Ring-opening hydrolysis of spiro-epoxyoxindoles using a reusable sulfonic acid functionalized nitrogen rich carbon catalyst

Article abstract of DOI:10.1039/d1ra01161h

Controlling the product selectivity of a ring-opening hydrolysis reaction remains a great challenge with mineral acids and to an extent with homogeneous catalysts. In addition, even trace amounts of metal impurities in a bioactive product hinder the reaction progress. This has necessitated the development of robust and metal-free catalysts to offer an alternative sustainable route. We report a nitrogen-rich sulfonated carbon as a catalyst derived from an inexpensive precursor for the synthesis of bioactive vicinal diols of spiro-oxindole derivatives. The well-characterized catalyst shows wide generality with different electronic and steric substituents in the substrates under mild reaction conditions. Hot filtration test confirms no leaching of the acid moiety and the catalyst could be reused for four cycles with retention of activities.

Full text of DOI:10.1039/d1ra01161h

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Ring-opening hydrolysis of spiro-epoxyoxindoles
using a reusable sulfonic acid functionalized
nitrogen rich carbon catalyst†
Cite this: RSC Adv., 2021, 11, 12808
ab
cd
Parth Patel,
Raj Kumar Tak,ac Bhavesh Parmar,
Shilpa Dabas,ac
Brijesh Patel,ac Eringathodi Suresh,
and Saravanan Subramanian
Noor-ul H. Khan
cd
abc
*
ac
*
Controlling the product selectivity of a ring-opening hydrolysis reaction remains a great challenge with
mineral acids and to an extent with homogeneous catalysts. In addition, even trace amounts of metal
impurities in a bioactive product hinder the reaction progress. This has necessitated the development of
robust and metal-free catalysts to offer an alternative sustainable route. We report a nitrogen-rich
sulfonated carbon as a catalyst derived from an inexpensive precursor for the synthesis of bioactive
vicinal diols of spiro-oxindole derivatives. The well-characterized catalyst shows wide generality with
different electronic and steric substituents in the substrates under mild reaction conditions. Hot filtration
test confirms no leaching of the acid moiety and the catalyst could be reused for four cycles with
retention of activities.
Received 11th February 2021
Accepted 15th March 2021
DOI: 10.1039/d1ra01161h
rsc.li/rsc-advances
other therapeutic activities28 (Fig. 1b). Given the ubiquity of the
hydroxy substituted oxindole core, the ring-opening of spiro-
Introduction
epoxyoxindoles avails a simple and practical approach to ach-
ieve vicinal diols and alkoxyalcohols with a spiro-quaternary
center. In fact, the hydrolysis of epoxide is an important reac-
tion in living organisms for the detoxication of exogeneous
substances catalyzed by epoxide hydrolases.29,30 Vicinal diols, in
turn, are versatile intermediates for antifreezes, polyester
resins, pharmaceuticals, and cosmetics.31 Ring-opening of
epoxides by various nucleophiles has been reported using Lewis
acids, Lewis bases, one-electron transfer reagents, metal
complexes and supported metal oxides.32–37 However, there
remain challenges such as low regioselectivity in the case of
Lewis acid catalyzed ring-opening of epoxides with alcohols,
The development of an effective strategy for the construction of
small molecules with biologically relevant molecular architec-
tures has been the subject of intense research in recent years.1–7
3,3-Substituted oxindoles are fascinating molecules with
unique structural skeleton pertaining to several complex
natural products such as XEN 402, chitosenine, spiro-
tryprostatin A, (ꢀ)-horsline (Fig. 1a).8–10 In an ideal scenario,
the transformation of isatin derivatives to spiro-epoxyindoles
followed by a ring-opening reaction and/or installation of
functionalities leads to an oxindole core, with varying degree of
substitutions for broad spectrum of applications.11–26 The
densely functionalized spiro-fused heterocyclic motif has drawn
much attention of biologists and synthetic chemists. In this
class of molecules, 3-hydroxy, 3-substituted-2-oxindole deriva-
tives are powerful building blocks and exhibit signicant bio-
logical activities such as proteasome inhibitory activity27 and
aInorganic Materials and Catalysis Division, CSIR-Central Salt & Marine Chemicals
Research Institute, G. B. Marg, Bhavnagar-364002, Gujarat, India. E-mail:
khan251293@yahoo.co.in; saravanans@csmcri.res.in
bCharotar University of Science and Technology, Changa, Anand-388421, Gujarat,
India
cAcademy of Scientic and Innovative Research (AcSIR), Ghaziabad-201002, India
dAnalytical and Environmental Science Division and Centralized Instrument Facility
CSIR-Central Salt & Marine Chemicals Research Institute, G. B. Marg, Bhavnagar-
364 002, Gujarat, India
† Electronic supplementary information (ESI) available. CCDC 1961234–1961238.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/d1ra01161h
Fig. 1 (a) Examples of biological important spirocyclic oxindoles, (b)
examples of 3-hydroxy, 3-substituted-2-oxindole derivatives.
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Table
1
Screening of different catalysts for hydrolysis of spiro-
and in case of metal complexes, deactivation occurs through the
loss of counterions during reactions, which are yet to over-
come.35 On the other hand, the increasing environmental
concerns have triggered the exploration of reusable solid-acid
catalysts, and becoming more important in academic and
industrial research.38–46 While gratifyingly acknowledging the
literature reports and their proven value, still there has been
a constant pursuit for a cost-effective catalytic system that could
work under mild reaction conditions resulting the product with
high yield and selectivity. Recently, carbon-based metal-free
catalysts have been studied extensively due to the availability
of abundant sources and low cost nature. Among the carbon
materials, heteroatom doped carbon has received special
attention in diverse catalytic applications. Particularly, nitrogen
doped carbon materials are quite well-known for tuning the
electronic distribution of the carbon-based network due to its
size similarity with carbon and higher electronegativity. On the
other hand, sulfonic acid functionalized carbon materials,
a class of solid-protonic acids characterized by its high Brønsted
acidity, low-production cost and eco-friendly alternative to
liquid H2SO4, are promising catalysts for industrial applica-
tions.47 Ironically, SO3H-functionalized carbon materials have
not been explored for their catalytic activity on the hydrolysis of
epoxides. Encouraged by this observation and our ongoing
interest in spiro-epoxyoxindole derivatives48 and the develop-
ment of a cost-effective bifunctional catalytic system,30,49 herein
we report the synthesis of nitrogen-rich sulfonated carbon as
a cost-effective and reusable heterogeneous catalyst for the rst-
time and its application in the ring-opening reaction of bioac-
tive spiro-epoxyoxindole derivatives. The developed heteroge-
neous catalytic system features (a) an inexpensive, reusable and
metal-free catalyst, (b) mild reaction conditions, and (c) high
yields of desired vicinal diol products.
epoxidea
Conversion
(%)
Selectivity
(%)
Entry
Catalyst
1
2
3
4
5
6
7
8
9
PTSAb
SO3H@N–C/CB6
CB6
96
97
18
9
58
32
43
n.r.
43
32
99
82
91
52
46
87
—
99
Cal-CB6
SO3H@CB6
Amberlyst-15
SO3H@C
No catalyst
SO3H@CHT
a
Reaction conditions: N-benzyl spiro-epoxyoxindole (0.2 mmol), H2O
(300 mL), 20 mg catalyst, 0.5 mL dry CH3CN, at 50 ꢁC for 24 h.
b
Reaction time – 3 h. Conversion was determined by using gas
chromatography.
experience, we envisaged that a catalyst developed from
a cucurbit[6]uril (CB6) based molecule will meet the demands
since it (1) is easy to synthesize and scale up, (2) has rich carbon
and heteroatom (nitrogen and oxygen) ratio, and (3) is tunable
for further functionalization. Consequently, we initiated the
synthesis from commercially available and inexpensive reagents
following the previously reported procedure52 with slight
modications. The obtained white CB6 powder was used further
to prepare Cal-CB6 by pyrolysis and subsequently, upon sulfo-
nation resulted in the black SO3H@N–C/CB6 (Fig. 2). The
prepared catalyst was characterized using a series of analytical
techniques.
Results and discussion
Developing a catalyst for transformations involving bioactive
starting materials is not a trivial task. The construction of
tertiary alcohols bearing different carbon substituents is chal-
lenging and has a potential role in biological applications.50,51
With this in mind, we are interested in studying the hydrolytic
ring-opening of spiro-epoxyoxindoles that lead to the formation
of differently substituted alcohols. We commenced our catalytic
study using p-toluenesulfonic acid (p-TSA) as a homogeneous
catalyst for the hydrolysis of N-benzyl spiro-epoxyoxindole as
a model substrate using dry acetonitrile at 50 ꢁC (Table 1, Entry
1). As expected, the formation of a diol product was observed,
but not as a sole-product, along with a noticeable amount of N-
benzyl isatin, the precursor of the starting epoxide. This is
possibly due to the strong acidity of p-TSA and being in the
same phase of the starting material. This nding shed light to
develop a heterogeneous solid-acid catalyst for liquid phase
hydrolytic ring-opening reaction. Thus, to retain the catalytic
performance of sulfonic acid, we envisaged to introduce the
same functionality on the surface of the nitrogen-doped carbon
support and make the catalytic process an alternative to
The functional groups attached to Cal-CB6 and SO3H@N–C/
CB6 were evaluated by FT-IR spectroscopy (Fig. 3a). Cal-CB6
showed a peak at 1631 cmꢀ1 corresponding to C]O stretching
vibrations in carboxylic acid and 3200–3500 cmꢀ1 due to O–H
stretching vibration in the hydroxyl group. Upon sulfonation,
SO3H@N–C/CB6 shows distinct peaks at 1064 and 1224 cmꢀ1
,
which are assigned to symmetric O]S stretching vibrations of
sulfonic groups. This conrms that the SO3H groups were
successfully anchored to the Cal-CB6 framework.
Fig.
2 Preparation of sulfonic acid functionalized nitrogen-rich
conventional acids. On the outset based on our previous carbon SO3H@N–C/CB6.
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CB6.53 The surface morphology of the synthesized sulfonated
material was characterized by scanning electron microscopy
(Fig. S3†) and the analyzed images showed irregular hollow
network with amorphous carbon nature.
With the characterized catalyst, we then focused on the
catalytic study of the synthesized material. Indeed, the reaction
catalyzed by SO3H@N–C/CB6 afforded the desired product in
97% conversion (Table 1, Entry 2). In order to understand the
catalyst activity, we screened different materials such as CB6, C-
CB6, SO3H@CB6, Amberlyst-15, and SO3H@C (sulfonated
carbon) under the same reaction conditions.
Fig. 3 (a) FTIR analysis (b) TGA analysis of Cal-CB6 and SO3H@N–C/
CB6.
The results are summarized in Table 1; the study using CB6
and Cal-CB6 depicts the role of sulfonation in the catalytic
activity (Entries 3 and 4), whereas, the materials such as
SO3H@CB6, Amberlyst-15, and SO3H@C also resulted in
slightly improved conversion of 58, 32, and 43%, respectively.
The lower activity of Amberlyst-15 indicates the strong inuence
of its inherent acidity on the epoxide, resulting in the reaction to
be unselective. Furthermore, under our reaction conditions, the
hydrolysis of the model substrate does not proceed without the
catalyst (Entry 8).
In order to investigate further the effect of nitrogen doped
carbon, we tested the sulphonic acid functionalized chitosan54
and observed a conversion of 43% under the optimized reaction
conditions. This might be due to the change in physical and
chemical features with the varied amount of nitrogen and sul-
phonic acid functionalization in the material.
The TGA curves of SO3H@N–C/CB6 and Cal-CB6 are depicted
in Fig. 3b. SO3H@N–C/CB6 shows a two-step weight loss; an
initial 8% weight loss was observed from 30 to 140 ꢁC due to the
evaporation of moisture and volatile material. However, Cal-CB6
shows lower weight loss than SO3H@N–C/CB6 due to the pres-
ence of a sulfonic group along with captured moisture in the
latter. Furthermore, a second weight loss in Cal-CB6 (1%) and
SO3H@N–C/CB6 (10%) occurred in the 140ꢀ350 ꢁC temperature
region.
The XRD pattern exhibits (Fig. S2†) two broad, weak
diffraction peaks (2q ¼ 15–30ꢁ, 40–50ꢁ) attributed to amorphous
carbon composed of aromatic carbon sheets oriented in
a considerably random fashion.
The XPS survey spectrum of the sulfonated material
SO3H@N–C/CB6 is provided in Fig. 4. It demonstrates ve peaks
centered at approximately 168, 233, 284.5, 401 and 531.5 eV.
These can be assigned to S 2p, S 2s, C 1s, N 1s and O 1s,
respectively. The C1s spectrum can be deconvoluted into three
peaks including C]C at 284.8 eV, C–S, C–N at 286.5 eV and
O]C–O at 289.1 eV. There are two peaks associated with the O
1s spectrum, centered at 531.6 eV (C–O) and 532.7 eV (S–O). The
S2p core level of SO3H@N–C/CB6 could be deconvoluted into
two peaks at 168.5 eV (S–OH) and 169.6 eV (S]O) and thus this
result conrms the presence of the SO3H groups in SO3H@N–C/
Encouraged with the catalytic activity, we then screened
other reaction parameters such as temperature, solvent and
Chart 1 Optimization of reaction conditionsa. Reaction conditions (a):
Catalyst (20 mg), N-benzyl spiro-epoxyoxindole (0.2 mmol), H2O (300
mL), dry CH3CN (0.5 mL), time 24 h. (b): Catalyst (20 mg), N-benzyl
spiro-epoxyoxindole (0.2 mmol), H2O (300 mL), solvents (0.5 mL), time
24 h. (c): Catalyst (mg), N-benzyl spiro-epoxyoxindole (0.2 mmol),
Fig. 4 XPS profile (a) survey, (b) C 1s, (c) O 1s, (d) S 2p of SO3H@N–C/ H2O (300 mL), dry CH3CN (0.5 mL), Time 24 h. aConversion was
CB6.
determined by gas chromatography.
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catalyst loading. With temperature variation studies, we iden-
tied that the reaction becomes sluggish by decreasing the
ꢁ
temperature from 50 C (Chart 1a). Solvents play a key role in
the ring-opening reaction of epoxides. Thus, we then varied the
solvent and a signicant solvent effect was observed for the
ring-opening hydrolysis of the model substrate and the results
are displayed in Chart 1b. Other than acetonitrile, all the other
polar aprotic solvents resulted in the hydrolysed product in less
conversion.
Next, we optimized the catalyst loading by varying it in the
series of 10 to 25 mg (Chart 1c). On decreasing the catalyst
loading from 20 to 10 and 15 mg, the yield of the diol product
also decreased from 97% to 85% and 70%, respectively, main-
taining the same reaction time of 24 h. Increasing the catalyst
loading to 25 mg showed detrimental effect in the product
formation. Thus, we optimized the catalyst loading as 20 mg for
the ring-opening hydrolysis of spiro-epoxyindoles.
Fig. 6 (a) Alcoholysis and (b) hydrochlorination of spiro-epoxyox-
indoles using SO3H@N–C/CB6. Substrate (0.2 mmol), nucleophile
(300 mL in case of 2j and 2.2 equiv. in 2k), catalyst (20 mg), CH3CN (0.5
mL), 50 ꢁC. Conversion was determined by gas chromatography.
the substrates having withdrawing groups gave slightly less
yield (2f–2i). Furthermore, we extended the protocol for hydro-
chlorination and alcoholysis with excellent yield (2k and 2j,
Fig. 6) and the characterization of the product conrms the
regioselectivity of the process.55
Substrate scope
With the optimal reaction condition in hand, the scope and
limitation of the catalyst was examined for the hydrolysis of
various substrates (Fig. 5). The effect of protecting groups on the
oxindole derivative was also investigated and observed excellent
yields of the desired product (2a–2c). In general, most of the
studied substrates underwent a smooth and clean reaction to
afford the vicinal diol product with good to excellent yields, but
It is essential to conrm the molecular structure of a new
molecule with single-crystal XRD analysis; thereby, we tried
recrystallizing the vicinal diol products and the quality of the
obtained crystals was good enough to conrm the structures.
1
Apart from this, all the products were characterized by H and
13C NMR spectroscopy, and the crystal structures of ve new
substituted 3,3-dihydroxy oxindole products have been estab-
lished (Fig. 7).
Based on the catalytic study, a plausible mechanism for the
ring-opening hydrolysis of spiro-epoxyindoles is proposed
(Scheme 1). Initially, the spiro-epoxide gets protonated (I) by the
sulfonic acid moiety in the catalyst. The protonated epoxide
then opened up the ring via SN1 fashion to form the benzylic
carbocationic intermediate (II).56 Successively, the oxygen from
the water molecule attacks the generated carbocation interme-
diate, followed by the abstraction of a proton by the nitrogen-
Fig.
7 Thermal ellipsoid plot depicting the crystal structure of
Fig. 5 Substrate (0.2 mmol), H2O (300 mL), catalyst (20 mg), CH3CN hydrolysis products (2A, 2B, 2C, 2E and 2G; 40% probability factor for
(0.5 mL), 50 ꢁC. Conversion was determined by gas chromatography. the thermal ellipsoids).
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Hot ltration test
To examine the leaching of the sulfonic acid group at reaction
temperature, a hot ltration test was performed. Then, ring-
opening of N-benzylspiroepoxide with water using the catalyst
ꢁ
SO3H@N–C/CB6 and acetonitrile as solvent at 50 C occurred.
Aer 4 h of reaction time, the solid SO3H@N–C/CB6 catalyst was
ltered off and the reaction mass was allowed to react further.
We found that no further reaction occurred aer the hot
ltration test. This experimental nding suggests that there is
no leaching from the SO3H@N–C/CB6 catalyst during the
progress of a reaction.
Conclusions
A highly active SO3H@N–C/CB6 catalyst was synthesized by
a calcination process followed by its functionalization using
sulfuric acid. The catalytic system has the following salient
features: (a) the catalyst was thermally stable, (b) the catalyst
eliminates intraparticle diffusion resistance, and (c) the catalyst
does not show any leaching behavior. SO3H@N–C/CB6 proves to
be efficient for the synthesis of versatile vicinal diol products,
which is difficult to achieve with homogeneous catalysts. The
catalyst was well-characterized using XRD, FT-IR spectroscopy,
TGA, XPS and elemental analysis. The catalyst can be reused
four times with minor changes in the catalytic activity.
Scheme 1 A plausible mechanism for the ring-opening hydrolysis of
spiro-epoxyindoles catalyzed by SO3H@N–C/CB6
rich center of the catalyst, resulting in the smoother formation
of the diol product.
Experimental section
All reagents and solvents were purchased from commercial
sources and were used without further purication. NMR
spectra were obtained on a Bruker spectrometer at (600 MHz
and 151 MHz for 1H and 13C NMR, respectively) and referenced
internally with TMS; splitting patterns were reported as s ¼
singlet, d ¼ doublet, dd ¼ doublet of doublet, t ¼ triplet, q ¼
quartet, m ¼ multiplet, br ¼ broad. IR spectra were recorded
using the KBr pellet method on a Perkin-Elmer GX FTIR spec-
trometer. For each IR spectra, 10 scans were recorded at 4 cmꢀ1
resolution. TGA analysis was carried out using Mettler Toledo
Star SW 8.10. TG analysis was performed in nitrogen environ-
ment while the heating rate was ramped from room tempera-
ture to 800 ꢁC at 10 ꢁC minꢀ1. Powder X-ray diffraction (PXRD)
data were collected using a PANalytical Empyrean (PIXcel 3D
detector) system with CuKa radiation. Single crystal structures
were determined using a BRUKER D8 QUEST diffractometer.
Catalyst reusability
The reusability reactions were carried out as described in the
experimental procedure. The reusability of SO3H@N–C/CB6 was
tested by carrying out four runs (Fig. 8). Aer each run, the
catalyst was recovered by ltration and was washed with
acetone and dried at 80 ꢁC for 6 h in a vacuum oven. The dried
catalyst was then used for the next cycle. The catalyst showed
retention of activity for four cycles with good yield.
Synthesis of glycoluril and CB6
Glycoluril was synthesized according to the previously pub-
lished procedure.52 Typically, in a single necked 500 mL RB
ask, 39–40% glyoxal (40 mL; 0.35 mol) and urea (53.4 g, 0.89
mol) were taken, and the resulting solution was stirred for
30 min. Subsequently, water (80 mL) was added to the reaction
mixture and further stirred for 20 min followed by the addition
of 8.5 mL conc. HCl in 20 mL of water very slowly. Aer the
complete addition of acid (pH ¼ 1.5–2), the reaction mixture
was reuxed on an oil bath that generated a white solid
precipitate. The heating and stirring were continued for about
Fig. 8 Reusability study of SO3H@N–C/CB6 catalyst for the hydrolytic
ring-opening reaction of spiro-epoxyoxindoles.
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60 min, then it was cooled to room temperature, poured into ice chromatography using silica gel 100–200 mesh as the stationary
water, ltered, and the white solid was washed with cold water phase and n-hexane/ethyl acetate 90 : 10 as the mobile phase.
(3 ꢂ 50 mL) and with acetone (2 ꢂ 40 mL). The resulting white
ꢁ
solid was allowed to dry for 6 h at 85 C (yield: 32.70 g, 66%).
Typical procedure for the hydrolysis of spiro-epoxyoxindole
CB6 was synthesized according to the previous procedure.57
In a 250 mL RB ask, which was equipped with a condenser and
The catalyst (20 mg) was weighed out in an oven dried sample
vial. Spiro-epoxyoxindole (0.2 mmol) and dry CH3CN (0.5 mL)
dean-stark apparatus, glycoluril (15 g, 106 mmol) and 37% aq.
was added and stirred. To this solution, the nucleophile (300
formaldehyde were taken to which conc. H2SO4 (15 mL) and
mL) was added and subsequently the reaction mixture was
water (100 mL) were added, and the resulting mixture was
heated to 50 ꢁC and allowed to run for 24 h. The progress of the
heated for 12 h. During that time water was removed from the
reaction was monitored by TLC. Aer completion of the reac-
reaction mixture, and aer that the reaction mixture was stirred
tion, the mixture was ltered and the ltrate was evaporated to
dryness. The crude product was puried by column chroma-
tography using silica gel 100–200 mesh as the stationary phase
and n-hexane/ethyl acetate 90 : 10 as the mobile phase.
at 160 ꢁC for the next 24 h. Then the reaction mixture was cooled
to room temperature and poured into water (250 mL). A
yellowish precipitate was ltered off, and the solid mass was
dissolved in conc. HCl. Next, the clear brown solution was
diluted with water to get a white precipitate that was washed
ꢁ
with water and dried at 140 C (yield: 81%).
Conflicts of interest
There are no conicts to declare.
Procedure for pyrolysis of CB6
The dried CB6 was rst ground to ne powder and transferred to
Acknowledgements
a calcination boat. Then, the calcination boat was placed in
a calcination tubular furnace for pyrolysis at 800 ꢁC with
The registration number of this publication is CSIR-CSMCRI –
216/2020. Financial support from DST and CSIR for SRF (PP),
a temperature gradient of 5 ꢁC minꢀ1 for 2 h under argon
atmosphere. The entire pyrolysis process was carried out in an
inert atmosphere until the calcined material was cooled down
to <40 ꢁC. Aer cooling the furnace temperature (<40 ꢁC), its
closed chamber was opened, and the black colored Cal-CB6 was
obtained (40–42% yield).
N. B. The temperature of the furnace should be cooled down
to <40 ꢁC under the inert atmosphere. Otherwise, the carbon
powder burns instantly with air contact.
RA (BP) and analytical support by AESD&CIF of CSIR-CSMCRI
are gratefully acknowledged. SS thanks DST for the INSPIRE
Faculty award (DST/INSPIRE/04-I/2017/000003).
References
1 C. V. Galliford and K. A. Scheidt, Angew. Chem., Int. Ed., 2007,
46, 8748–8758.
2 C. Marti and E. M. Carreira, Eur. J. Org. Chem., 2003, 2003,
2209–2219.
Procedure for sulfonation of Cal-CB6
3 N. Ye, H. Chen, E. A. Wold, P.-Y. Shi and J. Zhou, ACS Infect.
Dis., 2016, 2, 382–392.
4 M. Kaur, M. Singh, N. Chadha and O. Silakari, Eur. J. Med.
Chem., 2016, 123, 858–894.
5 B. Yu, D.-Q. Yu and H.-M. Liu, Eur. J. Med. Chem., 2015, 97,
673–698.
6 S. Subramanian, H. A. Patel, Y. Song and C. T. Yavuz, Adv.
Sustainable Syst., 2017, 1, 1700089.
7 S. B. Annes, R. Saritha, S. Subramanian, B. Shankar and
S. Ramesh, Green Chem., 2020, 22, 2388–2393.
8 K. Ding, Y. Lu, Z. Nikolovska-Coleska, S. Qiu, Y. Ding,
W. Gao, J. Stuckey, K. Krajewski, P. P. Roller, Y. Tomita,
D. A. Parrish, J. R. Deschamps and S. Wang, J. Am. Chem.
Soc., 2005, 127, 10130–10131.
9 S. Shangary, D. Qin, D. McEachern, M. Liu, R. S. Miller,
S. Qiu, Z. Nikolovska-Coleska, K. Ding, G. Wang, J. Chen,
D. Bernard, J. Zhang, Y. Lu, Q. Gu, R. B. Shah, K. J. Pienta,
X. Ling, S. Kang, M. Guo, Y. Sun, D. Yang and S. Wang,
Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 3933.
Sulfonation of Cal-CB6 was performed by adding 2 g of Cal-CB6
to a Teon autoclave. 20 mL of 4 : 1 concentrated H2SO4 : HNO3
was added slowly to the Teon vessel, and the slurry was mixed
well for 10 min and allowed to attain room temperature. The
ꢁ
Teon autoclave was kept in a heating oven for 12 h at 150 C.
Aer heating, the Teon vessel was allowed to cool down to
room temperature. The catalyst slurry was thoroughly washed
with ultrapure water until it reaches pH 7, and then dried at
70 ꢁC for 12 h. A total amount of 1.95 g of product was obtained
aer the purication process.
Typical procedure for the synthesis of spiro-epoxyoxindole
Spiroepoxide was synthesized by the previously reported
procedure.58,59 A mixture of trimethylsulfoxonium iodide (2.0
mmol) and cesium carbonate (4.0 mmol) in dry CH3CN was
stirred at 50 ꢁC for 1 h under a nitrogen atmosphere to generate
the sulfur ylide. An appropriate solution of spiro-epoxyoxindole
(2.0 mmol) in dry CH3CN (10 mL) was then added dropwise over
10 min. The progress of the reaction was monitored by TLC. 10 Y. Zhao, L. Liu, W. Sun, J. Lu, D. McEachern, X. Li, S. Yu,
Aer completion of the reaction, the mixture was ltered
through a pad of Celite and the ltrate was evaporated to
dryness. The crude product was puried by column
D. Bernard, P. Ochsenbein, V. Ferey, J.-C. Carry,
J. R. Deschamps, D. Sun and S. Wang, J. Am. Chem. Soc.,
2013, 135, 7223–7234.
© 2021 The Author(s). Published by the Royal Society of Chemistry
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RSC Advances
Paper
11 G. Zhu, G. Bao, Y. Li, W. Sun, J. Li, L. Hong and R. Wang, 37 R. Tak, M. Kumar, T. Menapara, N. Gupta, R. I. Kureshy,
Angew. Chem., Int. Ed., 2017, 56, 5332–5335.
12 S. Hajra, S. Maity and S. Roy, Adv. Synth. Catal., 2016, 358,
2300–2306.
13 B. M. Trost and M. K. Brennan, Synthesis, 2009, 2009, 3003–
3025.
14 F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352,
1381–1407.
15 A. Moyano and R. Rios, Chem. Rev., 2011, 111, 4703–4832.
N.-u. H. Khan and E. Suresh, Adv. Synth. Catal., 2017, 359,
3990–4001.
38 W. M. Van Rhijn, D. E. De Vos, B. F. Sels and W. D. Bossaert,
Chem. Commun., 1998, 317–318, DOI: 10.1039/A707462J.
39 D. Margolese, J. A. Melero, S. C. Christiansen, B. F. Chmelka
and G. D. Stucky, Chem. Mater., 2000, 12, 2448–2459.
40 J. A. Melero, G. D. Stucky, R. van Grieken and G. Morales, J.
Mater. Chem., 2002, 12, 1664–1670.
16 N. R. Ball-Jones, J. J. Badillo and A. K. Franz, Org. Biomol. 41 D. Das, J.-F. Lee and S. Cheng, J. Catal., 2004, 223, 152–160.
Chem., 2012, 10, 5165–5181.
17 L. Hong and R. Wang, Adv. Synth. Catal., 2013, 355, 1023–
1052.
18 Y. Liu, H. Wang and J. Wan, Asian J. Org. Chem., 2013, 2, 374–
386.
19 M. M. M. Santos, Tetrahedron, 2014, 70, 9735–9757.
20 H. Wu, Y.-P. He and F. Shi, Synthesis, 2015, 47, 1990–2016.
21 M. M. C. Lo, C. S. Neumann, S. Nagayama, E. O. Perlstein
42 V. Dufaud and M. E. Davis, J. Am. Chem. Soc., 2003, 125,
9403–9413.
43 Q. Yang, J. Liu, J. Yang, M. P. Kapoor, S. Inagaki and C. Li, J.
Catal., 2004, 228, 265–272.
44 Q. Yang, M. P. Kapoor, S. Inagaki, N. Shirokura, J. N. Kondo
and K. Domen, J. Mol. Catal. A: Chem., 2005, 230, 85–89.
45 D. J. Macquarrie, S. J. Tavener and M. A. Harmer, Chem.
Commun., 2005, 2363–2365, DOI: 10.1039/B501431J.
´
´
´
´
and S. L. Schreiber, J. Am. Chem. Soc., 2004, 126, 16077– 46 B. Rac, A. Molnar, P. Forgo, M. Mohai and I. Bertoti, J. Mol.
16086. Catal. A: Chem., 2006, 244, 46–57.
22 X.-H. Chen, Q. Wei, S.-W. Luo, H. Xiao and L.-Z. Gong, J. Am. 47 L. J. Konwar, P. M. Arvela and J. P. Mikkola, Chem. Rev., 2019,
Chem. Soc., 2009, 131, 13819–13825. 119, 11576–11630.
23 A. T. Londregan, S. Jennings and L. Wei, Org. Lett., 2010, 12, 48 R. K. Tak, P. Patel, S. Subramanian, R. I. Kureshy and
5254–5257.
N. H. Khan, ACS Sustainable Chem. Eng., 2018, 6, 11200–
11205.
49 P. Patel, S. Nandi, M. S. Maru, R. I. Kureshy and N. H. Khan,
J. CO2 Util., 2018, 25, 310–314.
24 D. Xie, L. Yang, Y. Lin, Z. Zhang, D. Chen, X. Zeng and
G. Zhong, Org. Lett., 2015, 17, 2318–2321.
25 T. Arai, H. Ogawa, A. Awata, M. Sato, M. Watabe and
M. Yamanaka, Angew. Chem., Int. Ed., 2015, 54, 1595–1599.
26 P.-F. Zheng, Q. Ouyang, S.-L. Niu, L. Shuai, Y. Yuan, K. Jiang,
¨
50 F. Kuhn, S. Katsuragi, Y. Oki, C. Scholz, S. Akai and
¨
H. Groger, Chem. Commun., 2020, 56, 2885–2888.
T.-Y. Liu and Y.-C. Chen, J. Am. Chem. Soc., 2015, 137, 9390– 51 Y.-L. Liu and X.-T. Lin, Adv. Synth. Catal., 2019, 361, 876–918.
9399.
52 S. Nandi, P. Patel, A. Jakhar, N. H. Khan, A. V. Biradar,
R. I. Kureshy and H. C. Bajaj, ChemistrySelect, 2017, 2,
9911–9919.
27 B. K. Albrecht and R. M. Williams, Proc. Natl. Acad. Sci. U. S.
A., 2004, 101, 11949–11954.
28 P. Sharma, K. R. Senwar, M. K. Jeengar, T. S. Reddy, 53 M. Fantauzzi, B. Elsener, D. Atzei, A. Rigoldi and A. Rossi,
V. G. M. Naidu, A. Kamal and N. Shankaraiah, Eur. J. Med.
Chem., 2015, 104, 11–24.
RSC Adv., 2015, 5, 75953–75963.
54 J. H. Advani, A. S. Singh, N. H. Khan, H. C. Bajaj and
A. V. Biradar, Appl. Catal., B, 2020, 268, 118456.
55 R. K. Tak, N. Gupta, M. Kumar, R. I. Kureshy, N. H. Khan and
E. Suresh, Eur. J. Org. Chem., 2018, 2018, 5678–5687.
56 S. Hajra, S. Roy, S. Maity and S. Chatterjee, J. Org. Chem.,
2019, 84(4), 2252–2260.
57 P. Patel, S. Nandi, T. Menapara, A. V. Biradar, R. K. Nagarale,
N. H. Khan and R. I. Kureshy, Appl. Catal., A, 2018, 565, 127–
134.
´
29 M. R. Monaco, S. Prevost and B. List, Angew. Chem., Int. Ed.,
2014, 53, 8142–8145.
30 S. Nandi, P. Patel, N.-u. H. Khan, A. V. Biradar and
R. I. Kureshy, Inorg. Chem. Front., 2018, 5, 806–813.
31 A. Lundin, I. Panas and E. Ahlberg, Phys. Chem. Chem. Phys.,
2007, 9, 5997–6003.
32 B. Tang, W. Dai, G. Wu, N. Guan, L. Li and M. Hunger, ACS
Catal., 2014, 4, 2801–2810.
33 A. Parulkar, R. Joshi, N. Deshpande and N. A. Brunelli, Appl. 58 B. Parmar, P. Patel, R. S. Pillai, R. K. Tak, R. I. Kureshy,
Catal., A, 2018, 566, 25–32.
N. H. Khan and E. Suresh, Inorg. Chem., 2019, 58, 10084–
34 A. Parulkar, A. P. Spanos, N. Deshpande and N. A. Brunelli,
Appl. Catal., A, 2019, 577, 28–34.
35 N. Deshpande, A. Parulkar, R. Joshi, B. Diep, A. Kulkarni and
N. A. Brunelli, J. Catal., 2019, 370, 46–54.
10096.
59 R. K. Tak, P. Patel, S. Subramanian, R. I. Kureshy and
N. H. Khan, ACS Sustainable Chem. Eng., 2018, 6, 11200–
11205.
36 B. Tang, W.-C. Song, S.-Y. Li, E.-C. Yang and X.-J. Zhao, New J.
Chem., 2018, 42, 13503–13511.
12814 | RSC Adv., 2021, 11, 12808–12814
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