Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene Derivatives Through 1,3-Dipolar Cycloaddition Reactions

Article abstract of DOI:10.1002/jhet.3534

A simple, straightforward, and versatile protocol for the synthesis of spiro indanone pyrrolidine/piperidine fused nitrochromene derivatives is described. The synthesis of a new series of spirocyclic molecules has been expediently accomplished via a one-p

Full text of DOI:10.1002/jhet.3534

Month 2019
Microwave-assisted One-pot, Three-component Regiospecific and
Sterospecific Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused
Nitrochromene Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Sabita Nayak,a,b
Pravati Panda,a,b Seetaram Mohapatra,a,b
Bishnuprasad Raiguru,a,b and Nilofar Barala,b
*
aDepartment of Chemistry, Ravenshaw University, Cuttack, Odisha, India
bNational Institute of Science Education and Research, Bhubaneswar, Odisha, India
*E-mail: sabitanayak18@gmail.com
Received September 23, 2018
DOI 10.1002/jhet.3534
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
A simple, straightforward, and versatile protocol for the synthesis of spiro indanone pyrrolidine/piperidine
fused nitrochromene derivatives is described. The synthesis of a new series of spirocyclic molecules has
been expediently accomplished via a one-pot, three component 1,3-dipolar cycloaddition reaction.
2-Phenyl-nitrochromene dipolarophiles were reacted with azomethine ylides, generated in situ by the
condensation of dicarbonyl compound indane-1,3-dione and secondary amino acid (L-proline/pipecolic
acid), to produce the corresponding cycloadducts in good yields (85–90%) under classical as well as under
microwave irradiation. The cycloaddition reaction was found to be highly regiospecific and diasterospecific.
The regiochemical and sterochemical outcome of the cycloaddition reaction is ascertained by 2D NMR
(COSY and NOESY) studies.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
and pharmaceutical activities [7]. In particular, highly
substituted pyrrolidine motifs containing spiro
a
1,3-Dipolar cycloaddition reactions are proved to be one
of the best and efficient method for the synthesis of highly
substituted five-membered heterocyclic rings in a single
reaction in a regioselective and steroselective manner
without purifying the intermediates [1,2]. Five-membered
cyclic heterocycles are an important class of compounds,
not only because of their natural abundance but also for
their chemical and biological significance [3]. Among the
dipoles, azomethine ylides have gained significance in
recent years as it serves as a reactive and versatile 1,3-
dipoles that react readily with various dipolarophiles
to afford pyrrolidines and pyrrolizidines [4,5]. These
compounds form the central skeletons of numerous
alkaloids with highly pronounced biological activities [6].
The highly substituted pyrrolidines are prevalent in many
natural products that exhibit a broad range of biological
quaternary stereogenic carbon center fused with indanone
are versatile synthetic motifs for the biologically active
natural products and pharmaceuticals and attracted the
attention of chemists and pharmacologists [8–11]. The
significance of those molecules has stimulated intensive
interests to develop numerous excellent manufacturing
approaches in current years.
On the other hand, chromenes and their derivatives are
widespread in the plant world and also possess valuable
biological and pharmacological properties [12]. The chiral
chromene unit is the core structure in a number of natural
products [13,14]. Several chromene derivatives are known
to exhibit a wide range of biological properties, for
example, anticancer, antidiuretic, anticoagulant, and anti-
anaphylactic activity [15–17]. Among these, 3-nitro-2H-
chromenes are very important units, which are recognized
© 2019 Wiley Periodicals, Inc.

S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
because of their biological activity and their importance as
precursors of flavonols, amines, and other important
targets [18–20]. In view of this, combining benzopyran
and pyrrolidine moieties in a single molecule seems a
synthetic task of current interest (Fig. 1) [4,5].
In continuation of our ongoing research, the biological
importance of these heterocycles prompted us to embark
on the assembly of their hybrids in a single framework
that could lead to the enhancement of biological activities.
Accordingly, the present work is a part of our study for
the construction of novel spiroindeno pyrrolidine/
piperidine nitrochromene hybrids employing domino/
multicomponent/1,3-dipolar cycloadditions by greener
protocols.
Before to this report, several methods have been reported
in the literature for the synthesis of spiroheterocycles using
various solvents [21]. Generally, isatin and its derivatives
have been employed as the starting material for 1,3-
dipolar cycloaddition reactions that yields the
spirooxindole core owing to the facile preparation of
azomethine ylides in the presence of α-amino acids.
Nitrochromenes as dipolarophile for the 1,3-dipolar
cycloaddition reaction of azomethine ylides generated
from isatin and its derivatives was first reported in the
literature in 2013 [4]. Then after, sugar derived 3-
nitrochromene derivatives as dipolarophile in 1,3-dipolar
cycloaddition reaction has come to the limelight in 2015
[5a]. In 2017, Korotaev et al. have reported the synthesis
of spiro[chromeno[3,4-a]pyrrolizidine-11,20-indene]-10,30-
diones via 1,3-dipolar cycloaddition strategy using
ninhydrin and 2-substituted nitrochromenes [5b]. But all
these methods for the synthesis of nitrochromene hybrid
pyrrolidine spiroheterocycles have been carried out in
solvent medium under reflux condition and took long
reaction time that encouraged us to move further.
Owing to the biological importance of this class of
compounds, there is a need to develop an efficient, green,
and rapid method to enrich the library of spiro indanone
pyrrolidine/piperidine fused nitrochromene derivatives.
In this endeavor, we decided to explore the utility of a
microwave (MW) irradiation technique in order to
develop an efficient, convenient, high yielding, and rapid
green protocol. Recently, MW irradiation has emerged as
a powerful tool as an alternative heating source because of
advantages like operational simplicity, enhanced reaction
rate, high yield, and purity of products [21b]. This
technique is a valuable alternative to conventional heating,
introduces energetic radiations into the reaction and
thereby enhances the rate and yields of the reaction, and
simultaneously decreases the reaction time.
Herein, we disclose a novel synthetic approach for the
regiospecific and diasterospecific synthesis of spiro
indanone fused benzopyrano pyrrolidine by the reaction of
indane-1,3-dione, proline/pipecolic acid, and 3-nitro-2-
phenyl-2H-chromene in neat condition under conventional
heating as well as under MW irradiation.
Initially, the 2-phenyl-3-nitrochromene derivatives
3(a–p) utilized for 1,3-dipolar cycloaddition were
Figure 1. Biologically important molecules containing indanone, benzopyran pyrrolidine, and nitrochromene core. [Color figure can be viewed at
wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
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Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
prepared by the treatment of β-nitroalkenes 2(a–c) with
salicyaldehydes 1(a–k) in the presence of DABCO under
solvent free conditions in a single step following
literature reported procedure (Scheme 1) [22].
that among all the solvents, in ethanol at 100 W/80°C for
10 min, excellent yield of the product was formed.
Increasing the time interval more than 10 min leads to
decrease in the yield of the product. To our delight in
MW irradiation, excellent yield of the product formation
was observed that encouraged us to move further.
Having 3-nitro-2H-chromenes in hand, we investigated
the scope of one-pot sequential three-component
cycloaddition reaction of 2-phenyl-3-nitrochromenes 3a
as dipolarophile with azomethine ylide generated in situ
from decarboxylative condensation of indane-1,3-dione 4
with proline 5. The reaction was investigated in various
solvents such as benzene, toluene, acetonitrile, methanol,
ethanol, dimethylformamide, and tetrahydrofuran at
different temperatures from room temperature to refluxing
(Table 1). As shown in Table 1, ethanol as solvent
provided higher yield 70% (Table 1, entry 5) in case of
conventional oil bath heating. Therefore, ethanol and
refluxing condition were chosen as optimal conditions for
all further reactions. The reaction afforded highly
substituted spiroproduct 6a as single diastereoisomer in
70% yield after recrystallization (Scheme 2).
In order to reduce the reaction time interval as well as to
enhance the yield of spiro cycloadducts, the reactions were
subsequently investigated under MW irradiation. Similar
to the conventional heating reactions, an equimolar
reaction mixture in different solvents such as methanol,
ethanol, acetonitrile, benzene, toluene, and H2O were
subjected to the MW irradiation. It has been observed
To check the generality as well as the effectiveness of the
developed protocol, a number of 3-nitro-2H-chromenes
derivatives having substituents such as methoxy, ethoxy,
and halogens were reacted with indanone and L-proline/
pipecolic acid using ethanol under reflux conditions. All
of them underwent the reaction smoothly affording the
corresponding spiro cycloadducts. The yields were not
improved further even on raising the temperature over
reflux temperature in a sealed tube. The results obtained
for both conventional as well as MW irradiation methods
are summarized in Table 2, which clearly shows that MW
irradiation led to an enhancement in the rate as well as
yield of the products (78–90%) over the conventional
thermal method (58–75%). As shown in Table 2, this
protocol could be applied to a large range of different
substituted aromatic rings of 3-nitro-2H-chromene
including electron-withdrawing groups (such as chloro
and bromo groups) and electron-donating groups (such as
methoxy and ethoxy groups). In all cases, the reaction
proceeded smoothly and only a single diasteroisomer of
spiro pyrrolidines were afforded in good to excellent
Scheme 1. Synthesis of 2-phenyl-3-nitro-2H-chromenes 3(a–p).
Table 1
Solvent and temperature for the synthesis of 3-nitro-2H-chromene fused pyrrolidine spiro indanone.
Entry
Solvent
Temp
Time (h)
Yield (%)
MW (W)
Temp (°C)
Time (min)
Yield (%)a
1
Methanol
Ethanol
CH3CN
Methanol
Ethanol
CH3CN
Benzene
Toluene
H2O
r.t
r.t
r.t
80°C
80°C
80°C
100°C
100°C
100°C
12
12
12
7
6
7
12
12
12
n.r
n.r
n.r
40
70
35
50
50
50
100
100
100
100
100
100
40
40
40
80
80
10
10
10
10
10
10
10
10
10
20
30
20
58
90
50
2
3
4
5
6
7
8
9
80
Complex mixture
Complex mixture
n.r
100
100
100
Complex mixture
Complex mixture
n.r
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S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
Scheme 2. Synthesis of 3-nitrochromane fused pyrrolidine spiro indanone.
Table 2
Synthesis of 3-nitrochromane hybrid pyrrolidinyl/piperidine spiro indanones.
Conventional method (EtOH, 80°C)
Microwave method (EtOH, 100 W) s
Entry
1
Producta
Time (h)
3
Yield (%)b
70
Time (min)
10
Yield (%)b
85
2
3
4
2
2
3
72
75
70
10
88
5
90
85
5
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
Table 2
(Continued)
Conventional method (EtOH, 80°C)
Microwave method (EtOH, 100 W) s
Entry
5
Producta
Time (h)
3
Yield (%)b
Time (min)
10
Yield (%)b
75
89
6
7
8
9
2
2
3
3
70
72
70
75
5
8
86
89
85
89
5
10
(Continues)
Journal of Heterocyclic Chemistry
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S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
Table 2
(Continued)
Conventional method (EtOH, 80°C)
Microwave method (EtOH, 100 W) s
Entry
10
Producta
Time (h)
2
Yield (%)b
70
Time (min)
5
Yield (%)b
86
11
12
13
14
2
2
2
3
72
72
72
70
8
8
8
5
89
89
89
85
(Continues)
Journal of Heterocyclic Chemistry
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Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
Table 2
(Continued)
Conventional method (EtOH, 80°C)
Microwave method (EtOH, 100 W) s
Entry
15
Producta
Time (h)
3
Yield (%)b
75
Time (min)
10
Yield (%)b
89
16
17
2
2
70
72
5
8
86
89
18
2
72
8
89
19
2
72
8
89
(Continues)
Journal of Heterocyclic Chemistry
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S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
Table 2
(Continued)
Conventional method (EtOH, 80°C)
Microwave method (EtOH, 100 W) s
Entry
20
Producta
Time (h)
2
Yield (%)b
72
Time (min)
8
Yield (%)b
89
21
2
72
8
89
aThe products were characterized by NMR and mass spectroscopy.
bIsolated yield after purification.
yields (85–90%). The region and sterochemical outcome
was determined by taking COSY and NOESY NMR of
compound 6k.
spectrum. The three pyrrolidine methylene carbon
resonates at 24.8, 30.0, and 50.4 ppm and was confirmed
by DEPT-135 NMR spectroscopy. These observed
chemical shift values are in good agreement with the
structure of the compound 6a. Furthermore, the presence
of molecular ion peak at m/z 467.1582 (M + 1) in the
mass spectrum confirmed the formation of the cycloadduct
6a. The regiochemical and sterochemical outcome of the
cycloaddition reaction was determined by comparing
previous literature reports [4,5]. With this initial success,
we treated different 2-phenyl-3-nitrochromenes 3(b–p)
with azomethine ylides generated in situ from indanone
4 and secondary amino acids proline 5 or pipecolic acid
50 under optimized reaction conditions. These reactions
successfully proceeded through [3 + 2] cycloaddition
to produce the corresponding 3-nitrochroman hybrid
pyrrolidinyl spiro indanones 6(b–u) in good yields
(Table 2).
The structure of the product 6a was elucidated from the
1H and 13C NMR spectroscopic data. The 1H NMR
spectrum of compound 6a exhibited a characteristic
singlet at δ 4.70 ppm corresponding to Ha proton of
pyrrolidine ring attached to chromane core and also the
Hb proton of the proline ring appeared as multiplet at
δ 3.85 ppm that clearly proved the incorporation of
spiro pyrrolidine indanone ring in 3-nitro-2H-chroman.
Furthermore, the characteristic singlet at δ 4.70 ppm
corresponding to Ha proton proved the formation of regio
isomer 6a. If the other regioisomer had formed, the Ha
proton would have appeared as a multiplet in the 1H NMR
spectrum. The two carbonyl carbon of indanone showed
characteristic peaks at 199.7 and 201.3 ppm in 13C NMR
spectrum. Further, the carbon attached to Ha proton, 2-C
carbon of nitrochromene, and spiro carbon appeared
at 69.1, 78.1, and 93.5 ppm respectively in 13C NMR
From mechanistic considerations, it is believed that the
cycloaddition reaction proceeds with an initial iminium
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
Figure 2. Mechanism for the formation of cycloadduct. [Color figure can be viewed at wileyonlinelibrary.com]
ion formation, which subsequently decarboxylates to
generate azomethine ylide (1,3-dipole) and which
attacks the dipolarophile to produce the cycloadducts in
high yields. The projection of NO2 group, Ha proton
and –Ph group in the cis-orientation as well as in the
β-face, was confirmed by 2D NMR (NOESY) as well
as by comparing literature reports (Fig. 2) [4,5].
nitrostyrenes 2 (1.0 mmol) were taken in one pot and
stirred under reflux condition at 40°C for 1–3 h. Reaction
was monitored by TLC, and after completion of reaction,
the reaction mixture was diluted with water and extracted
with ethyl acetate. The organic layer was separated, dried
over anhydrous Na2SO4, and evaporated under reduced
pressure. The crude reaction mixture was crystallized
by isopropanol. Also in some cases, the crude product
was purified by silica gel (100–200 mesh) column
chromatography using ethyl acetate/hexane to furnish the
pure compound 3(a–p) in 85–90% yield. All compounds
CONCLUSIONS
In conclusion, we have developed a simple and efficient
protocol for the synthesis of 2-phenyl-3-nitrochromane
hybrid pyrrolidine/piperidine spiroheterocycles through
1,3-dipolar cycloaddition methodology under con-
ventional heating as well as under MW irradiation. This
multicomponent reaction offers high yield, with simple
were characterized by NMR and mass spectral data.
3-Nitro-2-phenyl-2H-chromene (3a). Yellow solid; yield
1
94%; mp: 92–94°C; H NMR (CDCl3, 400 MHz): δ 8.07
(s, 1H), 7.40–7.32 (m, 7H), 7.03–7.00 (m, 1H), 6.90–
6.87 (m, 1H), 6.60 (s, 1H). 13C NMR (CDCl3,
100 MHz): δ 139.1, 137.1, 134.3, 132.2, 130.5, 129.4,
129.2, 128.9, 127.0, 122.5, 117.3, 74.3. ESI-HRMS:
Calcd for C15H11NO3 [M + H]+ 254.0812; Found
254.0954.
experimental procedure and formation of
a single
regiospecific and sterospecific product. Further, the
biological activities of the synthesized compounds are
currently under investigation, and further work in this
direction is in progress.
8-Methoxy-3-nitro-2-phenyl-2H-chromene (3b).
Yellow
solid; yield 92%; mp: 124–126°C; 1H NMR (CDCl3,
400 MHz): δ 8.04 (s, 1H), 7.43–7.41 (m, 2H), 7.32–7.30
(m, 3H), 6.95 (s, 3H), 6.68 (s, 1H), 3.81 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 148.7, 142.8, 141.4, 136.7,
129.4, 129.3, 128.8, 127.0, 122.5, 122.2, 118.8, 116.8,
74.2, 56.4. ESI-HRMS: Calcd for C16H13NO4 [M]+
283.0845; Found 283.1119.
EXPERIMENTAL
General. All melting points were uncorrected and were
taken using SMP10 melting point apparatus. Commercial
reagents were used without further purification. Solvents
were distilled by standard literature procedures. All the
reactions were carried out in anhydrous conditions,
and the progress of the reactions was monitored by thin-
layer chromatography (TLC) using hexanes/ethyl acetate
mixture. Column chromatography was performed on
silica gel. 1H NMR (JEOL 400 MHz) and 13C NMR
(100 MHz) spectra were recorded in CDCl3. The reaction
was done using CEM MW synthesizer.
6-Methoxy-3-nitro-2-phenyl-2H-chromene (3c).
Yellow
solid; yield 84%; mp: 129–131°C; 1H NMR (CDCl3,
400 MHz): δ 8.04 (s, 1H), 7.37–6.84 (m, 8H), 6.56 (s,
1H), 3.80 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 154.8,
147.5, 141.8, 136.6, 129.4, 128.8, 127.0, 120.7, 118.4,
118.2, 113.7, 74.0, 55.8. ESI-HRMS: Calcd for
C16H13NO4 [M + H]+ 284.0845; Found 284.3388.
6-Methoxy-2-(4-methoxyphenyl)-3-nitro-2H-chromene
(3d). Pale yellow solid; yield 79%; mp: 138–140°C; H
NMR (CDCl3, 400 MHz): δ 7.92 (s, 1H), 7.19 (d,
J = 4.0 Hz, 2H), 6.80 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 6.75–
6.73 (m, 3H), 6.69 (d, J = 8.0 Hz, 1H), 6.39 (s, 1H), 3.70
(s, 3H), 3.67 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
1
General procedure for preparation of 3-nitro-2-phenyl-2H-
chromenes 3(a–p).
Substituted salicylaldehydes 1,
(1.0 mmol), DABCO (0.2 mmol), and trans-β-
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S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
159.3, 153.7, 146.4, 140.9, 128.1, 127.6, 127.5, 119.5,
117.5, 117.2, 113.1, 112.6, 72.7, 54.8, 54.2. ESI-HRMS:
Calcd for C17H15NO5 [M + H]+ 314.1023; Found
2H), 6.59 (s, 1H), 5.44 (s, 1H), 3.78 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 160.7, 144.9, 141.6, 139.8,
129.1, 128.6, 128.4, 122.9, 121.7, 120.2, 118.1, 114.4,
314.3597.
74.6, 55.3.
2-(3,4-Dimethoxyphenyl)-6-methoxy-3-nitro-2H-chromene
(3e). Sticky faint red solid; yield 78%; mp: 152–154°C;
6,8-Dichloro-3-nitro-2-phenyl-2H-chromene (3l). Yellow
solid; yield 88%; mp: 144–146°C; 1H NMR (CDCl3,
400 MHz): δ 7.96 (s, 1H), 7.37–7.35 (m, 6H), 7.23–7.22
(m, 1H), 6.71 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ
148.0, 142.9, 135.7, 133.6, 129.9, 129.0, 127.9, 127.4,
126.8, 123.6, 120.4, 74.6. ESI-HRMS: Calcd for
C15H9Cl2NO3 [M + H]+ 320.9959; Found 321.0000.
1H NMR (CDCl3, 400 MHz): δ (ppm): δ 7.93 (s, 1H),
6.85 (d, J = 4.0 Hz, 1H), 6.82–6.74 (m, 3H), 6.71 (d,
J = 8.0 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 6.40 (s, 1H),
3.75 (s, 3H), 3.74 (s, 3H), 3.70 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 154.8, 149.9, 149.2, 147.4, 141.9,
129.2, 129.0, 120.5, 119.4, 118.5, 118.2, 113.7, 110.9,
110.5, 73.9, 55.9, 55.8, 55.8. ESI-HRMS: Calcd for
C18H17NO6 [M + Na]+ 366.0948; Found 366.3788.
6,8-Dibromo-3-nitro-2-phenyl-2H-chromene
(3m).
Yellow solid; yield 87%; mp: 166–168°C; 1H NMR
(CDCl3, 400 MHz): δ 7.95 (s, 1H), 7.67–7.66 (m, 1H),
7.41–7.32 (m, 6H), 6.74 (s, 1H); 13C NMR (CDCl3,
100 MHz): δ 149.6, 142.8, 139.0, 135.7, 131.5, 129.8,
8-Ethoxy-3-nitro-2-phenyl-2H-chromene (3f).
Amber
solid; yield 91%; mp: 117–119°C; 1H NMR (CDCl3,
400 MHz): δ 8.05 (s, 1H), 7.41–7.28 (m, 5H), 6.95 (s,
3H), 6.70 (s, 1H), 4.03 (q, J = 8.0 Hz, 2H), 1.37 (t,
J = 8.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 148.0,
143.3, 141.4, 136.7, 129.5, 129.3, 128.7, 126.9, 122.5,
129.0, 127.3, 126.8, 120.8, 114.6, 112.4, 74.7.
8-Bromo-6-chloro-3-nitro-2-phenyl-2H-chromene (3n).
Yellow solid; yield 87%; mp: 163–165°C; 1H NMR
(CDCl3, 400 MHz): δ 7.97 (s, 1H), 7.55–7.54 (m, 1H),
7.40–7.36 (m, 6H), 6.75 (s, 1H); 13C NMR (CDCl3,
100 MHz): δ 149.1, 142.8, 136.4, 135.6, 129.8, 129.0,
122.3, 119.1, 118.7, 73.9, 65.1, 14.7.
8-Ethoxy-2-(4-methoxyphenyl)-3-nitro-2H-chromene
(3g). Orange red solid; yield 88%; mp: 130–132°C; H
1
128.6, 127.8, 127.5, 126.8, 120.3, 112.1, 74.7.
6-Bromo-8-methoxy-3-nitro-2-phenyl-2H-chromene (3o).
NMR (CDCl3, 400 MHz): δ 8.03 (s, 1H), 7.32 (d,
J = 4.0 Hz, 2H), 6.95–6.93 (m, 3H), 6.81 (d, J = 8.0 Hz,
2H), 6.62 (s, 1H), 3.99 (q, J = 4.0 Hz, 2H), 3.76 (s, 3H),
1.35 (t, J = 4.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ
160.4, 148.0, 143.2, 141.5, 129.2, 128.8, 128.4, 122.3,
122.2, 119.1, 118.7, 114.0, 73.7, 65.1, 55.2, 14.7.
Chrome yellow solid; yield 86%; mp: 132–134°C; 1H
NMR (CDCl3, 400 MHz): δ 7.97 (s, 1H), 7.39–7.36 (m,
5H), 7.08 (d, J = 2.4 Hz, 2H), 6.68 (s, 1H), 3.84 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 149.4, 142.2, 142.0,
136.1, 129.8, 129.7, 128.9, 127.8, 126.9, 123.9, 119.9,
119.5, 114.2, 74.3. ESI-HRMS: Calcd for C16H12BrNO4
6-Chloro-3-nitro-2-phenyl-2H-chromene (3h).
Yellow
solid; yield 84%; mp: 123–125°C; 1H NMR (CDCl3,
400 MHz): δ 8.00 (s, 1H), 7.43–7.33 (m, 6H), 7.27–7.26
(m, 1H), 6.85–6.83 (m, 1H), 6.60 (s, 1H); 13C NMR
(CDCl3, 100 MHz): δ 152.0, 142.1, 136.2, 133.8, 129.7,
129.4, 129.0, 127.9, 127.4, 127.0, 119.2, 118.7, 74.4.
[M + H]+ 360.9949; Found 361.0000.
6-Bromo-8-methoxy-2-(4-methoxyphenyl)-3-nitro-2H-
chromene (3p).
Yellow solid; yield 86%; mp: 149–
151°C; 1H NMR (CDCl3, 400 MHz): δ 7.93 (s, 1H),
7.31–7.28 (m, 2H), 7.08 (s, 1H), 7.01 (s, 1H), 6.82 (d,
J = 8.0 Hz, 2H), 6.59 (s, 1H), 3.79 (s, 3H), 3.76 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 163.1, 139.2, 135.2,
133.3, 131.3, 128.7, 126.3, 122.7, 120.9, 119.6, 115.1,
114.1, 74.2, 56.7, 55.7. ESI-HRMS: Calcd for
C17H14BrNO5 [M + Na]+ 413.0055; Found 413.2653.
6-Bromo-3-nitro-2-phenyl-2H-chromene (3i).
Yellow
solid; yield 83%; mp: 125–127°C; 1H NMR (CDCl3,
400 MHz): δ 7.99 (s, 1H), 7.48–7.37 (m, 7H), 6.80–6.78
(m, 1H), 6.60 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ
152.5, 142.0, 136.7, 136.2, 132.4, 129.8, 129.0, 127.8,
127.1, 119.8, 119.1, 114.5, 74.5.
General procedure for the preparation of spiro indanone
pyrrolidine/piperidine fused nitrochromene derivatives 6(a–
u). Procedure A: L-Proline/Pipecolic acid (1 mmol) and
6-Bromo-2-(4-methoxyphenyl)-3-nitro-2H-chromene (3j).
Pale yellow solid; yield 85%; mp: 132–134°C; H NMR
1
2-phenyl-3-nitro-2H-chromene (1 mmol) were added to a
solution of indane-1,3-dione (1 mmol) in EtOH (2 mL)
and the mixture were refluxed for 2–3 h in a sealed tube.
The progress of the reaction was monitored by TLC.
On completion of the reaction, the reaction mixture
was cooled to room temperature and the solid mass
precipitated out was filtered off followed by washing
with cold ethanol to obtain a crude product, which was
further purified by recrystallization from EtOH:CHCl3
(9: 1) without carrying out column chromatography to
obtain pure compound 6(a–u) as a single diastereoisomer
(70–75%).
(CDCl3, 400 MHz): δ 7.85 (s, 1H), 7.35 (d, J = 4.0 Hz,
1H), 7.29 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 7.18 (d,
J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 6.64 (d,
J = 8.0 Hz, 1H), 6.42 (s, 1H), 3.67 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 160.7, 152.4, 142.2, 136.6, 132.3,
128.6, 128.3, 127.6, 119.8, 119.1, 114.7, 114.3, 74.2,
55.3. ESI-HRMS: Calcd for C16H12BrNO4 [M + H]+
360.9949; Found 362.0000.
2-(4-Methoxyphenyl)-3-nitro-2H-chromen-6-ol (3k).
1
Orange red solid; yield 74%; mp: 131–133°C; H NMR
(CDCl3, 400 MHz): δ 8.07 (s, 1H), 7.32–7.28 (m, 2H),
7.01–6.98 (m, 1H), 6.95–6.91 (m, 2H), 6.86–6.83 (m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
Procedure B: L-Proline/Pipecolic acid (1 mmol) and
2-phenyl-3-nitro-2H-chromene (1 mmol) were added into
a sealed 10-mL glass tube containing a solution of indane-
1,3-dione (1 mmol) in EtOH (2 mL), and the mixture was
irradiated under MW irradiation (100 W power) at 80°C
for 5–10 min. The progress of the reaction was monitored
by TLC. On completion of the reaction, the reaction
mixture was cooled to room temperature, whereupon a
solid mass precipitated out. The precipitate was filtered
off followed by washing with cold ethanol to obtain a
crude product that was purified just by recrystallization
from EtOH:CHCl3 (9:1) without carrying out column
chromatography to obtain pure compound 6(a–u) as a
(6S,6aS,6bS,11aR)-2-methoxy-6-(4-methoxyphenyl)-6a-
nitro-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6d).
Brown solid;
yield 75%; mp: 185–187°C; 1H NMR (CDCl3,
400 MHz): δ 1.92–2.09 (m, 4H), 2.72–2.76 (m, 1H),
2.91–2.98 (m, 1H), 3.19 (s, 3H), 3.76–3.85 (m, 4H), 4.63
(s, 1H), 5.61 (d, J = 2.4 Hz, 1H), 6.38 (s, 1H), 6.61–6.97
(m, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.83–8.14 (m, 4H);
13C NMR (CDCl3, 100 MHz): δ 24.8, 30.0, 47.5, 50.4,
55.2, 55.3, 69.0, 76.3, 78.8, 93.0, 113.2, 113.6, 119.2,
119.7, 123.6, 124.1, 126.1, 129.0, 130.0, 131.7, 136.7,
137.4, 141.3, 141.8, 153.2, 160.4, 199.5, 201.0. ESI-
HRMS: Calcd for C30H26N2O6 [M + H]+ 526.53664;
Found 527.2034.
single diasteroisomer (85–90%).
(6S,6aS,6bS,11aR)-6-(3,4-dimethoxyphenyl)-2-methoxy-6a-
nitro-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6e). Black solid; yield
(6S,6aS,6bS,11aR)-6a-nitro-6-phenyl-6a,6b,7,8,9,11a-
hexahydro-6H-spiro[chromeno[3,4-a]pyrrolizine-11,20-indene]-
10,30-dione (6a). Black solid; yield 79%; mp: 165–167°C;
1
1H NMR (CDCl3, 400 MHz): δ 1.61–2.11 (m, 4H), 2.70–
2.77 (m, 1H), 2.94–3.00 (m, 1H), 3.82–3.87 (m, 1H),
4.70 (s, 1H), 6.18 (d, J = 4.0 Hz, 1H), 6.51–6.54 (m,
2H), 6.93–6.95 (m, 1H), 7.04–7.09 (m, 1H), 7.44–7.50
(m, 5H), 7.78–8.14 (m, 4H); 13C NMR (CDCl3,
100 MHz): δ 24.8, 30.0, 47.7, 50.4, 69.1, 78.1, 93.5,
117.5, 117.6, 121.3, 123.5, 124.0, 127.0, 127.2, 127.8,
128.2, 128.7, 129.3, 134.7, 136.4, 137.1, 141.5, 142.0,
154.0, 199.7, 201.3. ESI-HRMS: Calcd for C28H22N2O5
75%; mp: 193–195°C; H NMR (CDCl3, 400 MHz): δ
1.62–2.10 (m, 4H), 2.69–2.78 (m, 1H), 2.91–2.98 (m,
1H), 3.19 (s, 3H), 3.82–3.93 (m, 7H), 4.64 (s, 1H), 5.62
(d, J = 2.8 Hz, 1H), 6.37 (s, 1H), 6.65 (d, J = 4.0 Hz,
1H), 6.87–7.28 (m, 4H), 7.83–8.14 (m, 4H); 13C NMR
(CDCl3, 100 MHz): δ 24.8, 30.1, 48.4, 50.5, 55.0, 55.8,
56.1, 69.1, 77.3, 93.6, 110.3, 110.4, 111.2, 115.5, 117.9,
118.4, 120.7, 123.4, 124.0, 126.9, 136.4, 137.1, 141.4,
142.0, 148.1, 148.7, 149.7, 153.5, 199.6, 201.4. ESI-
HRMS: Calcd for C31H28N2O8 [M + H]+ 556.18457;
[M + H]+ 466.15287; Found 467.1582.
(6S,6aS,6bS,11aR)-4-methoxy-6a-nitro-6-phenyl-
Found 556.1953.
(6S,6aS,6bS,11aR)-4-ethoxy-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6f). Black solid; yield
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6b).
Brown solid;
yield 77%; mp: 129–131°C; 1H NMR (CDCl3,
400 MHz): δ 1.61–2.08 (m, 4H), 2.69–2.75 (m, 1H),
2.91–2.96 (m, 1H), 3.78 (s, 3H), 3.82–3.85 (m, 1H), 4.70
(s, 1H), 5.78 (d, J = 8.0 Hz, 1H), 6.45–6.51 (m, 2H),
6.65 (d, J = 4.0 Hz, 1H), 7.43–7.52 (m, 5H), 7.80–8.13
(m, 4H); 13C NMR (CDCl3, 100 MHz): δ 24.9, 30.1,
47.7, 50.5, 56.0, 69.2, 78.8, 93.7, 111.0, 118.6, 119.0,
121.1, 123.6, 124.1, 125.3, 128.0, 128.3, 129.1, 129.3,
134.6, 136.4, 137.2, 141.6, 142.1, 144.0, 148.7, 199.6,
201.5. ESI-HRMS: Calcd for C29H24N2O6 [M + H]+
1
78%; mp: 164–166°C; H NMR (CDCl3, 400 MHz): δ
1.35 (t, J = 8.0 Hz, 3H), 1.57–2.08 (m, 4H), 2.68–2.74
(m, 1H), 2.93–2.98 (m, 1H), 3.85–3.89 (m, 1H), 4.00 (q,
J = 8.0 Hz, 2H), 4.71 (s, 1H), 5.77 (d, J = 8.0 Hz, 1H),
6.41–6.67 (m, 3H), 7.16–7.50 (m, 5H), 7.80–8.13 (m,
4H); 13C NMR (CDCl3, 100 MHz): δ 15.6, 24.8, 30.0,
47.7, 50.4, 64.9, 69.1, 78.2, 93.7, 113.3, 118.5, 119.2,
120.9, 123.4, 124.0, 125.2, 127.9, 128.0, 128.2, 129.0,
129.1, 134.7, 136.3, 137.1, 141.4, 142.0, 144.5, 147.9,
199.5, 201.4. ESI-HRMS: Calcd for C30H26N2O6
496.16344; Found 497.1471.
[M + H]+ 510.53724; Found 512.1832.
(6S,6aS,6bS,11aR)-2-methoxy-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione(6c). Brown solid; yield
(6S,6aS,6bS,11aR)-4-ethoxy-6-(4-methoxyphenyl)-6a-nitro-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6g).
Brown solid;
1
74%; mp: 165–167°C; H NMR (CDCl3, 400 MHz): δ
yield 76%; mp: 185–187°C; 1H NMR (CDCl3,
400 MHz): δ 1.34 (t, J = 8.0 Hz, 3H), 1.63–2.11 (m, 4H),
2.69–2.78 (m, 1H), 2.91–2.99 (m, 1H), 3.83–3.85 (m,
4H), 3.99 (q, J = 8.0 Hz, 2H), 4.69 (s, 1H), 5.76 (d,
J = 8.0 Hz, 1H), 6.40–6.44 (m, 2H), 6.65 (d, J = 4.0 Hz,
1H), 6.96 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H),
7.93–8.12 (m, 4H); 13C NMR (CDCl3, 100 MHz): δ
14.8, 24.8, 30.0, 47.8, 50.3, 55.2, 65.0, 69.2, 78.2, 93.7,
113.5, 119.2, 120.8, 123.4, 123.9, 126.8, 128.2, 129.1,
136.3, 137.0, 141.5, 142.0, 144.7, 147.9, 160.2, 199.5,
1.67–2.09 (m, 4H), 2.70–2.77 (m, 1H), 2.93–2.98 (m,
1H), 3.18 (s, 3H), 3.82–3.86 (m, 1H), 4.65 (s, 1H), 5.63
(d, J = 4.0 Hz, 1H), 6.44 (s, 1H), 6.62–6.65 (m, 1H),
6.87 (d, J = 8.0 Hz, 1H), 7.42–7.48 (m, 5H), 7.81–8.14
(m, 4H); 13C NMR (CDCl3, 100 MHz): δ 24.8, 30.0,
48.3, 50.4, 55.0, 69.0, 78.3, 93.6, 111.2, 115.5, 118.4,
123.4, 124.0, 127.7, 128.1, 128.2, 129.2, 134.7, 136.3,
137.1, 141.4, 142.0, 148.0, 153.5, 199.5, 201.4. ESI-
HRMS: Calcd for C29H24N2O6 [M + H]+ 496.16344;
Found 497.1471.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Nayak, P. Panda, S. Mohapatra, B. Raiguru, and N. Baral
Vol 000
201.4. ESI-HRMS: Calcd for C31H28N2O7 [M + H2O]+
540.18965; Found 558.1892.
(m, 2H), 8.14 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz): δ 24.7, 30.0, 47.3, 50.4, 68.8, 76.3, 78.7, 93.1,
120.4, 123.4, 123.7, 124.2, 125.3, 125.8, 127.6, 128.3,
129.3, 129.5, 133.7, 136.8, 137.5, 141.3, 141.8, 148.8,
199.2, 200.6. ESI-HRMS: Calcd for C28H20Cl2N2O5
(6S,6aS,6bS,11aR)-2-hydroxy-6-(4-methoxyphenyl)-6a-nitro-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6h). Black solid; yield
1
73%; mp: 199–201°C; H NMR (CDCl3, 400 MHz): δ
[M + H]+ 535.37480; Found 536.1145.
1.68–2.08 (m, 4H), 2.69–2.78 (m, 1H), 2.90–2.98 (m,
1H), 3.73–3.87 (m, 4H), 4.69 (s, 1H), 5.72 (d,
J = 8.0 Hz, 1H), 6.43–6.50 (m, 2H), 6.71 (d, J = 4.0 Hz,
1H), 6.98 (d, J = 8.0 Hz, 2H), 7.38–7.41 (m, 2H), 7.79
(d, J = 8.0 Hz, 1H), 7.88–7.97 (m, 2H), 8.12 (d,
J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 24.8,
30.0, 47.5, 50.4, 55.3, 69.1, 78.8, 93.7, 113.7, 114.2,
118.0, 118.2, 121.6, 123.3, 123.9, 128.8, 129.0, 136.4,
137.2, 141.4, 142.2, 144.7, 160.5, 199.7, 201.1. ESI-
HRMS: Calcd for C29H24N2O7 [M + H]+ 512.15835;
(6S,6aS,6bS,11aR)-2,4-dibromo-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6l). Black solid; yield
1
70%; mp: 110–112°C; H NMR (CDCl3, 400 MHz): δ
1.68–2.07 (m, 4H), 2.70–2.78 (m, 1H), 2.91–2.99 (m,
1H), 3.84–3.88 (m, 1H), 4.62 (s, 1H), 6.22 (s, 1H),
6.58 (s, 1H), 7.45–7.50 (m, 6H), 7.87 (d, J = 4.0 Hz,
1H), 7.94–8.02 (m, 2H), 8.16 (d, J = 4.0 Hz, 1H); 13C
NMR (CDCl3, 100 MHz): δ 24.9, 30.1, 47.5, 50.5,
68.9, 78.8, 93.2, 112.7, 113.2, 120.9, 123.8, 124.3,
127.8, 128.4, 129.2, 129.6, 133.8, 134.8, 136.9, 137.6,
141.4, 141.9, 151.2, 199.5, 200.8. ESI-HRMS:
Calcd for C28H20Br2N2O5 [M + H]+ 624.27680; Found
Found 512.1832.
(6S,6aS,6bS,11aR)-2-chloro-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6i). Green solid; yield
624.9711.
1
75%; mp: 179–181°C; H NMR (CDCl3, 400 MHz): δ
(6S,6aS,6bS,11aR)-4-bromo-2-chloro-6a-nitro-6-phenyl-
1.67–2.08 (m, 4H), 2.74–2.77 (m, 1H), 2.93–2.98 (m,
1H), 3.80–3.84 (m, 1H), 4.61 (s, 1H), 6.12 (d,
J = 2.8 Hz, 1H), 6.50 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H),
7.02 (d, J = 4.0 Hz, 1H), 7.49 (s, 5H), 7.84 (d,
J = 8.0 Hz, 1H), 7.93–8.01 (m, 2H), 8.15 (d, J = 8.0 Hz,
1H); 13C NMR (CDCl3, 100 MHz): δ 24.9, 30.1, 47.5,
50.5, 69.0, 76.7, 78.4, 93.1, 119.0, 119.3, 123.8, 124.2,
126.2, 127.1, 127.8, 128.3, 129.0, 129.6, 134.3, 136.8,
137.5, 141.4, 141.9, 152.7, 199.6, 201.0. ESI-HRMS:
Calcd for C28H21ClN2O5 [M + H]+ 500.92974; Found
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6m).
Black solid;
yield 78%; mp: 184–186°C; 1H NMR (CDCl3,
400 MHz): δ 1.69–2.08 (m, 4H), 2.73–2.78 (m, 1H),
2.93–2.99 (m, 1H), 3.85–3.89 (m, 1H), 4.63 (s, 1H), 6.10
(s, 1H), 6.55(s, 1H), 7.32–7.33 (m, 1H), 7.45–7.50 (m,
5H), 7.87 (d, J = 4.0 Hz, 1H), 7.93–8.00 (m, 2H), 8.15
(d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ
24.7, 30.0, 47.4, 50.4, 68.8, 76.3, 78.8, 93.2, 112.2,
120.8, 123.7, 124.2, 125.3, 126.1, 127.6, 128.3, 129.5,
132.1, 133.7, 136.8, 137.5, 141.3, 141.8, 149.7, 199.2,
200.6. ESI-HRMS: Calcd for C30H26N2O6 [M + H]+
501.1214.
(6S,6aS,6bS,11aR)-2-bromo-6-(4-methoxyphenyl)-6a-nitro-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6j). Green solid; yield
579.82580; Found 580.0663.
(6S,6aS,6bS,11aR)-2-bromo-4-methoxy-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6n). Black solid; yield
1
70%; mp: 120–122°C; H NMR (CDCl3, 400 MHz): δ
1.65–2.07 (m, 4H), 2.73–2.78 (m, 1H), 2.92–2.98 (m,
1H), 3.77–3.80 (m, 1H), 3.86 (s, 3H), 4.58 (s, 1H), 6.23
(d, J = 2.4 Hz, 1H), 6.42 (s, 1H), 6.82 (d, J = 8.0 Hz,
1H), 6.97 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 1H),
7.37 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 1H), 7.94–
7.99 (m, 2H), 8.15 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ 24.8, 30.0, 47.5, 50.4, 55.2, 69.0,
76.3, 78.8, 93.0, 113.2, 113.6, 119.2, 119.7, 123.6,
124.1, 126.1, 129.0, 130.0, 131.7, 136.7, 137.4, 141.3,
141.8, 153.2, 160.4, 199.5, 201.0. ESI-HRMS: Calcd for
1
71%; mp: 112–114°C; H NMR (CDCl3, 400 MHz): δ
1.65–2.06 (m, 4H), 2.70–2.76 (m, 1H), 2.91–3.00 (m,
1H), 3.77–3.83 (m, 4H), 4.60 (s, 1H), 5.86 (d,
J = 4.0 Hz, 1H), 6.46 (s, 1H), 6.75 (d, J = 4.0 Hz, 1H),
7.42–7.47 (m, 5H), 7.85 (d, J = 8.0 Hz, 1H), 7.92–7.98
(m, 2H), 8.14 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz): δ 24.9, 30.1, 47.5, 50.5, 56.2, 69.1, 78.5,
93.2, 113.1, 114.4, 120.0, 121.6, 123.7, 124.1, 127.9,
128.3, 129.5, 134.2, 136.7, 137.5, 141.4, 141.7,
141.9, 149.4, 199.5, 201.1. ESI-HRMS: Calcd for
C29H23BrN2O6 [M + H]+ 575.40672; Found 575.4118.
(6S,6aS,6bS,11aR)-2,4-dichloro-6a-nitro-6-phenyl-
C29H23BrN2O6 [M + H]+ 575.40672; Found 576.0844.
(6S,6aS,6bS,11aR)-2-bromo-4-methoxy-6-(4-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]
pyrrolizine-11,20-indene]-10,30-dione (6k). Green solid; yield
methoxyphenyl)-6a-nitro-6a,6b,7,8,9,11a-hexahydro-6H-
1
spiro[chromeno[3,4-a]pyrrolizine-11,20-indene]-10,30-dione
80%; mp: 175–177°C; H NMR (CDCl3, 400 MHz): δ
1
1.72–2.07 (m, 4H), 2.70–2.75 (m, 1H), 2.91–2.99 (m,
1H), 3.84–3.88 (m, 1H), 4.63 (s, 1H), 6.06 (d,
J = 2.4 Hz, 1H), 6.55 (s, 1H), 7.16 (d, J = 2.4 Hz, 1H),
7.46–7.51 (m, 5H), 7.85 (d, J = 8.0 Hz, 1H), 7.93–8.00
(6o). Black solid; yield 72%; mp: 146–148°C; H NMR
(CDCl3, 400 MHz): δ 1.59–2.05 (m, 4H), 2.62–2.68 (m,
1H), 2.84–2.88 (m, 1H), 3.69–3.77 (m, 7H), 4.50 (s, 1H),
5.77 (d, J = 2.0 Hz, 1H), 6.33 (s, 1H), 6.68 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted One-pot, Three-component Regiospecific and Sterospecific
Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene
Derivatives Through 1,3-Dipolar Cycloaddition Reactions
Month 2019
J = 4.0 Hz, 1H), 6.88 (d, J = 8.0 Hz, 2H), 7.32 (d,
J = 8.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 1H), 7.84–7.90 (m,
2H), 8.06 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz): δ 24.8, 30.0, 47.4, 50.3, 55.2, 56.1, 69.1,
78.2, 93.2, 113.6, 114.2, 119.9, 121.5, 123.6, 124.0,
128.1, 129.0, 129.1, 136.6, 137.3, 141.2, 141.9, 149.3,
1H), 7.40–7.45 (m, 5H), 7.81 (d, J = 8.0 Hz, 1H), 7.92–
8.00 (m, 2H), 8.20 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ 23.9, 24.2, 28.4, 47.7, 48.5, 65.6,
76.6, 79.8, 96.7, 114.1, 119.8, 120.6, 123.0, 123.6,
127.6, 128.1, 129.1, 130.1, 131.6, 134.7, 137.0, 137.1,
141.2, 141.8, 153.5, 200.0, 202.7. ESI-HRMS: Calcd for
160.4, 199.3, 201.1.
C29H23BrN2O5 [M + H]+ 559.40732; Found 560.0843.
(6S,6aS,6bS,12aR)-2,4-dichloro-6a-nitro-6-phenyl-
(6S,6aS,6bS,12aR)-6a-nitro-6-phenyl-6,6a,6b,7,8,9,10,12a-
octahydrospiro[chromeno[3,4-a]indolizine-12,20-indene]-10,30-
6,6a,6b,7,8,9,10,12a-octahydrospiro[chromeno[3,4-a]
1
dione (6p). Brown solid; yield 70%; mp: 80–82°C; H
indolizine-12,20-indene]-10,30-dione (6t). Green solid; yield
1
NMR (CDCl3, 400 MHz): δ 1.43–1.76 (m, 6H), 2.34–
2.40 (m, 1H), 2.64–2.67 (m, 1H), 3.95–3.97 (m, 1H),
5.04 (s, 1H), 5.83 (s, 1H), 6.39–6.56 (m, 2H), 6.88–7.05
(m, 2H), 7.39–7.49 (m, 5H), 7.77 (d, J = 8.0 Hz, 1H),
7.87–7.97 (m, 2H), 8.18 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ 23.5, 24.7, 27.1, 47.4, 54.9, 62.9,
76.1, 79.8, 91.7, 122.3, 123.1, 128.2, 128.6, 128.7,
132.5, 136.2, 136.4, 140.9, 141.9, 198.9, 203.1. ESI-
HRMS: Calcd for C29H24N2O5 [M + H]+ 480.51126;
75%; mp: 180–182°C; H NMR (CDCl3, 400 MHz): δ
1.45–1.79 (m, 6H), 2.32–2.42 (m, 1H), 2.63–2.67 (m,
1H), 3.96–3.99 (m, 1H), 4.98 (s, 1H), 5.90 (s, 1H), 6.27
(d, J = 4.0 Hz, 1H), 7.10 (d, J = 4.0 Hz, 1H), 7.38–7.47
(m, 5H), 7.82 (d, J = 8.0 Hz, 1H), 7.92–8.00 (m, 2H),
8.19 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz):
δ 23.7, 24.2, 28.3, 47.7, 48.5, 65.6, 76.0, 80.0, 96.7,
121.6, 123.0, 123.6, 124.2, 125.4, 126.6, 127.4, 128.1,
129.1, 129.2, 134.3, 137.1, 137.3, 141.4, 142.0, 199.8,
202.3. ESI-HRMS: Calcd for C29H22Cl2N2O5 [M + H]+
Found 481.1743.
(6S,6aS,6bS,12aR)-4-ethoxy-6-(4-methoxyphenyl)-6a-nitro-
6,6a,6b,7,8,9,10,12a-octahydrospiro[chromeno[3,4-a]
indolizine-12,20-indene]-10,30-dione (6q). Brown solid; yield
548.09058; Found 548.2849.
(6S,6aS,6bS,12aR)-2,4-dibromo-6a-nitro-6-phenyl-
6,6a,6b,7,8,9,10,12a-octahydrospiro[chromeno[3,4-a]
indolizine-12,20-indene]-10,30-dione (6u). Black solid; yield
1
74%; mp: 142–144°C; H NMR (CDCl3, 400 MHz): δ
1
70%; mp: 185–187°C; H NMR (CDCl3, 400 MHz): δ
1.29 (t, J = 8.0 Hz, 3H), 1.42–1.77 (m, 6H), 2.34–2.38
(m, 1H), 2.62–2.64 (m, 1H), 3.81 (s, 3H), 3.92 (q,
J = 8.0 Hz, 2H), 3.98–4.00 (m, 1H), 5.05 (s, 1H), 5.79
(s, 1H), 5.96 (d, J = 8.0 Hz, 1H), 6.42–6.45 (m, 1H),
6.59 (d, J = 4.0 Hz, 1H), 6.86 (d, J = 8.0 Hz, 2H), 7.36
(d, J = 8.0 Hz, 2H), 7.75 (d, J = 4.0 Hz, 1H), 7.84–7.95
(m, 2H), 8.15 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz): δ 14.8, 23.9, 24.5, 28.5, 47.8, 48.8, 55.2,
65.1, 66.0, 78.8, 97.6, 113.4, 113.5.19.2, 121.7, 122.9,
123.5, 128.2, 128.5, 129.1, 136.6, 136.8, 141.7, 142.2,
148.6, 159.7, 200.4, 202.4. ESI-HRMS: Calcd for
1.45–1.79 (m, 6H), 2.32–2.42 (m, 1H), 2.65–2.68 (m,
1H), 3.96–4.01 (m, 1H), 4.99 (s, 1H), 5.90 (s, 1H), 6.43
(s, 1H), 7.39–7.45 (m, 6H), 7.82 (d, J = 8.0 Hz, 1H),
7.94–8.02 (m, 2H), 8.20 (d, J = 4.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ 23.7, 24.2, 28.3, 47.7, 48.5, 65.6,
76.1, 80.0, 96.8, 113.3, 114.0, 122.8, 123.1, 123.6,
127.4, 128.1, 129.2, 134.2, 134.6, 137.1, 137.3, 141.2,
141.8, 150.4, 199.7, 202.3. ESI-HRMS: Calcd for
C29H22Br2N2O5 [M + H]+ 638.30338; Found 638.9725.
C32H30N2O7 [M + H]+ 554.58980; Found 555.2124.
(6S,6aS,6bS,12aR)-2-chloro-6a-nitro-6-phenyl-
Acknowledgments. S. N. and S. R. M. are thankful to CSIR
New Delhi [grant number 02(0218)/14/EMR-II], DRDO New
Delhi [grant number ERIP/ER/1203083/M/01] for providing
research grant and also thankful to DST-FIST for providing
NMR facility.
6,6a,6b,7,8,9,10,12a-octahydrospiro[chromeno[3,4-a]
indolizine-12,20-indene]-10,30-dione (6r). Green solid; yield
1
73%; mp: 183–185°C; H NMR (CDCl3, 400 MHz): δ
1.34–1.83 (m, 6H), 2.25–2.65 (m, 2H), 3.92 (s, 1H), 4.94
(s, 1H), 5.78–5.81 (m, 1H), 6.31–6.34 (m, 1H), 6.81–
6.96 (m, 2H), 7.39–7.40 (m, 5H), 7.81 (d, J = 4.0 Hz,
1H), 7.91–8.17 (m, 2H), 8.20 (m, J = 4.0 Hz, 1H); 13C
NMR (CDCl3, 100 MHz): δ 23.9, 24.4, 28.5, 47.8, 48.6,
65.7, 80.0, 96.9, 119.5, 123.1, 123.7, 127.2, 127.7,
128.1, 128.8, 129.2, 135.3, 137.2, 137.7, 141.2, 141.8,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet