A Catalyst-Free Expeditious Green Synthesis of Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives in Water under Ultrasound Irradiation

Full text of DOI:10.1080/00304948.2019.1596469

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
A Catalyst-Free Expeditious Green Synthesis
of Quinoxaline, Oxazine, Thiazine, and Dioxin
Derivatives in Water under Ultrasound Irradiation
Ankush Mishra, S. Singh, M. A. Quraishi & Vandana Srivastava
To cite this article: Ankush Mishra, S. Singh, M. A. Quraishi & Vandana Srivastava (2019):
A Catalyst-Free Expeditious Green Synthesis of Quinoxaline, Oxazine, Thiazine, and Dioxin
Derivatives in Water under Ultrasound Irradiation, Organic Preparations and Procedures
International, DOI: 10.1080/00304948.2019.1596469
To link to this article: https://doi.org/10.1080/00304948.2019.1596469
Published online: 09 Apr 2019.
Submit your article to this journal
Article views: 3
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=uopp20

Organic Preparations and Procedures International, 0:1–12, 2019
2019 Taylor & Francis Group, LLC
#
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2019.1596469
A Catalyst-Free Expeditious Green Synthesis
of Quinoxaline, Oxazine, Thiazine, and Dioxin
Derivatives in Water under Ultrasound Irradiation
Ankush Mishra, S. Singh, M. A. Quraishi, and Vandana Srivastava
Department of Chemistry, Indian Institute of Technology (BHU),
Varanasi- 221005, India
Quinoxaline, 1,4-oxazine, 1,4-thiazine and 1,4-dioxin derivatives are important hetero-
cycles gaining considerable attention due to their pharmacological importance and bio-
1
–9
logical activities. These derivatives are also basic scaffolds for the synthesis of solar
1
0
11
12
13
14
cells, dyes, pigments, organic semiconductors and chemical switches. There
are many drugs possessing these core structural units (Figure 1). Due to their wide
range of biological activities many synthetic strategies have been reported in the litera-
ture. Conventionally, quinoxaline derivatives were synthesized by using different cata-
1
5,16
17,18
19
22
lysts such as acetic acid,
montmorillonite K-10, polyaniline sulfate, nitrilotris(methylenephosphonic acid),
aqueous HF, sulfamic acid,
such as cerium(IV) ammonium nitrate (CAN), gallium(III) triflate, silica-supported
antimony(III) chloride, zirconium(IV) chloride, SnCl /SiO , ZnO, FeCl3,
Keplerate {Mo132} nanoballs and sulfated polyborate. A few methods for synthesis
molecular iodine,
o-iodoxybenzoic acid,
2
0
21
2
3
24,25
26
27
NH Cl-CH OH, Amberlyst-15 and metal catalysts
4 3
28
29
3
0
31
32
33
34
2
2
3
5
36
37–40
of quinoxalines have also been reported by microwave irradiation,
ultrasound
There are only a few reports on the
synthesis of indenoxazines and indenothiazines from the reaction of ninhydrin with o-
4
1,42
43–45
irradiation
and use of ball mill techniques.
4
6–48
aminophenol and o-aminothiophenol respectively;
and the reaction of ninhydrin
with catechol and 3-hydroxy-2-aminopyridine leading to the formation of 4b,10a-dihy-
droxy-4bH-benzo[b]indeno[1,2-e][1,4]dioxin-11(10aH)-one and 5a-hydroxyindeno[2,1-
b]pyrido[2,3-e][1,4]oxazin-6(5aH)-one has not been reported up to now. A number of
these reported methods for synthesis of the title heterocycles have drawbacks including
harsh reaction conditions, long reaction times, expensive catalysts, toxic solvents or
tedious workup. The development of facile and energy-efficient greener methods for
synthesis of these heterocyclic compounds is necessary.
The use of appropriate solvents in organic synthesis is also very important from the
green chemistry point of view. In this regard the use of water as solvent has attracted
a great deal of interest in recent years. Indeed, water offers many advantages because it
is cheap, readily available, nontoxic, nonflammable and can be more selective than
4
9,50
organic solvents.
Catalyst-free syntheses are in full agreement with the idea of
Received June 18, 2018; in final form January 10, 2019.
Address correspondence to Vandana Srivastava, Department of Chemistry, Indian Institute of
Technology (BHU), Varanasi- 221005, India. E-mail: vsrivastava.itbhu@gmail.com
1

2
Srivastava et al.
Figure 1. Structures of some pharmacologically active compounds containing quinoxaline, oxa-
zine, thiazine, or dioxin core moieties.
green chemistry because they reduce pollutant production, use of hazardous chemicals,
and cost.
In this context, ultrasound assisted reactions have gained much attention because
they offer milder reaction conditions, higher reaction rates, excellent yields and low
energy consumption. Many organic transformations have been successfully achieved
with the help of ultrasound irradiation. Therefore, ultrasound assisted organic synthesis,
51–54
as a green synthetic approach, is considered to be a powerful technique.
The fascinating nature of water as solvent and the beneficial effects of ultrasound
have prompted us to undertake the synthesis of quinoxaline, oxazine, thiazine and
dioxin derivatives. The catalyst-free reaction of ninhydrin and isatin derivatives with
1
,2-difunctionalized benzene/pyridine is here reported for the first time in water under
ultrasound irradiation.
In order to optimize conditions, the reaction of ninhydrin and o-phenylenediamine
was chosen as a model for the synthesis of quinoxaline derivatives (Scheme 1). The
reaction was carried out in various solvents under conventional and ultrasound irradi-
ation methods. The reaction was performed at room temperature with 1.0 mmol of nin-
hydrin and 1.0 mmol o-phenylenediamine in 5.0 mL of solvent without any catalyst.
The progress of the reaction was monitored by tlc (Table 1). It was observed that with
ultrasound irradiation the reaction was completed in shorter time in excellent yield.
Among the solvents tested, water was found to be the best, which gave 98% yield in
5
0 seconds (Table 1, entry 4). Pure products were separated as solids and collected by
filtration. There was no requirement for further purification.
The rate of reaction was faster with ultrasound. This is attributed to the cavitation
phenomena occurring during sonication. Cavitation results in formation and adiabatic
collapse of micro bubbles, giving the generation of local hotspots. These hotspots gen-
erate high temperature and pressures of several thousand atmospheres which cause the
5
3
reaction to occur rapidly.
To examine the effect of ultrasound energy on reaction time and yield, the model
reaction was carried out at different energies from 500 to 11000 J, and the results are
shown in Table 2.

Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives
3
Scheme 1. Reaction of ninhydrin with o-phenylenediamine.
Table 1
Effect of Solvents on the Yield of the Product 3a
under Conventional and Ultrasound Irradiation Methods
a
b
Conventional
Ultrasonication
c
c
Entry
Solvent
Ethanol
Methanol
Isopropanol
Water
Acetonitrile
Acetic acid
THF
Dioxane
Benzene
Toluene
Time (min)
Yield (%)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
15
30
35
10
60
80
75
72
85
60
78
–
10
12
15
50 sec
40
10
NR
NR
NR
NR
84
77
75
98
72
80
–
30
NR
NR
NR
NR
–
–
–
–
1
0
–
–
Reaction conditions:
a
Mixture of 1a (1.0 mmol) and 2a (1.0 mmol) in 5.0 mL of solvent was stirred at room tem-
ꢀ
perature (30 C).
b
Mixture of 1a (1.0 mmol) and 2a (1.0 mmol) in 5.0 mL of solvent was irradiated at 750 W,
ꢀ
2
000 J, 20% amplitude, 30 C.
c
Pure isolated yield.
Table 2
Effect of Ultrasound Energy on the Yield of the Product 3a
a
b
Entry
US Energy (Joule)
Time (sec.)
Yield (%)
1
2
3
4
5
6
7
500
1000
1500
2000
5000
7500
11000
260
180
100
50
45
35
90
92
95
98
95
96
95
35
a
Reaction condition: mixture of ninhydrin 1a (1 mmol) and o-phenylenediamine 2a (1 mmol)
ꢀ
in 5 mL of water irradiated at 750 W, 20% amplitude, at room temperature (30 C).
b
Pure isolated yield.

4
Srivastava et al.
The maximum yield of the product was obtained at 2000 J ultrasound energy. An
increase in the ultrasound energy above 2000 J did not show any significant improve-
ment in terms of yield and reaction time. So, 2000 J ultrasound energy is considered as
the optimum energy condition. In order to examine the effect of ultrasound amplitude
on reaction rate we carried out this reaction at different ultrasound amplitudes from
2
0–50% at room temperature. The maximum yield (98%) of the product (3a) was
obtained at 20% amplitude. An increase in amplitude did not improve the yield of
the reaction.
To explore the applicability of the optimized reaction conditions, several deriva-
tives of the title heterocycles were synthesized by reacting 1,2-difuncionalized benzenes
and pyridines with ninhydrin and isatin derivatives. The chemical structures of the syn-
thesized compounds were established from their spectral data. The structures of the
reaction products along with their time of reaction, m.p. and yields are summarized in
Table 3.
The results shown in Table 3 reveal that the substituents on the ring do not affect
the yield and reaction times. The reaction of ninhydrin with o-substituted amines were
completed within a minute in excellent yields (>90%) while isatin derivatives required
longer time. The lower reactivity of the isatin derivatives is attributed to the presence of
the amidic carbonyl groups in these compounds. It is worth noting that the ultrasound
irradiation facilitates nucleophilic addition-elimination reactions leading to the forma-
tion of fused quinoxaline, oxazine, thiazine, and dioxin derivatives.
In summary, we have developed an ultrasound-induced green methodology for the
synthesis of quinoxaline, 1,4-oxazine, 1,4-thiazine and 1,4-dioxin derivatives in water at
room temperature without using any catalyst. Pure products were separated as solids
after completion of the reaction and collected by filtration. Advantages include mild
reaction conditions, easy workup, isolation of products without the use of column chro-
matography, high yields, shorter reaction times, a green solvent, and absence
of catalysts.
Experimental Section
All the reactions were performed at room temperature. All reagents were purchased
from Sigma-Aldrich and used without further purification. Melting points were deter-
mined in open capillary melting point apparatus and are uncorrected. Ultrasonic irradi-
ation was performed using Sonics Vibra Cell Ultrasonic Processor Model VCX750
(Sonics & Materials, Inc.) with a fixed power of 750 W and amplitude variation from
2
0–80%, and a tapered micro tip was used as ultrasonic probe operating at a frequency
of 20 kHz. All reactions were performed at room temperature. The reactions were moni-
tored through analytical thin layer chromatography (TLC) precoated E. Merck 60
GF254 silica gel plates and spots were visualized using UV light or iodine vapor.
Infrared spectra were recorded on Perkin–Elmer Spectrum 100 FT–IR spectrophotom-
1
eter. Elemental analysis was done by Eurovector EA3000 elemental analyzer. H and
13
C NMR spectra were recorded on Bruker Avance 500 MHz spectrometer in CDCl3
and DMSO–d as solvents and tetramethylsilane (TMS) as an internal standard at 298
6
K; chemical shifts are given in d ppm. Routine coupling constant values for common
groups were in the range of 4-8 Hz (1-2 Hz for dd); these were not separately reported.
1
13
The H NMR and C NMR spectra of the products were compared with reported data
in the literature.

Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives
5
Table 3
Reaction of 1, 2-diketones with 1, 2-difunctionalized Benzene/Pyridine
a
in Water under Ultrasound Irradiation
Entry Diketone (1)
1, 2-
difunctionalized
benzene/
Product (3)
Time
(sec)
Yield
(%)
Mp
( C)
b
ꢀ
pyridine (2)
1
50
35
98
99
217–18
175–76
2
3
55
96
235–36
4
5
6
7
8
60
55
55
55
50
92
95
86
92
95
255
225–26
233–34
>300
252–53
(Continued)

6
Srivastava et al.
Table 3
(
Continued)
9
230
92
295–96
1
1
1
0
1
2
200
250
225
95
90
87
257–58
275–77
247–48
1
1
1
1
3
4
5
6
220
230
210
220
88
91
90
92
218–19
170–71
185–86
275–76
a
Reaction condition: mixture of 1,2-diketone (1.0 mmol) and 1,2-difunctionalized benzene/
pyridine (1.0 mmol) in 5 mL of water was irradiated at 750 W, 2000 J energy, 20% ultrasound
amplitude at room temperature.
b
Isolated yield.
General procedure for synthesis of products (3a–p). Equimolar amounts of 1,2-dike-
tone (1.0 mmol) and corresponding 1,2-difunctionalized benzene/pyridine were mixed in
5.0 ml of water. The reaction mixture was irradiated under ultrasonication at 750 W power,

Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives
7
2000 J, 20% amplitude at room temparature for the desired time. The progress of the reaction
was monitored using thin layer chromatography (ethyl acetate: n-hexane, 1:4). After comple-
tion of the reaction, solid products were separated by filtration, washed with distilled water
and recrystallized if necessary with appropriate solvents ethanol/toluene to obtain pure prod-
ucts (3a-p).
ꢀ
1
(
1
1H-Indeno[1,2-b]quinoxalin-11-one (3a). Yellow solid; yield 98%; m.p. 217–18 C
ꢀ
46
ꢁ1
lit. m.p. 220–21 C) ; IR (KBr) ꢀ (cm ): 3036, 2358, 1790, 1728, 1607, 1565, 1509,
462, 1336, 1247, 1190, 1118, 1040, 1001, 939, 867, 825, 775, 740; H NMR
1
(
500 MHz, DMSO-d ) d ppm: 8.21–8.01 (m, 3 H), 7.92–7.82 (m, 4 H), 7.71 (t, 1 H);
6
1
3
C NMR (126 MHz, DMSO-d ) d ppm: 189.29, 156.44, 149.81, 142.12, 141.82,
6
1
40.94, 136.93, 136.62, 132.76, 132.43, 130.95, 130.35, 129.35, 124.21, 122.27.
7
1
1
-Methyl-11H-indeno[1,2-b]quinoxalin-11-one (3b). Yellow solid; yield 99%; m.p.
ꢀ
ꢀ
55,56
ꢁ1
75–76 C (lit m.p. 176 C)
506, 1462, 1332, 1244, 1188, 1150, 1113, 1041, 1001, 965, 903, 834, 766, 731; H NMR
; IR (KBr) ꢀ (cm ): 3040, 2910, 1974, 1726, 1609, 1564,
1
13
(500 MHz, (CDCl ) d ppm: 8.12–7.90 (m, 4 H), 7.77–7.57 (m, 3 H), 2.53 (d, 3 H);
C
3
NMR (126 MHz, CDCl ) d ppm: 190.24, 156.97, 143.86, 143.37, 141.73, 141.26, 136.88,
3
1
36.80, 134.81, 132.62, 132.50, 131.26, 130.75, 129.29, 129.01, 124.83, 122.54, 22.19.
7
2
1
-Chloro-11H-indeno[1,2-b]quinoxalin-11-one (3c). Yellow solid; yield 96%; m.p.
ꢀ
ꢀ
55
ꢁ1
45–46 C (lit m.p. 233 C) ; IR (KBr) ꢀ (cm ): 3069, 2958, 2916, 2852, 2322, 1721,
1
609, 1555, 1496, 1329, 1256, 1182, 1017, 946, 877, 792; H NMR (500 MHz, CDCl ) d
3
1
3
ppm: 8.05 (t, 4 H), 7.84–7.48 (m, 3H); C NMR (126 MHz, CDCl ) d ppm: 189.53,
3
1
57.53, 149.46, 143.62, 141.24, 137.06, 133.04, 132.65, 131.29, 128.92, 124.98, 122.90.
1
9
1
7
1
0a-Hydroxybenzo[b]indeno[1,2-e][1,4]oxazin-11(10aH)-one (3d). White solid; yield
2%; m.p. 255–56 C (lit m.p. 255 C) ; IR (KBr) ꢀ (cm ): 3735, 2924, 2644, 2484,
ꢀ
ꢀ
46
ꢁ1
738, 1641, 1586, 1460, 1414, 1347, 1291, 1201, 1147, 1112, 1062, 966, 919, 855, 755,
1
12; H NMR (500 MHz, DMSO-d ) d ppm: 8.55 (s, 1 H, D O exchangeable), 8.18 (d,
6
2
13
H), 8.00 (dd, 2 H), 7.90–7.81 (m, 1 H), 7.61 (dd, 1 H), 7.37–7.13 (m, 3 H); C NMR
(
126 MHz, DMSO-d ) d ppm: 192.22, 157.98, 144.79, 141.64, 137.55, 135.93, 134.01,
6
1
33.90, 128.94, 127.57, 124.83, 123.70, 123.38, 118.04, 85.90.
1
9
1
7
1
0a-Hydroxybenzo[e]indeno[2,1-b][1,4]thiazin-11(10aH)-one (3e). Green solid; yield
5%; m.p. 225–26 C (lit m.p. 228 C) ; IR (KBr) ꢀ (cm ): 3738, 2949, 2701, 1728,
ꢀ
ꢀ
46
ꢁ1
635, 1636, 1585, 1458, 1398, 1340, 1251, 1165, 1114, 1074, 1005, 953, 854, 820,762,
1
09; H NMR (500 MHz, DMSO-d ) d ppm: 8.22 (d, 1 H), 8.08–7.97 (m, 2 H), 7.87 (t,
6
H), 7.80 (s, 1 H, D O exchangeable), 7.68 (dd, 1 H), 7.57 (dd, 1 H), 7.41 (m, 1 H), 7.30
2
13
(m, 1 H); C NMR (126 MHz, DMSO-d ) d ppm: 195.42, 155.79, 142.95, 142.23, 137.94,
6
1
34.99, 134.22, 129.42, 128.31, 127.31, 127.23, 124.86, 124.01, 120.86, 70.94.
4
b,10a-Dihydroxy-4bH-benzo[b]indeno[1,2-e][1,4]dioxin-11(10aH)-one (3f). White
ꢀ
ꢁ1
solid; yield 86%; m.p. 233–34 C; IR (KBr) ꢀ (cm ): 3742, 3615, 3380, 3312, 3187,
2
1
356, 1706, 1597, 1496, 1400, 1275, 1217, 1149, 1084, 941, 874, 762,722; H NMR

8
Srivastava et al.
(
500 MHz, DMSO-d ) d ppm: 9.45 (s, 1 H, D O exchangeable), 8.03–7.84 (m, 4 H),
6
2
7
.76–7.57 (m, 2 H), 6.94–6.79 (m, 1 H), 6.77–6.65 (m, 2 H), 6.58 (s, 1 H, D O exchange-
2
13
able); C NMR (126 MHz, DMSO-d ) d ppm: 199.38, 149.23, 144.54, 141.73, 136.58,
6
1
33.90, 130.90, 126.55, 125.20, 122.79, 121.55, 117.52, 115.43, 110.16, 82.97.
Anal. Calcd for C H O : C, 66.67; H, 3.73. Found: C, 66.59; H, 3.64.
1
5 10 5
6
3
1
1
H-Indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one (3g). Yellow solid; yield 92%; m.p. >
ꢀ
ꢀ
56
ꢁ1
00 C (lit m.p. 310–11 C) ; IR (KBr) ꢀ (cm ): 2912, 2350, 1914, 1714, 1555, 1490, 1375,
1
331, 1233, 1152, 1094, 1027, 934, 873, 781; H NMR (500 MHz, CDCl ) d ppm: 9.16 (d,
3
13
H), 8.60 (d, 1 H), 8.25 (d, 1 H), 7.96 (d, 1 H), 7.88–7.60 (m, 3 H); C NMR (126MHz,
CDCl ) d ppm: 188.86, 155.70, 140.35, 137.45, 133.56, 125.58, 125.08, 123.79.
3
5
9
1
8
a-Hydroxyindeno[2,1-b]pyrido[2,3-e][1,4]oxazin-6(5aH)-one (3h). White solid; yield
ꢀ
ꢁ1
5%; m.p. 252–53 C; IR (KBr) ꢀ (cm ): 3027, 2647, 1723, 1643, 1596, 1537, 1460, 1411,
1
334, 1245, 1195, 1145, 1084, 1036, 950, 868, 737; H NMR (DMSO-d ) d ppm:
6
1
3
.18–7.35 (m, 4 H), 6.88 (d, 2 H), 6.37 (d, 1 H), 5.41 (s, 1 H, D O exchangeable); C NMR
2
(
DMSO-d ) d ppm: 112.37, 114.02, 118.52, 119.08, 123.43, 123.88, 136.09, 137.21,
6
1
39.26, 145.98, 150.46, 197.05.
Anal. Calcd for C H N O : C, 66.67; H, 3.20; N, 11.11. Found: C, 66.48; H, 3.25;
1
4 8 2 3
N, 11.23.
ꢀ
H-Indolo[2,3-b]quinoxaline (3i). Yellow solid; yield 92%; m.p. 295–96 C (lit m.p.
6
2
1
57
ꢁ1
94–95) ; IR (KBr) ꢀ (cm ): 3071, 3007, 2831, 2779, 2682, 1945, 1710, 1608, 1461,
1
406, 1333, 1245, 1206, 1132, 1010, 924, 829, 748; H NMR (500 MHz, DMSO-d ) d
6
ppm: 12.04 (s, 1 H), 8.35 (d, 1 H), 8.24 (d, 1 H), 8.07 (d, 1 H), 7.80 (t, 1 H), 7.71 (dd,
1
3
2
1
1
H), 7.59 (d, 1 H), 7.37 (t, 1 H); C NMR (126 MHz, DMSO-d ) d ppm: 145.88,
6
44.04, 140.17, 139.82, 138.61, 131.38, 129.11, 129.01, 128.81, 127.55, 127.46,
26.03, 122.33, 122.24, 120.81, 120.75, 118.99, 112.04.
ꢀ
3
-Methyl-6H-indolo[2,3-b]quinoxaline (3j). Yellow solid; yield 95%; m.p. 257–58 C;
ꢁ
1
IR (KBr) ꢀ (cm ): 3065, 2916, 2850, 2353, 1895, 1737, 1595, 1459, 1399, 1331, 1242,
195, 1129, 1021, 816, 738; H NMR (CDCl ) d ppm: 9.56 (s, 1 H), 8.38 (t, 2 H),
3
.19–7.78 (m, 2 H), 7.67–7.25 (m, 4 H), 2.57 (d, 3 H); C NMR (CDCl ) d ppm: 165.44,
36.67, 131.43, 131.16, 131.00, 129.88, 129.12, 128.84, 128.54, 126.97, 126.48, 122.90,
22.75, 121.46, 121.40, 111.64, 21.77.
1
1
8
1
1
13
3
Anal. Calcd for C H N C, 77.23; H, 4.75; N, 18.01. Found: C, 77.13; H, 4.69;
1
5 11 3:
N, 17.89.
ꢀ
-Chloro-6H-indolo[2,3-b]quinoxaline (3k). Yellow solid; yield 90%; m.p. 275–77 C
3
(
1
ꢀ
58
ꢁ1
lit m.p. >275 C) IR (KBr) ꢀ (cm ): 3052, 2918, 2851, 2766, 1937, 1740, 1580, 1482,
1
452, 1401, 1331, 1234, 1182, 1107, 1068, 1021, 939, 824, 783, 737; H NMR (DMSO-
d ) d ppm: 12.17 (s, 1 H), 8.35 (d, 1 H), 8.27 (d, 1 H), 8.12 (d, 1 H), 7.79–7.70 (m, 2 H),
6
1
3
7
1
.60 (d, 1 H), 7.39 (t, 1 H); C NMR (DMSO-d ) d ppm: 146.14, 144.15, 140.58, 137.10,
6
32.96, 131.67, 130.72, 126.37, 126.09, 122.36, 121.00, 118.79, 112.12.

Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives
9
ꢀ
6
(
1
-Ethyl-6H-indolo[2,3-b]quinoxaline (3l). White solid; yield 87%; m.p. 247–48 C
ꢀ
59
ꢁ1
lit m.p. 248–51 C) ; IR (KBr) ꢀ (cm ): 3054, 2923, 2856, 2217, 1896, 1727,
579, 1462, 1405, 1354, 1279, 1235, 1116, 1009, 932, 860, 808, 740; H NMR
1
(
3
500 MHz, CDCl ) d ppm: 8.49 (d, 1 H), 8.30 (d, 1 H), 8.14 (d, 1 H), 7.72 (m,
H), 7.49 (d, 1 H), 7.38 (t, 1 H), 4.57 (q, 2 H), 1.53 (t, 3 H); C NMR (126 MHz,
3
13
CDCl ) d ppm: 145.42, 144.22, 140.73, 140.33, 139.36, 131.11, 129.47, 128.88,
3
1
27.86, 126.04, 122.98, 120.94, 119.68, 109.48, 36.33, 13.79.
ꢀ
-Propyl-6H-indolo[2,3-b]quinoxaline (3m). Yellow solid; yield 88%; m.p. 218–19 C
6
(
ꢀ
60
ꢁ1
lit m.p. 218 C) ; IR (KBr) ꢀ (cm ): 3056, 2922, 2856, 2359, 1729, 1579, 1461, 1405,
1
1
8
4
1
1
363, 1276, 1203, 1116, 1071, 983, 942, 893, 743; H NMR (500 MHz, CDCl ) d ppm:
3
.49 (d, 1 H), 8.30 (d, 1 H), 8.14 (d, 1 H), 7.80–7.63 (m, 3 H), 7.48 (d, 1 H), 7.38 (t, 1 H),
1
3
.46 (t, 2 H), 2.00 (dd, 2 H), 1.03 (t, 3 H); C NMR (126 MHz, CDCl ) d ppm: 145.87,
3
44.68, 140.79, 140.18, 139.36, 131.05, 129.44, 128.83, 127.92, 126.02, 122.90, 120.89,
19.58, 109.67, 43.20, 21.96, 11.74.
ꢀ
6
(
1
1
-Benzyl-6H-indolo[2,3-b]quinoxaline (3n). Yellow solid; yield 91%; m.p. 170–71 C
ꢀ
60
ꢁ1
lit m.p. 176 C) ; IR (KBr) ꢀ (cm ): 2920, 2856, 1729, 1574, 1459, 1396, 1344, 1274,
1
186, 1117, 1069, 982, 940, 850, 813, 736; H NMR (500 MHz, CDCl ) d ppm: 8.49 (d,
3
13
H), 8.32 (d, 1 H), 8.14 (d, 1 H), 7.83–7.54 (m, 3 H), 7.48–7.19 (m, 7 H), 5.71 (s, 2 H);
C
NMR (126 MHz, CDCl ) d ppm: 145.94, 144.40, 140.79, 140.17, 139.65, 136.63, 131.14,
3
1
1
29.47, 128.96, 128.93, 128.01, 127.81, 127.32, 126.26, 122.84, 121.30, 119.79,
10.28, 45.13.
Ethyl 2-(6H-indolo[2,3-b]quinoxalin-6-yl)acetate (3o). White solid; yield 90%; m.p.
ꢀ
ꢀ
61
ꢁ1
1
1
85–86 C (lit m.p. 188 C) ; IR (KBr) ꢀ (cm ): 3054, 2976, 2359, 1950, 1732, 1587,
1
475, 1417, 1357, 1213, 1112, 1019, 925, 866, 771, 737; H NMR (500 MHz, CDCl )
3
d ppm: 8.49 (d, 1 H), 8.31 (d, 1 H), 8.11 (d, 1 H), 7.83–7.61 (m, 3 H), 7.49–7.30 (m,
1
3
2
(
H), 5.24 (s, 2 H), 4.24 (d, J ¼ 7.1 Hz, 2H), 1.25 (t, J ¼ 7.1 Hz, 3H); C NMR
126 MHz, CDCl ) d ppm: 168.21, 145.70, 144.38, 140.55, 140.31, 139.87, 131.27,
3
1
29.50, 129.05, 127.92, 126.48, 122.99, 121.74, 119.97, 109.42, 62.00, 42.81, 14.27.
Ethyl 2-(9-chloro-6H-indolo[2,3-b]quinoxalin-6-yl)acetate (3p). White solid; yield
ꢀ
ꢀ
60
ꢁ1
9
1
2%; m.p. 275–76 C (lit m.p. 248 C) ; IR (KBr) ꢀ (cm ): 2921, 2854, 2346, 2213,
1
733, 1577, 1460, 1362, 1275, 1209, 1120, 1019, 952, 871, 811, 739; H NMR
(
3
500 MHz, CDCl ) d ppm: 8.46 (s, 1 H), 8.29 (d, 1 H), 8.11 (d, 1 H), 7.83–7.60 (m,
H), 7.29 (d, 1 H), 5.22 (s, 2 H), 4.24 (q, 2 H), 1.26 (t, 3 H); C NMR (126 MHz,
3
13
CDCl ) d ppm: 167.95, 145.78, 142.55, 140.79, 140.05, 139.15, 131.10, 129.67,
3
1
29.53, 128.00, 127.45, 126.81, 122.75, 121.19, 110.57, 62.12, 42.85, 14.27.
Acknowledgments
V. S. gratefully acknowledges IIT (BHU) for a research support grant and the Central
Instrumental Facility for all the characterizations. A. M. acknowledges IIT (BHU) for
a research fellowship.

1
0
Srivastava et al.
References
1
2
3
4
. H. S. A. El-Zahabi, Archiv der Pharmazie, 350, 1700028 (2017).
. D. H. Soliman, Int. J. Org. Chem., 3, 65 (2013).
. S. Paliwal, S. Sharma, J. Dwivedi and A. Mishra, J. Heterocyclic Chem., 54, 3689 (2017).
. U. A. Mohsen, L. Yurttas, U. Acar, Y. Ozkay, Z. Kaplacikli, H. K. Gencer and Z. Canturk,
Drug Res., 65, 266 (2015).
5
6
7
8
9
. G. Cheng, W. Sa, C. Cao, L. Guo, H. Hao, Z. Liu, X. Wang and Z. Yuan, Front.
Pharmacol., 7, 64 (2016).
. W. Gu, S. Wang, X. Jin, Y. Zhang, D. Hua, T. Miao, X. Tao and S. Wang, Molecules, 22,
1
154 (2017).
. T. Sindhu, S. Arikkatt, G. Vincent, M. Chanran, A. Bhat and K. Krishnakumar, Int. J.
Pharma. Sci. Res., 4, 134 (2013).
. G. Vincent, B. Mathew, J. Joseph, M. Chandran, A. Bhat and K. K. Kumar, Int. J. Pharm.
Chem. Sci., 3, 341 (2014).
. A. R. Das, G. Pal, P. Bhattacharyya, A. K. Ghosh, D. Mukherjee and D. Bandyopadhyay,
Tetrahedron Lett., 53, 7060 (2012).
1
0. C. Shen, Y. Wu, W. Zhang, H. Jiang, H. Zhang, E. Li, B. Chen, X. Duan and W.-H. Zhu,
Dyes Pigm., 149, 65 (2018).
1
1. A. Katoh, T. Yoshida and J. Ohkanda, Heterocycles, 52, 911 (2000).
1
2. E. Dietz and M. Urban, Process for the Preparation of Pigment Preparations Based on CI
Pigment Violet 23, (June 7, 1994) U.S. Patent No. 5,318,627. Washington, DC.
1
3. S. Dailey, W. J. Feast, R. J. Peace, I. C. Sage, S. Till and E. L. Wood, J. Mater. Chem., 11,
2
238 (2001).
1
1
4. M. J. Crossley and L. A. Johnston, Chem. Comm., 2002, 1122 (2002).
5. D. J. Brown, J. A. Ellman and E. C. Taylor, The Chemistry of Heterocyclic
Compounds, Cinnolines and Phthalazines, Supplement II; Vol. 64, John Wiley & Sons,
2
005, passim.
1
1
1
6. M. R. Islami and Z. Hassani, Arkivoc, (xv), 280 (2008).
7. S. V. More, M. Sastry, C.-C. Wang and C.-F. Yao, Tetrahedron Lett., 46, 6345 (2005).
8. R. S. Bhosale, S. R. Sarda, S. S. Ardhapure, W. N. Jadhav, S. R. Bhusare and R. P. Pawar,
Tetrahedron Lett., 46, 7183 (2005).
1
9. M. M. Heravi, K. Bakhtiari, M. H. Tehrani, N. M. Javadi and H. A. Oskooie, Arkivoc, (xvi),
1
6 (2006).
2
2
0. T.-k. Huang, R. Wang, L. Shi and X.-X. Lu, Catal. Commun., 9, 1143 (2008).
1. C. Srinivas, C. N. S. S. P. Kumar, V. J. Rao and S. Palaniappan, J. Mol. Catal. A Chem.,
2
65, 227 (2007).
2
2. S. Fathi and A. R. Sardarian, Phosphorus, Sulfur, Silicon Relat. Elem., 190, 1471 (2015).
2
3. A. Chandra Shekhar, A. Ravi Kumar, G. Sathaiah, K. Raju, P. Srinivas, P. Shanthan Rao and
B. Narsaiah, J. Heterocyclic Chem., 51, 1504 (2014).

Quinoxaline, Oxazine, Thiazine, and Dioxin Derivatives
11
2
4. H. R. Darabi, S. Mohandessi, K. Aghapoor and F. Mohsenzadeh, Catal. Commun., 8, 389
2007).
(
2
5. P. G. Hegade, M. M. Mane, J. D. Patil and D. M. Pore, Synth. Commun., 44, 3384 (2014).
6. H. R. Darabi, F. Tahoori, K. Aghapoor, F. Taala and F. Mohsenzadeh, J. Braz. Chem. Soc.,
2
1
9, 1646 (2008).
2
2
2
3
7. J.-Y. Liu, J. Liu, J.-D. Wang, D.-Q. Jiao and H.-W. Liu, Synth. Commun., 40, 2047 (2010).
8. S. V. More, M. Sastry and C.-F. Yao, Green Chem., 8, 91 (2006).
9. J.-J. Cai, J.-P. Zou, X.-Q. Pan and W. Zhang, Tetrahedron Lett., 49, 7386 (2008).
0. H. R. Darabi, K. Aghapoor, F. Mohsenzadeh, F.Taala, N. Asadollahnejad and A. Badiei,
Catal. Lett., 133, 84 (2009).
3
3
1. K. Aghapoor, H. R. Darabi, F. Mohsenzadeh, Y. Balavar and H. Daneshyar, Transition Met.
Chem., 35, 49 (2010).
2. H. R. Darabi, K. Aghapoor, F. Mohsenzadeh, M. R. Jalali, S. Talebian, L. Ebadi-Nia, E.
Khatamifar and A. Aghaee, Bull. Korean Chem. Soc., 32, 213 (2011).
3
3
3. M. J. Hosseini-Sarvari, Iran. Chem. Soc., 9, 535 (2012).
4. G. R. Bardajee, F. Mizani, I. Rostami and A. Mohamadi, Polycycl Aromat Compd, 33, 419
(
2013).
3
5. A. Rezaeifard, M. Jafarpour, R. Haddad, H. Tavallaei and M. Hakimi, J. Cluster Sci., 26,
1
439 (2015).
3
3
3
3
6. K. S. Indalkar, C. K. Khatri and G. U. Chaturbhuj, J. Chem. Sci., 129, 141 (2017).
7. M. Kidwai, S. Saxena and R. Mohan, J. Korean Chem. Soc., 49, 288 (2005).
8. A. Dwivedi, A. Singh and A. Mishra, Chem. Sci. Trans., 3, 465 (2014).
9. D. Bandyopadhyay, J. Cruz, L. D. Morales, H. D. Arman, E. Cuate, Y. S. Lee, B. K. Banik
and D. J. Kim, Future Med. Chem., 5, 1137 (2013).
4
4
4
0. D. Bandyopadhyay, S. Mukherjee, R. R. Rodriguez and B. K. Banik, Molecules, 15, 4207
(
2010).
1. W.-X. Guo, H.-L. Jin, J.-X. Chen, F. Chen, J.-C. Ding and H.-Y. Wu, J. Braz. Chem. Soc.,
2
0, 1674 (2009).
2. K. Aghapoor, F. Mohsenzadeh, S. Talebian, M. J. Tehrani, Y. Balavar, G. Khanalizadeh and
H. R. Darabi, Monatsh. Chem., 142, 619 (2011).
4
4
3. G. Kaupp and M. R. Naimi-Jamal, Eur. J. Org. Chem., 2002, 1368 (2002).
4. Z. T. Bhutia, G. Prasannakumar, A. Das, M. Biswas, A. Chatterjee and M. Banerjee,
ChemistrySelect, 2, 1183 (2017).
4
4
4
4
5. H. Etman, H. Metwally, M. Elkasaby, A. Khalil and M. Metwally, American Journal of
Organic Chemistry, 1, 10 (2011).
6. A. Schonberg, E. Singer, G. A. Hoyer and D. Rosenberg, Eur. J. Inorg. Chem., 110, 3954
(
1977).
7. V. Simakov, S. Kurbatov, O. Y. Borbulevych, M. Y. Antipin and L. Olekhnovich, Russ.
Chem. Bull., 50, 1064 (2001).
8. G. Kaupp, M. R. Naimi-Jamal and J. Schmeyers, Chem. Eur. J., 8, 594 (2002).

1
2
Srivastava et al.
4
9. M. B. Gawande, V. D. Bonif ꢀa cio, R. Luque, P. S. Branco and R. S. Varma, Chem. Soc. Rev.,
2, 5522 (2013).
4
5
0. U. M. Lindstrom, Organic Reactions in Water: Principles, Strategies and Applications; John
Wiley & Sons, 2008, passim.
5
5
5
5
1. J. S. Ghomi and Z. Akbarzadeh, Ultrason. Sonochem., 40, 78 (2018).
2. V. B. Nishtala, J. B. Nanubolu and S. Basavoju, Res. Chem. Intermed., 43, 1365 (2017).
3. B. Banerjee, Ultrason. Sonochem., 35, 1 (2017).
4. D. Bandyopadhyay, S. Mukherjee, L. C. Turrubiartes and B. K. Banik, Ultrason Sonochem.,
1
9, 969 (2012).
5
5
5. H. Junek, H. Fischer-Colbrie and H. Sterk, Chemische. Berichte., 110, 2276 (1977).
6. C. Zhang, S. Li., L. Ji, S. Lui, Z. Li, S. Li and X. Meng, Bioorg. Med. Chem. Lett., 25, 4693
(
2015).
5
5
5
7. G. Y. Sarkis and H. T. Al-Badri, J. Heterocycl. Chem., 17, 813 (1980).
8. R. S. Varma and I. A. Khan, ChemInform, 10 (19), (1979).
9. N. S. H. N. Moorthy, C. Karthikeyan and P.Trivedi, J. Enzyme Inhib. Med. Chem., 25, 394
(
2010)
6
6
0. S. Bajpai, S. Singh and V. Srivastava, Arab. J. Chem., article in press, https://doi.org/10.
1
016/j.arabjc.2014.11.037
1. K. Manna and Y. K. Agrawal, Bioorg. Med. Chem. Lett. 19, 2688 (2009).