MgSiO3 nanoparticle-catalyzed 1,3-dipolar cycloaddition reactions in the synthesis of novel spiroindane-1,3-diones derived from substituted chalcones

Article abstract of DOI:10.1002/jccs.201800445

Employment of metal nanoparticles has been one of the most promising synthetic strategies for a number of chemical transformations. New spiroindane-1,3-diones were synthesized through [3 + 2] cycloaddition in moderate to high yields by a three-component r

Full text of DOI:10.1002/jccs.201800445

Received: 20 November 2018
DOI: 10.1002/jccs.201800445
Revised: 28 March 2019
Accepted: 11 May 2019
A R T I C L E
MgSiO3 nanoparticle-catalyzed 1,3-dipolar cycloaddition
reactions in the synthesis of novel spiroindane-1,3-diones derived
from substituted chalcones
Subramanya Gopal Hegde1 | Lokesh Koodlur1 | Suman Y. Reddy2
Manjunatha Narayanarao3
|
1Department of Studies and Research in
Chemistry, Vijayanagara Sri
Krishnadevaraya University, Bellary, India
2Apotex Research, Bangalore, India
3East Point College of Engineering and
Technology, Visvesvaraya Technological
University, Bangalore, India
Employment of metal nanoparticles has been one of the most promising synthetic
strategies for a number of chemical transformations. New spiroindane-1,3-diones
were synthesized through [3 + 2] cycloaddition in moderate to high yields by a
three-component reaction of heterocyclic chalcone derivatives, ninhydrin, and sar-
cosine/L-proline. The presence of heterogenous MgSiO3 nanoparticles (NPs) under
microwave irradiation showed a robust effect in improving the yield of the desired
products. Furthermore, the catalyst may be recovered and reused without signifi-
cant loss of activity.
Correspondence
Lokesh Koodlur, Department of Studies and
Research in Chemistry, Vijayanagara Sri
Krishnadevaraya University, Bellary
583105, India.
K E Y W O R D S
Email: kslokesh@vskub.ac.in
1,3-dipolar cycloaddition, heterocyclic Chalcone derivatives, L-proline, MgSiO3NPs, sarcosine
Funding information
Science and Engineering Research Board,
Grant/Award Number: SR/FST/CSI-
274/2016; Vision Group of Science and
Technology, Govt of Karnataka, India,
Grant/Award Number: GRD No 555
[1,3-DC].[8,9] We anticipated that this methodology could be
extended to prepare spirocyclic compounds via 1,3-dipolar
1 | INTRODUCTION
cycloaddition with diverse dipolarophile.
The evolution of nanoparticle-catalyzed cycloaddition has
sprung into prominence opening up new prospects in various
fields such as supramolecules,[1] polymers,[2] functional
coatings,[3]and chemical synthesis.[4,5] Furthermore,
nanocatalysts can be extensively used in organic transforma-
tion because of their high selectivity, reactivity, and stabil-
ity.[6] The emergence of the metal oxide nanoparticles
(NPs), for the synthesis of stable heterocyclic compounds
via click chemistry, has been of intense interest and recently
enolate-mediated organo click reaction for the synthesis of
substituted triazoles has been reported.[7] For instance, our
laboratory reported the application of MgSiO3 NPs for the
stereoselective synthesis of polycyclic aromatic hydrocar-
bons by intramolecular 1,3-dipolar cycloaddition reaction
Chalcones because of their widespread applications,
pharmacological activity, and their ease of preparation com-
pelled us to consider them as dipolarophiles. Moreover, the
newly synthesized chalcones were found to have excellent
cytotoxic activity toward hepatocellular carcinoma cell lines
(HepG2 cell lines).[10] Based on the initial findings and to
explore the new class of functionalized spiroheterocyclic
derivatives and also to study their biological applications,
1,3 DC on chalcone substrates was chosen. In recent years, a
renaissance of interest in the development of methods for the
synthesis of bioactive natural products and medicines com-
prising spiroindene motif has been observed.[11–14] These
ring systems, which are connected through one atom, are a
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–5.
http://www.jccs.wiley-vch.de
1

2
HEGDE ET AL.
syntheses.[15–18] A number of methods have been developed
for constructing enantioselective spiro compounds through
1,3-dipolar cycloaddition reaction via azomethine
ylide[19–21] and organocatalytic reactions.[22] Consequently,
we believed that the incorporation of chalcone framework
into the more complex structures would be worthwhile to
design new potentially bioactive compounds.
Recently, a spirooxindole system obtained from various
approaches has been outlined for its application as anti-
tumor, antimicrobial, and anti-HIV agents as well as antipy-
retics.[23] Herein, we report an efficient, atom economic,
regioselective, and high yielding multicomponent reaction
(MCR) protocol for the one-pot facile synthesis of
functionalized spiroindane-1,3-diones. A new synthetic
methodology was implemented by the application of
MgSiO3 NPs for heterocyclic chalcones by the reaction of
ninhydrin with sarcosine/proline, in methanol under micro-
wave irradiation.
SCHEME 1 Synthesis of chalcone derivatives 3a–j. a. NaOH
(1.5 eq), methanol, rt, 2 hr
TABLE 1 Reaction of dione azomethine ylide with dipolarophile
(3d) under varied conditions
Time
(hr)
Isolated
yield (%)
Reaction conditions
Acetonitrile/reflux
Dioxane/reflux
Xylene/reflux
24
12
10
8
10
15
0
2 | RESULTS AND DISCUSSION
Toluene/reflux
15
30
60
Our experimental efforts began with the synthesis of a variety
of biologically active heterocyclic chalcones 3a–j as larger
dipolarophiles under the standard condition as described in
the preceding literature procedure.[10] To evaluate the feasibil-
ity of the approach, outlined in Scheme 2, we targeted ini-
tially with the thiophene-based system synthesized from the
readily available 3-acetyl thiophene 1 (Scheme 1).
Methanol/reflux
12
12
Methanol, MgSiO3NPs (10 mol%)
reflux
Methanol/MW, MgSiO3NPs
(10 mol%)
0.75
75
unique kind of structure in organic compounds. However,
there are fewer reports related to the rationalizing
azomethine-chalcone cycloadditions. Our initial concept for
the preparation of spiroindene was inspired by traditional
With chalcone derivative 3d in hand, we turned our atten-
tion to the implementation of 1,3-dipolar cycloaddition reac-
tion. Primarily, we attempted a few experiments of 3d in
various solvents viz. acetonitrile, toluene dioxane, and xylene
SCHEME 2 Synthesis of
spiroindane-1,3-dione derivatives 6a–j.
a. 4 (3.0 eq), 5 (3.0 eq), 3 (1.0 eq),
10 Mol% MgSiO3 NPs, methanol, MW,
and 0.5–1 hr
FIGURE 1 Retrosynthetic
strategy for the synthesis of
spiroindane-1,3-diones

HEGDE ET AL.
3
TABLE 2 Spiroindane-1,3-dione
hybrids 6a–j from MgSiO3NP-catalyzed
1,3-dipolar cycloadditiona
Entry
6a
R1
R2
R3
X
Time (hr)
Isolated yield (%)
H
H
S
0.75
75
6b
6c
H
H
H
H
S
S
0.75
1
72
68
6d
6e
H
H
H
H
S
S
0.5
0.5
88
85
6f
CH3
CH3
CH3
CH3
CH3
CH3
O
O
O
0.75
0.75
1
75
72
65
6g
6h
6i
6j
CH3
CH3
CH3
CH3
O
O
0.5
0.5
80
80
aReaction conditions: 3 (1 mmol), 4 (3.0 mmol), 5 (3.0 mmol), methanol (10 mL), 10 mol%MgSiO3NPs,
Methanol MW, and 0.5–1 hr.
under thermal conditions, which led to the formation of spiro
products, but in low yields (Table 1). Eventually, we found
that, the addition of a catalytic amount of nanocatalyst viz.
MgSiO3 to 3d in methanol under refluxing conditions worked
well and gave the desired cyclic adduct 6d in 60% yield.
There was a substantial increase in the yield of the cyclo-
adducts under microwave irradiation with a decrease in reac-
tion time to get a novel fused spiroindane-1,3-diones. The
reaction progressed through in situ generation of azomethine
ylide intermediate A (Scheme 2) followed by cyclization in
completely regioselective and stereoselective manners. The
MgSiO3 NPs were prepared according to the reported proto-
col.[24] These nanoparticles were believed to act as Lewis acid
by coordinating with chalcone for the formation of ylide inter-
mediates, as shown in the retrosynthetic analysis (Figure 1).
The structure of 6d was confirmed by the spectral data.
The stereochemistry was assigned based on H NMR and
1
NOE studies. The confirmative protons of the proposed
1
structure for 6d are H3 and H4 protons. In H NMR spec-
troscopy, the H4 proton appeared at δ 3.5 as a quartet with a
coupling constant J = 6.4 Hz, whereas the characteristic H3
proton appeared as a multiplet at δ = 4.4 ppm, respectively.
The stereochemistry of the cycloadduct 6d was presumed on
the basis of 2D NOESY experiments. There is no NOESY
between H4 and H3 of 6d clearly proved trans stereochem-
istry. Two triplets at δ 3.8 and 4.5 correspond to N-CH2 pro-
tons. The N-CH3 peak appeared as a singlet at δ 2.3 ppm.
This was further confirmed by carbonyl groups of indene
and thiophene of 13C NMR at δ 202.8, 200.5, and
191.7 ppm.
SCHEME 3 Synthesis of
spiroindane-1,3-diones derivatives 8a–
j. a. 4 (3.0 eq), 7 (3.0 eq), 3 (1.0 eq),
10 Mol% MgSiO3 NPs, methanol, MW,
and 0.5–1 hr

4
HEGDE ET AL.
To expand the scope of this reaction, we explored the use
proton at C-4 resonates as a multiplet at δ 3.81 (1H, m). In
the 13C NMR spectrum of the cycloadduct 8a, the car-
bonyl carbons of indene-1,3-dione and the thiophene-
carbonyl group carbons exhibit signals at δ 201.4, 200.1,
and 190.1, respectively. A molecular ion peak at m/z
458 (ESI-MS, M + 1) in the mass spectrum confirmed
the formation of the cycloadduct. The regiochemistry of
this type is established by the comparison with the analo-
gous type of compound that has been reported in the
literature.[9,13]
Finally, we also examined the catalytic effect of MgSiO3
NPs on 1,3-dipolar cycloaddition reaction and its
regiochemical outcome in terms of reusability. The catalyst
was recovered from the reaction medium by simple filtration
and was washed with cold methanol and further dried in the
air overnight. In two runs, there is no substantial decrease in
the isolated yield observed with recycled MgSiO3NPs. An
experimental work to assess the stability and efficiency of
the reused dried catalyst was carried out on compound 6d,
by following the optimized protocol. The isolated yield was
found to be 80%, after two runs and was achieved in
30 min., which is 15 min less than that of the original
single-pot reaction. The reason for the sustained perfor-
mance can be attributed to nanoparticle formation. However,
of various chalcone derivatives (3a–j) under optimized reac-
tion conditions, which led to the formation of the
corresponding cycloadducts 6a–j in good yields with com-
plete regioselectivity (Table 2). We first began the reaction
of 3a with acyclic amino acid (sarcosine) 5, ninhydrin 4 in
methanol (10 vol) in the presence of MgSiO3 NPs at 50ꢀC,
which efficiently afforded cyclic adduct 6a as a single dia-
stereoisomer in 75% yield (Table 2, entry 1).
Furthermore, this catalytic system was effective for the
methodology toward cyclic amino acid-derived ylides and
regiochemistry. These results demonstrate that this reaction
can be used to furnish novel corresponding cycloadducts
8a–j in good yields with complete selectivity (Scheme 3).
Only a single diastereomer was obtained throughout the
series and the structures of which were completely
1
established by H, 13C, and mass spectral studies (Table 3).
The 1H nuclear magnetic resonance (NMR) spectrum of
compound 8a shows multiplet signals in the region δ
1.77–2.64 for the protons of the pyrrolizidine system. The
signals in the region δ 6.80–8.08 are for the protons of aryl
groups. A doublet at δ 4.80 (1H, d, J = 11.2 Hz) indicates
the presence of a methine proton, next to the thiophene-
carbonyl group at C-3 of the pyrrolidine ring. The benzylic
TABLE 3 Spiroindane-1,3-dione
Entry
8a
R1
R2
R3
X
Time (hr)
Isolated yield (%)
hybrids 8a–j from MgSiO3NP-catalyzed
1,3-dipolar cycloadditiona
70
H
H
S
0.75
8b
8c
H
H
H
H
S
S
0.75
1
74
63
8d
8e
H
H
H
H
S
S
0.5
0.5
85
82
8f
CH3
CH3
CH3
CH3
CH3
CH3
O
O
O
0.75
0.75
1
70
72
60
8g
8h
8i
8j
CH3
CH3
CH3
CH3
O
O
0.5
0.5
82
80
aReaction conditions: 3 (1 mmol), 4 (3.0 mmol), 7 (3.0 mmol), methanol (10 vol), 10 mol%MgSiO3NPs, Methanol, MW, 0.5–1 hr.

HEGDE ET AL.
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ACKNOWLEDGMENTS
The authors express their gratitude to K-FIST L1 scheme of
VGST, Govt of Karnataka and DST-FIST scheme of DST
for financial support.
SUPPORTING INFORMATION
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How to cite this article: Hegde SG, Koodlur L,
Reddy SY, Narayanarao M. MgSiO3 nanoparticle-
catalyzed 1,3-dipolar cycloaddition reactions in the
synthesis of novel spiroindane-1,3-diones derived
from substituted chalcones. J Chin Chem Soc. 2019;
1–5. https://doi.org/10.1002/jccs.201800445
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