Carbon-SO3H: A novel and recyclable solid acid catalyst for the synthesis of spiro[4H-pyran-3,3′-oxindoles]

Article abstract of DOI:10.1016/j.tetlet.2013.02.089

A bioglycerol derived carbon-sulfonic acid is found to catalyze efficiently the three-component one-pot condensation of isatin, malononitrile, and 1,3-dicarbonyls to afford a wide range of spiro[4H-pyran-3,3′-oxindole] derivatives in good yields and selec

Full text of DOI:10.1016/j.tetlet.2013.02.089

Tetrahedron Letters 54 (2013) 2466–2471
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Carbon–SO3H: a novel and recyclable solid acid catalyst for the synthesis
of spiro[4H-pyran-3,30-oxindoles]
B. Maheshwar Rao a, G. Niranjan Reddy a, T. Vijaikumar Reddy b, B. L. A. Prabhavathi Devi b, R. B. N. Prasad b,
J. S. Yadav a, B. V. Subba Reddy a,
⇑
a Natural Product Chemistry, CSIR – Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
b Center for Lipid Research, CSIR – Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A bioglycerol derived carbon-sulfonic acid is found to catalyze efficiently the three-component one-pot
condensation of isatin, malononitrile, and 1,3-dicarbonyls to afford a wide range of spiro[4H-pyran-
3,30-oxindole]derivatives in good yields and selectivity. The use of a recyclable solid acid catalyst makes
this method simple, convenient, and cost-effective.
Received 13 December 2012
Revised 25 February 2013
Accepted 27 February 2013
Available online 13 March 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Domino reaction
Solid acid catalysis
1,3-Dicarbonyls
Isatins
Malononitrile
Spirooxindoles
The spirooxindoles are frequently found in many alkaloids and
pharmaceuticals with promising biological activities (Fig. 1).1–3
Furthermore, these spirocycles possess anticancer and antimi-
crobial activity.4 They are also known to exhibit anticonvulsant,
analgesic,5 herbicidal,6 fungicidal7,8, and antibacterial properties.9
As a result, several synthetic approaches have been developed for
the synthesis of multi-stereogenic spirooxindoles.10 A variety of
and also from glycerol pitch (waste from fat splitting industry) by
in situ partial carbonization and sulfonation in a one-pot operation.
This solid acid catalyst has opened a new avenue in the field of
green catalysis by demonstrating its effectiveness for various
transformations.23,25 Therefore, the use of cost-effective solid acids
would make the process more practical in view of environmental
perception. Following our interest on the catalytic application of
solid acid catalysts,26 we herein report a simple and highly efficient
approach for the synthesis of spirooxindoles from isatin, malono-
catalysts such as
L
-proline,11 triethylamine,12 ethylenediamine
diacetic acid,13 piperidine,14 porcine pancreas lipase,15 triethanola-
mine,16 and 1-N-butyl-3-methyl-imidazolium tetrafluoroborate17
have been reported for the synthesis of spiro[4H-pyran-3,30-oxin-
dole] derivatives.11–17 Other catalysts such as sodium octadecano-
ate, TBAF, TPP, and potassium tetrachloroaurate trihydrate have
also been reported for this conversion.18–20 More recently, MgO
has been employed as a recyclable heterogeneous catalyst.21 In re-
cent years, carbon-based solid acid catalysts22 have attracted sig-
nificant attention as they are highly efficient, sustainable, and
eco-friendly. Of these, bioglycerol- based sulfonic acid functional-
ized polycyclic aromatic carbon catalyst reported by Prabhavathi
et al.23 has gained lot of attraction due to its high stability, reactiv-
ity, recyclability, and also sustainable preparation protocol.24 The
catalyst was prepared from bioglycerol (a by-product of biodiesel)
nitrile, and a-methylenecarbonyl compounds using glycerol-based
carbon-sulfonic acid as a recyclable catalyst. The carbon catalyst
was fully characterized by CHN analysis, XRD, XPS, IR, 13C NMR,
Mass, and Raman spectroscopy to establish its physico-chemical
characteristics.23b,25b Elemental composition of the catalyst was
found to be CH0.74S0.02O0.51 with 1.6 mmol/g of acid density and
Me
H
O
O
N
N
CO2Me
H
H
O
O
N
N
H
H
Pteropodine
Gelsemine
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V.S. Reddy).
Figure 1. Naturally occurring spirooxindoles.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.02.089

B. Maheshwar Rao et al. / Tetrahedron Letters 54 (2013) 2466–2471
2467
with –SO3H, –COOH, and –OH functional groups as reported for
other carbon-based catalysts.22,23
CN
CN
O
O
As a model reaction, we attempted the coupling of isatin (1),
malononitrile (2), and 1,3-cyclohexadione (3) in ethanol in the
presence of 10 w/w% of carbon acid catalyst at room temperature.
Though the reaction was sluggish at 25 °C, it proceeded well at
80 °C to furnish the desired product 4a in 94% yield (Scheme 1).
To optimize the reaction conditions, the above experiment was
performed in various solvents including tetrahydrofuran, acetoni-
trile, water, 1,4-dioxane, dimethylformamide, ethanol, and
chloroform. Of these solvents, ethanol appears to give the best
results. Subsequently, the effect of various solid acids such as
montmorillonite K10, ion-exchange resin, heteroploy acids,
cellulose-sulfonic acid, and silica sulfonic acid was studied. To
our surprise, acidic ion-exchange resin and montmorillonite K10
clay afforded the product 4a in low yields (Table 1, entries a
and b). Other solid acids like phosphomolybdic acid, cellulose-
sulfonic acid, and silica-sulfonic acid also gave the product 4a
in moderate yields (Table 1, entries c, d, and e). Among them,
carbon-sulfonic acid was found to be superior in terms of conver-
sion (Table 1, entry f).
O
2
O
NH2
Carbon-SO3H
EtOH, reflux
O
+
CN
N
N
H
O
O
H
4a
1
3
Scheme 1. Three-component reaction for the synthesis of 4a.
Table 1
Screening of solid acid catalysts in the formation of 4a
Entry
Catalyst
Time (h)
Yield (%)
a
b
c
d
e
f
Amberlyst-15
12
18
8
6
4
20
15
65
50
60
94
Montmorillonite K10
Phosphomolybdic acid
Cellulose–SO3H
Silica–SO3H
Carbon–SO3H
3
surface area of 0.21 m2/g. All the physico-chemical characteriza-
tion studies indicate that the carbon catalyst is partially
crystalline material consisting of polycyclic aromatic carbon sheets
Interestingly, several substituted isatins such as 5-chloro-, 5-
bromo-, and 5-nitro- derivatives gave the products in excellent yields
under optimized reaction conditions (Table 2). Besides malononitrile,
a
Table 2
Carbon-sulfonic acid catalyzed synthesis of spiropyrans
Entry
Isatin
Malononitrile (2)
1,3-Diketone (3)
Product (4)a
Time (h)
3.0
Yieldb
94
O
CN
CN
O
O
O
O
O
O
NH2
NH2
a
N
O
O
O
H
CN
N
H
O
O
O
CN
O
CO2Et
O
O
b
c
3.0
3.0
92
81
N
H
CO2Et
N
H
O
CN
CN
O
O
O
O
N
H
NH2
CN
N
H
O
O
CN
O
CO2Et
O
O
O
O
O
N
H
d
4.0
78
NH2
CO2Et
N
H
O
O
O
O
CN
CN
O
O
O
O
O
O
NH2
CN
e
f
3.0
3.0
4.5
85
87
92
N
H
N
H
O
CN
O
O
CO2Et
NH2
CO2Et
N
H
N
H
O
CN
CN
O
O
Cl
O
O
O
Cl
NH2
g
N
H
CN
O
N
H
(continued on next page)

2468
B. Maheshwar Rao et al. / Tetrahedron Letters 54 (2013) 2466–2471
Table 2 (continued)
Entry
Isatin
Malononitrile (2)
1,3-Diketone (3)
Product (4)a
Time (h)
3.0
Yieldb
88
O
CN
O
O
EtO
Cl
O
CO2Et
OEt
O
O
O
Cl
NH2
h
i
N
CO2Et
H
N
H
O
O
CN
CN
O
Br
Br
O
O
O
Br
Br
NH2
3.0
5.0
85
82
N
H
O
CN
N
H
O
O
CN
CN
O
O
O
O
O
N
H
j
NH2
CN
N
H
O
O
CN
CN
OH
O
Br
O
N
H
O
O
k
5.0
85
O
Br
Br
NH2
NH2
CN
N
H
O
O
O
CN
CN
O
O
EtO
O
Br
O
OEt
O
O
l
5.0
6.0
6.0
89
90
88
N
H
CN
N
H
O
CN
CN
O
O2N
O
O
N
O
O2N
O2N
m
n
NH2
CN
H
N
O
H
O
CN
CN
O
O
EtO
O
O2N
O2N
O
OEt
O
O
NH2
N
H
CN
N
H
O
O
CN
CN
OH
O
O
O
N
H
O
O
O
o
5.0
5.0
86
85
O2N
O2N
NH2
CN
N
H
O
O
O
CN
OH
O
O2N
CO2Et
O
O
N
H
O
p
O
NH2
CO2Et
N
H
a
All products were characterized by NMR, IR, and mass spectrometry.
Yield refers to pure products after chromatography.
b
the reaction was also successful with ethyl cyanoacetate. As shown in
Table2, variouscyclic andacyclic1,3-diketonesorb-ketoestersand4-
hydroxycoumarin participated well in this reaction (Table 2).27
Inspired by the results obtained with 1,3-diketones, we turned
our attention to study the reactivity of acenaphthenequinone (5)
with malononitrile and ethyl cyanoacetate. The reaction proceeded
smoothly under similar conditions affording the corresponding
spiro-acenaphthylene derivatives in excellent yields and selectivity
(Table 3, entries a–d).
spiro[indoline-3,40-pyrano[2,3-c]pyrazole] derivatives (8) were
prepared by using this approach. To know the catalytic effect of
carbon sulfonic acid, the reaction was performed without the cat-
alyst. However, no desired product was obtained in the absence of
catalyst even in refluxing ethanol. The use of solid acid catalyst
makes this method quite simple and more convenient to prepare
a variety of spiropyrans in a single-step process.
A sequence of reactions such as Knoevenagel reaction, Michael
reaction followed by Thorpe–Ziegler reaction takes place during
the formation of the product. Mechanistically, the reaction was
proposed to proceed through the activation of isatin by carbon-
Next we extended our efforts to examine the reactivity of 3-
methyl-1H-pyrazol-5(4H)-ones. As shown in Table 4, numerous

B. Maheshwar Rao et al. / Tetrahedron Letters 54 (2013) 2466–2471
2469
Table 3
Carbon-sulfonic acid catalyzed synthesis of spiroacenaphthylenes
Entry
Acenaphthe quinone (5)
Malononitrile (2)
1,3-Diketone (3)
Product (6)
Time (h)
3.0
Yield (%)
O
CN
O
O
O
O
O
CN
a
O
91
90
NH2
CN
O
CN
O
O
O
CO2Et
O
O
O
b
3.5
NH2
NH2
NH2
CO2Et
O
O
CN
CN
O
O
O
O
O
O
O
c
3.0
3.0
93
92
O
O
CN
CN
O
O
O
CO2Et
d
CO2Et
Table 4
Carbon-sulfonic acid catalyzed synthesis of spiropyrans with pyrazoles
Entry
Isatin(1)
Malonoitrile(2)
1,3-Diketone(7)
Product (8)
Time (h)
5.0
Yield (%)
90
O
CN
CN
N NH
O
O
N
O
N
N
H
a
NH2
H
CN
N
O
H
O
CN
CN
N
NH
Cl
O
O
N
O
N
Cl
N
H
b
c
5.0
5.0
92
92
NH2
CO2Et
H
N
H
O
O
CN
CN
N NH
O2N
O
O
N
O
N
O2N
N
NH2
H
H
CN
N
O
H
O
CN
CN
Ph
Cl
N
N
N
O
O
N
N
H
O
d
e
f
5.0
5.0
5.0
94
95
94
Cl
Ph
NH2
CN
N
H
O
O
CN
CN
Ph
O
Br
N
N
O
N
O
N
N
H
Br
Ph
NH2
CN
N
H
O
N
O
CN
CN
Ph
O
O2N
N
O
N
O
N
N
H
O2N
Ph
NH2
CN
N
O
H

2470
B. Maheshwar Rao et al. / Tetrahedron Letters 54 (2013) 2466–2471
O
S
O
O
O
H
NC
O
CN
O
O
O
EWG
CN
EWG
O
EWG
N
-H2O
N
H
O
N
H
O
H
2
1
O
O
O
+
H
O
O
_
O
-
H
N
N
NH
EWG
C
EWG
EWG
N
H
N
O
O
N
H
O
H
O
O
NH2
EWG
N
H
O
4
Scheme 2. A plausible reaction mechanism.
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Shestopalov, A. M. Russ. Chem. Bull. Int. Ed. 2008, 57, 2373.
sulfonic acid to generate
quent 1,4-addition of 1,3-dione on
a
,b-unsaturated dicyano adduct. Subse-
,b-unsaturated dicyano ad-
a
duct followed by an intramolecular cyclization of the adduct
through [1,3]-sigmatropic proton shift of the iminopyrans led to
the formation of a stable 2-amino-4H-pyran ring system. In the
presence of both nitrile and ester groups, the nucleophilic addi-
tion of enolic oxygen occurs predominantly to nitrile rather than
to the ester group affording the desired 2-amino-4H-pyran. This
predominance can be explained by the higher electrophilicity
and lower steric hindrance of the nitrile group toward nucleo-
philic addition compared to ester functionality. Thus the forma-
tion of 2-amino-4H-pyran ring is highly regioselective
(Scheme 2).12
Finally, the reusability of the carbon acid catalyst was checked
by performing the reaction of isatin, malononitrile, and 1,3-cyclo-
hexadione using the recovered catalyst. The desired product 3a
was isolated in 94%, 93%, 90%, 89%, and 85% yields over five cycles
with a gradual decrease of activity.
13. Hari, G. S.; Lee, Y. R. Synthesis 2010, 3, 453.
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1789.
17. Kurosh, R.-M.; Leila, Y.-M. Tetrahedron 2011, 67, 5693.
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2010, 66, 339; (b) Gao, S.; Tsai, C. H.; Tseng, C.; Yao, C. Tetrahedron 2008, 64,
9143; (c) Riyaz, S.; Naidu, A.; Dubey, P. K. Lett. Org. Chem. 2012, 9, 101; (d)
Dounav, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945; (e) Madin, A.;
O’Donnell, C. J.; Oh, T.; Old, D. W.; Overman, L. E.; Sharp, M. J. J. Am. Chem. Soc.
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In summary, bioglycerol derived carbon-sulfonic acid has
proved to be a highly efficient solid acid catalyst for the synthesis
of spiro[4H-pyran-3,30-oxindole] derivatives by means of the Knoe-
venagel/Michael/cyclization reaction. The major advantages of the
present method are high conversions, low cost, and recyclability of
the catalyst, which makes this method more attractive.
19. (a) Zhu, S.-L.; Ji, S.-J.; Zhang, Y. Tetrahedron 2007, 63, 9365; (b) Shanthi, G.;
Subbulakshmi, G.; Perumal, P. T. Tetrahedron 2007, 63, 2057.
Acknowledgements
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B.M.R. thanks the UGC, New Delhi for the award of a fellowship.
References and notes
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Brenam, M. K. Synthesis 2009, 3003.
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Blais, C.; Lamothe, S.; Attardo, G.; Gourdeau, H.; Tseng, B.; Kasilbhatla, S.; Cai, S.
24. General procedure for the preparation of glycerol-based carbon catalyst: A mixture
of bioglycerol (10 g) and concentrated sulfuric acid (30 g) was heated at 180 °C
for 20 min, facilitating in situ partial carbonization and sulfonation. The
reaction mixture was allowed to remain at the same temperature for about
20 min (until foaming ceased) resulting in
a polycyclic aromatic carbon
product. The compound was cooled to ambient temperature and washed with

B. Maheshwar Rao et al. / Tetrahedron Letters 54 (2013) 2466–2471
2471
hot water until the washings indicated a neutral pH. The partially crystalline
product was filtered and dried till it was moisture-free to afford bioglycerol
based carbon catalyst (4 g).
J = 6.4 Hz, 2H, CH2), 6.75 (d, J = 8.0 Hz, 1H, ArH), 7.22–7.26 (m, 1H, ArH), 7.32 (s,
1H, ArH), 7.33 (s, 2H, NH2), 10.55 (s, 1H, NH). ESI-MS: m/z 385.
(4l)
pyran]-50-carboxylate: mp 260–262 °C. IR (KBr): mmax 3384, 3314, 3190, 2207,
1716, 1661, 1596, 1476, 1417, 1380, 1282, 1221, 1073 cmꢀ1 1H NMR
Ethyl
20-amino-5-bromo-30-cyano-60-methyl-2-oxo-spiro[indoline-3,40-
25. (a) Ramesh, K.; Murthy, S. N.; Karnakar, K.; Nageswar, Y. V. D.; Vijayalakhsmi,
K.; Devi, B. L. A. P.; Prasad, R. B. N. Tetrahedron Lett. 2012, 53, 1126; (b)
Karnakar, K.; Murthy, S. N.; Ramesh, K.; Nageswar, Y. V. D.; Reddy, T. V.; Devi, B.
L. A. P.; Prasad, R. B. N. Tetrahedron Lett. 1968, 2012, 53; (c) Ramesh, K.; Murthy,
S. N.; Karnakar, K.; Reddy, K. H.; Nageswar, Y. V. D.; Vijay, M.; Devi, B. L. A. P.;
Prasad, R. B. N. Tetrahedron Lett. 2012, 53, 2636; (d) Karnakar, K.; Murthy, S. N.;
Reddy, K. H.; Nageswar, Y. V. D.; Chandrakala, U.; Devi, B. L. A. P.; Prasad, R. B.
N. Tetrahedron Lett. 2012, 53, 3497.
;
(300 MHz, DMSO-d6): d 0.85 (t, J = 6.8 Hz, 3H, CH3), 2.33 (s, 3H, CH3), 3.80–
3.84 (m, 2H, CH2), 6.77 (d, J = 8.0 Hz, 1H, ArH), 7.23 (s, 2H, NH2), 7.29 (s, 1H,
ArH), 7.36 (d, J = 8.4 Hz, 1H, ArH), 10.55 (s, 1H, NH); ESI-MS: m/z 403.
(6a) 20-Aminno-70,70-dimethyl-2,50,60,70,80,-tetrahydro-2H-spiro[acenaphthylene-
1,40-chromene]-30-carboni-tirle: Solid, mp 266–268 °C. IR (KBr): mmax 3368,
3295, 2956, 2190, 1717, 1664, 1599 cmꢀ1 1H NMR (300 MHz, DMSO-d6): d
;
26. (a) Reddy, B. V. S.; Venkateswarlu, A.; Narayana Kumar, G. G. K. S.; Vinu, A.
Tetrahedron Lett. 2010, 51, 6511; (b) Reddy, B. V. S.; Venkateswarlu, A.; Madan,
Ch.; Vinu, A. Tetrahedron Lett. 1891, 2011, 52.
0.98 (s, 3H, CH3), 1.10 (s, 3H, CH3), 2.11 (d, J = 16.0 Hz, 1H), 2.13 (d, J = 16.0 Hz,
1H), 2.70 (s, 2H, CH2), 7.32 (s, 2H, NH2), 7.39–8.28 (m, 6H, ArH); 13C NMR
(100 MHz, DMSO-d6): d 28.1, 28.3, 32.8, 50.6, 51.5, 58.8, 64.6, 112.8, 118.4,
120.7, 122.2, 125.5, 129.1, 129.7, 130.7, 132.3, 133.3, 142.2, 145.1, 160.4, 164.9,
191.3, 206.3; ESI-MS: m/z 370.
27. General procedure for the preparation of spiro[4H-pyran-3,30-oxindole]derivatives:
A mixture of isatin (1 mmol), malononitrile or cyanoacetic esters (1 mmol),
1,3-dicarbonyl compounds (1 mmol), and the catalyst (10 wt %) in ethanol
(3 ml) was stirred at 80 °C for a specified time (see Table 2). After complete
conversion, as indicated by TLC, the reaction mixture was cooled to room
temperature. The resulting solid precipitate was filtered and dried along with
the catalyst. Further purification of the product was performed by
recrystallization using ethanol and the catalyst was recovered by filtration.
(4a)2-Amino-20,5-dioxo-5,6,7,8-tetrahydrospiro[chro-mene-4,30-indoline]-3-
(6b)
spiro[acenaphthylene-1,40-chromene]-30-carboxylate: Solid, mp 257–259 °C. IR
(KBr): mmax 3379, 3269, 2958, 1718, 1685, 1520 cmꢀ1 1H NMR (300 MHz,
Ethyl
20-amino-70,70-dimethyl-2,50-dioxo-50,60,70,80-tetrahydro-2H-
;
DMSO-d6): d 0.42 (t, J = 7.0 Hz, 3H, CH3), 1.06 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.99
(d, J = 16.0 Hz, 1H), 2.12 (d, J = 16.0 Hz, 1H), 2.61 (d, J = 17.6 Hz, 1H), 2.71 (d,
J = 17.6 Hz, 1H), 3.36 (q, J = 7.3 Hz, 2H), 8.01 (s, 2H, NH2), 8.16-7.30 (m, 6H,
ArH); 13C NMR (100 MHz, DMSO-d6): d 13.1, 27.6, 28.6, 32.4, 50.1, 51.6, 59.3,
68.6, 78.1, 115.7, 119.8, 120.1, 124.5, 128.6, 129.1, 130.1, 130.3, 136.9, 142.2,
146.1, 160.3, 163.6, 168.3, 196.1, 206.1; ESI-MS: m/z 417.
carbonitrile: Solid, mp 278–280 °C (dec). IR (KBr):
m
max 3370, 3286, 3132, 2191,
1709, 1680, 1655, 1630, 1471, 1351, 1211, 1076, 1011 cmꢀ1
;
1H NMR
(300 MHz, DMSO-d6): d 1.92 (t, J = 6.4 Hz, 2H), 2.27–2.16 (m, 2H, CH2), 2.66
(t, J = 6.2 Hz, 2H, CH2), 6.80 (d, J = 7.5 Hz, 1H, ArH), 6.90 (t, J = 7.6 Hz, 1H, ArH),
7.05 (d, J = 7.2 Hz, 1H, ArH), 7.14 (t, J = 7.6 Hz, 1H, ArH), 7.23 (s, 2H), 10.42 (s,
1H, NH); 13C NMR (300 MHz, DMSO-d6): d 20.3, 27.4, 37.0, 47.5, 58.2, 109.8,
112.5, 118.0, 122.3, 123.8, 128.8, 135.2, 142.5, 158.9, 166.7, 178.8, 195.7, 37.8,
41.3, 71.4, 72.7, 74.4, 75.7, 125.9, 127.5, 128.3, 128.4, 130.1, 133.6; ESI-MS: m/z
307.
(8a) 60-Amino-30-methyl-2-oxo-10H-spiro[indoline-3,40-pyrano[2,3-c]pyrazole]-
50-carbonitrile: Solid, mp 284–286 °C (dec). IR (KBr): mmax 3420, 3389, 3338,
3134, 2182, 2183, 1711, 1640, 1572, 1514, 1407, 1311, 1209, 1149, 1055,
939 cmꢀ1 1H NMR (300 MHz, DMSO-d6): d 1.54 (s, 3H, CH3), 6.91 (s, 1H, ArH),
;
7.02 (s, 2H, NH2), 7.22 (s, 1H, ArH), 10.51 (s, 1H, NH), 12.2 (s, 1H, NH). ESI-MS:
m/z 293.
(8b)
60-Amino-5-chloro-30methyl-2-oxo-10H-spiro[indoline-3,40-pyrano[2,3-
(4g)
indoline]-3-carbonitrile: Solid, mp 294–296 °C (dec). IR (KBr): mmax 3364,
3247, 3175, 2193, 1719, 1681, 1477, 1350, 1219, 1079, 1011 cmꢀ1 1H NMR
2-Amino-50-chloro-20,5-dioxo-5,6,7,8-tetrahydro-spiro[chromene-4,30-
c]pyrazole]-50-carbonitrile: Solid, mp 295–297 °C (dec). IR (KBr): mmax 3390,
3346, 3136, 2967, 2179, 1713, 1642, 1580, 1497, 1414, 1298, 1157, 1055, 823,
;
697 cmꢀ1 1H NMR (300 MHz, DMSO-d6): d 1.06 (s, 3H, CH3), 6.92 (d, J = 8.4 Hz,
.
(300 MHz, DMSO-d6): d 1.90–2.01 (m, 2H, CH2), 2.23 (t, J = 6.8 Hz, 2H, CH2),
2.66 (t, J = 6.4 Hz, 2H, CH2), 6.80 (d, J = 8.4 Hz, 1H, ArH), 7.16 (d, J = 2.0 Hz, 1H,
ArH), 7.26 (dd, J = 2.0, 8.0 Hz, 1H, ArH), 7.33(s, 2H), 10.55 (s, 1H, NH). ESI-MS:
m/z 341.
1H, ArH), 7.12 (s, 1H, ArH), 7.27 (s, 2H, NH2), 7.29–7.31 (m, 1H, ArH), 10.73 (s,
1H), 12.32 (s, 1H). ESI-MS: m/z 327.
(8d)
pyrano[2,3-c]pyrazole]-50-carbonitrile: Solid, mp 232–234 °C. IR (KBr): mmax
3440, 3264, 3172, 2196, 1698, 1653, 1577, 1175 cmꢀ1 1H NMR (300 MHz,
60-Amino-5-chloro-30-methyl-2-oxo-10-phenyl-10H-spiro[indoline-3,40-
(4d) Ethyl 2-amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahy-drospiro[chromene-
4,30-indoline]-3-carboxylate: Solid, mp 258–260 °C; IR (KBr): mmax 3370, 3236,
3180, 2957, 1715, 1690, 1670, 1648, 1615, 1525, 1470, 1344, 1316, 1289, 1220,
;
DMSO-d6): d 1.54 (s, 3H, CH3), 6.95 (d, J = 8.4 Hz, 1H), 7.34–7.42 (m, 3H), 7.52
(t, J = 8.2 Hz, 2H), 7.62 (s, 2H, NH2), 7.78 (d, J = 8.0 Hz, 2H), 10.88 (s, 1H); 13C
NMR (300 MHz, DMSO-d6): d 11.8, 47.8, 56.4, 95.5, 109.8, 118.0, 120.2, 125.5,
126.5, 129.5, 129.6, 131.7, 132.2, 137.3, 139.2, 144.1, 145.1, 161.1, 177.5; ESI-
MS: m/z 404.
11664, 1055, 905, 785, 745 cmꢀ1 1H NMR (300 MHz, DMSO-d6): d 0.81 (t,
;
J = 7.2 Hz, 3H, CH3), 0.95 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.98–2.15 (m, 2H, CH2),
2.45–2.62 (m, 2H, CH2), 3.63–3.73 (m, 2H, CH2O), 6.67 (d, J = 7.6 Hz, 1H, ArH),
6.76 (t, J = 7.2 Hz, 1H, ArH), 6.84 (d, J = 7.2, Hz, 1H, ArH), 7.03–7.07 (m, 1H,
ArH), 7.87 (s, 2H, NH2), 10.15 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6): d
13.7, 27.3, 28.4, 32.2, 47.2, 51.3, 59.5, 76.9, 108.8, 113.7, 121.2, 122.9, 127.8,
136.6, 144.7, 159.7, 160.8, 163.0, 168.3, 180.4, 195.3; ESI-MS: m/z 405.
(8e)
pyrano[2,3-c]pyrazole]-50-carbonitrile: Solid, mp 232–234 °C. IR (KBr): mmax
3436, 3268, 3168, 2198, 1705, 1650, 1576, 1168 cmꢀ1 1H NMR (300 MHz,
60-Amino-5-bromo-30-methyl-2-oxo-10-phenyl-10H-spiro[indoline-3,40-
.
DMSO-d6): d 1.57 (s, 3H, CH3), 6.91 (d, J = 7.6 Hz, 1H), 7.28 (t, J = 7.9 Hz, 1H),
7.43–7.52 (m, 4H), 7.64 (s, 2H, NH2), 7.78 (d, J = 7.8 Hz, 2H), 10.9 (s, 1H); 13C
NMR (300 MHz, DMSO-d6): d 12.1, 47.9, 56.5, 96.6, 110.2, 118.2, 120.8, 125.5,
126.6, 129.5, 129.6, 131.6, 132.3, 137.2, 139.2, 144.1, 145.0, 161.0, 178.8; ESI-
MS: m/z 448.
(4n)
pyran]-50-carboxylate: mp 244–246 °C. IR (KBr)): mmax 3405, 3300, 3200,
2200, 1725, 1668, 1632, 1579, 1475, 1382, 1355, 1283, 1223, 1083 cmꢀ1 1H
(Ethyl
20-amino-30-cyano-60-methyl-5-nitro-2-oxosp-iro[indoline-3,40-
;
NMR (300 MHz, DMSO-d6): d 0.84 (t, J = 7.2 Hz, 3H, CH3), 3.38 (s, 3H, CH3),
3.88–3.76 (m, 2H, CH2), 7.05 (d, J = 8.3 Hz, 1H, ArH), 7.41 (s, 1H, NH2), 8.08 (s,
1H, ArH), 8.18 (dd, J = 2.4, 7.2 Hz, 1H, ArH), 11.35 (s, 1H, NH). 13C NMR
(100 MHz, DMSO-d6): d 13.5, 19.5, 49.4, 49.5, 55.5, 61.0, 103.3, 110.0, 117.6,
119.5, 126.4, 136.3, 142.8, 148.8, 159.3, 160.7, 164.6, 179.4; ESI-MS: m/z 405.
(8f)
pyrano[2,3-c]pyrazole]-50-carbonitrile: Solid, mp 228–230 °C (dec). IR (KBr):
mmax 3268, 3175, 2209, 1710, 1650, 1576, 1178 cmꢀ1 1H NMR (300 MHz,
60-Amino-30-methyl-5-nitro-2-oxo-10-phenyl-10H-spiro[indoline-3,40-
;
DMSO-d6): d 1.57(s, 3H, CH3), 7.12 (d, J = 8.4 Hz, 1H), 7.38–7.54 (m, 3H), 7.67 (s,
2H, NH2), 7.78 (m, 2H), 7.98 (d, J = 6.8 Hz, 2H), 11.45 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): d 12.3, 47.8, 56.5, 96.5, 109.5, 118.1, 120.1, 125.6, 126.6,
132.0, 132.6, 131.7, 134.3, 137.6, 139.2, 144.9, 145.0, 161.2, 178.8; ESI-MS: m/z
415.
(4i)
indoline]-3-carbonitrile: mp 278–280 °C (dec). IR (KBr): mmax 3357, 3289,
3147, 2494, 1726, 1659, 1603, 1474, 1352, 1215, 1077, 1009 cmꢀ1 1H NMR
(300 MHz, DMSO-d6): d 1.92–1.97 (m, 2H, CH2), 2.23–2.26 (m, 2H, CH2), 2.72 (t,
2-Amino-50-bromo-20,5-dioxo-5,6,7,8-tetrahydro-spiro[chromene-4,30-
;