Nano n-propylsulfonated γ-Al2O3: A new, efficient and reusable catalyst for synthesis of spiro[indoline-3,4-pyrazolo[3, 4-e][1,4]thiazepine]diones in aqueous media

Article abstract of DOI:10.1002/aoc.2942

Nano n-propylsulfonated γ-Al₂O₃ is easily prepared by the reaction of nano γ-Al₂O₃ with 1,3-propanesultone. This reagent can be used as an efficient catalyst for the synthesis of spiro [indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]diones in aqueous media. This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be reused and recovered several times. Copyright

Full text of DOI:10.1002/aoc.2942

Full Paper
Received: 18 August 2012
Revised: 13 September 2012
Accepted: 5 October 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2942
Nano n-propylsulfonated g-Al2O3: a new,
efficient and reusable catalyst for synthesis of
spiro[indoline-3,4-pyrazolo[3,4-e][1,4]
thiazepine]diones in aqueous media
Li Qiang Wu*
Nano n-propylsulfonated g-Al2O3 is easily prepared by the reaction of nano g-Al2O3 with 1,3-propanesultone. This reagent can
be used as an efficient catalyst for the synthesis of spiro [indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]diones in aqueous media.
This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be
reused and recovered several times. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: nano n-propylsulfonated g-Al2O3; 1,4-thiazepine; spirooxindole; heterogeneous catalysis; nanoparticles; multicomponent
reactions
two methods are associated with one or more disadvantages such
Introduction
as prolonged reaction time, low yield and the use of toxic solvents.
Multicomponent reactions (MCRs) have attracted considerable
The recovery and reusability of the catalyst are also a problem.
attention since they are performed without the need to isolate
Therefore, it is still desirable to seek a green and eco-friendly
protocol that uses a highly efficient and reusable catalyst for the prep-
any intermediate during their processes, may reduce time and
save both energy and raw materials.[1–3] They have merits
aration of spiro[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]diones.
over two-component reactions in several aspects, including the
Organic reactions in water have become an important research
simplicity of a one-pot procedure, possible structural variations
area. Many reactions have been accomplished in aqueous
medium.[17,18] Water has therefore become an attractive medium
and building up complex molecules.
One aspect of MCRs that has received relatively little attention
for many organic reactions, not only for the advantages
is their development using nanocatalysts which would lead
concerning the avoidance of expensive drying reactants, cata-
to processes close to the ideal synthetic reaction.[4–7] Nanome-
ter-sized particles are easily dispersible in solution by forming
lysts and solvents, but also for some unique reactivity and
selectivity. We now report a highly efficient procedure for the
stable suspensions. Furthermore, nanoparticles as heterogeneous
preparation of spiro[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]
catalysts have high catalytic activities due to their larger surface
diones via a one-pot, four-component reaction of 3-aminocroto-
area-to-volume ratio. For these reasons, the development of
synthetically useful multicomponent reactions using nanocata-
nonitrile, phenylhydrazine, isatins and thioacid using nano
n-propylsulfonated g-Al2O3 as an efficient and versatile catalyst
lysts has gained considerable interest.
in aqueous media (Scheme 1).
The 1,4-thiazepine ring is one of the important moieties in
nitrogen- and sulfur-containing heterocycles, and aryl- and
heteroaryl-fused derivatives of thiazepine represent an important
Experimental
group of compounds with interesting pharmaceutical properties.
Some of these compounds exhibited angiotensin-converting
Materials and Instrumentation
enzyme inhibition,[8] leading to the development of temocapril,[9]
a drug used for the treatment of hypertension.
g-Alumina powder with a particle size of about 20 nm was
purchased from aladdin (Shanghai, China) and used without
further purification. Other reagents and starting materials were
purchased from commercial sources and used as received. All
products were characterized by comparison of their spectral
The heterocyclic spirooxindole ring system is a widely distributed
structural framework present in a number of pharmaceuticals
and natural products,[10] including such cytostatic alkaloids as
spirotryprostatins A[11] an B[12] and strychnophylline.[13] The unique
structural array and the highly pronounced pharmacological
activity displayed by the class of spirooxindole compounds have
made them attractive synthetic targets.[14]
Recently, Chen et al.[15] and Karnakar et al.[16] reported
respectively the three-component synthesis of spiro[indoline-3,
4-pyrazolo[3,4-e][1,4]thiazepine]diones using p-TsOH or sulfonic
acid-functionalized carbon as a catalyst in CH3CN. However, the
*
Correspondence to: Li Qiang Wu, School of Pharmacy, Xinxiang Medical
University, Xinxiang, Henan 453003, China. E-mail: wliq1974@sohu.com
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003,
China
Appl. Organometal. Chem. 2013, 27, 148–154
Copyright © 2013 John Wiley & Sons, Ltd.

Nano n-propylsulfonated g-Al2O3: a new, efficient and reusable catalyst
SO3H
SO3H
SO3H
6'
7'
R2
O
R1
nano
¦Ã-Al2O
5'
7'a N1'
O
O
R3
2'
3 O
3'a
NC
4'
S7O
6
OH
+
8
1
+
R
O
+
2
HS
8a
3a
R3
N
N
R1
H2N
CH3
H2O, reflux
NHNH2
2
O
2 N3
1''
5
N
H4
2''
4''
O
3
3''
4
6''
1
5
5''
Scheme 1. Synthesis of spiro[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine] diones using nano n-propylsulfonated g-Al2O3.
and physical data with those previously reported. Progress of the
reactions were monitored by thin-layer chromatography.
CH3), 13C NMR (100 MHz, DMSO-d6): 179.2 (C5), 170.9 (C2’), 150.2
00
0
0
(C3a), 144.3 (C1), 137.8 (C7’a), 136.9 (C1 ), 130.2 (C6 ), 128.5 (C4 ),
00
00
0
0
0
X-ray powder diffraction (XRD) patterns were recorded using a
Cu Ka radiation source on a Bruker D8 Advance powder diffrac-
tometer. Scanning electron microscopy (SEM) studies were
conducted on a JSM-6390LV instrument. Transmission electron
microscopy (TEM) studies were performed using a JEM 2100
transmission electron microscope at an accelerating voltage of
150 kV. TGA curves were recorded using a DT-40 thermoanalyzer.
IR spectra were determined on an FTS-40 infrared spectrometer.
NMR spectra were determined on a Bruker AV-400 spectrometer
at room temperature using tetramethylsilane (TMS) as an
internal standard (DMSO-d6 solution); coupling constants (J) were
measured in Hz. Elemental analyses were performed by a Vario-III
elemental analyzer. Melting points were determined on an XT-4
binocular microscope and were uncorrected.
126.9 (C3 ), 126.0 (C4 ), 125.8 (C3 a), 125.6 (C5 ) , 124.2 (C7 ), 114.5
00
(C2 ), 106.4 (C8a), 47.9 (Cspiro), 31.6 (C6), 11.8 (CH3). Anal. calcd
for C20H15ClN4O2S: C 58.46, H 3.68, N 13.64, S 7.80; found:
C 58.57, H 3.70, N 13.53, S 7.78.
6-Chloro-30,60-dimethyl-10-phenyl-60,80-dihydrospiro[indoline-3,40-pyrazolo
[3,4-e][1,4]thiazepine]- 2,70(10H)-dione (5n; R1 = H, R2 = 6-Cl, R3 = CH3)
M.p. 276–278ꢀC. IR (KBr) n: 3366 (NH), 3244 (NH), 2925, 1718 (C O),
1655 (C N), 1462, 1382, 1243, 1199, 1056, 952, 915, 769, 691 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6): 11.02 (s, 1H, NH), 9.90 (s, 1H, NH),
7.60–7.39 (m, 5H, H-200-600), 7.22 (d, J = 7.6 Hz, 1H, H-50), 7.12
(s, 1H, s, 1H, H-70), 7.10 (d, J = 7.6 Hz, 1H, H-40), 4.77 (q, J = 7.6 Hz,
1H, CH), 1.52 (s, 3H, CH3), 1.30 (d, J = 7.6 Hz, 3H, CH3); 13C NMR
0
(100 MHz, DMSO-d6): 178.9 (C5), 174.2 (C2 ), 147.3(C3a), 142.9
0
00
0
0
00
(C1), 140.1 (C7 a), 137.2 (C1 ), 130.1 (C6 ), 128.4 (C4 ), 128.0 (C3 ),
00
0
0
0
00
127.5 (C4 ), 125.9 (C3 a), 125.5 (C5 ), 124.0 (C7 ), 114.2 (C2 ), 105.9
(C8a), 49.3 (Cspiro), 34.5 (C6), 16.3 (CH3), 12.3 (CH3). Anal. calcd for
C21H17ClN4O2S: C 59.36, H 4.03, N 13.19, S 7.55; found: C 59.44,
H 3.98, N 13.26, S 7.50.
Synthesis of Nano n-Propylsulfonated g-Al2O3
Nano g-Al2O3 (6 g) was suspended in 600 ml of 0.1 M toluene
solution of 1,3-propanesultone and the colloidal solution was
refluxed for 48 h. The sulfonated nano g-Al2O3 was isolated and
purified by repeated washing and centrifugation.
Results and Discussion
General Procedure for the Synthesis of Spiro[indoline-3,4-
pyrazolo[3,4-e][1,4]thiazepine]diones
Nano n-propylsulfonated g-Al2O3 was easily prepared by the
reaction of nano g-Al2O3 with 1,3-propanesultone (Scheme 2),
and was characterized by FT-IR, XRD, TGA, SEM and TEM. The
amount of sulfonic acid loaded on the surface of nanog-Al2O3
was determined by TGA and confirmed by ion-exchange pH
analysis.
A mixture of 3-aminocrotononitrile (1 mmol) and phenylhydrazine
(1 mmol) was refluxed for 10 min in the presence of nano
n-propylsulfonated g-Al2O3 (100 mg) in water. Then, an equimolar
mixture of isatins (1mmol) and thioacid (1mmol) was added,
and the resulting reaction mixture heated under reflux for 5–10 h.
After completion of the reaction (TLC), the resulting solid was
collected by filtration. EtOAc (20 ml) was added, and the solid
catalyst was removed by filtration, washed with EtOH, dried and
reused for a consecutive run under the same reaction conditions.
The solvent was evaporated and the crude product was purified
by silica gel column chromatography using hexane and EtOAc
(80:20) as eluent to give the title compound.
FT-IR Analysis
Figure 1 presents the FT-IR spectra of nano g-Al2O3 and nano
n-propylsulfonated g-Al2O3. As shown in this figure, the presence
of an extra sulfonic acid group in the nano n-propylsulfonated
g-Al2O3 increases the number of vibrational modes and brings a
completely different FT-IR spectrum. The FT-IR spectra of nano
n-propylsulfonated g-Al2O3 exhibits two characteristic peaks at
589 and 758 cmꢁ1 due to the stretching vibrations of the Al-O
Spectral Data of the Unknown Compounds
6-Chloro-30-methyl-10-phenyl-60,80-dihydrospiro[indoline-3,40-pyrazolo[3,4-e]
[1,4]thiazepine]-2,70(10H)-dione (5 m; R1 = H, R2 = 6-Cl, R3 = H)
SO3H
O
O
O
nano
¦Ã-Al2O
OH
OH
OH
S
M.p. 253–255ꢀC; IR (KBr) n: 3205 (NH), 3115 (NH), 2929, 1705 (C O),
SO3H
SO3H
O
nano
¦Ã-Al2O3
O
3 O
1624 (C N), 1450, 1398, 1319, 1205, 1132, 1054, 958, 779,
Toluene, reflux
1
682 cmꢁ1; H NMR (400 MHz, DMSO-d6): 11.08 (s, 1H, NH), 9.88
(s, 1H, NH), 7.52–7.44 (m, 5H, H-200-600), 7.38 (d, J = 7.6 Hz, 1H,
H-50), 7.25 (d, J = 7.6 Hz, 1H, H-40), 7.12 (s, 1H, H-70), 4.53
(d, J = 14.4 Hz, 1H, CH2), 3.22 (d, J = 14.4 Hz,1H, CH2), 1.48 (s, 3H,
nano n-propylsulfonated ¦Ã-Al2O3
Scheme 2. Synthesis of nano n-propylsulfonated g-Al2O3.
Appl. Organometal. Chem. 2013, 27, 148–154
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Q. Wu
Figure 1. FT-IR spectra of nano g-Al2O3 (top) and nano n-propylsulfonated g-Al2O3 (bottom).
bond in g-Al2O3. Moreover, two important peaks at 1043 and
1187 cmꢁ1 are assigned to S-O stretching vibration. The broad
peak at 3444 cmꢁ1 belongs to the stretching of OH groups in
SO3H. These results indicate that reaction of nano g-Al2O3 with
1,3-propanesultone succeed in incorporating sulfated groups in
nano g-Al2O3.
The average crystallite sizes are calculated to be 14.9 nm
using the Scherrer equation, which are in good accordance
with TEM results.
TGA
The stability of the nano g-Al2O3 and nano n-propylsulfonated
g-Al2O3 is determined by thermogravimetric analysis (Fig. 3). A sig-
nificant decrease in the weight percentage of the nano g-Al2O3
and nano n-propylsulfonated g-Al2O3 at about 150ꢀC is related
to desorption of water molecules from the catalysts surface. In
the TG curve of nano n-propylsulfonated g-Al2O3, complete loss
of all the covalently attached organic structure is seen in the tem-
perature range of 230–960ꢀC. The shouldering observed from
328ꢀC onwards may be due to the decomposition of alkyl-sulfonic
acid groups. According to the TGA, the amount of nano
XRD Analysis
XRD measurements of nano g-Al2O3 and nano n-propylsulfonated
g-Al2O3 exhibit diffraction peaks at around 19.5, 32.6, 36.6, 39.5,
45.8, 60.6 and 67.2, corresponding to the (111), (220), (311),
(222), (400), (511) and (440) faces (Fig. 2). The observed diffraction
peaks agree well with the cubic structure of g-Al2O3 (JCPDS file no.
29-0063). It is clear that the ordered structure of nano g-Al2O3
is retained after introducing the propylsulfonic acid group.
Figure 2. XRD patterns of nano g-Al2O3 (top) and nano n-propylsulfonated g-Al2O3 (bottom).
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Appl. Organometal. Chem. 2013, 27, 148–154

Nano n-propylsulfonated g-Al2O3: a new, efficient and reusable catalyst
Figure 3. TG analyses of nano g-Al2O3 (top) and nano n-propylsulfonated g-Al2O3 (bottom).
n-propylsulfonated g-Al2O3 is evaluated to be 0.78 mmol gꢁ1. This
shown in Figs 4 and 5. The low-magnification SEM images (Fig. 4)
result is in agreement with that of ion-exchange pH analysis.
show small nano-sized grains having spherical and quasi-spherical
morphology with a narrow size distribution, which indicates the
nano crystalline nature of g-Al2O3 nano particles. The presence of
SEM and TEM Analysis
The morphology and size of the nano g-Al2O3 and nano
n-propylsulfonated g-Al2O3 are analyzed by SEM and TEM as
Figure 4. SEM images of (a) nano g-Al2O3 and (b)nano n-propylsulfonated
g-Al2O3.
Figure 5. TEM images of (a) nano g-Al2O3 and (b) nano n-propylsulfonated
g-Al2O3.
Appl. Organometal. Chem. 2013, 27, 148–154
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Q. Wu
some larger particles attributes aggregating or overlapping
of smaller particles. The sizes of nano g-Al2O3 and nano
n-propylsulfonated g-Al2O3 are further analyzed by TEM and the
results (Fig. 5) show that the nano particles have a nano
dimension ranging from 10 to 20 nm. In TEM images, the
shapes of g- Al2O3 particles are relatively round, and those of
treated n-propylsufonated g-Al2O3 are rather rectangular, which
is attributed to the presence of sulfonic acid groups covalently
attached to the g-Al2O3 surfaces.
in Table 2 that the reaction using H2O (91%) or CH3CN (89%) as
the solvent gave the corresponding product 5a in high yield
(Table 2, entries 3 and 10). From the economical and environ-
mental points of view, H2O was chosen as the reaction medium
for all further reactions. Furthermore, the relation between the
yields of the model reaction and temperature was also studied.
We carried out the reaction at temperatures ranging from 25ꢀC
to reflux temperature using water as the reaction medium
(Table 2, entries 6–10), finding that the yields of desired product
5a were improved as the temperature was increased. Therefore,
the best reaction conditions were obtained in water under
refluxed temperature.
Ion-Exchange pH Analysis
The generality of this reaction was examined using several
types of isatins. In all cases, the reactions gave the corresponding
products in good to excellent yield (Table 3). This methodology
offers significant improvements with regard to the scope of this
transformation, simplicity of operation and green aspects by
avoiding expensive or corrosive catalysts. In addition, when this
reaction was carried out with 5-nitroisatin, TLC and 1H NMR
To an aqueous solution of NaCl (1 M, 25 ml) with a primary pH of
5.93, the catalyst (500 mg) was added and the resulting mixture
was stirred for 2 h, after which the pH of the solution decreased
to 1.81. This is equal to a loading of 0.78 mmol SO3H gꢁ1
.
Synthesis of Spiro[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]
diones Using Nano n- propylsulfonated g-Al2O3
First, to achieve suitable conditions for the synthesis of spiro
[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]diones, we tested the
four-component condensation reaction of 3-aminocrotononitrile,
phenylhydrazine, isatin and 2-mercaptoacetic acid as a simple
model system in water at reflux temperature using various
catalysts (Table 1). As can be seen in Table 1, the best result
was obtained with 100mg mmolꢁ1 of nano n-propylsulfonated
g-Al2O3 as the catalyst in water at reflux temperature (entry 3).
Using less catalyst resulted in lower yields, whereas higher amounts
of catalyst did not affect reaction times and yields. When this reaction
was carried out without nano n-propylsulfonated g-Al2O3 or with
other catalysts such as FeCl3, AlCl3 or nano g-Al2O3 the yield of
the expected product was trace. In the presence of p-TsOH, Fe
(HSO4)3, sulfamic acid or other nano n-propylsulfonated metal
oxide such as nano n-propylsulfonated SiO2 or nano n-propylsulfo-
nated ZnO the product was obtained in low yield.
Table 2. Solvent optimization for the synthesis 5aa
Entry
Solvent
Temperature (ꢀC)
Time (h)
Yield (%)b
1
2
EtOH
MeOH
CH3CN
CH2Cl2
DMF
H2O
Reflux
Reflux
Reflux
Reflux
100
8
12
7
69
65
89
49
68
45
51
63
79
91
3
4
12
8
5
6
25
16
16
12
8
7
H2O
40
8
H2O
60
9
H2O
80
10
H2O
Reflux
5
aReaction conditions: 3-aminocrotononitrile (1mmol); phenylhydrazine
(1mmol); isatin (1mmol); 2-mercaptoacetic acid (1mmol); nano
n-propylsulfonated g-Al2O3 (100mg).
To find the optimal solvent for this reaction, the model
reaction was carried out at 100ꢀC or reflux temperature using
EtOH, MeOH, H2O, CH2Cl2, DMF and CH3CN as solvent. It is shown
bIsolated yield.
Table 1. Catalyst optimization for the synthesis 5aa
Entry
Catalyst
mg mmolꢁ1
Time (h)
Yield (%)b
1
—
—
10
7
Trace
70
2
Nano n-propylsulfonated g-Al2O3
Nano n-propylsulfonated g-Al2O3
Nano n-propylsulfonated g-Al2O3
Nano n-propylsulfonated g-Al2O3
Nano n-propylsulfonated g-Al2O3
p-TsOH
50
3
100
150
200
250
100
100
100
100
100
100
100
100
5
91
4
5
91
5
5
90
6
5
90
7
12
12
12
5
62
8
Fe(HSO4)3
49
9
Sulfamic acid
57
10
11
12
13
14
Nano n-propylsulfonated SiO2
Nano n-propylsulfonated ZnO
AlCl3
62
5
69
24
24
24
Trace
Trace
Trace
Nano g-Al2O3
FeCl3
aReaction conditions: 3-aminocrotononitrile (1mmol); phenylhydrazine (1mmol); isatin (1mmol); 2-mercaptoacetic acid (1mmol); H2O (10ml); reflux.
bIsolated yield.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 148–154

Nano n-propylsulfonated g-Al2O3: a new, efficient and reusable catalyst
Table 3. Preparation of spiro[indoline-3,4- pyrazolo[3,4-e][1,4]thiazepine]dionesa
Entry
R1
R2
R3
Time (h)
Product
Yield (%)b
1
H
H
H
H
5
5
5a
5b
5c
5d
5e
5f
91
92
2
H
CH3
CH3
H
3
H
5-Cl
5-Br
5-F
8
88
4
H
8
87
5
H
H
5
90
6
H
5-F
CH3
H
5
93
7
H
5-CH3
5-CH3
H
7
5g
5h
5i
87
8
H
CH3
H
7
86
9
CH3
CH3
H
6
90
10
11
12
13
14
15
16
H
CH3
H
6
5j
92
5-NO2
5-NO2
6-Cl
6-Cl
6-Br
6-Br
10
10
7
5k
5l
Tracec
Tracec
91
H
CH3
H
H
5m
5n
5o
5p
H
CH3
H
8
88
H
7
88
H
CH3
8
90
aReaction conditions: 3-aminocrotononitrile (1 mmol); phenylhydrazine (1 mmol); thioacid (1 mmol); isatins (1 mmol); nano n-propylsulfonated
g-Al2O3 (100 mg); H2O (10 mL); reflux.
bIsolated yield.
cA combination of starting materials and numerous products.
spectra of the reaction mixture showed a combination of starting
materials and numerous products, and the yield of the expected
product was very poor.
The reusability of the catalyst was tested in the synthesis of 5a.
The catalyst was recovered after each run, washed with EtOH,
dried in an oven at 100ꢀC for 30 min prior to use and tested for
its activity in the subsequent run with no fresh catalyst added.
The catalyst was tested for seven runs. It was seen that the
catalyst displayed very good reusability (Fig. 6).
A plausible mechanism for the formation of the spiro-
heterocycles is proposed in Scheme 3. The domino sequence
Figure 6. Reusability of nano n-propylsulfonated g-Al2O3 synthesis of 5a.
of reactions is presumably triggered by the formation of 5-amino-
H3C
HN
H3C
N
CN
H+
+
H2NHN
-NH3
NH
NH2
6
NH2
H3C
N
N
Ph
Ph
2
1
O
SO3H
SO3H
SO3H
O
O
R2
nano
¦Ã-Al2O
O
H+
N
R1
3 O
3
R1
N
R2
R1
R1
N
R2
R3
N
R2
O
OH
O
H3C
HS
S
O
H+
,
OH
H3C
R3
S
O
OH
O
4
N
N
N
NH2
N
H
-H2O
N
N
-H2O
NH2
8
O
Ph
N
Ph
Ph
5
7
Scheme 3. A plausible mechanism for the spiro[indoline-3,4-pyrazolo[3,4-e][1,4]thiazepine]diones.
Appl. Organometal. Chem. 2013, 27, 148–154
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wileyonlinelibrary.com/journal/aoc

L. Q. Wu
3-methyl- 1-phenylpyrazole 6 from the acid-catalyzed reaction of
phenylhydrazine with 3-aminocrotononitrile. Intermediate 6, upon
reaction with isatin 3, affords intermediate 7, which on further
dehydration and upon reaction with the starting thioacid under
acidic conditions presumably furnishes intermediate 8, which
subsequently undergoes dehydration leading to the final spiro-
heterocycles.
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Conclusion
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[13] J. Leclercq, M. C. De Pauw-Gillet, R. Bassleer, L. Angenot, J.
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We have successfully developed a novel and more environmentally
friendly procedure for the preparation of spiro[indoline-3,
4-pyrazolo[3,4-e][1,4]thiazepine]diones of potential synthetic and
pharmacological interest. The use of nano n-propylsulfonated
g-Al2O3 in water as a non-toxic and low loading of catalytic system
with short reaction times and excellent product yields are the main
advantages of this methodology, which appears to have a broad
scope to represent a straightforward procedure for the synthesis
of spiro[indoline-3,4-pyrazolo[3,4-e] [1,4]thiazepine]diones.
[14] P. B. Alper, C. Meyers, A. Lerchner, D. R. Siegel, E. M. Carreira, Angew.
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Reddy, Y. V. D. Nageswar, U. Chandrakala, B. L. A. Prabhavathi Devi,
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Acknowledgment
We are pleased to acknowledge the financial support from
Xinxiang Medical University.
wileyonlinelibrary.com/journal/aoc
Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 148–154

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