N-Bromosulfonamides catalyzed synthesis of new spiro [indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives

Article abstract of DOI:10.1002/jhet.2605

An efficient approach for the synthesis of pharmacologically important spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives from tandem, four component reaction of various hydrazines, isatins, β-ketoesters, and malononitrile or methyl(ethyl)cyanoester i

Full text of DOI:10.1002/jhet.2605

Month 2016
N-Bromosulfonamides catalyzed synthesis of new spiro [indoline-3,4’-
pyrano[2,3-c]pyrazole] derivatives
Ramin Ghorbani-Vaghei* and Seyedeh Mina Malaekehpoor
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 65174 Hamedan, Iran
*
E-mail: #rgvaghei@yahoo.com
Received October 9, 2015
DOI 10.1002/jhet.2605
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
An efficient approach for the synthesis of pharmacologically important spiro[indoline-3,4’-pyrano[2,3-c]
pyrazole] derivatives from tandem, four component reaction of various hydrazines, isatins, β-ketoesters, and
malononitrile or methyl(ethyl)cyanoester in the presence of N,N,N’,N’-tetrabromobenzene-1,3-
disulfonamide [TBBDA] and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] as efficient
organocatalysts was reported.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
report an efficient procedure for the synthesis of medici-
nally important spiropyrano[2,3-c]pyrazole derivatives,
which contain various heterocyclic moieties, using
N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide (TBBDA)
and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide)
(PBBS) [30] as efficient catalysts via four component
cyclocondensation reaction under mild conditions
(Scheme 1).
N,N,N’,N’-Tetrabromobenzene-1,3-disulfonamide
(TBBDA) and PBBS are inexpensive and non-hazardous
catalysts, provided the TBBDA and PBBS are easy and
stable under atmospheric conditions for two months. Also,
after completion of the reaction, the catalyst is recovered
and can be reused several times without significantly
decreasing the yield (Scheme 2).
Heterocyclic structures with a broad spectrum of biological
properties exist in many natural products and applied in the ag-
ricultural and pharmaceutical sectors. Spiro heterocycles, espe-
cially spirocyclic oxindole nucleus, are a substantial category
of natural alkaloids that possess various biological and phar-
macological activities, such as spirotryptostatin A, B, which
are isolated from the fermentation broth of Aspergillus fumi-
gates, inhibits of cell cycle at G2/M phase [1] and Koumine,
which is one of the alkaloids isolated from the Gelsemium
sempervirens plant that has antitumor and analgesic activities
[
2]. Chitosenine as a Gardneria multiflora oxindole alkaloid
has ganglioblocking action (Fig. 1) [3]. Subsequently, various
approaches for the construction of spiroheterocyclic com-
pounds have been reported [4–8]. Pyranopyrazoles are one
of the most pharmacologically important fragments that
condensed to 2-oxindole nucleus, which have been exhibited
anti-inflammatory, [9] hypotensive, [10], and analgesic
activities [11]. Because of unprecedented structural array and
extremely biological activities of these compounds, during
the last years, the synthesis of various spirooxindole systems
has been receiving much attention [12–19].
In order to optimize the reaction conditions, we first
examined the effect of TBBDA, PBBS, N,N,N’,N’-
tetrachlorobenzene-1,3-disulfonamid
(TCBDA)
[31],
trichloroisocyanuric acid (TCCA), and N-Chlorosuccinimide
(NCS) as well as a variety of solvents for the synthesis of 5a
from four component reaction between phenyl hydrazine,
malononitrile, ethylacetoacetate, and isatin as a model reac-
tion. We found that in the absence of a catalyst, no product
was formed even after prolonged reaction time. We found that
the optimized reaction conditions for this reaction were
TBBDA (0.035g, 0.06 mmol) and/or PBBS (0.02g) and
RESULTS AND DISCUSSION
CH CN as solvent system (Table 1, entries 8, 11). The results
3
As a part of our studies on the role and application
of N-halosulfonamides in organic synthesis [20–29], we
are listed in Table 1. These results encouraged us to investi-
gate the scope and generality of this procedure for synthesis
©
2016 Wiley Periodicals, Inc.

R. Ghorbani-Vaghei and S. M. Malaekehpoor
Vol 000
Figure 1. Structure of some biologically active spirocyclic oxindole alkaloids.
of spiro[indoline-3,4’-pyrano[2,3-c]pyrazole] derivatives un-
der optimized reaction conditions. The cyclocondensation
reaction of various hydrazines with either electron-
withdrawing or electron-donating groups and isatin
substituted with β-ketoester and malononitrile or ethyl
catalytic activity of TBBDA. It is possible that the posi-
tive brominum moiety also has some role in facilitating
the process.
CONCLUSION
(methyl)cyanoester with 1:1:1:1 molar ratios proceeded
smoothly at ambient temperature, and corresponding prod-
ucts were prepared in good to high yields.
It is noteworthy that steric and electronic variation in the
β-ketoester, isatin, and hydrazine derivatives have effected
on speed of reaction and yield of products. The results are
summarized in Table 2.
As demonstrated in Table 2, when ethyl(methyl)
cyanoacetate was applied for this synthesis, ester substituent
in products (5d, 5k) was hydrolyzed to the corresponding
acid.
In summary, we have described regioselective, conve-
nient synthesis of new spiro[indoline-3,4’-pyrano [2,3-c]
pyrazole] derivatives from hydrazine derivatives, β-
ketoester, substituted isatins, and malononitrile or ethyl
(
methyl)cyanoester in the presence of TBBDA or PBBS
as efficient organocatalysts at ambient temperature under
mild conditions. Good yields, simple procedure, easy of
purification, and reusability of the catalyst are advan-
tages of this process.
Also, our experiments determined that TBBDA is a
reusable catalyst; therefore, it is applied for the synthesis
of 5a that after three runs reused of the catalyst its
catalytic activity is almost the same as that of a fresh cata-
lyst (Table 2, entry 1). The average chemical yield for three
consecutive runs of reused of the catalyst was (77%). The
results are shown in Table 2.
EXPERIMENTAL
All commercially available chemicals were purchased
from Merck and Fluka companies and used without further
1
13
purification unless otherwise stated. H and C-NMR
spectra were recorded on Bruker Avance 400MHz FT
and Varian 90MHz NMR instrument. Chemical shifts were
expressed in parts per million (ppm), J in hertz (Hz). Infra-
red (IR) spectroscopy was performed on a Perkin Elmer
GX FT-IR spectrometer. Mass spectra were recorded on a
Shimadzu QP 1100 BX Mass Spectrometer. Elemental
analyses (C,H,N) were performed with CHNS-932, Leco,
USA.
Probable reaction mechanism in this way that initially
+
these catalysts releases Br in situ, which act as an
electrophilic species and accelerated the formation of
products. Therefore, the following mechanism can be
suggested for the synthesis of spiro[indoline-3,4’-
pyrano[2,3-c]pyrazole] derivatives (Scheme 3) [15,27].
Also, using a catalytic amount of aqueous 48% HBr
instead of TBBDA to afford no desired product, this
result indicates that the generation of the protic acid
HBr may not be the only factor responsible for the
Typical Procedure for the Synthesis of 6′-Amino-3′-
methyl-2-oxo-1′-(phenyl)-1′H-spiro[indoline-3,4′-pyrano[2,3-
c]pyrazole]-5′-carbonitrile Using N,N,N’,N’-tetrabromoben
Scheme 1. Synthesis of new spiro pyranopyrazole derivatives using N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide (TBBDA) or poly(N,N’-dibromo-
N-ethyl-benzene-1,3-disulfonamide) (PBBS).
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Synthesis of new spiro [indoline-3,4’-pyrano[2,3-c]pyrazole]
Scheme 2. Structure of N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide (TBBDA) and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide) (PBBS).
zene-1,3-disulfonamide or poly(N,N’-dibromo-N-ethyl-ben
zene-1,3-disulfonamide) (Table 2, entry 1). A mixture of
phenylhydrazine (0.108 g, 1 mmol), ethyl acetoacetate
123.0, 125.3 (C Ar), 129.7, 130.2, 132.6 (C Ar), 135.3,
136.4 (C Ar), 142.0, 144.0, 145.2, 161.5 (C=O), 177.9.
MS m/z = 383 [M ] (8), 355 (70), 317 (64), 208 (55),
+
(
(
(
0.130g, 1mmol), isatin (0.147g, 1mmol), malononitrile
0.066g, 1mmol), TBBDA (0.035g, 0.06mmol), or PBBS
188 (82), 90 (100); Anal. calcd. for C H N O : C,
68.92; H, 4.47; N, 18.27%; Found: C, 68.01; H, 4.31;
N, 17.95%.
2
2 17 5 2
0.02g) in CH CN (2mL) was stirred at room temperature
3
for appropriate time (Table 2, entry 1). The progress of the
reaction was monitored by TLC (9:3, n-hexane/acetone).
6′-Amino-3′-methyl-2-oxo-1′-(p-chlorophenyl)-1′H-spiro
[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5c). Yield
0.28 g (71%); Yellow powder; m.p.: 234–236°C; IR (KBr,
After completion of the reaction, CH CN (10mL) was
3
À1
added. The solid product was collected by filtration, washed
with acetonitrile, and dried and purified by recrystallization
from ethanol. After evaporation of the solvent under
reduced pressure, CH Cl was added and the catalyst was
νmax/cm ): 3366, 3307, 3169, 3087, 2202, 1693, 1644,
1
1521, 1487, 1394, 1216, 1090, 753; H-NMR (90 MHz,
DMSO-d ) δH (ppm) 1.51 (s, 3H, CH ), 7.02–7.19 (m,
6
3
4H, ArH), 7.55–7.57 (d, J= 1.8 Hz, 2H, ArH), 7.85–7.87
2
2
removed by filtration.
Physical and Spectroscopic Data. 6′-Amino-3′-methyl-2-
(d, J = 1.8 Hz, 2H, ArH), 8.84 (d, 2H, NH ), 10.77 (s,
2
13
1H, NH). C-NMR (100 MHz, DMSO-d ) δ (ppm)
6 C
oxo-1′-(p-tolyl)-1′H-spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-
11.67 (CH ), 47.76 (C), 56.14, 96.33, 109.8, 117.9,
3
5
′-carbonitrile (5b). Yield 0.28g (75%); Yellow powder;
120.1, 122.6 (C Ar), 124.8, 126.5, 129.2 (C Ar), 129.4
(C Ar), 132.1, 137.2 (C Ar), 141.5, 143.9, 144.9, 161.0
(C=O), 177.4. MS m/z= 403 [M ] (3), 384 (30), 309
À1
m.p.: 213–214°C; IR (KBr, νmax/cm ): 3448, 3328, 3186,
3
7
+
030, 2191, 1712, 1649, 1619, 1530, 1396, 1223,
À1
1
52cm ; H-NMR (400 MHz, DMSO-d ) δ (ppm) 1.53
(17), 208 (91), 195 (55), 168 (38), 79 (100). Anal.
calcd. for C H ClN O : C, 62.46; H, 3.49; N, 17.34%;
6
H
(
s, 3H, CH ), 2.36 (s, 3H, CH ), 6.93-6.95 (d, J=7.6Hz,
3 3
21 14
5 2
1
1
7
H, ArH), 7.00–7.04 (m, 1H, ArH), 7.16–7.18 (d, J = 8.0 Hz,
Found: C,61.71; H, 3.48; N, 16.70%.
H, ArH), 7.26–7.32 (m, 3H, ArH), 7.54 (s, 2H, NH ),
6′-Amino-5-chloro-3′-phenyl-2-oxo-1′-(pyridyl)-1′H-spiro
[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carboxylic acid (5d).
Yield 0.36 g (70%); Yellow powder; m.p.: 325–326°C;
2
1
3
.64–7.66 (m, 2H, ArH), 10.72 (s, 1H, NH). C-NMR
(
(
100 MHz, DMSO-d ) δ (ppm) 12.11 (CH ), 20.96
CH ), 48.24 (C), 56.60, 96.56, 110.2, 118.4, 120.6,
6 C 3
À1
IR (KBr, νmax/cm ): 3261, 3153, 3013, 2806, 1729, 1688,
3
Table 1
Optimization of reaction conditions for the synthesis of 6′-amino-3’-methyl-2-oxo-1′-(phenyl)-1′H-spiro[indoline-3,4′-pyrano[2,3-c]
pyrazole]-5′-carbonitrile.
Entry
Conditions
Time (hours)
Yield (%)
1
2
3
4
5
6
7
8
9
TCBDA (0.05 g), CH
TCBDA (0.03 g), Acetone, rt
TCBDA (0.055 g), Solvent-free, rt
2
TCBDA (0.04 g), EtOH/H O (8:2), rt
BNBTS (0.02 g), Pryidine, rt
TCCA (0.03 g), EtOAc, rt
NCS (0.07 g), THF, rt
3
CN, rt
5
3
3
3
4
4
4
4
4
4
4
4
60
—
—
—
50
35
—
80
65
30
70
—
TBBDA (0.035 g), CH
TBBDA (0.05 g), CH CN, rt
PBBS (0.04 g), EtOH, ref.
PBBS (0.02 g), CH CN, rt
No Catalyst, EtOH, rt
3
CN, rt
3
10
11
12
3
a
Experimental conditions: phenyl hydrazine (1 mmol), ethyl acetoacetate (1 mmol), isatin (1 mmol), and malononitrile (1 mmol).
TCBDA, N,N,N’,N’-tetrachlorobenzene-1,3-disulfonamid; TBBDA, N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide; PBBS, poly(N,N’-dibromo-N-
ethyl-benzene-1,3-disulfonamide); BNBTS, N,N’-Dibromo-N,N’-1,2-ethanediylbis(p-toluenesulphonamide).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei and S. M. Malaekehpoor
Vol 000
Table 2
Substrate scope of spiro[indoline-3,4’-pyrano[2,3-c]pyrazole derivatives.
Time (hours)
Yield (%)
2
3
Entry
1
Hydrazine
R
X
R
Product
TBBDA PBBS TBBDA
PBBS
70
Ref.
15
b
Me
H
CN
4
4
80
2
Me
H
CN
3
4
75
80
—
3
Me
H
CN
4.5
5
71
68
—
4
Ph
5-Cl
CO
2
Et
4.5
4
70
80
—
—
—
5
Ph
H
CN
3
4
70
65
6
Me
H
CN
2.5
2
80
80
7
Ph
5-Cl
CN
2
3.5
60
50
—
(Continues)
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Month 2016
Synthesis of new spiro [indoline-3,4’-pyrano[2,3-c]pyrazole]
Table 2
(Continued)
Time (hours)
Yield (%)
2
R
3
R
Ent rEy ntry
Hydrazine
X
Product
TBBDA PBBS TBBDA
PBBS
Ref.
8
Me
Me
Ph
5-Cl
5-NO
5-NO
CN
CN
CN
1.5
4
80
86
70
71
80
60
—
—
—
9
2
2
3
1
0
2
4
4.5
11
NH
2
NH
2
Ph
5-Cl
2
CO Me
1
1
86
80
—
a
Products were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods.
b
Isolated yield after three consecutive runs: 80, 77, 75.
TBBDA, N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide; PBBS, poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide).
À1
1
1
572, 1438, 1305, 1200, 769cm ; H-NMR (400 MHz,
129.2 (C Ar), 139.3 (C Ar), 139.6, 148.7, 152.5, 155.0,
159.3 (C=O), 163.4 (C=O). MS m/z=515 [M ] (17), 413
+
DMSO-d ) δ (ppm) 6.85–6.87 (d, J = 8 Hz, 1H, ArH),
6
H
6
7
.94–6.96 (d, J= 8.4Hz, 1H, ArH), 6.99 (s, 1H, ArH),
.07–7.10 (t, J =6.8 Hz, 1H, ArH), 7.29–7.33 (m, 2H,
(25), 384 (67), 368 (58), 320 (67), 272 (100).
6′-Amino-3′-phenyl-2-oxo-1′-(pyridyl)-1′H-spiro[indoline-3,4′-
ArH), 7.45–7.47 (d, J =8.4 Hz, 1H, ArH), 7.61–7.64 (m,
pyrano[2,3-c]pyrazole]-5′-carbonitrile (5e).
Yield 0.30g
1
8
1
H, ArH), 7.79–7.88 (m, 1H, ArH), 8.22 (s, 1H, ArH),
.28–8.29 (d, J= 4.0Hz, 1H, ArH), 8.37 (s, 1H, ArH),
(70%); Pale yellow powder; m.p.: 211–214°C;
À1
IR (KBr, νmax/cm ): 3373, 3295, 3075, 2960, 2940,
À1
0.67 (s, 1H, NH), 11.24 (br, 2H. NH ), 12.75 (s, 1H,
1722, 1693, 1608, 1485, 1377, 1219, 1181, 1073cm
;
2
1
3
1
OH). C-NMR (100 MHz, DMSO-d ) δ (ppm) 107.9,
H-NMR spectrum (400 MHz, DMSO-d ) δH (ppm)
6
C
6
1
12.6, 119.3, 119.4, 122.8 (C Ar), 126.7(C Ar), 129.0,
6.91–6.97 (m, 2H, ArH), 7.04–7.24 (m, 4H, ArH),
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R. Ghorbani-Vaghei and S. M. Malaekehpoor
Vol 000
Scheme 3. Postulated mechanism for the synthesis of spiropyranopyrazole derivatives.
7
.27–7.31 (t, J = 7.6 Hz, 1H, ArH), 7.45–7.50 (m, 2H,
(80), 175 (82), 115 (57), 78 (63); Anal. Calc. for
C H N O : C, 64.86; H, 3.81; N, 22.69%; Found: C,
64.78; H, 3.74; N, 21.88%.
ArH), 7.55–7.59 (t, J = 7.2 Hz, 2H, ArH), 7.82–7.86 (t,
J = 8.4 Hz, 2H, ArH), 8.05–8.08 (t, J = 6.8 Hz, 1H, ArH),
8
2
0
14
6
2
13
.26–8.27 (d, 2H, NH ), 11.11 (s, 1H, NH). C-NMR
6′-Amino-5-chloro-3′-phenyl-2-oxo-1′-(pyridyl)-1′H-spiro
[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5g). Yield
0.27 g (60%); Pale yellow powder; m.p.: 228–230°C; IR
2
(100 MHz, DMSO-d ) δ (ppm) 107.1, 110.7, 116.3,
6 C
1
1
1
2
18.5, 119.2, 122.1 (C Ar), 122.5 (C Ar), 127.3 (C Ar),
27.9, 129.5 (C Ar), 131.9 (C Ar), 133.3 (C Ar), 138.8,
48.2, 148.5. MS m/z=432 [M ] (80), 325 (28), 234 (84),
06 (74), 160 (12), 115 (16), 91 (18); Anal. calcd. for
À1
(KBr, νmax/cm ): 3309, 3166, 2853, 2183, 1723, 1633,
+
À1
1
1595, 1561, 1451, 1201, 769 cm ; H-NMR (400 MHz,
DMSO-d ) δ (ppm) 6.83–6.85 (d, J =8.4 Hz, 1H, ArH),
6
H
C H N O : C, 69.44; H, 3.73; N, 19.43%; Found: C,
6.95–6.97 (m, 1H, ArH), 7.25–7.27 (d, J = 8.4Hz, 1H,
2
5 16 6 2
6
9.04; N, 19.27%.
ArH), 7.32–7.34 (m, 3H, ArH), 7.44–7.54 (m, 7H, ArH,
6
′-Amino-3′-methyl-2-oxo-1′-(pyridyl)-1′H-spiro[indoline-
13
NH ), 10.64 (s, 1H, NH). C-NMR (100 MHz, DMSO-
2
3
0
,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5f).
Yield
.29g (80%); White powder; m.p.: 258–259°C; IR (KBr,
d6) δC (ppm) 81.69, 95.96, 107.9, 112.7, 119.3, 119.4,
1
22.8 (C Ar), 126.7 (C Ar), 129.0 (C Ar), 129.2, 134.8
À1
νmax/cm ): 3341, 3310, 3182, 3022, 2203, 1711, 1662,
1
(C Ar), 139.3 (C Ar), 139.6, 148.7, 155.0 (C Ar), 157.8,
À1
1
591, 1472, 1393, 1220, 1129, 1084, 785cm ; H-NMR
+
1
63.5 (C=O), 176.3. MS m/z = 466 [M ] (2), 402 (48),
(
400 MHz, DMSO-d ) δ (ppm) 1.55 (s, 3H, CH3),
6
H
384 (60), 310 (100), 237 (46), 204 (40), 78 (72); Anal.
Calc. for C H ClN O : C, 64.31; H, 3.24, N, 18.00%;
6
.94–6.96 (d, J = 8.0 Hz, 1H, ArH), 7.01–7.05 (m, 1H,
2
5
15
6 2
ArH), 7.15–7.17 (d, J = 7.2 Hz, 1H, ArH), 7.27–7.31
m, 1H, ArH), 7.39–7.43 (m, 1H, ArH), 7.47 (s, 2H,
NH ), 7.71–7.73 (d, J = 8.0 Hz, 2H, ArH), 7.98–8.02
Found: C, 64.87; H, 4.06; N, 18.66%.
6′-Amino-5-chloro-3′-methyl-2-oxo-1′-(pyridyl)-1′H-spiro
[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5h). Yield
(
2
(
1
(
m, 1H, ArH), 8.53–8.54 (d, J = 5.6 Hz, 1H, ArH),
0.32g (80%); Yellow powder; m.p.: 214–215°C; IR (KBr,
1
3
À1
0.75 (s, 1H. NH). C-NMR (100 MHz, DMSO-d ) δ
νmax/cm ): 3353, 3311, 3186, 3083, 2984, 2208, 1713,
6
C
À1
1
ppm) 12.17 (CH ), 48.11 (C), 56.5, 97.5, 110.3,
1660, 1592, 1472, 1393, 1086, 787cm ; H-NMR (400
3
1
1
15.8, 118.4, 122.9 (C Ar), 123.1, 125.3 (C Ar), 129.7,
32.5 (C Ar), 139.7, 142.0 (C Ar), 145.2 (C Ar), 146.1
MHz, DMSO-d ) δ (ppm) 1.59 (s, 3H, CH ), 6.95–6.98
(d, J = 6.8 Hz, 1H, ArH), 7.34–7.36 (m, 1H, ArH),
6
H
3
(
C Ar), 148.8, 150.6, 161.6 (C=O), 177.9. MS
7.40–7.43 (m, 1H, ArH), 7.55 (s, 2H, NH ), 7.71–7.73
(d, J = 8.4 Hz, ArH), 7.99–8.03 (m, 1H, ArH), 8.53–8.54
2
+
m/z = 370 [M ] (7), 342 (52), 304 (80), 276 (100), 195
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Synthesis of new spiro [indoline-3,4’-pyrano[2,3-c]pyrazole]
1
3
(
(
d, J = 4.0Hz, 1H, ArH), 10.90 (s, 1H, NH). C-NMR
7.65–7.67 (t, J=7.2Hz, 2H, ArH), 8.05 (d, J=2.0Hz, 1H,
ArH), 9.04 (s, 2H, NH ), 10.48 (s, 1H, NH), 12.03 (br,
H, OH). C-NMR (100MHz, DMSO-d ) δ (ppm)
100 MHz, DMSO-d ) δ (ppm) 12.2 (CH ), 48.3(C),
5.8, 96.8, 111.8, 115.9, 118.3, 122.9 (C Ar), 125.5,
27.1 (C Ar), 129.7 (C Ar), 134.6 (C Ar), 139.7, 140.9
C Ar), 145.0, 146.2 (C Ar), 148.8 (C Ar), 150.6, 161.6
C=O), 177.7. MS m/z = 404 [M ] (14), 376 (67), 339
2
6
C
3
13
1
1
5
1
(
(
(
6
C
11.2, 111.8, 117.3, 118.4, 122.6, 124.5 (C Ar), 125.1
(C Ar), 125.4, 125.6 (C Ar), 126.0 (C Ar), 126.8, 127.3
(
C Ar), 128.1 (C Ar), 128.3, 129.2 (C Ar), 137.5, 139.5,
+
+
1
66.1 (C=O). MS m/z= 408 [M ] (4), 384 (10), 195
84), 160 (100), 138 (84), 103 (94), 77 (55); Anal. Calc.
for C H ClN O : C, 58.76; H, 3.21; N, 13.71%;
35), 229 (64), 175 (75), 134 (48), 78 (100); Anal. Calc.
for C H ClN O : C, 59.34; H, 3.24; N, 20.76%;
(
20
13
6 2
20
13
4 4
Found: C, 58.05; H, 3.01; N, 20.62%.
Found: C, 58.54; H, 3.06; N, 12.22%.
6
′-Amino-3′-methyl-5-nitro-2-oxo-1′-(pyridyl)-1′H-spiro
[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5i). Yield
0
.35g (86%); Pale yellow powder; m.p.: 268–269°C; IR
Acknowledgments. We would like to thank Bu-Ali Sina University,
Center of Excellence in Development of Environmentally Friendly
Methods for Chemical Synthesis (CEDEFMCS) for financial
support of this study.
À1
(KBr, νmax/cm ): 3402, 3307, 3192, 3090, 2205, 1721,
À1
1
670, 1626, 1594, 1462, 1340, 1079, 840, 633cm
;
1
H-NMR (400 MHz, DMSO-d ) δ (ppm) 1.59 (s, 3H,
6
H
CH ), 7.17–7.19 (d, J =8.8 Hz, 1H, ArH), 7.41–7.44
3
(
m, 1H, ArH), 7.64 (s, 2H, NH ), 7.73–7.75 (d,
2
J =8.0 Hz, 1H, ArH), 7.99–8.04 (m, 1H, ArH),
.17–8.18 (d, J =2.4Hz, 1H, ArH), 8.26–8.29 (m, 1H,
ArH), 8.54–8.56 (m, 1H, ArH), 11.48 (s, 1H, NH).
REFERENCES AND NOTES
8
[
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13
C-NMR (100 MHz, DMSO-d ) δ (ppm) 12.3 (CH3),
6
C
4
8.2 (C), 55.2, 96.1, 110.7, 116.0, 118.2, 121.3, 123.0
2
006, 69, 715.
(
(
1
C Ar), 127.0 (C Ar), 133.7, 139.7 (C Ar), 143.6, 144.9
[
3] Harada, M.; Ozaki, Y. Chem Pharm Bull 1978, 26, 48.
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C Ar), 146.4, 148.2 (C Ar), 148.8, 150.5, 161.8 (C=O),
+
1677.
4805.
78.4. MS m/z = 415 [M ] (2), 382 (4), 240 (68), 210
[
[
5] Stork, G.; Zhao, K. J Am Chem Soc 1990, 112, 5875.
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6
′-Amino-5-nitro-3′-phenyl-2-oxo-1′-(pyridyl)-1′H-spiro
[
7] Ibrahim, M. N.; El-Messmary, M. F.; Elarfi, M. G. A. Eur J
[
0
(
1
7
6
indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile (5j). Yield
Chem 2010, 7, 55.
.33g (70%); Opalescent powder; m.p.: 193–195°C; IR
[
8] Yang, J.; Wearing, X. Z.; Le Quesne, P. W.; Deschamps, J. R.;
À1
KBr, νmax/cm ): 3341, 3315, 3187, 2959, 2203, 1721,
Cook, J. M. J Nat Prod 2008, 71, 1431.
[9] Zaki, M. E. A.; Soliman, H. A.; Hiekal, O. A.; Rashad, A. E. Z.
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659, 1627, 1587, 1528, 1467, 1338, 1289, 1074,
À1
1
45cm
;
H-NMR (400 MHz, DMSO-d ) δH (ppm)
6
[
.92–6.94 (d, J=8.4 Hz, 3H, ArH), 7.15–7.19 (m, 3H,
3
5
ArH), 7.25–7.29 (m, 1H, ArH), 7.48–7.51 (q, J=5.6Hz,
1
8
ArH), 11.31 (s, 1H, NH). C-NMR (100MHz, DMSO-d6)
δC (ppm) 110.5, 113.4, 116.8, 117.9, 121.2, 123.5, 125.3
(
39.
H, ArH), 7.65 (s, 1H, ArH), 7.86–7.88 (d, 2H, NH2),
.06–8.17 (m, 3H, ArH), 8.61–8.62 (d, J=3.2Hz, 1H,
[
[
12] Dworczak, R. Monatsh Chem 1991, 122, 731.
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G. I. Mol Divers 2009, 13, 47.
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7, 1090.
1
3
[
4
C Ar), 126.8, 127.8 (C Ar), 128.5, 129.1 (C Ar), 132.0,
[
15] Zou, Y.; Hu, Y.; Liu, H.; Shi, D. ACS Comb Sci 2012, 14, 38.
1
1
1
33.0 (C Ar), 134.6 (C Ar), 138.6, 139.8 (C Ar), 143.3,
46.9 (C Ar), 148.4, 149.0 (C Ar), 155.5, 156.9, 161.3,
67.1, 178.5 (C=O), 183.0. MS m/z=477 [M ] (3), 267
[16] Feng, J.; Ablajan, K.; Sali, A. Tetrahedron 2014, 70, 484.
[
17] Satasia, S. P.; Kalaria, P. N.; Avalani, J. R.; Raval, D. K.
Tetrahedron 2014, 70, 5763.
18] Paul, S.; Pradhan, K.; Ghosh, S.; De, S. K.; Das, A. R.
Tetrahedron 2014, 70, 6088.
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J. D.; Undale, K. A. Tetrahedron Lett 2013, 54, 5876.
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+
[
(3), 239 (3), 169 (10), 113 (13), 102 (74), 79 (100); Anal.
[
Calc. for C H N O : C, 62.89; H, 3.17; N, 20.54%;
Found: C, 62.86; H, 3.10; N, 20.10%.
25 15 7 4
[
6
′-Amino-5-chloro-3′-phenyl-2-oxo-1′H-spiro[indoline-3,4′-
Soc 2004, 51, 1373.
pyrano[2,3-c]pyrazole]-5′-carboxylic acid (5k).
Yield
.35 g (86%); Yellow powder. m.p.: 204–206°C; IR (KBr,
[21] Ghorbani-Vaghei, R.; Chegini, M.; Veisi, H.; Karimi-Tabar,
M. Tetrahedron Lett. 2009, 50, 861.
0
[22] Ghorbani-Vaghei, R.; Akbari-Dadamahaleh, S. Tetrahedron
À1
νmax/cm ): 3404, 3270, 3187, 3095, 1742, 1715, 1633,
Lett 2009, 50, 1055.
À1
1
1614, 1579, 1465, 1203, 1146, 820 cm ; H-NMR
[23] Ghorbani-Vaghei, R.; Veisi, H. Mol Divers 2010, 14, 249.
[
24] Ghorbani-Vaghei, R.; Shahbazi, H.; Veisi, H. Tetrahedron Lett
012, 53, 2325.
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RSC Adv 2013, 3, 25924.
(
400MHz, DMSO-d ) δ (ppm) 5.88 (s, 1H, NH),
6
H
2
6.82–6.88 (m, 1H, ArH), 7.22–7.24 (m, 1H, ArH),
[
7.25–7.32 (m, 1H, ArH), 7.38–7.41 (m, 2H, ArH),
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R. Ghorbani-Vaghei and S. M. Malaekehpoor
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[
[
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