), 4.34 (q, 2H, JHH =7.32Hz, OCH2), 6.10 (s, 1H, Ar–CH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Rapid and an Efficient Route to the One-Pot, Multicomponent Synthesis
of 1H-Pyrazolo[1,2-b]phthalazine-5,10-dione Ring Systems
7.12–7.56 (m, 4H, Ar–H), 7.74 (br s, 2H, NH2), 7.86–7.88
(m, 2H), 8.18–8.26 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 13.8, 54.1, 60.8, 72.3, 123.8, 125.3, 126.4, 127.1, 129.3,
131.2, 132.0, 134.2, 141.3, 149.0, 156.5, 158.7, 161.7; Anal.
Calcd for C20H16ClN3O4: C, 60.38; H, 4.05; N, 10.56; found:
C, 60.18; H, 3.89; N, 10.43.
6.16 (s, 1H, Ar–CH), 6.88–7.62 (m, 4H, Ar–H), 7.86–7.89 (m, 2H),
8.33–8.41 (m, 2H), 8.53 (br s, 2H, NH2), 11.01 (br s, 1H, OH);
13C NMR (CDCl3, 100 MHz) d: 13.7, 38.9, 69.6, 72.2, 114.8,
122.2, 127.2, 127.9, 128.6, 128.7, 129.1, 131.7, 152.9, 153.3,
156.6, 161.6, 168.5; Anal. Calcd for C20H17N3O5: C, 63.32;
H, 4.52; N, 11.08; found: C, 63.17; H, 4.39; N, 10.97.
Ethyl-3-amino-5,10-dihydro-1-(4-chlorophenyl)-5,10-dioxo-1H-
Ethyl-3-amino-5,10-dihydro-1-(3-hydroxyphenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5l). Yellow solid, IR
(nmax, nujol) 3467, 3286, 2872, 2226, 1725, 1655, 1624 cmÀ1; 1H
pyrazolo[1,2-b]phthalazine-2-carboxylate (5f).
Light brown
solid, IR (nmax, nujol) 3448, 3334, 3066, 2925, 2249, 1793, 1727,
1704, 1669, 1648cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS)
NMR (CDCl3, 400MHz, TMS) d: 1.33 (t, 3H, JHH = 6.6 Hz,
3
d: 1.34 (t, 3H, 3JHH = 7.32 Hz, CH3), 4.33 (q, 2H, JHH = 7.30Hz,
OCH2), 6.16 (s, 1H, Ar–CH), 7.07–7.69 (m, 4H, Ar–H), 7.77
(br s, 2H, NH2), 7.86–7.88 (m, 2H), 8.14–8.27 (m, 2H); 13C
NMR (CDCl3, 100 MHz) d: 13.9, 53.7, 62.7, 70.5, 127.4, 128.1,
129.3, 129.5, 132.0, 134.3, 148.6, 162.5, 163.0, 165.1, 168.0;
Anal. Calcd for C20H16ClN3O4: C, 60.38; H, 4.05; N, 10.56;
found: C, 60.20; H, 3.93; N, 10.44.
CH3), 4.31 (q, 2H, JHH = 6.6 Hz, OCH2), 6.16 (s, 1H, Ar–CH),
3
3
6.85–7.04 (m, 4H, Ar–H), 7.78 (br s, 2H, NH2), 7.85–7.88
(m, 2H), 8.22–8.32 (m, 2H), 9.88 (br s, 1H, OH); 13C NMR
(CDCl3, 100MHz) d: 14.1, 62.8, 63.9, 87.2, 115.6, 116.1, 119.6,
124.5, 129.0, 130.5, 132.5, 145.2, 155.8, 156.6, 162.5, 165.0,
165.3; Anal. Calcd for C20H17N3O5: C, 63.32; H, 4.52; N, 11.08;
found: C, 63.20; H, 4.42; N, 10.92.
Ethyl-3-amino-5,10-dihydro-1-(4-bromophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b] phthalazine-2-carboxylate (5g). Yellow solid, IR
Ethyl-3-amino-5,10-dihydro-1-(4-hydroxyphenyl)-5,10-dioxo-
1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5m). Pale
yellow solid, IR (nmax, nujol) 3450, 3265, 2896, 2233, 1733,
(nmax, nujol) 3448, 3322, 3165, 2876, 2225, 1722, 1667, 1631 cmÀ1
;
3
1
1H NMR (CDCl3, 400 MHz, TMS) d: 1.40 (t, 3H, JHH =7.30Hz,
1662, 1589 cmÀ1; H NMR (DMSO-d6, 400 MHz, TMS) d: 1.37
3
3
3
CH3), 4.38 (q, 2H, JHH =7.30Hz, OCH2), 6.22 (s, 1H, Ar–CH),
(t, 3H, JHH = 6.8 Hz, CH3), 4.34 (q, 2H, JHH = 6.6 Hz, OCH2),
6.19 (s, 1H, Ar–CH), 6.90–7.20 (m, 4H, Ar–H), 7.65 (br s, 2H,
NH2), 7.83–7.86 (m, 2H), 8.20–8.30 (m, 2H), 9.68 (br s, 1H,
OH); 13C NMR (DMSO-d6, 100MHz) d: 13.5, 55.2, 61.1, 73.2,
118.8, 126.6, 128.5, 131.0, 132.4, 138.4, 148.6, 152.7, 156.6,
160.2, 162.4; Anal. Calcd for C20H17N3O5: C, 63.32; H, 4.52; N,
11.08; found: C, 63.18; H, 4.40; N, 10.93.
7.31–7.65 (m, 4H, Ar–H), 7.84–7.86 (m, 2H), 8.18 (br s, 2H,
NH2), 8.24–8.35 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 13.2,
61.8, 69.3, 71.8, 124.6, 127.1, 129.4, 130.3, 131.4, 131.6, 141.7,
152.6, 160.9. 163.2, 165.8; Anal. Calcd for C20H16BrN3O4: C,
54.31; H, 3.65; N, 9.50; found: C, 54.18; H, 3.55; N, 9.37.
Ethyl-3-amino-5,10-dihydro-1-(2-nitrophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5h). Yellow solid, IR
Ethyl-3-amino-5,10-dihydro-1-(4-dimethylaminophenyl)-5,10-
dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5n). Brown
solid, IR (nmax, KBr) 3356, 3274, 2922, 2211, 1726, 1687, 1637,
1
(nmax, KBr) 3452, 3328, 2895, 1710, 1663, 1644 cmÀ1; H NMR
(CDCl3, 400 MHz, TMS) d: 1.43 (t, 3H, 3JHH =7.32Hz, CH3), 4.45
1595 cmÀ1 1H NMR (CDCl3, 400MHz, TMS) d: 1.35 (t, 3H,
;
3
(q, 2H, JHH =7.32Hz, OCH2), 6.56 (s, 1H, Ar–CH), 7.53–7.82
3JHH =7.36Hz, CH3), 3.08 (s, 6H, 2 Â CH3), 4.31 (q, 2H,
3JHH = 6.6 Hz, OCH2), 5.64 (s, 1H, Ar–CH), 6.57–6.69 (m, 4H,
Ar–H), 7.71–7.73 (m, 2H), 7.88–7.93 (m, 2H), 8.05 (br s, 2H,
NH2); 13C NMR (CDCl3, 100 MHz) d: 13.1, 45.4, 60.4, 69.1,
92.0, 110.3, 124.2, 128.0, 130.6, 132.0, 132.7, 140.0, 152.4,
154.3, 162.6, 163.7; Anal. Calcd for C22H22N4O4: C, 65.01; H,
5.46; N, 13.78; found: C, 64.87; H, 5.29; N, 13.52.
(m, 4H, Ar–H), 7.88–7.92 (m, 2H), 8.30 (br s, 2H, NH2), 8.35–8.42
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 13.7, 46.0, 57.8, 74.2,
121.8, 125.4, 126.7, 128.0, 130.1, 131.6, 134.2, 138.6, 145.8,
151.3, 159.6, 161.2, 164.3; Anal. Calcd for C20H16N4O6: C, 58.82;
H, 3.95; N, 13.72; found: C, 58.72; H, 3.77; N, 13.58.
Ethyl-3-amino-5,10-dihydro-1-(3-nitrophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5i). Yellow solid, IR
1
(nmax, KBr) 3422, 3307, 2898, 1719, 1680, 1664, 1607cmÀ1; H
Ethyl-3-amino-5,10-dihydro-1-(styryl)-5,10-dioxo-1H-pyrazolo
[1,2-b]phthalazine-2-carboxylate (5o). Yellow solid, IR (nmax, nujol)
3
NMR (CDCl3, 400 MHz, TMS) d: 1.42 (t, 3H, JHH = 7.32Hz,
1
3422, 3276, 2923, 2221, 1713, 1694, 1638 cmÀ1; H NMR (CDCl3,
3
CH3), 4.43 (q, 2H, JHH = 7.30 Hz, OCH2), 6.35 (s, 1H, Ar–CH),
3
400 MHz, TMS) d: 1.36 (t, 3H, JHH = 7.32 Hz, CH3), 4.33
7.50–7.82 (m, 4H, Ar–H), 7.87–7.89 (m, 2H), 8.31 (br s, 2H,
NH2), 8.37–8.43 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 13.2,
62.0, 63.7, 99.2, 124.3, 124.5, 126.0, 129.7, 131.3, 131.9, 147.4,
151.2, 154.6, 160.4, 165.0, 166.7; Anal. Calcd for C20H16N4O6:
C, 58.82; H, 3.95; N, 13.72; found: C, 58.71; H, 3.81; N, 13.61.
Ethyl-3-amino-5,10-dihydro-1-(4-nitrophenyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5j). Yellow solid, IR
3
(q, 2H, JHH = 7.32 Hz, OCH2), 6.26 (m, 1H, Ar–CH), 6.69
(m, 1H), 6.73 (d, 1H, J= 14.6 Hz), 7.29 (br s, 2H, NH2), 7.41–7.60
(m, 5H, Ar–H), 7.98–8.01 (m, 2H), 8.20–8.27 (m, 2H); 13C NMR
(CDCl3, 100MHz) d: 14.1, 54.6, 62.3, 76.7, 123, 126.3, 127.4,
127.6, 127.9, 128.5, 129.1, 131.2, 134.6, 148.8, 162.3, 164.1,
165.8; Anal. Calcd for C22H19N3O4: C, 67.86; H, 4.92; N, 10.79;
found: C, 67.72; H, 4.75; N, 10.66.
(nmax, KBr) 3446, 3331, 2905, 1719, 1702, 1659, 1626, 1518cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 1.42 (t, 3H, 3JHH = 7.36Hz,
Ethyl-3-amino-5,10-dihydro-1-(4-hydroxy-3-methoxyphenyl)-
5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5p). Light
3
CH3), 4.43 (q, 2H, JHH = 7.32 Hz, OCH2), 6.33 (s, 1H, Ar–CH),
yellow solid, IR (nmax, KBr) 3426, 3364, 2897, 1710, 1662, 1635 cmÀ1
;
7.53–7.82 (m, 4H, Ar–H), 7.87–7.89 (m, 2H), 8.24 (br s, 2H,
NH2), 8.32–8.41 (m, 2H); 13C NMR (CDCl3, 100MHz) d: 14.2,
59.8, 63.2, 70.4, 123.6, 124.3, 127.8, 131.5, 133.8, 145.7, 147.7,
151.7, 154.0, 157.1, 161.4; Anal. Calcd for C20H16N4O6: C,
58.82; H, 3.95; N, 13.72; found: C, 58.70; H, 3.84; N, 13.59.
Ethyl-3-amino-5,10-dihydro-5,10-dioxo-1-(2-hydroxyphenyl)-
1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5k). Yellow
solid, IR (nmax, KBr) 3422, 3312, 2876, 1742, 1663, 1487, 1298,
1H NMR(CDCl3, 400MHz, TMS)d:1.39(t, 3H, 3JHH =7.30Hz, CH3),
3
3.98 (s, 3H, OCH3), 4.38 (q, 2H, JHH = 7.30 Hz, OCH2), 6.23
(s, 1H, Ar–CH), 6.99–7.53 (m, 3H, Ar–H), 7.85–7.87 (m, 2H),
8.14 (br s, 2H, NH2), 8.24–8.38 (m, 2H), 9.83 (br s, 1H, OH);
13C NMR (CDCl3, 100 MHz) d: 14.2, 56.1, 57.0, 62.4, 99.0,
114.9, 116.4, 119.5, 128.8, 131.8, 132.1, 136.0, 142.3,
146.8, 150.9, 162.0, 163.1, 164.8; Anal. Calcd for
C21H19N3O6: C, 61.61; H, 4.68; N, 10.26; found: C, 61.48;
H, 4.59; N, 10.15.
1
1081, 856, 791 cmÀ1; H NMR (CDCl3, 400 MHz, TMS) d: 1.34
3
3
(t, 3H, JHH =7.32Hz, CH3), 4.26 (q, 2H, JHH =7.30Hz, OCH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Kidwai and R. Chauhan
Vol 000
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Ethyl-3-amino-5,10-dihydro-1-(1-naphthyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5q). Brown solid,
IR (nmax, nujol) 3464, 3058, 2874, 2225, 1735, 1726, 1689,
1
1646 cmÀ1; H NMR (CDCl3, 400 MHz, TMS) d: 1.13 (t, 3H,
3
3JHH = 8.0 Hz, CH3), 4.13 (q, 2H, JHH = 7.32 Hz, OCH2), 6.11
1, 47.
(s, 1H, Ar–CH), 7.28–7.85 (m, 7H, Ar–H), 7.95–7.98 (m, 2H),
8.04 (br s, 2H, NH2), 8.12–8.22 (m, 2H); 13C NMR (CDCl3,
100 MHz) d: 13.8, 61.0, 69.9, 72.3, 122.4, 125.0, 125.4, 126.2,
126.4, 127.4, 127.6, 128.8, 132, 132.4, 132.8, 133.0, 134.6,
152.3, 161.7, 165.5, 166.0; Anal. Calcd for C24H19N3O4: C,
69.72; H, 4.63; N, 10.16; found: C, 69.60; H, 4.54; N, 10.02.
Ethyl-3-amino-5,10-dihydro-1-(1-benzo[1,3]-dioxol-5-yl)-5,10-
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2011, DOI: 10.1002/jhet.1037; (b) Suryakiran, N.; Reddy, T. S.;
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dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate (5r).
Yellow
solid, IR (nmax, KBr) 3324, 3167, 2900, 2219, 1725, 1654, 1620 cmÀ1
;
3
1H NMR (CDCl3, 400MHz, TMS) d: 1.39 (t, 3H, JHH =7.32Hz,
3
CH3), 4.36 (q, 2H, JHH =7.32Hz, OCH2), 6.09 (s, 2H), 6.30 (s, 1H,
Ar–CH), 6.80–6.93 (m, 3H, Ar–H), 7.90–7.93 (m, 2H), 8.12 (br s, 2H,
NH2), 8.29–8.38 (m, 2H); 13C NMR (CDCl3, 100 MHz) d: 14.2, 55.6,
62.5, 70.4, 99.8, 109.0, 116.0, 121.0, 125.9, 129.7, 132.0, 136.8, 145.6,
148.6, 152.2, 159.7, 163.0, 168.5; Anal. Calcd for C21H17N3O6: C,
61.91; H, 4.21; N, 10.31; found: C, 61.77; H, 4.03; N, 10.20.
Ethyl-3-amino-5,10-dihydro-1-(2-furanyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5s). Off white solid,
IR (nmax, KBr) 3412, 3158, 2926, 2214, 1734, 1657, 1606cmÀ1
;
1H NMR (CDCl3, 400MHz, TMS) d: 1.36 (t, 3H, 3JHH = 6.80Hz,
3
CH3), 4.28 (q, 2H, JHH = 6.80 Hz, OCH2), 6.24 (s, 1H, Ar–CH),
6.75–6.92 (m, 3H, Ar–H), 7.88–7.92 (m, 2H), 8.05 (br s, 2H,
NH2), 8.18–8.28 (m, 2H); 13C NMR (CDCl3, 100MHz) d: 14.0,
54.6, 60.3, 74.3, 106.8, 111.3, 126.3, 128.5, 129.7, 139.3, 147.6,
149.0, 157.4, 158.5, 160.6; Anal. Calcd for C18H15N3O5: C,
61.19; H, 4.28; N, 11.89; found: C, 61.10; H, 4.16; N, 11.80.
Ethyl-3-amino-5,10-dihydro-1-(2-thienyl)-5,10-dioxo-1H-
pyrazolo[1,2-b]phthalazine-2-carboxylate (5t). Green solid, IR
1
(nmax, KBr) 3448, 3165, 2896, 2227, 1735, 1661, 1600 cmÀ1; H
3
NMR (CDCl3, 400 MHz, TMS) d: 1.37 (t, 3H, JHH = 7.30Hz,
3
CH3), 4.32 (q, 2H, JHH = 7.30 Hz, OCH2), 6.17 (s, 1H, Ar–CH),
6.65–6.90 (m, 3H, Ar–H), 7.65 (br s, 2H, NH2), 7.83–7.86
(m, 2H), 8.22–8.32 (m, 2H); 13C NMR (CDCl3, 100MHz)
d: 14.1, 52.8, 62.5, 74.6, 122.1, 125.7, 126.4, 127.8, 129.2, 129.8,
135.6, 148.1, 157.4, 159.6, 161.7; Anal. Calcd for C18H15N3O4S:
C, 58.53; H, 4.09; N, 11.38; found: C, 58.45; H, 4.02; N, 11.24.
Acknowledgments. The author (R. Chauhan) is thankful to the
University Grants Commission for providing Junior Research
Fellowship and also to the director of the University Science and
Instrumentation Centre, University of Delhi, Delhi for providing
the data for spectral analysis.
[26] Kidwai, M.; Bhatnagar D. Tetrahedron Lett 2010, 51, 2700.
[27] (a) Kidwai, M.; Chauhan, R.; Bhatnagar, D. J Sulf Chem
2011, 32, 37; (b) Kidwai, M.; Bhatnagar D. RSC Adv 2012, 20, 7660;
(c) Kidwai, M.; Chauhan, R.; Bhatnagar, D.; Singh, A. K.; Mishra, B.;
Dey, S. Monatsh Chem 2012, DOI 10.1007/s00706-012-0742-4;
(d) Kidwai, M.; Jahan, A.; Chauhan, R.; Mishra, N. K. Tetrahedron Lett
2012, 53, 1728.
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[1] Gerencser, J.; Dorman, G.; Darvas, F. QSAR Comb Sci 2006, 25, 439.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet