One pot, three component synthesis of spiroindenoquinoxaline pyrrolidine fused nitrochromene derivatives following 1,3-dipolar cycloaddition

Article abstract of DOI:10.1080/00397911.2019.1606919

An expedient one-pot sequential three-component synthesis of a series of diverse spiroindenoquinoxaline pyrrolidine fused nitrochromene derivatives following 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the condensation of indenoqui

Full text of DOI:10.1080/00397911.2019.1606919

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
One pot, three component synthesis of
spiroindenoquinoxaline pyrrolidine fused
nitrochromene derivatives following 1,3-dipolar
cycloaddition
Sabita Nayak, Priyabrata Pattanaik, Seetaram Mohapatra, Deepak Ranjan
Mishra, Pravati Panda, Bishnuprasad Raiguru, Nilima Priyadarshini Mishra,
Subhrakant Jena & Himansu Sekhar Biswal
To cite this article: Sabita Nayak, Priyabrata Pattanaik, Seetaram Mohapatra, Deepak Ranjan
Mishra, Pravati Panda, Bishnuprasad Raiguru, Nilima Priyadarshini Mishra, Subhrakant Jena &
Himansu Sekhar Biswal (2019): One pot, three component synthesis of spiroindenoquinoxaline
pyrrolidine fused nitrochromene derivatives following 1,3-dipolar cycloaddition, Synthetic
Communications, DOI: 10.1080/00397911.2019.1606919
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https://doi.org/10.1080/00397911.2019.1606919
One pot, three component synthesis of
spiroindenoquinoxaline pyrrolidine fused nitrochromene
derivatives following 1,3-dipolar cycloaddition
a
a
a
Sabita Nayak , Priyabrata Pattanaik , Seetaram Mohapatra , Deepak Ranjan
a
a
a
a
Mishra , Pravati Panda , Bishnuprasad Raiguru , Nilima Priyadarshini Mishra ,
Subhrakant Jena , and Himansu Sekhar Biswal
b
b
a
b
Department of Chemistry, Ravenshaw University, Cuttack, Odisha, India; National Institute of Science
Education and Research, Bhubaneswar, Odisha, India
ABSTRACT
ARTICLE HISTORY
An expedient one-pot sequential three-component synthesis of a
series of diverse spiroindenoquinoxaline pyrrolidine fused nitrochro-
mene derivatives following 1,3-dipolar cycloaddition of azomethine
ylides generated in situ by the condensation of indenoquinoxalone
and a-amino acids (L-proline and L-phenyl alanine) with 3-nitrochro-
menes as dipolarophile under classical as well as microwave irradi-
ation is described. The protocol provides a mild reaction condition,
high yield of the products, high regioselectivity, and operational sim-
plicity to assemble complex structural entity in a single operation
with good to excellent yield. The regio and stereochemical outcome
of the cycloaddition reaction is ascertained by spectroscopic and sin-
gle crystal X-ray analysis.
Received 18 December 2018
KEYWORDS
Azomethine ylides; 1,3-
dipolar cycloaddition;
indenoquinoxaline; multi-
component reactions; spiro
compounds; nitrogen
heterocycles; 3-nitro-
2H-chromene
GRAPHICAL ABSTRACT
Ph
O
Ph
O
2
N
O
R
3
H N
CO H
O
N
2
2
2
O
R
3
Ph
N
COOH
R
2
N
H
HN
R2
Ph
N
H
H
Ethanol, 80 o
C
NO
N
Ethanol, 80 o
R
1
C
N
R
1
R
1
2
R
NO
N
1
2
N
N
R
2
O
Ph
R
O
Ph
2
R
3
R
3
Yield = 75-83%
R
R
1
3
= H, Cl, Br; R
2
= H, OMe;
Yield =80-92%
= H, OMe, OEt, Cl; Napthal
Introduction
The search for the efficient transformation of simple starting materials to highly func-
tionalized complex products that combine economic, environmental and green aspects
has been an active objective in organic synthesis. In this regard, the development and
use of multi-component reactions (MCRs) have emerged as a highly valuable synthetic
tool to fulfill this goal. In recent years, the area of 1,3-dipolar cycloaddition reactions
has been well developed for the synthesis of spiro-heterocycles in a multicomponent
CONTACT Sabita Nayak
sabitanayak18@gmail.com; Seetaram Mohapatra
seetaram.mohapatra@gmail.com
Department of Chemistry, Ravenshaw University, Cuttack 753 003, Odisha, India.
Supplemental data for this article is available online at on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
S. NAYAK ET AL.
fashion. Spiro heterocycles are ubiquitously imperative structural units of many natural
or synthetic molecules and constitute the largest diversity of organic molecules of chem-
[
1,2]
ical, biomedical, and industrial significance.
One of the most effective direct meth-
ods for the synthesis of spiroheterocycles with pyrrolidine and pyrrolizidine rings
following intermolecular 1,3-dipolar cycloaddition of azomethine ylides to dipolaro-
philes has attracted the attention of synthetic organic chemists because of their highly
pronounced pharmacological and biological activities such as anti-tumor, anti-cancer,
anti-bacterial, antioxidant and acetylcholine esterase inhibitory activity etc and also
[
3,4]
serve as synthetic intermediates of drug precursors.
1,3-DC) reactions of azomethine ylides with olefin is an elegant and efficient method-
ology for regio- and stereoselective synthesis of structurally complex pyrrolidine and
The 1,3-dipolar cycloaddition
(
[
5–8]
spiropyrrolidine heterocycles from relatively simple precursors.
Nitrogen-containing
heterocycles constructed through 1,3-dipolar cycloaddition of azomethine ylides gener-
ated in situ from the decarboxylative condensation of carbonyl compounds with
a-amino acids have been well documented and are widely applied in organic synthesis
[
9–12]
for the construction of an important cluster of significant bioactive compounds.
In
recent years, spiro indenoquinoxaline-pyrrolidines, prepared from 1,3-DC between azo-
methine ylides with olefinic dipolarophiles, have attracted the increasing interests due to
their potentially pronounced biological activities such as acetylcholine esterase inhibitory
[
13–16]
activity, anticancer and antioxidant properties (Fig. 1).
The abundance of natural
and unnatural bioactive spiroquinoxaline pyrrolizine derivatives have encouraged the
design and synthesis of novel spirocyclic indenoquinoxaline with relevant and notable
medicinal properties.
On the other hand, pyrans and chromenes are important classes of heterocycles
because of their core fragments are incorporated in a large variety of natural products
and biologically active compounds. They are of considerable interest as they display a
broad range of pharmaceutical properties such as anti-tumor, anti-cancer, anti-micro-
[
17,18]
bial, anti-fungal and anti-HIV character.
Among the different types of chromenes,
we focused on 3-nitro-2H-chromene scaffolds due to their interesting biological activ-
ities, such as anticancer (S14161, BENC511) antimicrobial, antioxidant, and anti-inflam-
[
19,20]
matory, etc (Fig. 1).
Literature survey reveals a large number of reports on 1,3-dipolar cycloaddition reac-
tion of indenoquinoxalone derivatives with vinyl nitro olefins, a,b-unsaturated carbonyl,
H
H
O
NO2
O
Cl
N
NO2
R
NO2
N
O
N
R
O
O
N
N
OEt
OEt
N
N
Nitrochromene
S14161
BENC-511
Spirocyclicindenoquinoxaline
R=H, Br
R= F (S14161)
R= H, CN, OMe
Anticancer
R= Br (BENC-511)
Anticancer and antioxidant
activity
Acetylcholineesterase
inhibitory activity
Anticancer
Figure 1. Some important bioactive spiroindenoquinoxaline/nitrochromene containing molecules.

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3
[
13–16]
a,b-unsaturated ester and a,b-unsaturated nitrile compounds, etc.
Despite these
recent advances, to the best of our knowledge, stereoselective 1,3-dipolar cycloaddition
reaction of indenoquinoxalone derivatives with cyclic a,b-unsaturated nitro has not
been reported yet.
As a continuation of our interest in developing a new methodology for the synthesis
of highly functionalized spiro compounds and 3-nitro-2H-chromene containing hetero-
cycles, we have reported a three component 1,3-dipolar cycloaddition reaction to form
spiropyrrolidinyl indenoquinoxaline derivatives.
Herein we report an atom economic, high yielding, regio- and diastereoselective mul-
ticomponent protocol for facile synthesis of highly substituted spiro-indenoquinoxaline
pyrrolizine fused 3-nitro-2H-chromene scaffold by the reaction of indenoquinoxalone,
L-proline/L-phenyl alanine, and 3-nitro-2H-chromene in ethanol under conventional
heating/microwave irradiation. It is interesting that regio- and sterospecifically a single
product was obtained.
Results and discussion
Initially, the 3-nitro-2H-chromene derivatives 3(a–k) utilized for 1,3-dipolar cycloadd-
ition were prepared by the treatment of trans-b-nitro styrene 2 with salicylaldehydes
1(a–k) in the presence of DABCO under solvent-free conditions in a single step follow-
ing oxa-Michael-Aldol reaction. Synthesized 3-nitro-2H-chromene derivatives were
1
13
[21]
characterized by H, C, and HRMS spectra (Scheme 1).
The long-term goal of our research is to expand the useful repertoire of 3-nitro-2H-
chromene, which are important as complexity-generating tools in both combinatorial
and diversity-oriented synthesis. Having 3-nitro-2H-chromene in hand, the one-pot
sequential three-component reaction involving, indenoquinoxalone 4, L-proline 5 and
3-nitro-2H-chromene 3a were investigated to establish the feasibility of the strategy and
optimize the reaction conditions (Scheme 2). The reaction was examined by taking an
equimolar reaction mixture in different solvents such as methanol, ethanol, acetonitrile,
benzene, toluene, and H O at a different temperature ranging from room temperature
2
to refluxing. As shown in Table 1, ethanol as solvent provided a higher yield of 75%
(Table 1, entry 5) in the case of conventional oil bath heating. Therefore, ethanol and
refluxing condition were chosen as optimal conditions for all further reactions. The
R1
NO2
R1
R2
CHO
OH
o
NO2
DABCO, 40 C
R2
O
Ph
1-3 h
Ph
R3
R3
7
3
4-94%
(a-k)
2
1(a-k)
R = H, Cl, Br; R = H, OMe;
1
2
R = H, OMe, OEt, Cl; Napthal
3
Scheme 1. Synthesis of 3-nitro-2H-chromene.

4
S. NAYAK ET AL.
Ph
O
O N
2
O
NO2
Ph
N
CO H
2
/MW
N
N
H
Solvent
H
N
N
4
O
3a
5
N
6a
Scheme 2. Model reaction.
Table 1. Solvent and temperature for the synthesis of spiroindenoquinoxaline pyrrolidine fused 3-
nitro-2H-chromene.
Time
(h)
Temp
( C)
o
o
a
Entry
Solvent
Temp ( C)
Yield (%)
MW
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
a
Methanol
Ethanol
r.t
r.t
r.t
80
80
12
12
12
3
3
3
3
3
3
n.r
n.r
n.r
50
75
45
30
30
n.r
50
50
50
50
50
50
50
50
50
40
40
40
80
80
80
80
80
100
10
10
10
10
10
10
10
10
10
30
40
30
68
90
50
50
50
n.r
CH
3
CN
Methanol
Ethanol
CH
3
CN
80
Benzene
Toluene
100
100
100
2
H O
Isolated yields. n.r means no result obtained and the entry in bold indicates optimal condition.
reaction afforded highly substituted spiroproduct 6a as single diastereoisomer in 75%
yield after recrystallization.
In order to reduce the reaction time interval as well as to enhance the yield of spiro
cycloadducts, the reactions were subsequently investigated under microwave irradiation.
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. Similar to the conventional heating
reactions, an equimolar reaction mixture in different solvents such as methanol, ethanol,
acetonitrile, benzene, toluene, and H O was subjected to the microwave irradiation. It
2
ꢀ
has been observed that among all the solvents, in ethanol at 50W/80 C for 10 min, an
excellent yield of the product was formed. Increasing the time interval for more than
10 min leads to a decrease in the yield of the product. To our delight, in microwave
irradiation, an excellent yield of the product formation was observed as well as the reac-
tion time period reduced from hours to minutes which encouraged us to move further.
To check the generality as well as the effectiveness of the developed protocol, a num-
ber of 3-nitro-2H-chromene derivatives having substituents such as methoxy, ethoxy,
naphthyl, halogens were reacted with indenoquinoxalone and L-proline/L-phenyl ala-
nine 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 microwave irradiation methods are
summarized in Table 2, which clearly shows that microwave irradiation led to an
enhancement in the rate as well as the yield of the products (75–92%) over the conven-
tional thermal method (55–80%).

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5
Table 2. Synthesis of spiro indenoquinoxaline pyrrolidine fused 3-nitro-2H-chromene.
Conventional Method
Microwave Method
(EtOH, 80 C, 50W)
o
o
(EtOH, 80 C)
Producta
Ph
Yield(%)b
Time (mins) Yield(%)b
Entry
Time (h)
O N
2
O
N
1
3
75
10
10
90
92
H
N
N
Ph
O N
2
O
OMe
3
78
2
N
H
N
N
Ph
O N
2
O
N
OMe
3
3
80
10
10
92
3
4
H
H
N
N
Ph
O N
2
O
78
90
N
N
OMe
OEt
N
Ph
O N
2
O
N
H
N
5
3
78
10
88
N
(
continued)

6
S. NAYAK ET AL.
Ph
O N
2
O
N
H
N
6
3
3
3
80
70
70
10
90
Cl
N
Ph
O N
2
O
Br
N
H
7
8
N
Br
10
10
85
N
Ph
O N
2
O
Br
N
H
N
Cl
80
N
Ph
O N
2
O
OMe
N
H
N
Br
9
1
3
72
10
82
N
Ph
O N
O
2
N
H
0
1
3
75
10
90
N
N
Ph
O N
2
O
Ph
HN
H
N
3
62
10
78
1
N
(continued)

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7
Ph
O N
2
O
Ph
HN
OMe
H
N
1
2
3
65
10
78
83
N
Ph
O N
2
O
OEt
Ph
HN
H
3
62
10
13
N
N
Ph
O N
2
O
Ph
HN
78
14
3
63
10
H
N
Cl
N
Ph
O N
2
O
Ph
Ph
3
63
10
78
HN
15
H
N
Br
N
Ph
O N
2
O
Br
HN
H
N
3
55
10
75
16
Br
N
Ph
O N
2
O
Br
Cl
Ph
17
3
60
10
78
HN
H
N
N
Ph
O N
2
O
OMe
Br
Ph
18
3
65
10
80
HN
H
N
N
a
The products were characterized by NMR, IR and Mass spectroscopy.
Isolated yield after purification.
b

8
S. NAYAK ET AL.
Ph
O
2
bO N
H
R3
R
2
N
2
CO H
H
a
R
1
N
H
N
5
O
N
R
1
NO
2
6(a-j)
Yield: 80-92%
N
Δ/MW
R
2
O
Ph
N
0W, 80 o
Ethanol
5
C
Ph
O
2
O N
R
3
Hb
4
R
3
3
(a-m)
Ph
R
R
1
3
= H, Cl, Br; R
2
= H, OMe;
H
2
N
CO
2
H
R
2
HN
= H, OMe, OEt, Cl; Napthal
H
a
N
R
1
5'
Ph
N
6
'(a-h)
Yield: 75-83%
Scheme 3. Synthesis of compounds 6(a–j) and 6’(a–h).
1
The H NMR spectrum of compound 6a (Table 2, entry 1) exhibited a characteristic
singlet at d 5.11 ppm corresponding to benzylic Ha proton attached to the chromane
core and also the Hb proton of the proline ring appeared as multiplet at d 4.53 ppm,
the 2H-protons of the 3-nitro-2H-chromene appeared as singlet at 6.34 ppm in the
cycloadduct 6a and all other protons appeared in respective positions clearly indicates
the formation of spiropyrrolidinyl indenoquinoxalines. Furthermore, the characteristic
singlet at d 5.11 ppm corresponding to Ha proton proved the formation of regioisomer
6
a. If the other regioisomer has formed, the Ha proton would have appeared as a multi-
1
plet in the H NMR spectrum. The carbon attached to Ha and Hb protons resonates at
6.6 and 69.0 ppm, the 2-C and 3-C of 3-nitro-2H-chromene, and spiro carbon of the
4
13
cycloadduct appeared at 78.5, 117.0, and 95.3 ppm respectively in the C NMR spec-
trum. The three pyrrolidine methylene carbon resonates at 25.0, 28.7, and 53.1 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 pres-
ence of the molecular ion peak at m/z 539.2542 (M þ 1) in the mass spectrum con-
firmed the formation of the cycloadduct 6a. Further extension of this protocol was
carried out to delineate the scope of different nitrochromene 6(a–j) with azomethine
ylides generated in situ from indenoquinoxalone and L-proline and L-Phenyl alanine
under optimized reaction conditions and the [3 þ 2]cycloaddition reactions proceeded
0
well to give 6(a–j) and 6 (a–h) in good yield (Scheme 3).
As shown in Table 2, this protocol could be applied to a large range of different sub-
stituted 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) as well as naphthalene ring. In all cases, the reaction proceeded
smoothly and only a single diastereoisomer of spiro-pyrrolidines was afforded in good
to excellent yields (75–92%). From Table 2, it is clear that product yields were depend-
ent on the substituents and their positions at the aromatic ring of the 3-nitro-2H-chro-
mene. Presence of electron donating groups gave 88–92% yield (Table 2, entries 2–5).
However, in the case of 7-methoxy-3-nitro-chromene 6b and 6c (entries 2 and 3),

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9
CO H
2
O
N
H
N
N
N
N
N
5
4
A
NO2
Ph
O N
2
O
Ph
O
3
a
3a
path B
path A
O
X
Ph
N
NO2
N
H
O
O N
2
Ph
O N
N
2
Ph
O
H
6a''
Not observed
N
N
N
N
N
N
Exo approach
Endo approach
b
a
Ph
O
Ph
O
O N
2
H
b
O N
H
2
b
N
Ha
N
Ha
N
N
N
N
6a'
6
a
Not observed
Observed
Scheme 4. Proposed mechanism for the formation of 6a.
excellent yields were obtained over 6d and 6e. Halogenated 3-nitro-chromene deriva-
tives were also well tolerated and gave a better yield of the product 6(f–h) (80–90%).
Presence of halogens such as –Cl at 6-position of the chromene ring 6f gave a slightly
better yield (entries 6, 90%) in comparison to their halogenated derivative (6g and 6h).
However, when both the ꢁ I and þ I-effect groups such as –Br and –OMe were present
in the aromatic ring of 3-nitro-2H-chromene 6i, a slight decrease in the yield of the
product formation was observed (Table 2, entry 9, 82%). Excitingly, naphthalene deriva-
tives 6j also undergo the reaction to afford good yield of product (Table 2, entry 10,
90%). In order to extend the substrate scope of this protocol proline was replaced by
pipecolic acid. Unfortunately, in the case of pipecolic acid, the desired product was not

1
0
S. NAYAK ET AL.
Figure 2. ORTEP diagram of compound 6’b.
formed, starting materials remain unreacted even after a long period of heating. Only in
the case of L-phenyl alanine, we were able to get the desired product with excellent dia-
stereoselectivity which encouraged us to move further. Our experimental results showed
that a slight decrease in the yield of the product formation was observed in the case of
0
L-phenyl alanine in comparison to L-proline 6 (a–h) (Table 2, entries 11–18, 75–83%).
0
The identification of the spiro indenoquinoxaline pyrrolidines 6(a–j) and 6 (a–h) was
unequivocally ascertained by their H, C NMR, IR, and HRMS spectra.
1
13
A reasonable mechanism of the reaction is given in Scheme 4. From mechanistic consid-
erations, it is believed that the dipolar cycloaddition reaction of azomethine ylide generated
in situ by the decarboxylative condensation reaction of indenoquinoxalone with proline to
dipolarophile (3-nitro-2H-chromene), could proceed by two possible paths, A or B, leading
to two corresponding regioisomers, as shown in Scheme 4. In fact, the reaction proceeded
exclusively by path A, in which the electron-rich carbon of the azomethine ylide added to
the b-carbon of the 3-nitro-2H-chromene, resulting in a single regioisomer 6a, while no
00
trace of another regioisomer 6a was detected. Furthermore, this reaction was also found to
be diastereoselective. The 1,3-dipolar cycloaddition of the azomethine ylide with 3-nitro-
2
H-chromene could proceed by two methods a or b, as shown in Scheme 4, but only a sin-
0
gle endo product was obtained (method a), whereas, exo isomers such as 6a resulting from
method b was not observed. The formation of the regio- and diastereoisomer 6a by method
a is more favorable due to the presence of a secondary orbital interaction (SOI) occurring
between the nitro group of dipolarophile 3a with those of the azomethine ylide as shown
in Scheme 4. This kind of SOI is not possible in method b. Hence, the reaction proceeded
through method a only, leading to regio- and diastereoselective spiropyrrolidinyl indenoqui-
noxalines products. The stereochemistry of this cycloaddition was ascertained by single crys-
tal X-ray, in which both the protons Ha and Hb are present in trans- orientation (Fig. 2).
Conclusions
In summary, we have developed an operationally simple, autocatalytic, one-pot, three-
component reaction to synthesize new spiro indenoqunoxaline pyrrolidine by employing

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SYNTHETIC COMMUNICATIONS
11
indenoquinoxalone, L-proline/L-phenyl alanine and 3-nitro-2H-chromene. This multi-
component reaction offers a high yield, short reaction time with simple experimental
procedure, and formation of a single regio- and stereospecific product, without column
chromatographic purification. Further, the biological activities of the synthesized com-
pounds are currently under investigation.
Experimental section
General
Melting points were recorded on SMP10 digital melting point apparatus using open
capillary tubes and uncorrected. IR spectra were recorded on a Nicolet FT-IR500 spec-
1
trophotometer using KBr. H NMR spectra were recorded on 400 MHz (100 MHz for
1
3
C NMR) JEOL NMR spectrometer (JEOL, Japan) with CDCl as solvent and tetrame-
3
thylsilane (TMS) as internal standard. Chemical shifts were reported in parts per million
(
7
ppm, d scale) downfield from TMS at 0.00 ppm and referenced to the CDCl at
.26 ppm (for H NMR) or 77.00 ppm (for C NMR). HRMS analyses were conducted
3
1
13
on a Bruker micro-TOF-Q-MS analyzer (Bruker, MA, USA). All reagents and solvents
used in this study were commercially available (from Sigma-Aldrich) and were used
without further purification.
Experimental
All reactions were carried out under a positive pressure of argon and with oven-dried
glassware. Melting points are uncorrected and were determined with SMP10 digital
1
melting point apparatus using open capillary tubes. Proton magnetic resonance ( H
NMR) spectra were recorded using JEOL 400 MHz spectrometers. Chemical shifts are
reported in parts per million (ppm) relative to internal standards (tetramethylsilane, dH
¼
0.00; CDCl , d ¼ 7.26). Data are presented as follows: chemical shift (d, ppm),
3
H
multiplicity (s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quadruplet, m ¼ multiplet,
dd ¼ doublet of doublet, br ¼ broad), coupling constant (J) values are presented in Hz,
1
3
integration. Carbon magnetic resonance ( C NMR) spectra were recorded using JEOL
400 MHz spectrometers. Chemical shifts are reported in parts per million (ppm) relative
to internal standard (tetramethylsilane, d ¼ 0.00; CDCl , d ¼ 77.00). Reactions were
C
3
C
monitored with analytical Thin Layer Chromatography (TLC) which was carried out
using Merck commercial aluminum sheets coated (0.2mm layer thickness) with
Kieselgel 60 F254 (Merck, NJ, USA), with visualization by ultraviolet light. Mass spectra
were determined on an Agilent Technology (HP) mass spectrometer (CA, USA) operat-
0
ing at an ionization potential of 70 eV. The final products 6(a–j) and 6 (a–h) were syn-
thesized using CEM microwave synthesizer (Model no.-908010). All reagents and
solvents used in this study were commercially available (from Sigma-Aldrich) and were
used without further purification. The intermediate compounds were prepared accord-
ing to the literature methods.

1
2
S. NAYAK ET AL.
General procedure for preparation of 3-nitro-2-phenyl-2H-chromenes 3(a–k)
Substituted salicylaldehydes 1, (1.0 mmol), DABCO (0.2 mmol) and trans-b-nitrostyr-
ꢀ
enes 2 (1.0 mmol) were taken in one pot and stirred under reflux condition at 40 C for
1–3 h. The reaction was monitored by TLC and after completion of the reaction, the
reaction mixture was diluted with water and extracted with ethyl acetate. The organic
layer was separated, dried over anhydrous Na SO , and evaporated under reduced pres-
2
4
sure. 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 in 74–94% yield. All com-
pounds were characterized by NMR and Mass spectral data.
General procedure for the synthesis of spiropyrrolidinyl indenoquinoxaline
derivatives 6(a–j) and 6’(a–h)
Procedure A
L-Proline/L-phenyl alanine (1 mmol) and 2-phenyl-3-nitro-2H-chromene (1 mmol) were
added to a solution of indenoquinoxalone (1 mmol) in EtOH (2 mL) and the mixture
was refluxed for 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 tempera-
ture 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:CHCl (9:1) without carrying out column chromatography to obtain pure com-
3
pound 6(a–j) as a single diastereoisomer (80–92%).
Procedure B
L-Proline/L-phenyl alanine (1 mmol) and 2-phenyl-3-nitro-2H-chromene (1 mmol) were
added into a sealed 10 mL glass tube containing a solution of indenoquinoxalone
(
(
1 mmol) in EtOH (2 mL) and the mixture was irradiated under microwave irradiation
50 W power) at 80 C for 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 which was
purified just by recrystallization from EtOH:CHCl (9:1) without carrying out column
3
0
chromatography to obtain pure compound 6 (a–h) as a single diastereoiso-
mer (75–83%).
1
13
Full experimental detail, H and C NMR spectra, HRMS spectra. This material can
be found via the “Supplementary Content” section of this article’s webpage.
Acknowledgments
SN and SRM are thankful to CSIR, New Delhi [02(0218)/14/EMR-II], DRDO, New Delhi ERIP/
ER/1203083/M/01 for providing research grant and also thankful to DST-FIST, New Delhi for
providing NMR facility.

V
R
SYNTHETIC COMMUNICATIONS
13
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