A Green Synthesis of Highly Functionalized 3-amino-2-phenylsulfonyl-1-alkyl/aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-diones and Their Reduction and Photophysical Studies

Article abstract of DOI:10.1002/jhet.3061

3-Amino-2-benzenesulfonyl-1-alkyl/aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives were synthesized by the one-pot, three-component condensation of phthalhydrazide, aldehydes, and (phenylsulfonyl)acetonitrile in EtOH using 2-hydroxyethylammonium acetate as catalyst. The advantages of this method include environmental friendliness, easy work-up, and excellent yields. The reduction of some products and photophysical properties were also investigated.

Full text of DOI:10.1002/jhet.3061

Month 2017 A Green Synthesis of Highly Functionalized 3-amino-2-phenylsulfonyl-1-
alkyl/aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-diones and Their Reduction
and Photophysical Studies
Xin Shi,
Maohua Ding, Conghao Li, Wang Wang, and Hongyun Guo*
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China
*
E-mail: hyguo1234@126.com
Received May 18, 2017
DOI 10.1002/jhet.3061
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
3
-Amino-2-benzenesulfonyl-1-alkyl/aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives were
synthesized by the one-pot, three-component condensation of phthalhydrazide, aldehydes, and
phenylsulfonyl)acetonitrile in EtOH using 2-hydroxyethylammonium acetate as catalyst. The advantages
(
of this method include environmental friendliness, easy work-up, and excellent yields. The reduction of
some products and photophysical properties were also investigated.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
covering cytotoxic, anticancer, antimicrobic [16], anti-
HIV [17], and trypanocidal [18]. Phenyl-substituted and
heteroaryl-substituted sulfones are known as protecting
group and important reactants in the Julia-type olefination
reaction for the synthesis of variously useful
intermediates and compounds [19]. In addition, some
studies show that the sulfone functionalities can also
be transformed into other useful functional groups [20].
Herein, considering the important biological properties
of phthalazine derivatives and the powerful effect of
Multicomponent reactions (MCRs) have attracted many
attentions in organic, combinatorial, and medicinal
chemistry and have been designed to produce elaborate
biologically active compounds [1]. The MCR strategy
offers significant advantages over conventional linear-
type synthesis because of its convergence, atom efficient,
operational simplicity, facile automation, easy work-up
nature [2]. On the other hand, the synthesis of
combinatorial small-molecule heterocyclic libraries has
emerged as a valuable tool in the search for novel lead
structures [3]. The success of combinatorial chemistry
plays an important role in the discovery process of
the new drug. Our studies show that the most promising
and powerful method for generating combinatorial
polyfunctionalized heterocyclic compounds is by
sequential MCRs.
MCRs, we wish to report
a
highly efficient,
convenient, and facile method for synthesis of highly
functionalized 3-amino-2-phenylsulfonyl-1-alkyl/aryl-1H-
pyrazolo[1,2-b]phthalazine-5,10-diones derivatives via a
three-component condensation reaction.
RESULTS AND DISCUSSION
Heterocycles containing pyrazole ring have been found to
be of broad pharmacological and biological interest such as
cytotoxic [4], analgesic [5], antihyperglycemic [6], anti-
inflammatory [7], antibacterial, [8] and antiviral activities
At the onset of the research, we investigated the
conversion of
a
mixture of benzaldehyde (1a)
(1.0 mmol), phthalhydrazide (2) (1.0 mmol), and
(phenylsulfonyl) acetonitrile [21] (3) (1.0 mmol) in
different conditions. The reaction conditions were
optimized, and the results were summarized in Table 1.
Among all the catalysts tested in the solvent of EtOH
at room temperature for 12 or 24 h (Table 1, entries 2–6),
[
9]. Heterocycles fused with a phthalazine moiety are
reported to possess anxiolytic [10], cytotoxic [11],
anticonvulsant [12], antifungal [13], and anticancer [14].
Sulfones are an important class of compounds present in
many natural products due to their properties and reactivity
+
[
15], which possess wide spectrum of biological activities
2-hydroxyethylammonium acetate [H N CH CH OH]
3
2
2
©
2017 Wiley Periodicals, Inc.

X. Shi, M. Ding, C. Li, W. Wang, and H. Guo
Vol 000
Table 1
a
Optimization of the reaction condition for product 4a .
b
Entry
Condition
Yield (%)
1
2
3
4
5
6
7
8
9
No catalyst, C
20 mol% L-Proline, C
20 mol% [bmim]OH,C
2
H
5
OH, rt, 24 h
Trace
56
83
35
77
86
63
75
Trace
86
2
H
H
5
OH,rt,12 h
OH,rt, 12 h
2
5
20 mol% PTSA,C
20 mol% Et N,C
20 mol% HEAA,C
20 mol% HEAA, DMF, rt, 12 h
2
H
5
OH,rt, 12 h
OH, rt, 12 h
OH, rt, 12 h
3
2
H
5
2
H
5
20 mol% HEAA, CH
20 mol% HEAA, H
10 mol% HEAA, C
5 mol% HEAA, C
3
CN, rt, 12 h
O, rt, 24 h
2
10
2
H
5
OH, rt, 12 h
OH, rt, 12 h
11
2
H
5
74
DMF, dimethylformamider; HEAA, hydroxyethylammonium acetate.
a
The reaction was conducted with 1a (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol), and catalyst in 3.0 mL of solvent.
Isolated yields.
b
À
[
CH COO ] (HEAA)[22] performed the best. EtOH
20 mol%; 10 mol% catalyst was sufficient for this
reaction. It is worthwhile to mention that when the
reaction was stirred in water or without catalyst, only a
trace amount of the product was formed even after
prolonged heating.
The generality of this three-component reaction was
studied under optimal conditions by various structures of
aldehydes. The results were summarized in Table 2.
3
turned out to be the optimal solvent as compared
with dimethylformamide, MeCN, and H O (Table 1,
2
entries 7–9). The catalyst HEAA loading of 5 mol%
resulted in the formation of 4a with 74% yield; however,
when with 10 mol% catalyst, the yield significantly
increased to 86%. No obvious improvement was
observed by further increasing the catalyst loading to
Table 2
Synthesis of 3-amino-2-phenylsulfonyl-1-alkyl/aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives.
b
Entry
R
Products
Yield (%)
1
2
3
4
5
6
7
8
9
C
6
H
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
86
94
90
93
96
79
80
84
76
65
70
69
61
6 4
4-Cl-C H
4-F-C H
6 4
3-Br-C
4-NO
4-CH
4-OH-C
4-isopropylC
4-MeO-C
CH
n-C
6
H
4
2
-C
6
H
4
3
-C
6
H
4
6
H
4
6
H
4
6
H
4
10
3
4j
4k
4l
1
1
3
H
7
1
1
2
3
iso-C
iso-C
3
H
7
H
4
9
4m
a
The reaction was conducted with 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol), and 10 mol% hydroxyethylammonium acetate in 3.0 mL of ethanol at room
temperature for 12 h.
b
Isolated yields.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Green Chemistry Ionic Liquid
Table 3
UV–visible and fluorescence data of the examined derivatives of 4.
abs
ext
em
À1
À1
À1
a
Compound
λ
(nm)
λ
(nm)
λ
(nm)
ε (M cm
)
Δν (cm
)
Φ
f
4
4
4
4
4
a
c
e
f
351
351
489
31 400
47 200
30 200
22 900
47 400
8040.13
8161.49
8409.38
8000.93
8003.41
0.065
0.068
0.075
0.165
0.048
349
345
352
353
349
345
352
353
488
486
490
492
i
abs
ext
em
λ
(nm), absorbance maxima; λ (nm), excitation wavelength; λ (nm), fluorescence maxima; ε, molar absorptivity; Δν, Stoke’s lines.
a
Reference: 9,10-diphenylanthracene with Φ = 1.00.
À5
Generally, aromatic aldehydes were more active than
aliphatic aldehydes in this reaction. Electronic effect of
substituents on the phenyl ring of aromatic aldehydes was
observed. The electron-withdrawing group substituted
substrates gave relatively higher yields of the
corresponding products than those with electron-donating
groups. Moreover, no expected product was obtained
when ketones were applied to this reaction.
were measured at room temperature at 1 × 10 M. The
solvents were all freshly distilled and deoxygenized
before use.
We extended our study to find out the reduction of 4a.
There are numerous examples of desulfonylation via
Julia-type elimination. Sodium and magnesium metals
have been used for the various reductively desulfonylated
reactions where they act as a source of reductant [23].
However, it was not envisioned that the reductive nature
of sodium or magnesium metal could be used for the
deprotection of the phenylsulfonyl group, and 4a was cut
into two parts that is 2 and 7. Reductive reaction of 4a
using lithium chloride and potassium borohydride in
EtOH/tetrahydrofuran (1:10) gave the corresponding
hydride reductant 5 (Scheme 1). The proposed structure
of compound 5 was further unequivocally confirmed by
single crystal X-ray crystallography (Fig. 1) [24].
Electronic absorption and photoluminescent properties:
UV–visible absorption and fluorescence emission spectra
Figure 1. X-ray structure of compound 5. [Color figure can be viewed at
wileyonlinelibrary.com]
Scheme 1. The reduction of 4a. [Color figure can be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

X. Shi, M. Ding, C. Li, W. Wang, and H. Guo
Vol 000
1.0
1
0
0
0
0
0
.0
.8
.6
.4
.2
.0
0.8
0.6
0.4
0.2
0.0
3
00 325 350 375 400 425 450 475 500
Wavelength nm
400
450
500
550
600
Wavelength nm
2
Figure 2. Absorption (left) and emission (right) spectra of 4e (NO ), 4c (F), 4a (H), 4f (Me), and 4i (OMe) and the dimethylsulfoxide as the solvent.
[Color figure can be viewed at wileyonlinelibrary.com]
Five compounds were chosen which included the
compound 4a (H), 4f (Me), 4i (OMe), 4c (F), and 4e
CONCLUSION
(
(
NO ). The absorption spectra (left) and emission spectra
In summary, highly functionalized 1H-pyrazolo[1,2-b]
phthalazine-5,10-dione derivatives are of great interest
due to their potential biological and pharmacological
activities. A series of well-defined 3-amino-1-phenyl-
2-(phenylsulfonyl)-1H-pyrazolo-[1,2-b]phthalazine-5,10-
dione was synthesized and fully characterized. Their
reduction and photophysical properties were also studied,
and the results obtained by the absorption and emissive
spectra demonstrated a certain fluorescent structure–
property relationship.
2
À5
right) in dimethylsulfoxide (DMSO) at 10
M
concentrations was shown in Figure 2. Unexpectedly, no
obvious electronic effects were seen both in absorption
spectra and in emission spectra, just a main peak
presented respectively. Both the main peak in absorption
and emission spectra were attributed to the intrinsic value
of the 1H-pyrazolo[1,2-b]phthalazine-5,10-dione nuclear.
The contribution of strong electron-withdrawing group
NO in compound 4e and F in compound 4c was not
2
apparently so did the strong electron-donating group Me
in compound 4f and OMe in compound 4i, the probable
reason was that the substituted phenyl ring in 1-position
was not coplanar with its nucleus 1H-pyrazolo[1,2-b]
phthalazine-5,10-dione, so the substituent located on the
phenyl ring could not transfer electronic effect effectively
to the nucleus.
EXPERIMENTAL SECTION
General information.
All chemicals and solvents
(analytical grade) were received from commercial sources
and used without further purification. Infrared (IR)
spectra were recorded on a Nicolet 6700 spectrometer in
KBr. H nuclear magnetic resonance (NMR) (500 MHz)
and C NMR spectra (125 MHz) were recorded on an
Avance III 500 NMR spectrometer (Bruker) using
Although the electronic effect was not apparent, but it
existed to some extent. As seen in Figure 2, the
1
1
3
maximum absorption peak of 4e (NO ), 4c (F), 4a (H),
2
4
f (Me), and 4i (OMe) was 345, 349, 351, 352, and
3
53 nm, respectively, electron-withdrawing group NO2
tetramethylsilane as internal standard and DMSO-d as
6
solvent. Low-resolution and high-resolution mass spectra
were taken on an Agilent 6210 TOF LC/MS spectrometer
using the electrospray ionization (ESI).
(
4e) and F (4c) caused the blue shift, while the electron-
donating group Me (4f) and OMe (4i) caused the red
shift compared with H (4a). Moreover, it was reasonable
that NO2 group caused a larger blue shift than that
caused by F group, while the OMe group caused a larger
red shift than that caused by Me group. Similarly, the
regularity could be observed in emission spectra in
General procedures for the synthesis of compounds 4.
The mixture of the aldehydes
1
(1.0 mmol),
phthalhydrazide (1.0 mmol), (phenylsulfonyl)
2
acetonitrile 3 (1.0 mmol), and HEAA (0.1 mmol) in
EtOH (3 ml) was stirred at room temperature for 12 h
(monitored by thin-layer chromatography). After
completion of the reaction, the solid product
was collected by filtration and recrystallized from
methanol to give the pure compound 4. The ionic liquid
HEAA was successively recovered extracting from the
filtrate and reused.
Figure 2 (right). The maximum emission of 4e (NO ), 4c
2
(F), 4a (H), 4f (Me), and 4i (OMe) was located at 486,
4
88, 489, 490, and 492 nm, respectively; the electron
withdrawing groups NO and F caused a blue shift, and
2
the shift value caused by NO2 was larger. The same
phenomenon was seen when the groups changed to Me
and OMe.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Green Chemistry Ionic Liquid
3
-Amino-2-(phenylsulfonyl)-1-phenyl-1H-pyrazolo2-[1,2-b]
3-Amino-2-phenylsulfonyl-1-(4-nitro-phenyl)-1H-pyrazolo-
[1,2-b]phthalazine-5,10-dione (4e).
phthalazine-5,10-dione (4a).
vmax): 3463, 3336, 3065, 3303, 1645, 1396, 1290,
130, 1097 cm ; H NMR (500 MHz, DMSO-d , δ):
Yellow powder; IR (KBr)
Yellow powder; IR
(KBr) (vmax): 3460, 3336, 3025, 2894, 1642, 1396,
(
1
À1
1
À1
1
1352, 1294, 1134, 1097 cm ; H NMR (500 MHz,
6
8
.29–8.21 (1H, m), 8.06–8.00 (1H, m), 7.98–7.78 (4H,
DMSO-d6, δ): 8.28 (1H, dt, J = 5.8 Hz, 3.2), 8.03 (1H,
dt, J = 7.3, 3.2 Hz), 7.99–7.87 (6H, m), 7.60–7.55 (2H,
m), 7.52–7.46 (3H, m), 7.36–7.31 (2H, m), 6.15 (1H, s);
m), 7.52–7.45 (1H, m), 7.42–7.40(2H, m), 7.35–7.28
(
(
2H, m), 7.25–7.19 (2H, m), 7.19–7.08 (3H, m), 6.05
1H, s);
13
13
C
NMR (125 MHz,DMSO-d6, δ):
C NMR (125 MHz, DMSO-d6, δ): 157.47, 153.42,
1
1
1
57.44,153.21, 147.42, 142.94, 137.35, 134.70, 133.61,
32.29, 128.76, 128.73, 128.68, 127.90, 127.86, 127.59,
147.86, 146.98, 144.87, 142.88, 134.72, 133.77, 132.42,
128.97, 128.89, 128.76, 128.39, 127.29, 126.57, 125.57,
+
27.28, 126.55, 125.58, 84.89, 64.97; MS (ESI): ([M
123.00, 83.96, 63.06; MS (ESI): ([M + H] ) 477.2;
+
+
+
H] ) 432.1; HRMS (ESI) calcd for C H N O S
HRMS (ESI) calcd for C H N O S ([M + H] )
2
3
17
3
4
23 16 4 6
+
([M + H] ) 432.1018, found 432.1030.
477.0869, found 477.0882.
3
-Amino-2-phenylsulfonyl-1-(4-chloro-phenyl)-1H-pyrazolo-
3-Amino-2-phenylsulfonyl-1-p-tolyl-1H-pyrazolo-[1,2-b]
phthalazine-5,10-dione (4f).
[1,2-b]phthalazine-5,10-dione (4b).
Yellow powder; IR
Yellow powder; IR (KBr)
(vmax): 3457, 3339, 3057, 2919, 1653, 1399, 1372,
(KBr) (vmax): 3456, 3332, 3062,1635, 1395, 1300, 1135,
À1
1
À1
1
1
8
094 cm
;
H NMR (500 MHz, DMSO-d , δ):
1293, 1132, 1100 cm ; H NMR (500 MHz, DMSO-d6,
δ): 8.25(1H, s), 8.03 (1H, d, J = 2.9 Hz), 7.95 (2H, d,
J = 3.0 Hz), 7.82 (2H, s), 7.50 (1H, d, J = 6.9 Hz), 7.41
(2H, d, J = 7.3 Hz), 7.33 (2H, d, J = 7.4 Hz), 7.08 (2H,
d, J = 7.6 Hz), 6.89 (2H, d, J = 7.4 Hz), 6.00 (1H, s),
6
.28–8.22 (1H, m), 8.06–8.01 (1H, m), 7.97–7.93 (2H,
m), 7.93–7.72 (2H, m), 7.54 (1H, t, J = 7.4 Hz),
7
J = 8.4 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.03 (1H, s);
NMR (125 MHz, DMSO-d , δ): 157.44, 153.27, 147.55,
1
1
8
.49–7.43 (2H, m), 7.37 (2H, d, J = 7.5 Hz), 7.27 (2H, d,
13
C
13
2.23 (3H, s); C NMR (125 MHz, DMSO-d6, δ):
157.38, 153.10, 147.28, 142.93, 137.18, 134.65, 134.41,
133.55, 132.14, 128.71, 128.62, 128.38, 127.47, 127.24,
126.49, 125.62, 85.15, 63.71, 20.60; MS (ESI):
6
42.95, 136.47, 134.68, 133.65, 132.51, 132.32,129.47,
28.82, 128.73, 128.57, 127.79, 127.25, 126.52, 125.58,
+
4.51, 63.22; MS (ESI): ([M + H] ) 466.1; HRMS (ESI)
+
+
calcd for C H ClN O S ([M + H] ) 466.0628, found
4
([M + H] ) 446.2; HRMS (ESI) calcd for C H N O S
23
16
3
4
24 19 3 4
+
66.0646.
([M + H] ) 446.1175, found 446.1171.
3
-Amino-2-phenylsulfonyl-1-(4-fluoro-phenyl)-1H-pyrazolo-
3-Amino-2-phenylsulfonyl-1-(4-hydroxy-phenyl)-1H-
pyrazolo-[1,2-b]phthalazine-5,10-dione (4g).
[1,2-b]phthalazine-5,10-dione (4c).
Yellow powder; IR
Yellow
powder; IR (KBr) (vmax): 3447, 3356, 3324, 3062, 1674,
(KBr) (vmax): 3435, 3320, 3020, 2895, 1640, 1395,
À1
1
À1
1
1
300, 1140, 1095 cm ; H NMR (500 MHz, DMSO-
1396, 1350, 1295, 1137, 1097 cm
;
H NMR
d6, δ): 8.25 (1H, m), 8.06–8.02 (1H, m), 7.95 (2H, m),
.89 (2H, s), 7.53 (1H, t, J = 7.3 Hz), 7.46 (2H, d,
J = 7.5 Hz), 7.36 (2H, t, J = 15.55 Hz), 7.27 (2H, m),
(500 MHz, DMSO-d6, δ): 9.35(1H, s), 8.24(1H, m), 8.04
(1H, m), 7.97–7.92 (2H, m), 7.79 (2H, s), 7.53–7.50 (1H,
m), 7.45 (2H, dd, J = 8.3, 1.1 Hz), 7.35 (2H, dd,
J = 8.1 Hz, 7.5), 6.98 (2H, m), 6.47 (2H, m), 5.96 (1H,
7
1
3
6
.90 (2H, m), 6.05 (1H, s); C NMR (125 MHz,
13
DMSO-d , δ): 157.44, 153.25, 147.46, 143.00, 134.65,
s); C NMR (125 MHz, DMSO-d6, δ): 157.37, 157.20,
153.04, 147.17, 142.99, 134.66, 133.51, 132.23, 128.84,
128.81, 128.66, 127.46, 127.22, 126.49, 125.69, 114.56,
6
1
1
6
33.61, 132.33, 129.73, 129.67, 128.80, 128.71,
28.63, 127.24, 126.51, 125.57, 114.64, 114.47, 84.57,
+
+
3.21; MS (ESI): ([M + H] ) 450.1; HRMS (ESI) calcd
85.19, 63.59.; MS (ESI): ([M + H] ) 448.1; HRMS (ESI)
+
+
for C23H16FN3O4S ([M + H] ) 450.0924, found
calcd for C H N O S ([M + H] ) 448.0967, found
2
3 17 3 5
4
50.0939.
448.0986.
3
-Amino-2-phenylsulfonyl-1-(3-bromo-phenyl)-1H-pyrazolo-
3-Amino-2-phenylsulfonyl-1-(4-isopropyl-phenyl)-1H-
pyrazolo-[1,2-b]phthalazine-5,10-dione (4h).
[
1,2-b]phthalazine-5,10-dione (4d).
Yellow powder; IR
Yellow
powder; IR (KBr) (vmax): 3444, 3317, 3059, 2953,
(KBr) (vmax): 3405, 3307, 3016, 2900, 1665, 1400,
À1
1
À1
1
1
360, 1294, 1138, 1097 cm
;
H NMR (500 MHz,
1665, 1411, 1373, 1298, 1131, 1079 cm ; H NMR
(500 MHz, DMSO-d6, δ): 8.27–88.23 (1H, m), 8.05–
8.01 (1H, m), 7.97–7.93 (2H, m), 7.83 (2H, s), 7.47 (1H,
t, J = 7.3 Hz), 7.36 (2H, m), 7.29 (2H, dd, J = 8.2,
7.5 Hz), 7.09 (2H, d, J = 8.1 Hz), 6.94 (2H, d,
J = 8.1 Hz), 6.04 (1H, s), 2.79 (1H, dt, J = 13.8,
6.9 Hz), 1.16 (6H, dd, J = 6.9 Hz, 2.8); C NMR
(125 MHz, DMSO-d6, δ):157.42, 153.16, 148.02,
147.28, 142.96, 134.67, 134.53, 133.59, 132.20, 128.72,
128.60, 127.48, 127.27, 126.54, 125.79, 125.61, 85.00,
DMSO-d6, δ): 8.26–8.24 (1H, m), 8.07–8.03 (1H, m),
.97–7.93 (2H, m), 7.91–7.87 (2H, m), 7.52 (1H, t,
J = 7.3 Hz), 7.43 (2H, d, J = 7.3 Hz), 7.36–7.31 (5H, m),
7
1
3
7
.11 (1H, t, J = 7.8 Hz), 6.03 (1H, s); C NMR
(125 MHz, DMSO-d6, δ): 157.50, 153.36, 147.62,
1
3
1
1
1
42.86, 139.77, 134.61, 133.63, 132.53, 132.48, 130.80,
30.14, 129.87, 128.97, 128.70, 128.55, 127.23, 127.17,
26.54, 125.45, 125.10, 121.53, 84.08, 63.39; MS (ESI):
+
([M
+
H] ) 510.1; HRMS (ESI) calcd for
+
+
C H BrN O S ([M + H] ) 510.0123, found 510.0141.
63.74, 33.10, 23.90, 23.75.; MS (ESI): ([M + H] )
23
16
3 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

X. Shi, M. Ding, C. Li, W. Wang, and H. Guo
Vol 000
+
4
4
74.2; HRMS (ESI) calcd for C H N O S ([M + H] )
74.1488, found 474.1504.
3-Amino-2-phenylsulfonyl-1-isobutyl-1H-pyrazolo-[1,2-b]
phthalazine-5,10-dione (4m).
2
6 23 3 4
Yellow powder; IR (KBr)
(vmax): 3455, 3316, 3076, 2960, 2870, 1658, 1401,
3
-Amino-2-phenylsulfonyl-1-(4-methoxy-phenyl)-1H-
À1
1
pyrazolo-[1,2-b]phthalazine-5,10-dione (4i).
Yellow
1
370, 1285, 1134, 1099 cm ; H NMR (500 MHz,
powder; IR (KBr) (vmax): 3455, 3336, 3066, 3000,
DMSO-d6, δ): 8.23 (1H, dd, J = 1.5, 1.65 Hz), 8.17
(1H, dd, J = 1.6, 1.35 Hz), 8.00–7.94 (4H, m), 7.76
À1
1
2
906, 1650, 1392, 1356, 1295, 1134, 1089 cm ; H
NMR (500 MHz, DMSO-d6, δ): 8.26–8.23 (1H, m),
(2H, s), 7.71–7.68 (1H, m), 7.65–7.59 (2H, m), 5.18
8
7
.05–8.01 (1H, m), 7.96–7.82 (2H, m), 7.82 (2H, s),
.52–7.49 (1H, m), 7.43 (2H, m), 7.34 (2H, m), 7.10
(1H, t, J = 3.8 Hz), 2.03 (1H, ddd, J = 14.5, 8.7, 3.6),
1.71 (1H, dt, J = 14.5, 4.2 Hz), 1.62 (1H, dd, J = 13.0,
13
(2H, m), 6.63 (2H, m), 6.00 (1H, s), 3.70 (3H, s);
C
6
.6 Hz), 0.70 (3H, d, J = 6.7 Hz), 0.64 (3H, d,
13
NMR (125 MHz, DMSO-d6, δ): 159.00, 157.40, 153.12,
J = 6.6 Hz); C NMR (125 MHz, DMSO-d6, δ):
1
1
8
47.23, 143.02, 134.66, 133.55, 132.26, 129.16, 128.88,
28.76, 128.71, 128.68, 127.24, 126.50, 125.67, 113.28,
157.55, 153.94, 148.13, 142.92, 134.91, 133.62, 132.98,
1
29.45, 128.65, 128.24, 127.27, 126.62, 125.92, 82.22,
+
+
5.00, 63.51, 55.09.; MS (ESI): ([M + H] ) 462.2;
59.87, 23.66, 23.36, 22.39.; MS (ESI): ([M + H] )
+
+
HRMS (ESI) calcd for C H N O S ([M + H] )
412.1; HRMS (ESI) calcd for C H N O S ([M + H] )
2
4
19
3
5
21 21 3 4
4
62.1124, found 462.1116.
4
12.1331, found 412.1336.
3
-Amino-2-phenylsulfonyl-1-methyl-1H-pyrazolo-[1,2-b]
Typical procedure for the synthesis of compound 5.
(3-
phthalazine-5,10-dione (4j).
Yellow powder; IR (KBr)
amino-5-phenyl-4-(phenylsulfonyl)-4,5-dihydro-1H-pyrazol-1-
yl)(2-(hydroxymethyl)phenyl)methanone (5). A mixture of
(vmax): 3446, 3322, 3166, 3018, 2898, 1659, 1397,
À1
1
1
368, 1299, 1140, 1079 cm
; H NMR (500 MHz,
3
-amino-2-(phenylsulfonyl)-1-phenyl-1H-pyrazolo-[1,2-b]
phthalazine-5,10-dione (4a) (1.0 mmol), lithium chloride
1.0 mmol), and potassium borohydride (2.0 mmol) in
DMSO-d6, δ): 8.18 (1H, m), 8.12 (1H, m), 7.97–7.87
(4H, m), 7.83–7.69 (2H, m), 7.68 (1H, m),7.63 (2H, m),
(
13
5
.08 (1H, q, J = 5.9), 1.51(3H, d, J = 5.9 Hz); C NMR
EtOH/tetrahydrofuran (1:10) (5.0 mL) was stirred at room
temperature for 1 h. The reaction mixture was filtered,
and the solvent evaporated in vacuo to give the crude
product, which was purified by recrystallization from
EtOH: H O = 1:1 to afford the compound 5 (93%) as a
colorless transparent crystal; colorless transparent crystal
(125 MHz, DMSO-d6, δ): 157.46, 153.55, 147.75,
1
1
1
43.22, 134.67, 133.48, 132.94, 132.52, 129.43, 128.80,
28.52, 127.12, 126.50, 125.83, 125.09, 83.99, 57.01,
9.45; MS (ESI): ([M + H] ) 370.1; HRMS (ESI) calcd
+
2
+
for C H N O S ([M + H] ) 370.0862, found 370.0875.
18
15
3
4
3
-Amino-2-(phenylsulfonyl)-1-propyl-1H-pyrazolo[1,2-b]
IR(KBr) (vmax): 3440, 3325, 3274, 3181, 3063, 3033,
phthalazine-5,10-dione (4k).
Yellow powder; IR (KBr)
À1
2
949, 1650, 1614, 1597, 1399, 1309, 1134, 1082 cm
;
(vmax): 3410, 3298, 3075, 2963, 2931, 2871, 1657,
1
H NMR (500 MHz, DMSO-d6, δ): δH (500 MHz,
À1
1
1
(
8
(
401, 1362, 1299, 1134, 1086 cm
500 MHz, DMSO-d6, δ): 8.21 (1H, m), 8.16 (1H, m),
.01–7.93 (4H, m), 7.77 (2H, s), 7.70 (1H, m), 7.67–7.61
2H, m), 5.22 (1H, t, J = 3.0), 2.29–2.15 (1H, m), 1.70–
.57 (1H, m), 1.01–0.88 (2H, m), 0.58 (3H, t,
;
H NMR
DMSO): 8.06–8.02 (2H, m), 7.92 (1H, dd, J = 11.7,
4
.3 Hz), 7.79 (2H, t, J = 7.8 Hz), 7.47 (1H, d,
J = 7.7 Hz), 7.40 (2H, dd, J = 10.2, 4.5), 7.34 (2H, ddd,
J = 12.9, 6.3, 2.5), 7.17 (1H, t, J = 7.3 Hz), 7.06 (2H, d,
J = 7.3 Hz), 6.75–6.67 (1H, m), 6.42 (2H, s), 5.73 (1H,
d, J = 2.5 Hz), 5.04 (1H, t, J = 5.7 Hz), 4.78 (1H, d,
J = 2.6 Hz), 4.35 (1H, dd, J = 14.4, 5.6), 4.26 (1 H, dd,
1
13
J = 7.3 Hz); C NMR (125 MHz, DMSO-d6, δ): 157.48,
1
1
5
3
3
53.67, 148.09, 143.06, 134.82, 133.60, 133.03, 129.47,
28.62, 128.43, 127.25, 126.64, 125.98, 81.40, 60.83,
6.06, 32.27, 18.57, 14.88, 13.37; MS (ESI): ([M + H] )
13
J = 14.4, 5.6); C NMR (125 MHz, DMSO-d6, δ):
+
1
1
1
63.96, 150.20, 139.49, 138.25, 135.70, 135.27, 133.81,
29.90, 129.24, 129.14, 128.67, 128.24, 126.85, 126.05,
+
98.2; HRMS (ESI) calcd for C H N O S ([M + H] )
98.1175, found 398.1183.
2
0 19 3 4
25.73, 125.05, 75.12, 61.78, 60.27; MS (ESI):
3
-Amino-2-phenylsulfonyl-1-isopropyl-1H-pyrazolo-[1,2-b]
+
(
(
[M + H] ) 436.1; HRMS (ESI) calcd for C H N O S
[M + H] ) 436.1331, found 436.1346.
phthalazine-5,10-dione (4l).
Yellow powder; IR (KBr)
23 22 3 4
+
(vmax): 3430, 3283, 3061, 2959, 2873, 1632, 1401,
À1
1
1
357, 1287, 1130, 1083 cm
DMSO-d6, δ): 8.23 (1H, m), 8.16 (1H, m), 8.04–7.93
4H, m), 7.74–7.56 (5H, m), 5.09 (1H, d, J = 1.7 Hz),
.32–2.25 (1H, m), 0.93 (3H, d, J = 7.0 Hz), 0.73 (3H, d,
; H NMR (500 MHz,
(
2
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13
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1
1
3
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28.74, 128.31, 127.26, 126.70, 125.88, 81.59, 64.87,
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+
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+
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0
19
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4
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SUPPORTING INFORMATION
[13] (a) Butnariu, R. M.; Caprosu, M. D.; Bejan, V.; Ungureanu,
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Additional Supporting Information may be found online
in the supporting information tab for this article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet