A selective, expeditious and sustainable entry en route to benzopyrazines and bis-benzopyrazines

Article abstract of DOI:10.2174/1386207318666150131125053

A convenient green synthesis of benzopyrazines and bis-benzopyrazines has been performed by the condensation of diversely substituted diamines and dicarbonyl compounds in water using indium powder as catalyst under controlled microwave exposure. The effects of microwave power, and temperature on this reaction are investigated in detail to identify the best condition. A wide range of diversely substituted diamines and dicarbonyl compounds produce excellent yield of the corresponding benzopyrazines and bis-benzopyrazines. A comparative study has also been made between microwave-induced procedure and conventional method. The present method is atom-economical, environmentally friendly, and affords synthetically useful and challenging products very rapidly.

Full text of DOI:10.2174/1386207318666150131125053

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Combinatorial Chemistry & High Throughput Screening, 2015, 18, 53-62
53
A Selective, Expeditious and Sustainable Entry en Route to
Benzopyrazines and bis-Benzopyrazines
Debasish Bandyopadhyay*, Sanghamitra Mukherjee and Bimal K. Banik*
Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, Texas 78539,
USA
Abstract: A convenient green synthesis of benzopyrazines and bis-benzopyrazines has been
performed by the condensation of diversely substituted diamines and dicarbonyl compounds in
water using indium powder as catalyst under controlled microwave exposure. The effects of
microwave power, and temperature on this reaction are investigated in detail to identify the best
condition. A wide range of diversely substituted diamines and dicarbonyl compounds produce
excellent yield of the corresponding benzopyrazines and bis-benzopyrazines. A comparative study
has also been made between microwave-induced procedure and conventional method. The present
method is atom-economical, environmentally friendly, and affords synthetically useful and
challenging products very rapidly.
Keywords: Aqueous, benzopyrazine, green chemistry, indium, microwave, nitrogen heterocycles, quinoxaline.
the desired product in highly selective manner with minimal,
or preferably, no waste formation. Our laboratory is engaged
in the green synthesis of novel pharmacophores for many
years. To fulfill this goal we have comprehensively used
automated microwave and ultrasound to induce green
technologies in chemical synthesis. Ultrasound-promoted
synthesis of novel anticancer pyrroles was reported from our
laboratory [9]. The diverse uses of nontoxic, ecofriendly
bismuth nitrate pentahydrate as a catalyst for the Paal–Knorr
reaction [10], nitrating agent [11] as well as oxidizing agent
[12] for the one-step synthesis of vanillin from curcumin
were also reported. In several studies it was found that
solventless condition gives highest yield of the expected
products in comparison to the use of solvents. Synthesis of
pyrroles from primary amines [13, 14], stereoselective
preparation of 3-pyrrole substituted β-lactams [15] and
electrophilic substitution of indoles [16] proceeded very well
under solventless condition. In contrast, it was discovered
that ultrasound-assisted aza-Michael reaction proceeded
much faster in water than organic solvents or solvent-free
condition without using any catalysts or supports [17]. The
same reaction was studied under microwave irradiation and
similar result was noticed [18]. During the investigation to
synthesize pyrrole fused with indolinone [19] and α-
aminonitriles (precursor of α-amino acids) [20] in water
using indium metal as a catalyst, it was perceived that
indium could be used as an ecofriendly catalyst under
microwave exposure to synthesize benzopyrazine
(quinoxaline) scaffold, one of the important class of
medicinally privileged azaheterocycles. Benzopyrazines are
found to be the fundamental structural motif in various
classes of natural and biologically important molecules [21-
25]. Consequently, several methods for the synthesis of
benzopyrazine have been reported in the recent past [26-32]
still the search for simple, cost-effective, easy, and practical
green route is an interesting and continually evolving field of
green chemistry. As a part of our ongoing research to
1. INTRODUCTION
Protection of nature is one of the major criteria in modern
science and technology and the concept of ‘Green
Chemistry’ has been globally adopted to protect human
health and environment. Since the last decade of twentieth
century, protection of environment has been considering as
one of the major issues by the chemical scientists and R&D
experts all over the world [1]. The most significant way to
accomplish this eco-requirement is to avoid or reduce the use
of hazardous solvents, toxic chemicals and to develop new
reaction methodologies which can minimize unnecessary
formation of the byproducts (wastes). Development of such
methodologies can provide substantial contribution to green
chemistry [2, 3]. Consequently, search for new expeditious
reaction strategies using nontoxic reagents/catalysts in green
solvent like aqueous medium following green technologies is
being considered as an important research area.
It has been found that organic synthesis in aqueous media
may be rapid and produce excellent yields in many instances.
Subsequently, organic synthesis in aqueous media has drawn
growing attention in green methodology development. It is
worth to mention that water is abundant, nontoxic and
possesses high dielectric constant (polarity). A huge number
of reactions have been reported where water behaves as a
more selective solvent with higher reactivity than organic
solvents. Strong hydrogen bonding ability and dipole
moment of the water molecules make water as a solvent of
choice for many reactions [4-8]. Emphasis has been given to
develop new and novel alternate synthetic routes which yield
*Address correspondence to these authors at the Department of Chemistry,
The University of Texas-Pan American, 1201 West University Drive,
Edinburg, Texas 78539, USA; Tel: +1(956)5789414; Fax: +1(956)6655006;
E-mail: bandyopad@utpa.edu, bimalbanik10@gmail.com.
Present address of BKB: Community Health Systems of South Texas, 3135
Sugar Road, Edinburg, TX 78539, USA
1875-5402/15 $58.00+.00
© 2015 Bentham Science Publishers

54 Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1
Bandyopadhyay et al.
R2
R1
N
N
R2
R3
O
R1
NH2
NH2
In powder (5 mol%)/water
+
MWI (260 W, 60 °C, 24-50 psi)
R3
O
R1 = H, Cl, OMe, NO2; R2 = H, CH3, Ph
R3 = H, Ph, 3,4-difluorophenyl, 3,4,5-Trimethoxyphenyl (3,4,5-TMP)
Scheme 1. Indium catalyzed microwave-induced chemoselective synthesis of benzopyrazines in water.
synthesize novel pharmacophores following green pathway,
we report herein microwave-assisted convenient and
expeditious synthesis of benzopyrazines and bis-
benzopyrazines in water using trace amount of indium as
catalyst following Scheme 1.
(dichloromethane-hexane). The spectral and analytical data
for all the benzopyrazines and bis-benzopyrazines (Tables 2
and 3) are as follows:
2.2.1. Benzopyrazine (1, Entry 1, Table 2)
White crystals (92%); m.p. 30-32 °C; IR (KBr) 1562,
1
1490, 1361, 1199, 1126, 1022, 949, 870, 755, 599 cm-1; H
2. MATERIALS AND METHODS
2.1. General
NMR (600 MHz, CDCl3) δ 7.77 (dd, J = 4.98, 3.00 Hz, 2H),
8.11 (dd, J = 4.95, 2.94 Hz, 2H), 8.84 (s, 2H); 13C NMR (150
MHz, CDCl3) 129.48, 130.05, 143.02, 144.94. Anal. Calcd
for C8H6N2: C, 73.83; H, 4.65; N, 21.52. Found: C, 73.76; H,
4.57; N, 21.46.
Melting points were determined in a Fisher Scientific
electrochemical Mel-Temp* manual melting point apparatus
(Model 1001) equipped with a 300°C thermometer. FT-IR
spectra were recorded on a Bruker Alpha modular Platinum-
ATR FT-IR spectrometer with OPUS software, using the
2.2.2. 2-Phenylbenzopyrazine (2, Entry 2, Table 2)
1
samples directly (neat) without making pallets. H-NMR
Light brown crystalline solid (95%); m.p. 77-79 °C; IR
(KBr) 1727, 1538, 1482, 1303, 1124, 1027, 951, 760, 682,
(600 MHz), 13C-NMR (150 MHz), and F19-NMR (564 MHz)
spectra were obtained at room temperature with Bruker
superconducting UltrashieldTM Plus 600 MHz NMR
spectrometer with central field 14.09 Tesla, coil inductance
89.1 Henry and magnetic energy 1127.2 kJ using CDCl3 or
d6-DMSO as solvent. Elemental analyses (C, H, N) were
conducted using the Perkin-Elmer 2400 series II elemental
analyzer, their results were found to be in good agreement (
0.4%) with the calculated values for C, H, N. Automated
microwave (CEM Corporation, Matthews, NC, USA)
Discover model was used for microwave irradiation. Indium
powder, 99.99% (Cat # 277959), purchased from Sigma-
Aldrich Corporation was used. All the reagents (analytical
grade) were purchased from Sigma-Aldrich Corporation (St.
Louis, MO, USA). Throughout the project solvents were
purchased from Fisher-Scientific (Pittsburgh, PA, USA).
Deionized water was used for the preparation of all aqueous
solutions.
1
550 cm-1; H NMR (600 MHz, CDCl3) δ 7.52-7.59 (m, 3H),
7.74-7.80 (m, 2H), 8.14 (d, J = 8.16 Hz, 1H), 8.17 (d, J =
8.22 Hz, 1H), 8.21 (d, J = 7.62 Hz, 2H), 9.34 (s, 1H); 13C
NMR (150 MHz, CDCl3) 127.57, 129.14, 129.16, 129.54,
129.65, 130.20, 130.28, 136.80, 141.60, 142.32, 143.37,
151.85. Anal. Calcd for C14H10N2: C, 81.53; H, 4.89; N,
13.58. Found: C, 81.39; H, 4.78; N, 13.47.
2.2.3. 2-(3,4-Difluorophenyl)Benzopyrazine (3, Entry 3,
Table 2)
White flaky solid (91%); m.p. 146 °C; IR (KBr) 1612,
1
1525, 1421, 1329, 1273, 1115, 974, 880, 822, 757 cm-1; H
NMR (600 MHz, CDCl3) δ 7.38 (dd, J = 13.29, 9.78 Hz,
1H), 7.79-7.85 (m, 2H), 7.96-7.98 (m, 1H), 8.12-8.15 (m,
3H), 9.30 (s, 1H); 13C NMR (150 MHz, CDCl3) 116.66,
116.79, 117.95, 118.06, 123.61, 123.63, 123.65, 129.19,
129.61, 129.99, 130.63, 141.72, 142.14, 142.50; 19F NMR
(564 MHz, CDCl3) -136.07 (d, J = 20.88 Hz, 1F), and -
135.01 (d, J = 21.67 Hz, 1F). Anal. Calcd for C14H8F2N2: C,
69.42; H, 3.33; N, 11.57. Found: C, 69.33; H, 3.29; N, 11.48.
2.2. General Procedure for the Synthesis of
Benzopyrazines and bis-Benzopyrazines
Equimolar ratio of the diamine and dicarbonyl compound
(1 mmol scale) was mixed in water (0.5 mL). In case of bis-
analog 1:2 molar ratio (diamine: dicarbonyl) was taken.
Catalytic amount (6 mg, ~5 mol%) of indium powder was
added and the mixture was placed under microwave
irradiation as described in Tables 2 and 3 and the reaction
was monitored by TLC. After the completion of the reaction,
dichloromethane (5 mL) was added to the reaction in two
batches (3 mL and 2 mL) for extraction. The combined
organic layer was then washed successively with brine (3
mL) and water (3 mL). The organic layer was dried with
anhydrous sodium sulfate and concentrated. The products
2.2.4. 2-(3,4,5-Trimethoxyphenyl)Benzopyrazine (4, Entry
4, Table 2)
Brownish white crystalline solid (90%); m.p. 86-87 °C;
IR (KBr) 2941, 1590, 1461, 1349, 1238, 1131, 1002, 767
1
cm-1; H NMR (600 MHz, CDCl3) δ 3.86 (s, 3H), 3.94 (s,
6H), 7.67 (td, J = 8.22, 1.32 Hz, 1H), 7.70 (td, J = 8.25, 1.32
Hz, 1H), 7.35 (s, 2H), 8.04 (dd, J = 8.25, 1.08 Hz, 1H), 8.07
(dd, J = 8.28, 0.96 Hz, 1H), 9.20 (s, 1H); 13C NMR (150
MHz, CDCl3) 56.71, 61.02, 104.92, 129.14, 129.47, 129.50,
130.34, 132.25, 140.28, 141.53, 142.19, 143.18, 151.46,
153.88. Anal. Calcd for C17H16N2O3: C, 68.91; H, 5.44; N,
9.45. Found: C, 68.77; H, 5.31; N, 9.37.
1
were found to be >95% pure from TLC and H-NMR study.
Pure products were isolated through crystallization

Benzopyrazines and bis-Benzopyrazines
Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1 55
2.2.5. 2,3-Diphenylbenzopyrazine (5, Entry 5, Table 2)
2.2.10. 6-Chloro-2-(3,4-difluorophenyl)Benzopyrazine (10,
Entry 10, Table 2)
Colorless crystals (88%); m.p. 119 °C; IR (KBr) 1665,
1560, 1489, 1240, 1184, 1077, 1012, 877, 807, 758, 698 cm-
1; 1H NMR (600 MHz, CDCl3) δ 7.36-7.40 (m, 6H), 7.55 (m,
4H), 7.79 (dd, J = 4.86, 3.00 Hz, 2H), 8.21 (dd, J = 4.86,
2.88 Hz, 2H); 13C NMR (150 MHz, CDCl3) 128.30, 128.83,
129.24, 129.89, 129.98, 139.13, 141.27, 153.49. Anal. Calcd
for C20H14N2: C, 85.08; H, 5.00; N, 9.92. Found: C, 84.97;
H, 4.92; N, 9.87.
Dark brown amorphous solid (95%); m.p. 172 °C; IR
(KBr) 1610, 1521, 1438, 1326, 1279, 1170, 1123, 1075, 885,
562 cm-1; 1H NMR (600 MHz, CDCl3) δ 7.70 (dd, J = 13.70,
10.38 Hz, 1H), 7.89 (dd, J = 5.61, 2.34 Hz, 1H), 8.15 (d, J =
8.88 Hz, 1H), 8.39-8.43 (m, 1H), 9.64 (s, 1H); 13C NMR
(150 MHz, CDCl3) 116.62, 116.74, 118.33, 118.45, 124.89,
127.86, 130.71, 130.80, 133.25, 135.12, 139.80, 141.55,
143.99, 149.71; 19F NMR (564 MHz, CDCl3) -135.80 (d, J =
22.58 Hz, 1F), and -134.27 (d, J = 22.58 Hz, 1F). Anal.
Calcd for C14H7ClF2N2: C, 60.78; H, 2.55; N, 10.13. Found:
C, 60.71; H, 2.47; N, 10.05.
2.2.6. 6-Methoxy-2-Phenylbenzopyrazine (6, Entry 6, Table 2)
White crystalline solid (91%); m.p. 75-77 °C; IR (KBr)
1616, 1541, 1508, 1489, 1456, 1374, 1314, 1212, 1117,
1
1019, 827, 754, 687 cm-1; H NMR (600 MHz, CDCl3) δ
2.2.11. 6-Chloro-2-(3,4,5-Trimethoxyphenyl)Benzopyrazine
(11, Entry 11, Table 2)
3.90 (s, 3H), 7.30 (dd, J = 8.95, 2.76 Hz, 1H), 7.35 (d, J =
2.70 Hz, 1H), 7.43-7.49 (m, 3H), 7.90 (d, J = 9.06 Hz, 1H),
8.07 (s, 1H), 8.08 (m, 1H), 9.08 (s, 1H); 13C NMR (150
MHz, CDCl3) 55.84, 106.91, 122.89, 127.52, 129.10, 129.12,
130.05, 137.02, 137.80, 140.76, 143.98, 151.95, 161.08.
Anal. Calcd for C15H12N2O: C, 76.25; H, 5.12; N, 11.86.
Found: C, 76.14; H, 5.01; N, 11.78.
Deep brown amorphous solid (92%); m.p. 130-132 °C;
IR (KBr) 2940, 2834, 1590, 1456 1419, 1343, 1234, 1172,
1
1131, 1066, 994, 856 cm-1; H NMR (600 MHz, CDCl3) δ
3.96 (s, 3H), 4.03 (s, 6H), 7.43 (s, 2H), 7.68 (dd, J = 8.88,
2.10 Hz, 1H), 8.04-8.11 (m, 1H), 8.16 (d, J = 1.86 Hz, 1H),
9.28 (s, 1H); 13C NMR (150 MHz, CDCl3) 56.41, 61.03,
104.87, 104.95, 128.36, 130.34, 130.40, 131.35, 131.67,
140.00, 143.19, 143.94, 153.89, 153.90. Anal. Calcd for
C17H15ClN2O3: C, 61.73; H, 4.57; N, 8.47. Found: C, 61.64;
H, 4.49; N, 8.37.
2.2.7. 2-(3,4-Difluorophenyl)-6-Methoxybenzopyrazine (7,
Entry 7, Table 2)
Reddish amorphous solid (92%); m.p. 184 °C; IR (KBr)
1
1508, 1428, 1330, 1219, 1114, 1025, 830 cm-1; H NMR
(600 MHz, CDCl3) δ 3.98 (s, 3H), 7.51 (m, 2H), 7.67 (dd, J
= 13.74, 10.20 Hz, 1H), 8.02 (d, J = 9.84 Hz, 1H), 8.22 (br.
s, 1H) 8.39 (t, J = 9.78 Hz, 1H), 9.44 (s, 1H); 13C NMR (150
MHz, CDCl3) 55.93, 106.94, 116.27, 116.40, 118.21, 118.32,
123.09, 124.45, 129.90, 133.84, 137.33, 140.60, 142.94,
148.73, 160.79; 19F NMR (564 MHz, CDCl3) -136.24 (d, J =
20.47 Hz, 1F), and -135.34 (d, J = 20.94 Hz, 1F). Anal.
Calcd for C15H10F2N2O: C, 66.17; H, 3.70; N, 10.29. Found:
C, 66.12; H, 3.66; N, 10.24.
2.2.12. 6-Chloro-3-Methyl-2-Phenylbenzopyrazine (12,
Entry 12, Table 2)
Dark reddish-brown amorphous solid (96%); m.p. 119
°C; IR (KBr) 1604, 1552, 1477, 1372, 1332, 1173, 1126,
1063, 1001, 870, 765, 703 cm-1; 1H NMR (600 MHz, CDCl3)
δ 2.79 (s, 3H), 7.53-7.57 (m, 3H), 7.66-7.71 (m, 3H), 8.00-
8.07 (m, 1H), 8.12 (s, 1H); 13C NMR (150 MHz, CDCl3)
24.42, 128.61, 128.90, 128.92, 129.19, 129.25, 129.62,
130.25, 130.46, 130.69, 134.89, 141.32, 155.74. Anal. Calcd
for C15H11ClN2: C, 70.73; H, 4.35; N, 11.00. Found: C,
70.64; H, 4.41; N, 11.01.
2.2.8.
6-Methoxy-2-(3,4,5-Trimethoxyphenyl)Benzopyr-
azine (8, Entry 8, Table 2)
Yellowish brown crystalline solid (94%); m.p. 120-121
°C; IR (KBr) 2944, 2836, 1617, 1502, 1460, 1425, 1344,
2.2.13. 6-Nitro-2-Phenylbenzopyrazine (13, Entry 13, Table
2)
1
1215, 1129, 1000, 854 cm-1; H NMR (600 MHz, CDCl3) δ
3.86 (s, 3H), 3.92 (s, 3H), 3.94 (s, 6H), 7.32 (m, 1H), 7.33 (s,
2H), 7.36 (d, J = 2.70 Hz, 1H), 7.91 (d, J = 9.12 Hz, 1H),
9.04 (s, 1H); 13C NMR (150 MHz, CDCl3) 55.82, 56.39,
61.02, 104.84, 106.83, 122.79, 130.04, 132.49, 137.71,
140.13, 140.54, 143.86, 151.54, 153.83, 161.13. Anal. Calcd
for C18H18N2O4: C, 66.25; H, 5.56; N, 8.58. Found: C, 66.21;
H, 5.53; N, 8.57.
Pale yellow crystalline solid (97%); m.p. 210-211 °C; IR
(KBr) 1616, 1556, 1522, 1348, 1316, 1077, 851, 832, 791,
1
764, 691 cm-1; H NMR (600 MHz, CDCl3) δ 7.52-7.55 (m,
3H), 8.16-8.21 (m, 3H), 8.47 (dd, J = 9.12, 2.52 Hz, 1H),
8.95 (d, J = 2.46 Hz, 1H), 9.42 (s, 1H); 13C NMR (150 MHz,
CDCl3) 123.79, 125.67, 127.95, 129.43, 131.19, 131.41,
135.64, 140.36, 144.93, 145.50, 147.47, 154.33. Anal. Calcd
for C14H9N3O2: C, 66.93; H, 3.61; N, 16.73. Found: C,
66.78; H, 3.49; N, 16.66.
2.2.9. 6-Chloro-2-Phenylbenzopyrazine (9, Entry 9, Table 2)
Light brown crystalline solid (93%); m.p. 146-147 °C; IR
(KBr) 1699, 1540, 1481, 1449, 1315, 1223, 1132, 1073, 958,
829, 756, 711, 687 cm-1; 1H NMR (600 MHz, CDCl3) δ 7.47-
7.51 (m, 3H), 7.61 (dd, J = 8.85, 2.22 Hz, 1H), 7.98 (d, J =
8.82 Hz, 1H), 8.01-8.04 (m, 1H), 8.08 (d, J = 2.16 Hz, 1H),
8.10-8.12 (m, 1H), 9.24 (s, 1H); 13C NMR (150 MHz,
CDCl3) 127.54, 127.63, 129.24, 130.37, 130.46, 130.54,
130.57, 136.34, 140.12, 142.68, 143.44, 152.59. Anal. Calcd
for C14H9ClN2: C, 69.86; H, 3.77; N, 11.64. Found: C, 69.74;
H, 3.69; N, 11.52.
2.2.14. 2-(3,4-Difluorophenyl)-6-Nitrobenzopyrazine (14,
Entry 14, Table 2)
Pink flaky crystal (91%); m.p. 211 °C; IR (KBr) 1525,
1
1465, 1428, 1344, 1188, 1125, 890, 821 cm-1; H NMR (600
MHz, d6-DMSO) δ 7.71-7.75 (m, 1H), 8.32-8.36 (m, 2H), 8.49
(t, J = 9.54, 1H), 8.58 (d, J = 9.06 Hz, 1H), 8.92 (s, 1H), 9.82 (s,
1H); 13C NMR (150 MHz, d6-DMSO) 115.51, 117.05, 117.18,
118.47, 118.58, 124.06, 124.89, 125.45, 131.10, 139.84, 143.82,
146.03, 147.39, 151.46; 19F NMR (564 MHz, CDCl3) -137.11

56 Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1
Bandyopadhyay et al.
(d, J = 22.58 Hz, 1F), and -134.34 (d, J = 22.58 Hz, 1F). Anal.
2.2.20. 2,3'-Dimethyl-2',3-diphenyl-6,6'-Dibenzopyrazine
(20, Entry 4, Table 3)
Calcd for C14H7F2N3O2: C, 58.54; H, 2.46; N, 14.63;. Found: C,
58.44; H, 2.47; N, 14.52.
Pale yellow crystalline solid (94%); m.p. 229 °C; IR
(KBr) 1705, 1645, 1554, 825, 698 cm-1; 1H NMR (600 MHz,
CDCl3) δ 2.85 (s, 6H), 7.53-7.59 (m, 6H), 7.71-7.73 (m, 6H),
8.16-8.28 (m, 6H), 8.46-8.48 (m, 2H), 8.52-8.54 (m, 2H);
13C NMR (150 MHz, CDCl3) 24.45, 126.58, 126.66, 127.56,
128.62, 129.06, 129.13, 129.32, 129.96, 129.97, 138.95,
141.27, 141.44. Anal. Calcd for C30H22N4: C, 82.17; H, 5.06;
N, 12.78. Found: C, 82.01; H, 4.97; N, 12.66.
2.2.15. 6-Nitro-2-(3,4,5-Trimethoxyphenyl)Benzopyrazine
(15, Entry 15, Table 2)
Bright yellow crystalline solid (93%); m.p. 237-238 °C;
IR (KBr) 2946, 1700, 1552, 1466, 1342, 1133 cm-1; 1H NMR
(600 MHz, CDCl3) δ 3.89 (s, 3H), 3.96 (s, 6H), 7.43 (s, 2H),
8.20 (d, J = 9.12 Hz, 1H), 8.48 (dd, J = 9.15, 2.46 Hz, 1H),
8.95 (d, J = 2.46 Hz, 1H), 9.37 (s, 1H); 13C NMR (150 MHz,
CDCl3) 56.49, 61.09, 105.35, 123.84, 125.66, 130.88,
130.98, 140.22, 141.41, 144.86, 145.29, 147.35, 153.81,
154.03. Anal. Calcd for C17H15N3O5: C, 59.82; H, 4.43; N,
12.31. Found: C, 59.67; H, 4.38; N, 12.25.
2.2.21. 2,2',3,3'-Tetraphenyl-6,6'-Dibenzopyrazine (21,
Entry 5, Table 3)
Brownish yellow crystalline solid (90%); m.p. 301 °C; IR
(KBr) 1709, 1616, 1550, 1346, 1185, 1062, 1022, 977, 768,
697 cm-1; 1H NMR (600 MHz, CDCl3) δ 7.38-7.43 (m, 12H),
7.58-7.59 (m, 8H), 8.26 (dd, J = 4.35, 1.92 Hz, 2H), 8.34 (d,
J = 8.64 Hz, 2H), 8.62 (s, 2H); 13C NMR (150 MHz, CDCl3)
127.50, 128.32, 128.96, 129.50, 129.89, 129.97, 139.02,
140.98, 141.26, 141.49, 153.75, 154.18. Anal. Calcd for
C40H26N4: C, 85.38; H, 4.66; N, 9.96. Found: C, 85.29; H,
4.57; N, 9.82.
2.2.16. 3-Methyl-6-Nitro-2-Phenylbenzopyrazine (16, Entry
16, Table 2)
Light yellow crystalline solid (89%); m.p. 132 °C; IR
(KBr) 1519, 1398, 1328, 1071, 1003, 897, 818, 764, 741,
1
693, 588 cm-1; H NMR (600 MHz, CDCl3) δ 2.78 (s, 3H),
7.49 (t, J = 1.56 Hz, 3H), 7.61 (d, J = 5.58 Hz, 2H), 8.10-
8.17 (m, 1H), 8.40-8.44 (m, 1H), 8.94 (s, 1H); 13C NMR
(150 MHz, CDCl3) 23.85, 12211, 124.67, 127.73, 127.91,
127.93, 128.72, 128.99, 136.88, 138.82, 142.64, 155.32,
156.15. Anal. Calcd for C15H11N3O2: C, 67.92; H, 4.18; N,
15.84. Found: C, 67.81; H, 4.11; N, 15.77.
3. RESULTS AND DISCUSSION
Microwave technology has acquired an important role in
organic synthesis due to its unique features [33, 34].
Application of microwave technology for the rapid synthesis
of biologically significant heterocyclic molecules is very
encouraging and challenging because development of
cleaner technologies is a major emphasis in green chemistry.
We have extensively used microwave technology to develop
many new reaction methodologies. Some examples are
synthesis of biologically active β-lactams in stereoselective
manner [35, 36], synthesis of novel heterocycles [37, 38] etc.
Alternatively, indium, the group 13 post-transition metal can
generate organoindium species by reacting with the
substrates during the progress of the reaction. The use of
indium can circumvent the use of toxic, costly or air and
moisture sensitive organometallics [39-41].
2.2.17. 2,3'-Diphenyl-6,6'-Dibenzopyrazine (17, Entry 1,
Table 3)
Deep yellow crystalline solid (92%); m.p. 220 °C; IR
(KBr) 1700, 1648, 1539, 1315, 1051, 959, 827, 764, 689 cm-
1
1; H NMR (600 MHz, CDCl3) δ 7.56-7.64 (m, 6H), 8.20-
8.32 (m, 8H), 8.53-8.58 (m, 2H), 9.40 (m, 2H); 13C NMR
(150 MHz, CDCl3) 127.50, 127.61, 127.93, 129.23, 129.90,
130.40, 136.68, 140.76, 141.56, 142.10, 143.65, 144.08.
Anal. Calcd for C28H18N4: C, 81.93; H, 4.42; N, 13.65.
Found: C, 81.79; H, 4.36; N, 13.53.
2.2.18. 2,3'-bis(3,4-Difluorophenyl)-6,6'-Dibenzopyrazine
(18, Entry 2, Table 3)
In order to optimize the reaction conditions, the reaction
of o-phenylenediamine (1 mmol) with phenylglyoxal
monohydrate (1 mmol) catalyzed by indium powder (0.2
mmol, 20 mol% relative to reactants) in water (0.5 mL) was
investigated under microwave irradiation (300 Watts wave
power) at 50°C and 24-50 psi pressure for 15 sec. An
excellent yield of 87% of the corresponding benzopyrazine
was successfully isolated. In the next step the amount of the
catalyst was optimized. The result has been summarized in
Table 1. It was found that a catalyst loading of 5 mol%
indium powder produced the highest yield of the desired
product (Entry 4, Table 1). The model reaction was
performed under similar condition (only microwave
irradiation) without using any catalyst which yielded only
19% desired product within the given time.
Dark brown amorphous solid (86%); m.p. 178 °C; IR
1
(KBr) 1616, 1518, 1283, 1116, 773 cm-1; H NMR (600
MHz, CDCl3) δ 7.18-7.40 (m, 4H), 7.96-8.15 (m, 4H), 8.25-
8.27 (m, 2H), 9.23 (m, 2H), 9.28 (s, 2H); 19F NMR (564
MHz, CDCl3) -136.07 (d, J = 20.38 Hz, 1F), and -135.01 (d,
J = 20.77 Hz, 1F) Anal. Calcd for C28H14N4: C, 69.71; H,
2.93; N, 11.61. Found: C, 69.63; H, 2.81; N, 11.46.
2.2.19. 2,3′-Bis(3,4,5-Trimethoxyphenyl)-6,6′-Dibenzopyr-
azine (19, Entry 3, Table 3)
Deep yellow crystalline solid (97%); m.p. 234 °C; IR
(KBr) 2940, 1708, 1587, 1462, 1422, 1231, 1129, 998, 831
1
cm-1; H NMR (600 MHz, CDCl3) δ 3.87 (s, 6H), 3.95 (s,
12H), 7.41 (s, 4H), 8.16-8.23 (m, 4H), 8.44-8.45 (m, 2H),
9.28 (s, 2H); 13C NMR (150 MHz, CDCl3) 56.45, 61.06,
104.94, 127.79, 129.82, 129.87, 130.26, 132.05, 140.47,
140.59, 141.75, 141.96, 143.90, 153.93. Anal. Calcd for
C34H30N4O6: C, 69.14; H, 5.12; N, 9.49. Found: C, 69.02; H,
4.98; N, 9.34.
Other indium-based reagents like indium(I) chloride,
indium(III) chloride, indium(III) bromide, indium(III)
selenide, indium hydroxide, indium(III) fluoride trihydrate,
indium(III) fluoride, indium(III) oxide and indium(III)
trifluoromethanesulfonate were screened using the same

Benzopyrazines and bis-Benzopyrazines
Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1 57
model reaction. In the cases of indium(III) trifluoromethane-
sulfonate and indium(III) chloride almost similar results
were obtained.
have virtually minimum effect (or no effect) on the success
of the reaction. It is important to be mentioned that the
reaction between diamines and α-ketoaldehydes proceeds in
faster rate than with diketo compounds. A comparison has
also been made between microwave-induced syntheses of
benzopyrazines with conventional stirring at room
temperature. The results are summarized in Table 2.
Table 1. Microwave-assisted synthesis of benzopyrazine from
1 mmol of o-phenylenediamine with 1 mmol of
phenylglyoxal monohydrate in water (0.5 mL) using
indium powder as catalyst at 50 °C for 15 sec:
optimization of the catalyst amount.
A
plausible mechanism for the synthesis of
benzopyrazines catalyzed by indium powder can be
hypothesized by the nucleophilic attack of one of the amino
group of the diamine to one of the carbonyl group of the
dicarbonyl compound. Indium catalyzes the reaction
possibly through coordination. Because of the presence of
vacant py, pz orbitals and half-filled px orbital, indium can
attract electron density of the lone pair on carbonyl oxygen
to make the carbonyl carbon more electron deficient. This
acts as the driving force to accelerate the reaction in
chemoselective manner. The subsequent step involves a
second attack of the other amino moiety of the diamine to
the available carbonyl carbon of the dicarbonyl compound.
Finally, a cyclodehydration step leads to the product
benzopyrazines (Scheme 3).
Entry
In Powder (mol %)
Yield (%)a
1
2
3
4
5
6
7
20
88
90
89
93
49
46
19
15
10
5
2
1
No catalyst
aIsolated yield.
To optimize the reaction temperature, the mixture was
heated at different temperatures ranging from 30 to 100 °C
with an augmentation of 10 °C using the same model
reaction as described before. The reaction of o-phenylenedi-
amine (1 mmol) with phenylglyoxal monohydrate (1 mmol)
catalyzed by indium metal powder (0.2 mmol, 20 mol%
relative to reactants) in water (0.5 mL) was investigated
under microwave irradiation (300 Watts wave power) at the
pressure 24-50 psi for 15 sec. The yield of the product
benzopyrazine was increased when the temperature was
raised from 30 to 60 °C. However, no increase in the yield of
product was observed when the reaction temperature was
raised from 60 to 100 °C. At 60 °C temperature 91% yield of
the product benzopyrazine was isolated whereas at 50 °C
88% yield was obtained (Entry 1, Table 1). Therefore, 60 °C
was chosen as the reaction temperature for all the subsequent
reactions. To determine the optimum microwave power, the
model reaction was conducted from 100 to 300 Watts wave
power with an escalation of 20. The highest yield (96%) of
the corresponding benzopyrazine was obtained at 260 Watts
wave power. This indicates that 260 Watts wave power is
ideal to achieve the best result in this reaction. Consequently,
all the subsequent reactions were carried out at 60 °C in the
presence of 5 mol% of indium powder under microwave
exposure of 260 Watts wave power at a pressure 24-50 psi in
water. Following the standardized conditions, a wide variety
of diversely substituted benzopyrazines have been
synthesized and in all the events excellent yield (88-97%) of
desired benzopyrazine was isolated. The results have been
depicted in Table 2. It is interesting to note that diversely
substituted o-phenylenediamines with electron donating
(OCH3) and electron withdrawing (NO2, Cl) groups along
with unsubstituted o-phenylenediamine undergo the reaction
in chemoselective manner to produce the corresponding
benzopyrazines. In a similar fashion, diversely substituted
diketones and α-ketoaldehydes as well as glyoxal produced
excellent yields of the corresponding benzopyrazine.
Therefore, the diamines or dicarbonyl compounds bearing
either electron-donating or electron-withdrawing groups
It is known that the electric component of the microwave
is responsible for microwave heating as it results in a force
being applied to all the polar or charged species. The dipolar
species (including the solvent water) under controlled
microwave exposure (260 Watts wave power), collide with
the nearby charged or neutral species. As a result of
intermolecular collision internal heat is generated which
accelerate the rate of reaction [34, 35]. Because of high
dipole moment water can play a pivotal role in the reaction.
Under the influence of microwaves, indium increases the
“anionic activation” [43] because of its affinity to coordinate
with the electronegative atom using its vacant p-orbitals.
Successively, the relative permittivity of the carbonyl
functionalities increases and consequently the microwave
heating is aided due to better coupling with microwave [34,
35, 44]. When the substrates (o-phenylenediamine and the
diketo compound) are placed in a microwave vial in water
and the vial is subjected under controlled microwave
exposure, microwave directly heats the reaction mixture
without heating the glass wall of the microwave vial. As a
result, unnecessary formation of the byproducts (wastes) is
inhibited and the desired product is obtained in high yield
with excellent purity. A concurrent effect of the use of the
green catalyst indium, the green solvent water and the green
technique (controlled microwave exposure) can be
hypothesized for extreme rapidity and excellent yields of the
corresponding benzopyrazines.
Next, the investigation was extended to the synthesis of
bis-benzopyrazines using 3,3′-diaminobenzidine (tetramine)
following Scheme 2.
Five reactions were studied and in all the cases excellent
yields of the corresponding bis-benzopyrazine were
obtained.
A
comparison between microwave-induced
procedure with room temperature stirring has been carried
out with α-ketoaldehyde, substituted α-ketoaldehydes and
diverse diketo compounds. The results are summarized in
Table 3.

58 Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1
Bandyopadhyay et al.
Table 2. Microwave-assisted (260 Watts wave power) synthesis of benzopyrazines from equimolar ratio (1:1) of o-
phenylenediamines with dicarbonyl compounds in water (0.5 mL) using 5 mol% indium powder as catalyst at 60 °C.
Condition A: MWI
(260 Watts, 60 °C, 24-50 psi)
Condition B: Stirring at
Room Temperature
Entry
Diamine
Dicarbonyl
Product
Time (min)
Yield (%)a
Time (min)
Yield (%)a
1
2
0.25
92
5
88 [42]
0.25
0.5
95
91
5
93 [22]
87
3
4
15
1
90
88
15
90
91 [22]
83 [26]
5
0.5
6
7
0.5
0.5
91
92
10
20
89 [22]
81
8
1
94
15
90 [22]
9
1
3
93
95
20
30
87 [22]
83
10
11
12
3
3
92
96
30
89 [22]
90
240

Benzopyrazines and bis-Benzopyrazines
Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1 59
(Table 2) contd…..
Condition A (MWI) 2
60 Watts, 60 °C, 24-50 psi
Condition B Stirring at
Room Temperature
Entry
Diamine
Dicarbonyl
Product
Time (min)
Yield (%)a
Time (min)
Yield (%)a
13
14
0.5
97
30
89 [22]
2
91
60
82
15
2
1
93
89
60
87 [22]
16
180
85
aIsolated yield.
R1
NH2
N
R2
R1
R2
O
In powder (5 mol%)/water
N
H2N
H2N
NH2
+
2
N
MWI (260 W, 60 °C, 24-50 psi)
O
R1
N
R2
R1 = H, CH3, Ph
R2 = H, Ph, 3,4-difluorophenyl,
3,4,5-Trimethoxyphenyl (3,4,5-TMP)
Scheme 2. Indium powder catalyzed microwave-induced reaction of 3,3′-diaminobenzidine with dicarbonyl compounds in water.
H
OH
In
N
R1
R2
R1
R2
O
O
NH2
NH2
O
NH2
H2O
N
R1
R2
R1 = H, Cl, OMe, NO2; R2 = H, CH3, Ph
R3 = H, Ph, 3,4-difluorophenyl, 3,4,5-Trimethoxyphenyl (3,4,5-TMP)
O
NH
N
N
R1
N
N
R1
R2
In
H2O
OH
R2
H
Scheme 3. Plausible mechanism for the Indium powder catalyzed synthesis of benzopyrazines.

60 Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1
Bandyopadhyay et al.
Table 3. Indium powder catalyzed reaction of 3,3′-diaminobenzidine with dicarbonyl compounds in water: synthesis of bis-
benzopyrazines.
Condition A (MWI) 260
Watts, 60 °C, 24-50 psi
Condition B Stirring at
Room Temperature
Entry
Dicarbonyl
Product
Time (min)
Yield (%)a
Time (min)
Yield (%)a
1
0.5
92
30
98
2
3
0.5
0.5
86
97
30
20
91
93
4
1
94
90
60
91
5
1
240
86 [45]
aIsolated yield.
The structure of the representative bis-benzopyrazine
derivative [2,3′-bis(3,4,5-trimethoxyphenyl)-6,6′-dibenzopyra-
zine Entry 3, Table 3] has been confirmed by X-ray
crystallographic analysis. The ORTEP projection is shown in
Fig. (1). The asymmetric unit comprises half a molecule of
the compound situated about an inversion center (½, ½, 0)
[46]. Packing of these molecules is dominated by π -π
interactions between molecules (average distance 3.36 Ǻ).
CONCLUSION
In conclusion, the present method demonstrates an
operationally simple, controlled microwave-assisted clean
procedure for the synthesis of benzopyrazines and bis-
benzopyrazines using a catalytic amount of indium powder
in water. The present economical method satisfies most of
the principles of green chemistry such as: cost-effectiveness,
low toxicity, air and moisture compatibility of the catalyst as
well as the use of green solvent water. The excellent yield of
the products within shorter reaction time make this
methodology a valid contribution to the existing processes in
the same field. This procedure tolerates a relatively wide
range of substrates and excellent results are obtained for
gram-scale reactions “on water” [47], which opens up a new
pathway to various biologically important heterocycles
through one-pot route. Benzopyrazines and bis-
benzopyrazines are valuable compounds and their
expeditious synthesis as described herein will find wide
applications in future drug discovery research.
CONFLICT OF INTEREST
Fig. (1). X-ray crystallographic structure (ORTEP projection) of
2,3′-bis(3,4,5-trimethoxyphenyl)-6,6′-dibenzopyrazine (Entry 3,
Table 3): Thermal ellipsoids are shown with 50% probability.
The authors confirm that they do not have any conflicts
of interest.

Benzopyrazines and bis-Benzopyrazines
Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1 61
[21]
[22]
Saifina, D.F.; Mamedov, V.A. New and modified classical methods
for the synthesis of quinoxalines. Russ. Chem. Rev., 2010, 79, 351-
370.
Bandyopadhyay, D.; Cruz, J.; Morales, L.D.; Arman, H.D.; Cuate,
E.; Lee, Y.S.; Banik, B.K.; Kim, D.J. A green approach toward
quinoxalines and bis-quinoxalines and their biological evaluation
against A431, human skin cancer cell lines. Future Med. Chem.,
2013, 5, 1377-1390.
Kalinin, A.A.; Mamedov, V.A. Pyrrolo[1,2-a] quinoxalines based
on pyrroles. Chem. Heterocycl. Compd., 2011, 46, 1423-1442.
Kamal, A.; Reddy, K.L.; Devaiah, V.; Shankaraiah, N.; Rao, M.V.
Recent advances in the solid-phase combinatorial synthetic
strategies for the quinoxaline, quinazoline and benzimidazole based
privileged structures. Mini-Rev. Med. Chem., 2006, 6, 71-89.
Ghosh, P.; Bagchi, M.C. QSAR modeling for quinoxaline
derivatives using genetic algorithm and simulated annealing based
feature selection. Curr. Med. Chem., 2009, 16, 4032-4048.
Kadam, H.K.; Khan, S.; Kunkalkar, R.A.; Tilve, S.G. Graphite
catalyzed green synthesis of quinoxalines. Tetrahedron Lett., 2013,
54, 1003-1007.
Hou, J.-T.; Liu, Y.-H.; Zhang, Z.-H. NbCl5 as an efficient catalyst
for rapid synthesis of quinoxaline derivatives. J. Heterocycl.
Chem., 2010, 47, 703-706.
Bardajee, G.R.; Malakooti, R.; Jami, F.; Parsaei, Z.; Atashin, H.
Covalent anchoring of copper-Schiff base complex into SBA-15 as
a heterogeneous catalyst for the synthesis of pyridopyrazine and
quinoxaline derivatives. Catal. Commun. 2012, 27, 49-53.
Karami, B.; Khodabakhshi, S. A facile synthesis of phenazine and
quinoxaline derivatives using magnesium sulfate heptahydrate as a
catalyst. J. Serb. Chem. Soc., 2011, 76, 1191-1198.
ACKNOWLEDGEMENTS
We gratefully acknowledge the funding support from the
Kleberg Foundation of Texas (Award# 5KLEBERG and
5KLEBERG1) and the University of Texas-Pan American.
SUPPLEMENTARY MATERIAL
[23]
[24]
Supplementary material is available on the publisher’s
web site along with the published article.
REFERENCES
[25]
[26]
[27]
[28]
[1]
[2]
Anastas, P.T.; Warner, J.C. Green Chemistry, Theory and Practice,
Oxford University Press, Oxford, UK, 1998.
Polshettiwar, V.; Varma, R.S. Aqueous microwave chemistry: A
clean and green synthetic tool for rapid drug discovery. Chem. Soc.
Rev., 2008, 37, 1546-1557.
[3]
[4]
[5]
Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chem. Rev.,
2000, 100, 1025-1074.
Ogawa, C.; Kobayashi, S. Chiral Lewis acid catalysis in water.
Curr. Org. Synth., 2011, 8, 345-355.
Liu, L.; Wang, D. "On water” for green chemistry. In: Handbook of
Green Chemistry, P.T. Anastas, Ed.; Wiley: New York, 2010; Vol.
5, pp. 207-228.
[29]
[30]
[31]
[32]
[6]
Fraile, J.M.; Herrerias, C.I.; Mayoral, J.A. Green bases in water. In:
Handbook of Green Chemistry, P.T. Anastas, Ed.; Wiley, New
York, 2010, Vol. 5, pp 57-73.
Kumaravel, K.; Vasuki, G. Multicomponent reactions in water.
Curr. Org. Chem., 2009, 13, 1820-1841.
Huang, T.-Q.; Qu, W.-Y.; Ding, J.-C.; Liu, M.-C.; Wu, H.-Y.;
Chen, J.-X. Catalyst-free protocol for the synthesis of quinoxalines
and pyrazines in PEG. J. Heterocycl. Chem., 2013, 50, 293-297.
Jafari, F.; Khodabakhshi, S. MnSO4·H2O: A highly efficient and
inexpensive catalyst for the synthesis of benzo-2-pyrones and
benzopyrazines. Bulgarian Chem. Commun., 2014, 46, 36-42.
Khodabakhshi, S.; Karami, B. Rapid and eco-friendly synthesis of
novel and known benzopyrazines using silica tungstic acid (STA)
as a new and recyclable catalyst. Catal Sci. Technol., 2012, 2,
1940-1944.
[7]
[8]
Klijn, J.E.; Engberts, J.B.F.N. Pericyclic reactions in water.
Towards green chemistry. In: Handbook of Green Chemistry, P.T.
Anastas, Ed.; Wiley: New York, 2010, Vol 5, pp. 229-271.
Bandyopadhyay, D.; Mukherjee, S.; Granados, J.C.; Short, J.D.;
Banik, B.K. Ultrasound-assisted bismuth nitrate-induced green
synthesis of novel pyrrole derivatives and their biological
evaluation as anticancer agents. Eur. J. Med. Chem., 2012, 50, 209-
215.
[9]
[33]
[34]
[35]
Bandyopadhyay, D.; Cruz, J.; Yadav, R.M.; Banik, B.K. An
expeditious iodine-catalyzed synthesis of 3-pyrrole-substituted 2-
azetidinones. Molecules, 2012, 17, 11570-11584.
[10]
[11]
[12]
[13]
Bandyopadhyay, D.; Rhodes, E.; Banik, B.K.
A
green,
chemoselective, and practical approach toward N-(2-azetidinonyl)
2,5-disubstituted pyrroles. RSC Adv., 2013, 3, 16756–16764.
Canales, L.; Bandyopadhyay, D.; Banik, B.K. Bismuth nitrate
pentahydrate-induced novel nitration of Eugenol. Org. Med. Chem.
Lett., 2011, 1, 9.
Bandyopadhyay, D.; Maldonado, S.; Banik, B.K. A microwave-
assisted bismuth nitrate-catalyzed unique route toward 1,4-
dihydropyridines. Molecules, 2012, 17, 2643-2662.
Bandyopadhyay,
D.;
Banik,
B.K.
Microwave-induced
Bandyopadhyay, D.; Banik, B.K. Bismuth nitrate-induced
microwave-assisted expeditious synthesis of vanillin from
curcumin. Org. Med. Chem. Lett., 2012, 2, 15.
Bandyopadhyay, D.; Mukherjee, S.; Banik, B.K. An expeditious
synthesis of N-substituted pyrroles via microwave-induced iodine-
catalyzed reaction under solventless conditions. Molecules, 2010,
15, 2520-2525.
Rivera, S.; Bandyopadhyay, D.; Banik, B.K. Facile synthesis of N-
substituted pyrroles via microwave-induced bismuth nitrate-catalyzed
reaction under solventless conditions. Tetrahedron Lett., 2009, 50,
5445-5448.
stereoselectivity of β-lactam formation with dihydrophenanthrenyl
imines via Staudinger cycloaddition. Helv. Chim. Acta, 2010, 93,
298-301.
[36]
[37]
[38]
Bandyopadhyay, D.; Rivera, G.; Salinas, I.; Aguilar, H.; Banik,
B.K. Iodine-catalyzed remarkable synthesis of novel N-
polyaromatic β-lactams bearing pyrroles. Molecules, 2010, 15,
1082-1088.
[14]
Bandyopadhyay, D.; Banik, A.; Bhatta, S.; Banik, B.K.
Microwave-assisted ruthenium trichloride catalyzed synthesis of
pyrroles fused with indole systems. Heterocycl. Commun., 2009, 15,
121-122.
Bandyopadhyay, D.; Mukherjee, S.; Rodriguez, R.R.; Banik, B.K.
An effective microwave-induced iodine-catalyzed method for the
synthesis of quinoxalines via condensation of 1,2-dicarbonyl
compounds. Molecules, 2010, 15, 4207-4212.
Frost, C.G.; Hartley, J.P. New applications of indium catalysts in
organic synthesis. Mini-Rev. Org. Chem., 2004, 1, 1-7.
Schneider, U.; Kobayashi, S. Low-oxidation state indium-catalyzed
C-C bond formation. Acc. Chem. Res., 2013, 45, 1331-1344.
Frimpong, K.; Wzorek, J.; Lawlor, C.; Spencer, K.; Mitzel, T. Use
of N-methylformamide as a solvent in indium-promoted Barbier
reactions en route to enediyne and epoxy diyne formation:
comparison of rate and stereoselectivity in C-C bond-forming
reactions with water. J. Org. Chem., 2009, 74, 5861-5870.
Chakraborty, S.; Brennessel, W.W.; Jones, W.D. A molecular iron
catalyst for the acceptorless dehydrogenation and hydrogenation of
N-heterocycles. J. Am. Chem. Soc., 2014, 136, 8564-8567.
[15]
[16]
Bandyopadhyay, D.; Cruz, J.; Banik, B.K. Novel synthesis of 3-
pyrrole substituted β-lactams via microwave-induced bismuth
nitrate-catalyzed reaction. Tetrahedron, 2012, 68, 10686-10695.
Iglesias, L.; Aguilar, C.; Bandyopadhyay, D.; Banik, B.K. A new
bismuth nitrate-catalyzed electrophilic substitution of indoles with
carbonyl compounds under solventless conditions. Synth.
Commun., 2010, 40, 3678-3682.
[39]
[40]
[41]
[17]
[18]
[19]
[20]
Bandyopadhyay, D.; Mukherjee, S.; Turrubiartes, L.C.; Banik,
B.K.; Ultrasound-assisted aza-Michael reaction in water: A green
procedure. Ultrason. Sonochem., 2012, 19, 969-973.
Kall, A.; Bandyopadhyay, D.; Banik, B.K. Microwave-induced
aza-Michael reaction in water: A remarkable simple procedure.
Synth. Commun., 2010, 42, 1730-1735.
Abrego, D.; Bandyopadhyay, D.; Banik, B.K. Microwave-induced
indium-catalyzed synthesis of pyrrole fused with indolinone in
water. Heterocycl. Lett., 2011, 1 (Spl. Issue), 94-95.
[42]
Bandyopadhyay, D.; Velazquez, J.M.; Banik, B.K. A truly green
synthesis of α-aminonitriles via Strecker reaction. Org. Med. Chem.
Lett., 2011, 1, 11.

62 Combinatorial Chemistry & High Throughput Screening, 2015, Vol. 18, No. 1
Bandyopadhyay et al.
[43]
[44]
[45]
Kranjc, K.; Kočevar, M. Microwave-assisted organic synthesis:
General considerations and transformations of heterocyclic
compounds. Curr. Org. Chem., 2010, 14, 1050-1074.
(average distance 3.36 Ǻ). All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were located in a difference
Fourier map and were refined with Uiso(H) = 1.2Ueq (C). The title
compound was dissolved in carbon tetrachloride/ methylene
chloride solution and heated for ten minutes. After four days,
suitable yellow crystals formed through slow evaporation of
solvent. (Crystal system: monoclinic). An X-ray quality yellow
platelet-shaped crystal of dimensions 0.30 x 0.20 x 0.0.1 mm was
selected for structural analysis. The ORTEP projection is shown in
Fig. (1). Crystallographic data for the compound have been
deposited as DBQ-19 with Cambridge Crystallographic Data
Centre as CCDC 812742. Copies of the data can be obtained, free
of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 IEZ, UK (fax: +44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
Blackwell, H.E. Out of the oil bath and into the oven—Microwave-
assisted combinatorial chemistry heats up. Org. Biomol. Chem.,
2003, 1, 1251-1255.
Lian, M.; Li, Q.; Zhu, Y.; Yin, G.; Wu, A. Logic design and
synthesis
of
quinoxalines
via
the
integration
of
iodination/oxidation/cyclization sequences from ketones and 1,2-
diamines. Tetrahedron, 2012, 68, 9598-9605.
[46]
X-ray crystallographic data of the representative bis-benzopyrazine
derivative (Entry 3, Table 3) were recorded with an automatic
single crystal X-ray diffractometer consists of a 3kw X-ray
generator, Saturn 724 CCD detector, AFC12K goniometer, and X-
stream 2000 (for nitrogen generation). The compound crystallizes
in the P21/c space group with half a molecule in the asymmetric
unit, situated about an inversion center (½, ½, 0). Packing of these
molecules is dominated by π―π interactions between molecules
[47]
Klijn, J.E.; Engberts, J.B.F.N. Organic chemistry: Fast reactions
‘on water’. Nature, 2005, 435, 746-747.
Received: May 30, 2014
Revised: October 27, 2014
Accepted: January 26, 2015