Synthesis of bisindolylindeno[1,2-b]quinoxaline and bisindolylindeno[3,4-b] pyrazine with poly(N,N ′-dibromo-N-ethylnaphthyl-2,7-disulfonamide)

Article abstract of DOI:10.1080/00397911.2013.829237

Poly(N,N′-dibromo-N-ethylnaphthyl-2,7-disulfonamide) (PBNS) as novel reagent was synthesized. Bisindolylindeno[1,2-b]quinoxaline and bisindolylindeno[3,4-b]pyrazine derivatives were synthesized in a simple and efficient method from the three-component condensation reaction of indole, indane-1,2,3-trione, and diamine aromatic compounds by PBNS under solvent-free conditions at 80 °C in good to excellent yields, short reaction times, and a simple procedure for new derivatives. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.] Copyright

Full text of DOI:10.1080/00397911.2013.829237

This article was downloaded by: [Gazi University]
On: 17 August 2014, At: 14:38
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of Bisindolylindeno[1,2-
b]quinoxaline and Bisindolylindeno[3,4-
b]pyrazine with Poly(N,N′-dibromo-N-
ethylnaphthyl-2,7-disulfonamide)
Ardeshir Khazaei a , Abdolhossien Massoudi b & Mahdieh Chegeni b
a Faculty of Chemistry , Bu-Ali Sina University , Hamedan , Iran
b Department of Chemistry, Faculty of Science , Payame Noor
University (PNU) , Tehran , Iran
Accepted author version posted online: 28 Oct 2013.Published
online: 27 Dec 2013.
To cite this article: Ardeshir Khazaei , Abdolhossien Massoudi & Mahdieh Chegeni (2014) Synthesis
of Bisindolylindeno[1,2-b]quinoxaline and Bisindolylindeno[3,4-b]pyrazine with Poly(N,N′-dibromo-
N-ethylnaphthyl-2,7-disulfonamide), Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 44:5, 633-639, DOI: 10.1080/00397911.2013.829237
To link to this article: http://dx.doi.org/10.1080/00397911.2013.829237
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,

systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 44: 633–639, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.829237
SYNTHESIS OF BISINDOLYLINDENO[1,2-b]-
QUINOXALINE AND BISINDOLYLINDENO[3,4-b]-
PYRAZINE WITH POLY(N,N’-DIBROMO-N-
ETHYLNAPHTHYL-2,7-DISULFONAMIDE)
Ardeshir Khazaei,1 Abdolhossien Massoudi,2 and
Mahdieh Chegeni2
1Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
2Department of Chemistry, Faculty of Science, Payame Noor University
(PNU), Tehran, Iran
GRAPHICAL ABSTRACT
Abstract Poly(N,N0-dibromo-N-ethylnaphthyl-2,7-disulfonamide) (PBNS) as novel reagent
was synthesized. Bisindolylindeno[1,2-b]quinoxaline and bisindolylindeno[3,4-b]pyrazine
derivatives were synthesized in a simple and efficient method from the three-component
condensation reaction of indole, indane-1,2,3-trione, and diamine aromatic compounds by
PBNS under solvent-free conditions at 80 ꢀC in good to excellent yields, short reaction times,
and a simple procedure for new derivatives.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Diamine aromatic; indane-1,2,3-trione; PBNS; pyrazine derivatives;
quinoxaline derivatives
Received May 8, 2013.
Address correspondence to Mahdieh Chegeni, Department of Chemistry, Faculty of Science,
Payame Noor University (PNU), Tehran, Iran. E-mail: mahdiehchegeni@gmail.com
633

634
A. KHAZAEI, A. MASSOUDI, AND M. CHEGENI
INTRODUCTION
The exploitation of reagents for developing new synthetic methods is an art and
a challenging process in organic chemistry. N-Halo compounds are versatile reagents
that have been employed as potentially reactive intermediates and are widely used
in organic synthesis. N-Halo reagents are easy to handle with all of the halogen being
consumed, not half, as in the case of elemental halogens. Depending on the conditions,
a number of highly reactive intermediates can be formed: halogen radicals, halogen
cations, halogen anions, N-radicals, N-cations, N-anions, etc. Derivatives pyrazines
are well known for their antitumor, antibiotic, and diuretic activities.[1] Quinoxaline
derivatives are a very important class of nitrogen-containing compounds and have been
widely used in dyes, pharmaceuticals,[2,3] and electrical=photochemical materials.[4–9]
Quinoxaline ring moiety constitutes part of the chemical structures of various anti-
biotics such as echinomycin, levomycin, and actinoleutin[10,11] that are known to
inhibit growth of Gram-positive bacteria and are active against various transplantable
tumors. A number of synthetic strategies have been developed for the preparation of
substituted quinoxalines.[12–14] There is only one report on the synthesis of bisindoly-
lindeno[1,2-b]quinoxaline, that is, using montmorillonite K-10 under microwave
irradiation.[15] Herein we disclose our results for the synthesis of quinoxalines and pyra-
zines derivatives using by poly(N,N0-dibromo-N-ethylnaphthyl-2,7-disulfonamide)
(PBNS) under solvent-free conditions at 80ꢀC (Scheme 1).
RESULTS AND DISCUSSION
As part of our current studies on the design of new routes for the preparation
of biologically active heterocyclic compounds, Herein, we describe a simple and con-
venient method for the efficient synthesis of new bisindolylindeno[1,2-b]quinoxaline
and bisindolylindeno[3,4-b]pyrazine derivatives by the synthesized PBNS (see
supplementary data) with short time and good yields (Schemes 2 and 3). A series
Scheme 1. Synthesis of bisindolylindeno[1,2-b]quinoxaline and bisindolylindeno[3,4-b]pyrazine with
PBNS. (Figure is provided in color online.)

BISINDOLYLQUINOXALINE, BISINDOLYLPYRAZINE
635
Scheme 2. Synthesis of bisindolylindeno[1,2-b]quinoxaline derivatives. (Figure is provided in color
online.)
of substituted indole and diamine aromatics compounds with electron-donating
or electron-withdrawing groups attaching indane-1,2,3-trione were investigated.
Quinoxaline and pyrazine derivatives with both electron-donating or electron-
withdrawing groups gave good yields of the desired products (Table 1).
The advantages to use PBNS as reagent are as follows:
1. The preparation of PBNS is easy and not expensive.
2. It is a versatile reagent and can be separated by a simple method.
3. PBNS is stable for 4 months.
4. The present methodology offers a simple procedure rather than microwave
irradiation.[15]
The results of the synthesis (4a) using a variety of N-halo compounds and
acid catalyst as reagents are shown (Table 2). We employed N-bromosuccinimide
(NBS), trichloroisocyanuric acid (TCCA), N-bromosaccharin (NBSa), silica sulfuric
acid (SSA), and Al(HSO4)3. Comparison of these compounds showed that greater
activity and yields could be achieved using PBNS. None of these compunds were
Scheme 3. Synthesis of bisindolylindeno[1,2-b]pyrazine derivatives.

636
A. KHAZAEI, A. MASSOUDI, AND M. CHEGENI
Table 1. Formation of bisindolylindeno[1,2-b]quinoxaline and bisindolylin-
deno[3,4-b]pyrazine with PBNS under solvent-free conditions at 80 ꢀC
Entry
Product
Time (min)
Yield (%)
1
2
4a
4b
4c
4d
4e
4f
6
5
6
8
6
7
6
6
6
7
5
6
8
8
6
7
97
93
94
95
94
94
94
94
94
93
95
90
89
90
95
93
3
4
5
6
7
4g
4h
4i
8
9
10
11
12
13
14
15
16
4j
6a
6b
6c
6d
6e
6f
carried out under room temperature. PBNS can be separated by a simple method
and gave the best yield of the desired product (Table 2).
When the same reaction was carried out using different amounts of reagent the
greatest yield was obtained in the presence of 0.1 mmol%. Lower and higher amounts
of the reagent did not improved the yield of the product even after longer reaction
time (Table 2).
We carried out the reaction in various solvents to compare the outcome of the
reaction in terms of the yield and the rate of the reaction. None of them were carried
out under room temperature. Better yields were obtained with using solvent-free
conditions at 80 ꢀC (Table 3).
The reagent releases Brþ in situ, which can act as an electrophilic species.
A plausible mechanism for the synthesis of bisindolylindeno[1,2-b]quinoxaline and
bisindolylindeno[3,4-b]pyrazine derivatives with PBNS is shown (Scheme 4).[15]
Table 2. Comparison of different compounds employed for preparation of 4a under
solvent-free conditions at 80 ꢀC after 6 min
Entry
N-Halo compounds
Catalyst amount (mmol %)
Yield (%)
1
2
NBS
NBSa
0.20
0.20
0.10
0.10
0.1
50
50
3
TCCA
SSA
65
65
4
5
Al(HSO4)3
Montmorillonite K-10(mW)
PBNS
PBNS
PBNS
PBNS
55
6
0.5
94[15]
82
7
0.05
0.10
0.15
0.2
8
97
92
9
10
88

BISINDOLYLQUINOXALINE, BISINDOLYLPYRAZINE
637
Table 3. Evaluation of solvents and temperature for 4a
Entry
Conditions
Time (min)
Temperature ꢀC
Yield (%)
1
2
3
4
5
6
7
8
CH2Cl2
CHCl3
60
60
60
60
60
6
80
80
80
80
80
50
80
100
30
25
15
10
25
85
97
93
CH3OH
CH3CN
n-Hexane
solvent-free
solvent-free
solvent-free
6
6
Ninhydrin is in equilibrium with indane-1,2,3-trione (1). Initially the
condensation of ninhydrin (1) and 1,2-phenylenediamine (3a–3c) took place to
produce the intermediate A, which reacted with 2 mol of indoles (2a–2d, 5a–5b)
via the intermediate A to generate 4a–6f in good yield.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus and
infrared (IR) spectra were recorded on a Perkin-Elmer FT-IR spectrum Gx; KBr
1
pellets were used for solid samples. H and 13C spectra were recorded on Bruker
Avance 300- and 500-MHz FT NMR spectrometers with CDCl3 and (CD3)2CO
as solvent and tetramethylsilane (TMS) as internal standard. Mass spectra were
recorded on a Shimadzu QP 1100 BX mass spectrometer. Elemental analyses (C,
H, N) were performed with a Heraeus CHN-O-Rapid analyzer. Gel permeation
chromatography (GPC) was taken on a 1100 Agilent Detector RI. Weight change
curve in nitrogen was measured on a TA instrument of TGA Q50 V6.3 with
Scheme 4. Proposed mechanism.

638
A. KHAZAEI, A. MASSOUDI, AND M. CHEGENI
maximum heating rate of 10 ꢀC=min. All commercially available chemicals were
obtained from Merck and Fluka companies and used without further purifications.
Typical Procedure for the Preparation of Bisindolylindeno[1,2-b]-
quinoxaline and Bisindolylindeno[3,4-b]pyrazine Derivatives
A mixture of 0.178 g (1 mmol) indane-1,2,3-trione, 0.108 g (1 mmol) diamine
aromatics, 0.234 g (2 mmol) indole, and 0.1 mmol% PBNS was heated at 80 ꢀC. After
completion of the reaction [monitored by thin-layer chromotography (9:1, carbon
tetrachloride=acetone)], the mixture was cooled, filtered, and washed with methanol.
The product was insoluble in methanol.
6,6-Bis-(1H-indol-3-yl)-6H-indeno[1,2-b]pyrido[3,2-e]pyrazine (6a)
Color yellow, mp ¼ 274–278 ꢀC. FT-IR (KBr)t (cmꢁ1) ¼ 3396, 1653, 1456, 766.
1H NMR (300 MHz, DMSO-d6) ¼ 6.71–6.75 (t, J ¼ 1.2 Hz, 2H), 6.88 (s, 2H),
6.97–7.06 (t, J ¼ 2.7 Hz, 2H), 7.33–7.35 (d, J ¼ 0.6 Hz, 2H), 3H), 7.58–7.66 (m,
3H), 7.92 (t, J ¼ 0.6 Hz, 1H), 7.78–7.82 (t, J ¼ 1.2 Hz, 1H), 7.90–7.92 (d, J ¼ 0.3 Hz,
2H), 1H), 8.16–8.18 (d, J ¼ 0.3 Hz, 1H), 8.28–8.30 (d, J ¼ 0.2 Hz, 1H), 10.99 (s, 2H).
13C NMR (300 MHz, DMSO-d6) ¼ 53.6, 112.19, 116.12, 120.12, 121.29, 121.47,
122.62, 125.20, 126.29, 126.88, 129.15, 129.26, 129.61, 129.76, 130.06, 132.42,
135.77, 137.52, 141.23, 142.09, 153.25, 153.77, 165.98. [Found: C, 80.18; H, 4.23;
N, 15.50. C30H19N5 requires C, 80.16; H, 4.26; N, 15.58]. MS: m=z ¼ 405(5),
376(80), 319(80), 232(80), 176(35), 104(40), 90(80), 76(65), 43(70). HRMS (ESI)
m=z 449.1900 (M þ Hþ) calcd. for C16H10N2O þ Hþ 449.1900.
11H-Indeno[1,2-b]quinoxaline-11-one (4H)[16]
Color yellow, mp ¼ 218–220 ꢀC. FT-IR (KBr)t (cmꢁ1) ¼ 1730, 1642, 1610,
1
1475, 741. H NMR (300 MHz, DMSO-d6) ¼ 7.86 (m, 4H, Ar), 8.11 (m,4H, Ar).
13C NMR (300 MHz, DMSO-d6) ¼ 126.51, 127.00, 128.91, 129.92, 130.22, 130.75,
133.15, 134.05, 134.51, 145.23, 146.11, 147.43, 147.51, 158.00, 185.00. [Found: C,
77.51; H, 3.43; N, 12.10. C15H8N2O requires C, 77.58; H, 3.47; N, 12.06; O, 6.89].
MS: m=z ¼ 231.0000 (Mþ).
SUPPORTING INFORMATION
1
Full experimental detail, H and 13C NMR, mass spectra, GPC, and TGA
can be found via the Supplementary Content section of this article’s Web page.
REFERENCES
1. Brown, H. C.; Baude, E. A.; Nachod, F. C. Determination of Organic Structures by
Physical Methods; Academic Press: New York, 1955.
2. Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki, A.; Bohmer, F. D. Tyrphostins: Potent
inhibitors of platelet-derived growth factor receptor tyrosine kinase: Structure–activity
relationships in quinoxalines, quinolines, and indole tyrphostins. J. Med. Chem. 1996, 39, 2170.

BISINDOLYLQUINOXALINE, BISINDOLYLPYRAZINE
639
3. Sehlstedt, U.; Aich, P.; Bergman, J.; Vallberg, H.; Norden, B.; Graslund, A. Interactions
of the antiviral quinoxaline derivative 9-OH-B220 f2,3-dimethyl-6-(dimethylaminoethyl)-
9-hydroxy-6H-indolo-[2,3-b]quinoxalineg with duplex and triplex forms of synthetic DNA
and RNA. J. Mol. Bio. 1998, 278, 31.
4. Dailey, S.; Feast, J. W.; Peace, R. J.; Sage, I. C.; Till, S.; Wood, E. L. Synthesis and device
characterisation of side-chain polymer electron transport materials for organic semicon-
ductor applications. J. Mater. Chem. 2001, 11, 2238.
5. O’Brien, D.; Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C. Use of poly(phenyl quino-
xaline) as an electron transport material in polymer light-emitting diodes. Appl. Phys.
Lett. 1996, 69, 881.
6. Yamamoto, T.; Sugiyama, K.; Kushida, T.; Inoue, T.; Kanbara, T. Use of poly(phenyl
quinoxaline) as an electron transport material in polymer light-emitting diode. J. Am.
Chem. Soc. 1996, 118, 3930.
7. Yamamoto, T.; Zhou, Z. H.; Kanbara, T.; Shimura, M.; Kizu, K.; Maruyama, T.;
Nakamura, Y.; Fukuda, T.; Lee, B. L.; Ooba, N.; Tomaru, S.; Kurihara, T.; Kanno,
T.; Kubota, K.; Sasaki, S. Preparation of new electron-accepting p-conjugated
polyquinoxalines: Chemical and electrochemical reduction, electrically conducting
properties, and use in light-emitting diodes. J. Am. Chem. Soc. 1996, 118, 10389.
8. Nurulla, I.; Yamaguchi, I.; Yamamoto, T. Preparation and properties of new p-conju-
gated polyquinoxalines with aromatic fused rings in the side chain. Polym. Bull. 2000,
44, 231.
9. Yamamoto, T.; Lee, B. L.; Kokubo, H.; Kishida, H.; Hirota, K.; Wakabayashi, T.;
Okamoto, H. Synthesis of a new thiophene=quinoxaline CT-type copolymer with high
solubility and its basic optical properties. Macromol. Rapid Commun. 2003, 24, 440.
10. Dell, A.; William, D. H.; Morris, H. R.; Smith, G. A.; Feeney, J.; Roberts, G. C. K.
Structure revision of the antibiotic echinomycin. J. Am. Chem. Soc. 1975, 97, 2497.
11. Bailly, C.; Echepare, S.; Gago, F.; Waring, M. The design of cobalt(III) complexes of
phenazine-1-carboxamides as prointercalators and potential hypoxia-selective cytotoxins.
J. Anti-Cancer Drug Des. 1999, 15, 291.
12. Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles; Thieme: New York, 1995;
p. 434.
13. Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P. One-pot synthesis of quinoxalines and
2,3-dihydropyrazines via oxidative aminomercuriation of propargyl alcohols. Synthesis
1985, 313.
14. Petukhov, P. A.; Tkachev, A. V. Synthesis of chiral hexahydrophenazines by treatment of
dimeric nitrosochlorides with 1,2-diaminoarenes. Tetrahedron 1997, 53, 9761.
15. Naskar, S.; Paira, P.; Paira, R.; Mondal, M.; Maity, M.; Hazra, A.; B. Sahu, K.; Saha, P.;
Banerjee, S.; Luger, P.; Webe, M.; B. Mondal, N. Montmorillonite K–10 clay–catalyzed
solvent-free synthesis of bis-indolylindane-1,3-dione,2-(10,30-dihydro-1H-[2,30]biindolyl-
20-ylidene)-indan-1,3-dione and bisindolylindeno[1,2-b]quinoxaline under microwave
irradiation. Tetrahedron 2010, 66, 5196.
16. Mervyn, I.; Lynne, C. J.; Edward, J. M. 6H-indeno[1,2-b]pyrido[3,2-e]pyrazines: A new
heterocyclic ring system. J. Heterocycl. Chem. 1972, 9, 255–262.