An efficient synthesis of quinoxaline derivatives mediated by stannous chloride

Article abstract of DOI:10.1002/jhet.5570450637

(Chemical Equation Presented) Various biologically important quinoxaline derivatives were efficiently synthesized in excellent yields by the reaction of 1,2-diketones and 2-nitroaniline, benzofuroxan or 1,2-dinitrobenzene promoted by SnCl₂·2H₂O. The role of stannous chloride is acting as both reductive agent and catalyst in this synthesis. This new method has the advantages of accessible starting materials, convenient manipulation, short reaction time and high yields.

Full text of DOI:10.1002/jhet.5570450637

Nov-Dec 2008
1797
An Efficient Synthesis of Quinoxaline Derivatives Mediated by
Stannous Chloride
Da-Qing Shi*,a,b Guo-Lan Doub Sai-Nan Nib Jing-Wen Shib Xiao-Yue Lib
a College of Chemistry and Chemical Engineering, Key Laboratory of Organic Synthesis of Jiangsu Province,
Suzhou University, Suzhou 215123, P. R. China
b Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, P. R. China
E-mail: dqshi@suda.edu.cn
Received November 29, 2007
NH2
X
X
NO2
O
N
O
N
R
R
SnCl2 2H2O
N
N
R
R
+
95% EtOH, reflux
O
X
O
X
NO2
NO2
Various biologically important quinoxaline derivatives were efficiently synthesized in excellent yields
by the reaction of 1,2-diketones and 2-nitroaniline, benzofuroxan or 1,2-dinitrobenzene promoted by
SnCl2·2H2O. The role of stannous chloride is acting as both reductive agent and catalyst in this synthesis.
This new method has the advantages of accessible starting materials, convenient manipulation, short
reaction time and high yields.
J. Heterocyclic Chem., 45, 1797 (2008).
metal precursors, expensive and inaccessible starting
materials, and harsh reaction conditions, which limit their use
under the aspect of environmentally benign processes.
The use of stannous chloride in organic synthesis has
been known for a long time. In recent years, stannous
chloride has received considerable attention as an
inexpensive, nontoxic, readily available catalyst for
various organic reactions [17] under mild and convenient
conditions to afford the corresponding products in
excellent yields with high selectivity. In this letter, we
report the synthesis of quinoxalines by the reaction of 2-
nitroanilines and 1,2-dicarbonyl compounds mediated by
SnClꢀ·2H2O (Scheme 1).
INTRODUCTION
Quinoxaline derivatives are an important class of nitrogen-
containing heterocycles and they constitute useful
intermediates in organic synthesis. Quinoxaline derivatives
are well known in the pharmaceutical industry and have been
shown to possess a broad spectrum of biological activities
such as antibacterial, anti-inflammatory, antiviral and
anticancer activity [1]. Besides this, it has been reported for
their application in dyes [2], efficient electroluminescent
materials [3], organic semiconductors [4], building blocks for
the synthesis of anion receptor [5], cavitands [6], dehydro-
annulenes [7], and DNA cleaving agents [8]. A number of
synthetic strategies have been developed for the preparation
of substituted quinoxalines. By far, the most common
method is the condensation of an aryl 1,2-diamine with a 1,2-
dicarbonyl compound in refluxing ethanol or acetic acid for
2-12 h giving 34-85% yields [9]. Recently, many improved
methods have been reported for the synthesis of quinoxalines
derivatives including the Bi-catalyzed oxidative coupling of
epoxides and ene-1,2-diamines [10], from ꢀ-hydroxy
ketones via a tandem oxidation process using Pd(OAc)2 [11]
and MnO2 [12] as catalyst, cyclization of ꢀ-arylimino oximes
of ꢀ-dicarbonyl compounds under reflux in acetic anhydride
[13], the condensation of o-phenylene diamines and 1,2-
dicarbonyl compounds in MeOH/AcOH under microwave
irradiation [14] or using molecular iodine as the catalyst [15]
and solid phase synthesis [16]. Nevertheless, most of these
methods suffer from unsatisfactory product yields, critical
product isolation procedures, expensive and detrimental
Scheme 1
R
R
NH2
NO2
O
O
R
R
N
N
SnCl2 2H2O
+
95 % EtOH, reflux 20 min
X
X
1
2
3
RESULTS AND DISCUSSION
We began our study of the reaction shown in Scheme 1 by
optimizing the reaction conditions for the preparation of 3a. A
summary of the optimization experiments is provided in Table
1. The results showed that at room temperature, no reaction
takes place (Table 1, entry 1). To our delight, under reflux the
reaction proceeded smoothly in high yield. To find the
optimum ratio of substrates with reductive agent, the reaction

1798
D.-Q. Shi, G.-L. Dou, S.-N. Ni, J.-W. Shi, X.-Y. Li
Vol 45
was carried out in 95% EtOH using ratio of substrates with
reductive agent from 1:1 to 1:6 (Table 1, entries 4,5,6,7,3,8),
leading to 3a in 0%, 0%, 85%, 89%, 97%, 85%, respectively.
We concluded the best ratio of substrates with reductive agent
is 1:5. Moreover, different organic solvents were further
investigated as shown in Table 1, we concluded that 95%
EtOH was the best solvent for this reaction.
Although a detailed mechanism of the above reaction
has not yet been clarified, the formation of quinoxaline
derivatives can be explained by the tentative mechanism
presented in Scheme 2. The intermediates in this
transformation were 1,2-diaminobenzenes 4, which were
generated in situ by reduction of the 2-nitroanilines 1 by
stannous chloride and subsequently reacted with 1,2-
diketones to give the target compounds 3. In this reaction,
stannous chloride was oxidized to tin tetrachloride. This
species or the excess of stannous chloride present in the
reaction medium can catalyze the cyclization of 1,2-
diaminobenzenes with 1,2-diketones.
Table 1
Optimization of temperature, ratio and solvents in the synthesis of 3a
Ratio of 1a:
catalyst
Time
/min
Yield
(%)
Entry Solvent
T/˚C
1
2
3
4
5
6
7
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
DMF
r.t
60
1:5
1:5
1:5
1:1
1:2
1:3
1:4
1:6
1:5
1:5
1:5
1:5
1:5
1:5
120
120
20
90
90
20
20
20
120
20
20
60
270
270
0
10
97
0
Scheme 2
reflux
reflux
reflux
reflux
reflux
reflux
reflux
90
reflux
reflux
reflux
reflux
SnCl4
SnCl2
NH2
0
excess SnCl2
or SnCl4
85
89
85
65
90
68
13
95
93
N
N
R
R
NH2
NH2
O
R
X
X
X
NO2
9
3
1
4
O
R
10
11
12
13
14
Acetone
CHCl3
MeOH
EtOH
To support this, we studied the stannous chloride or tin
tetrachloride catalyzing the cyclization of 1,2-diamino-
benzene with 1,2-diketone (Scheme 3). The results are
summarized in Table 3. As shown in Table 3, both
stannous chloride and tin tetrachloride have high
efficiency catalyzing this reaction. Other Lewis acid or
BrÖnsted acid can also catalyze this cyclization.
In order to demonstrate the efficiency and the
applicability of the present method, we performed the
reaction of a variety of 2-nitroanilines 1 and 1,2-diketones
2 with stannous chloride in refluxing 95% ethanol. The
results are summarized in Table 2. As shown in Table 2,
for series of 1 and 2, either the aromatic ring containing
electron-withdrawing groups (such as halides) or electron-
donating groups (such as alkyl group), reacted well with
stannous chloride to give the corresponding products 3 in
high yields under the same reaction conditions. So we
concluded that no obvious effects from the electronic
nature of the aromatic ring substrates were observed in the
above reactions.
Scheme 3
O
Lewis acid
or Bronsted acid
NH2
NH2
N
N
+
O
95 % EtOH
4a
2
3a
Table 2
Table 3
The Synthesis of Quinoxalines by the Reaction of 2-Nitroanilines and
1,2-Dicarbonyl Compounds Mediated by SnClꢀ·2H2O
The results of cyclization of 1,2-diaminobenzene with 1,2-diketone
catalyzed by acida
Product
3a
X
H
R
C6H5
Isolated yield (%)a
97
91
95
93
96
91
92
95
93
92
93
91
97
Time
(min.)
Temperature
(˚C)
Yield
(%)b
Entry
Catalyst
3b
3c
3d
3e
3f
3g
H
H
CH3
CH3
CH3
F
4-CH3C6H4
Furan-2-yl
C6H5
4-CH3C6H4
Furan-2-yl
C6H5
1
2
3
4
5
6
7
8
9
10
No
reflux
reflux
reflux
reflux
reflux
reflux
reflux
r.t
45
15
15
15
65
15
15
2
60
93
94
92
86
77
80
92
81
89
SnCl2ꢀ2H2O
SnCl4ꢀ5H2O
AlCl3
CoCl2ꢀ6H2O
FeCl3ꢀ6H2O
CaCl2
TsOH
H2SO4
HCl
3h
3i
3j
3k
3l
3m
F
F
4-CH3C6H4
Furan-2-yl
C6H5
4-CH3C6H4
Furan-2-yl
C6H5
Br
Br
Br
CH3O
reflux
reflux
20
30
a
a The ratio of SnClꢀ·2H2O, 1 and 2 is 5 : 1 : 1, in 95 % EtOH, reflux for
All reactions were performed at 1 mmol scale using 10 mol% of
catalyst in 10 mL of 95% EtOH. b Isolated yields
20 min.

Nov-Dec 2008
An Efficient Synthesis of Quinoxaline Derivatives Mediated by Stannous Chloride
1799
Moreover, the reaction of benzofuroxan 5 and 1,2-
dicarbonyl compound 2 with the same reagent afforded
quinoxalines 3 (Scheme 4) and the results are summarized
in Table 4.
In summary, a series of substituted quinoxalines were
synthesized via reductive cyclization of 1,2-dicarbonyl
compounds with 2-nitroanilines or benzofuroxanes or 1,2-
dinitrobenzenes induced by SnClꢀ·2H2O. The advantages
of this new method are the easily accessible starting
materials, convenient manipulation, short reaction time
and high yields.
Scheme 4
N
N
R
R
O
N
R
R
SnCl2 2H2O
O
+
EXPERIMENTAL
95% EtOH, reflux 1 h
N
O
X
X
O
5
3
2
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on
a Tensor 27
spectrometer. 1H NMR spectra were measured on a Bruker
DPX-400 M Hz spectrometer using TMS as internal standard,
DMSO-d6 as solvent. High resolution mass spectra were
obtained using TOF-MS instrument.
Table 4
The Synthesis of Quinoxalines by Reaction of Benzofuroxanes and
1,2-Dicarbonyl Compounds Mediated by SnCl2·2H2O
General procedure for the synthesis of quinoxaline 3. The
general procedure for the synthesis of quinoxaline is represented
as follow: SnCl2·2H2O (15 mmol) was added to a solution of
1,2-dicarbonyl compound (3 mmol) and 2-nitroaniline or
benzofuroxan or 1,2-dinitrobenzene (3 mmol) in 95 % ethanol
(10 mL) at r.t. The mixture was stirred at refluxing for 2-4 h.
When the reaction was completed, the mixture was poured into 3
% HCl aqueous (100 mL). The solid that separated was collected
by filtration, washed with water, and then recrystallized from
ethanol to afford pure quinoxaline 3.
2,3-Diphenylquinoxaline (3a). This compound was obtained
as solid with mp 124-126 °C (Lit. [15a] 126-127 °C); IR (KBr)
ꢀ: 3056, 1504, 1495, 1478, 1441, 1395, 1347, 1290, 1247, 1219,
1177, 1155, 1142, 1128, 1075, 1058, 1022, 977, 928, 817, 801,
771, 730, 697 cm-1. 1H nmr (DMSO-d6): 7.34-7.43 (m, 6H,
ArH), 7.45-7.50 (m, 4H, ArH), 7.88-7.91 (m, 2H, ArH), 8.15-
8.19 (m, 2H, ArH).
Product
X
R
Isolated yield (%)a
3a
3n
3c
3o
3i
3p
3q
3r
3s
3t
H
H
H
F
C6H5
95
95
95
97
96
95
99
98
97
93
95
4-CH3OC6H4
Furan-2-yl
4-CH3OC6H4
Furan-2-yl
C6H5
F
Cl
Cl
Cl
H
F
4-CH3OC6H4
Furan-2-yl
4-BrC6H4
4-BrC6H4
4-BrC6H4
3u
Cl
a The ratio of SnClꢀ·2H2O, 4 and 2 is 5 : 1 : 1, in 95 % EtOH, reflux for 1 h.
However, treatment of 1,2-dinitrobenzene 6 and 1,2-
dicarbonyl compounds 2 with SnClꢀ·2H2O in 95 % EtOH
under the same reaction conditions, the desired products
quinoxalines 3 were obtained in good yields (Scheme 5).
The results are summarized in Table 5.
2,3-Di(4-methylphenyl)quinoxaline (3b). This compound
was obtained as solid with mp 142-143 °C (Lit. [18] 144-145
°C); IR (KBr) ꢀ: 3029, 2912, 1611, 1555, 1539, 1514, 1474,
1407, 1393, 1343, 1307, 1248, 1222, 1212, 1184, 1141, 1110,
1
1055, 1019, 976, 951, 819, 761, 723 cm-1. H nmr (DMSO-d6):
2.33 (s, 6H, 2 ꢀ CH3), 7.18 (d, J = 8.0 Hz, 4H, ArH), 7.39 (d, J =
8.0 Hz, 4H, ArH), 7.85-7.89 (m, 2H, ArH), 8.11-8.15 (m, 2H,
ArH).
Scheme 5
Cl
NO2
NO2
O
O
R
R
Cl
N
R
R
SnCl2 2H2O
2,3-Di(furan-2-yl)quinoxaline (3c). This compound was
obtained as solid with mp 129-130 °C (Lit. [19] 131-132 °C); IR
(KBr) ꢀ: 3107, 3061, 1571, 1537, 1499, 1489, 1479, 1449, 1400,
1336, 1226, 1171, 1163, 1139, 1129, 1089, 1077, 1059, 1033,
+
EtOH, reflux 4 h
N
3
6
2
1
1009, 993, 913, 887, 762, 751 cm-1. H nmr (DMSO-d6): 6.71-
6.75 (m, 4H, ArH), 7.88-7.90 (m, 2H, ArH), 7.91-7.93 (m, 2H,
ArH), 8.10-8.13 (m, 2H, ArH).
Table 5
The Synthesis of Quinoxalines by the Reaction of 1,2-Dinitro-
benzenes and 1,2-Dicarbonyl Compounds Mediated by SnClꢀ·2H2O
6-Methyl-2,3-diphenylquinoxaline (3d). This compound was
obtained as solid with mp 112-113 °C (Lit. [20] 115-116 °C); IR
(KBr) ꢀ: 3054, 2975, 1619, 1556, 1497, 1484, 1445, 1419, 1400,
1345, 1308, 1287, 1201, 1138, 1078, 1060, 1023, 979, 833, 775,
752, 703 cm-1. 1H nmr (DMSO-d6): 2.61 (s, 3H, CH3), 7.34-7.40
(m, 6H, ArH), 7.46-7.48 (m, 4H, ArH), 7.74 (d, 1H, J = 8.4 Hz,
ArH), 7.96 (s, 1H, ArH), 8.06 (d, 1H, J = 8.4 Hz, ArH).
Product
3p
3q
3u
3r
R
Isolated yield (%)a
C6H5
94
98
94
94
4-CH3OC6H4
4-BrC6H4
Furan-2-yl
6-Methyl-2,3-di(4-methylphenyl)quinoxaline (3e). This
compound was obtained as solid with mp 128-130 °C (Lit. [15a]
135.5-136 °C); IR (KBr) ꢀ: 3029, 2916, 1611, 1554, 1533, 1514,
1487, 1455, 1405, 1378, 1324, 1305, 1252, 1204, 1183, 1142,
a The ratio of SnClꢀ·2H2O, 6 and 2 is 5 : 1 : 1, in 95 % EtOH, reflux for 4 h.
1
1
1110, 1056, 1018, 979, 834, 819, 795, 748, 721 cm-1. H nmr
The structures of products 3 were confirmed by IR, H
NMR and HRMS.
(DMSO-d6): 2.33 (s, 6H, 2 ꢀ CH3), 2.59 (s, 3H, CH3), 7.18 (d,

1800
D.-Q. Shi, G.-L. Dou, S.-N. Ni, J.-W. Shi, X.-Y. Li
Vol 45
4H, J = 8.0 Hz, ArH), 7.37 (d, 4H, J = 8.0 Hz, ArH), 7.70 (d,
1H, J = 8.4 Hz, ArH), 7.92 (s, 1H, ArH), 8.02 (d, 1H, J = 8.4
Hz, ArH).
6-Methoxy-2,3-diphenylquinoxaline (3m). This compound
was obtained as solid with mp 154-156 °C (Lit. [23] 154-155
°C); IR (KBr) ꢀ: 3058, 2960, 1617, 1559, 1496, 1483, 1438,
1410, 1351, 1331, 1286, 1235, 1205, 1166, 1158, 1125, 1079,
2,3-Di(furan-2-yl)-6-methyl-quinoxaline (3f). This
compound was obtained as solid with mp 175-177 °C (Lit. [21]
176 °C); IR (KBr) ꢀ: 3114, 1619, 1568, 1528, 1489, 1382, 1336,
1216, 1169, 1152, 1079, 1064, 1016, 991, 913, 887, 824, 754
1
1060, 1024, 976, 932, 835, 781, 771, 753, 704 cm-1. H nmr
(DMSO-d6): 3.99 (s, 3H, CH3O), 7.33-7.41 (m, 6H, ArH), 7.44-
7.49 (m, 4H, ArH), 7.52-7.56 (m, 2H, ArH), 8.06 (d, 1H, J =
10.0 Hz, ArH).
1
cm-1. H nmr (DMSO-d6): 2.59 (s, 3H, CH3), 6.68-6.72 (m, 4H,
ArH), 7.73 (d, 1H, J = 8.4 Hz, ArH), 7.89-7.94 (m, 3H, ArH),
8.00 (d, 1H, J = 8.4 Hz, ArH).
2,3-Di(4-methoxyphenyl)quinoxaline (3n). This compound
was obtained as solid with mp 140-142 °C (Lit. [19] 145.5-146
°C); IR (KBr) ꢀ: 3055, 2962, 2931, 1606, 1577, 1515, 1475,
1458, 1392, 1344, 1298, 1250, 1170, 1138, 1111, 1057, 1028,
1013, 975, 832, 810, 792, 767 cm-1. 1H nmr (DMSO-d6): 3.79 (s,
6H, 2 ꢀ CH3O), 6.95 (d, 4H, J = 8.4 Hz, ArH), 7.46 (d, 4H, J =
8.4 Hz, ArH), 7.84 (dd, 2H, J1 = 6.4 Hz, J2 = 3.6 Hz, ArH), 8.11
(dd, 2H, J1 = 6.4 Hz, J2 = 3.2 Hz, ArH).
6-Fluoro-2,3-diphenylquinoxaline (3g). This compound was
obtained as solid with mp 130-132 °C; IR (KBr) ꢀ: 3047, 1620,
1561, 1542, 1497, 1479, 1446, 1437, 1345, 1285, 1243, 1224,
1205, 1183, 1153, 1115, 1074, 1059, 1025, 980, 961, 866, 834,
1
822, 802, 776, 758, 701, 695 cm-1. H nmr (DMSO-d6): 7.37-
7.41 (m, 6H, ArH), 7.47-7.49 (m, 4H, ArH), 7.82-7.87 (m, 1H,
ArH), 7.95-7.98 (m, 1H, ArH), 8.24-8.28 (m, 1H, ArH). HRMS
[Found: m/z 300.1061 (M+), cacld for C20H13FN2: M, 300.1063]
6-Fluoro-2,3-di(4-methylphenyl)quinoxaline (3h). This
compound was obtained as solid with mp 112-114 °C; IR (KBr)
ꢀ: 3031, 2918, 1616, 1560, 1541, 1515, 1481, 1458, 1397, 1343,
1247, 1205, 1183, 1154, 1117, 1054, 1019, 981, 960, 864, 837,
6-Fluoro-2,3-bis(4-methoxyphenyl)quinoxaline (3o). This
compound was obtained as solid with mp 146-147 °C; IR (KBr)
ꢀ: 3067, 2932, 1607, 1577, 1563, 1538, 1513, 1483, 1463, 1414,
1343, 1304, 1292, 1251, 1226, 1208, 1175, 1160, 1119, 980,
1
961, 885, 839, 796, 787, 758 cm-1. H nmr (DMSO-d6): 3.79 (s,
6H, 2 ꢀ CH3O), 6.95 (d, 4H, J = 8.8 Hz, ArH), 7.44-7.47 (m,
4H, ArH), 7.75-7.79 (m, 1H, ArH), 7.87-7.91 (m, 1H, ArH),
8.16-8.20 (m, 1H, ArH). HRMS [Found: m/z 360.1268 (M+),
cacld for C22H17FN2O2: M, 360.1274].
1
818, 756, 721 cm-1. H nmr (DMSO-d6): 2.34 (s, 6H, 2 ꢀ CH3),
7.19 (d, 4H, J = 8.4 Hz, ArH), 7.38 (d, 4H, J = 8.4 Hz, ArH),
7.38-7.83 (m, 1H, ArH), 7.91-7.94 (m, 1H, ArH), 8.20-8.24 (m,
1H, ArH). HRMS [Found: m/z 328.1362 (M+), cacld for
C22H17FN2: M, 328.1376]
6-Chloro-2,3-diphenylquinoxaline (3p). This compound was
obtained as solid with mp 118-119 °C (Lit. [24] 119-121 °C); IR
(KBr) ꢀ: 3055, 1606, 1593, 1551, 1497, 1472, 1444, 1393, 1341,
1286, 1251, 1239, 1221, 1192, 1182, 1159, 1068, 1024, 976,
6-Fluoro-2,3-di(furan-2-yl)-quinoxaline (3i). This
compound was obtained as solid with mp 116-117 °C; IR (KBr)
ꢀ: 3115, 1619, 1566, 1536, 1486, 1329, 1216, 1171, 1114, 1079,
1
919, 873, 830, 802, 725, 712, 694 cm-1. H nmr (DMSO-d6):
1
1063, 1016, 992, 968, 913, 890, 868, 833, 755 cm-1. H nmr
7.35-7.43 (m, 6H, ArH), 7.47-7.49 (m, 4H, ArH), 7.92 (dd, 1H,
J1 = 1.6 Hz, J2 = 8.8 Hz, ArH), 8.20 (d, 1H, J = 8.8 Hz, ArH),
8.26 (d, 1H, J = 1.6 Hz, ArH).
(DMSO-d6): 6.71-6.77 (m, 4H, ArH), 7.80-7.85 (m, 1H, ArH),
7.90-7.94 (m, 3H, ArH), 8.17-8.21 (m, 1H, ArH). HRMS
[Found: m/z 280.0645 (M+), cacld for C16H9FN2O2: M,
280.0648]
6-Chloro-2,3-di(4-methoxyphenyl)quinoxaline (3q). This
compound was obtained as solid with mp 147-148 °C; IR (KBr)
ꢀ: 3074, 2961, 2935, 2838, 1607, 1576, 1535, 1512, 1466, 1441,
1394, 1342, 1304, 1286, 1257, 1247, 1172, 1109, 1071, 1026,
6-Bromo-2,3-diphenylquinoxaline (3j). This compound was
obtained as solid with mp 116-117 °C (Lit. [22] 124-125 °C); IR
(KBr) ꢀ: 3055, 1593, 1546, 1497, 1445, 1393, 1341, 1285, 1250,
1238, 1221, 1191, 1182, 1159, 1075, 1061, 1024, 976, 915, 902,
1
978, 922, 877, 844, 837, 799, 692 cm-1. H nmr (DMSO-d6):
3.79 (s, 6H, 2 ꢀ CH3O), 6.95 (d, 4H, J = 8.0 Hz, ArH), 7.46 (d,
4H, J = 8.8 Hz, ArH), 7.85 (dd, 1H, J1 = 2.0 Hz, J2 = 8.8 Hz,
ArH), 8.13 (d, 1H, J = 8.8 Hz, ArH), 8.18 (d, 1H, J = 2.0 Hz,
ArH). HRMS [Found: m/z 376.0985 (M+), cacld for
C22H17ClN2O2: M, 376.0979].
1
874, 829, 801, 768, 724, 697 cm-1. H nmr (DMSO-d6): 7.35-
7.43 (m, 6H, ArH), 7.47-7.49 (m, 4H, ArH), 8.03 (dd, 1H, J1 =
8.8 Hz, J2 = 2.0 Hz, ArH), 8.12 (d, 1H, J = 8.8 Hz, ArH), 8.41
(d, 1H, J = 2.0 Hz, ArH). HRMS [Found: m/z 360.0266 (M+),
cacld for C20H13N279Br: M, 360.0262].
6-Chloro-2,3-di(furan-2-yl)-quinoxaline (3r). This
compound was obtained as solid with mp 128-129 °C (Lit. [25]
122 °C); IR (KBr) ꢀ: 3062, 1602, 1565, 1549, 1528, 1479, 1414,
1398, 1378, 1333, 1254, 1218, 1200, 1156, 1082, 1065, 1015,
6-Bromo-2,3-di(4-methylphenyl)quinoxaline (3k). This
compound was obtained as solid with mp 174-176 °C; IR (KBr)
ꢀ: 3056, 2916, 1608, 1594, 1546, 1513, 1470, 1422, 1404, 1391,
1337, 1278, 1245, 1181, 1138, 1110, 1056, 1018, 977, 908, 874,
1
988, 938, 912, 876, 823, 783, 752 cm-1. H nmr (DMSO-d6):
1
841, 819, 791, 724 cm-1. H nmr (DMSO-d6): 2.33 (s, 6H, 2 ꢀ
6.74-6.78 (m, 4H, ArH), 7.89 (dd, 1H, J1 = 1.6 Hz, J2 = 8.8 Hz,
ArH), 7.93-7.96 (m, 3H, ArH), 8.12 (d, 1H, J = 8.8 Hz, ArH),
8.19 (d, 1H, J = 2.0 Hz, ArH).
2,3-Bis(4-bromophenyl)quinoxaline (3s). This compound
was obtained as solid with mp 188-189 °C (Lit. [26] 188-190 °C);
IR (KBr) ꢀ: 3058, 1585, 1557, 1541, 1521, 1487, 1475, 1389,
1342, 1219, 1125, 1068, 1047, 1007, 975, 842, 827, 818, 803, 760,
746, 721 cm-1. 1H nmr (DMSO-d6): 7.45 (d, J = 8.4 Hz, 4H, ArH),
7.62 (d, J = 8.4 Hz, 4H, ArH), 7.92 (dd, J1 = 3.2 Hz, J2 = 6.4 Hz,
2H, ArH), 8.26 (dd, J1 = 6.0 Hz, J2 =8.8 Hz, 2H, ArH).
CH3), 7.19 (d, 4H, J = 8.0 Hz, ArH), 7.39 (d, 4H, J = 8.0 Hz,
ArH), 7.99 (dd, 1H, J1 = 8.8 Hz, J2 = 1.6 Hz, ArH), 8.08 (d, 1H,
J = 8.8 Hz, ArH), 8.37 (d, 1H, J = 1.6 Hz, ArH). HRMS [Found:
m/z 388.0563 (M+), cacld for C22H17BrN2: M, 388.0575]
6-Bromo-2,3-di(furan-2-yl)-quinoxaline (3l). This
compound was obtained as solid with mp 131-133 °C; IR (KBr)
ꢀ: 3113, 1591, 1566, 1535, 1496, 1484, 1468, 1410, 1334, 1256,
1219, 1198, 1163, 1151, 1128, 1089, 1076, 1062, 1053, 1030,
1
1017, 992, 928, 911, 871, 830, 756, 741 cm-1. H nmr (DMSO-
d6): 6.73-6.78 (m, 4H, ArH), 7.93-7.96 (m, 2H, ArH), 8.00 (dd,
1H, J1 = 8.8 Hz, J2 = 2.0 Hz, ArH), 8.05 (d, 1H, J = 8.8 Hz,
ArH), 8.35 (d, 1H, J = 2.0 Hz, ArH). HRMS [Found: m/z
339.9841 (M+), cacld for C16H9BrN2O2: M, 339.9847]
2,3-Bis(4-bromophenyl)-6-fluoroquinoxaline (3t). This
compound was obtained as solid with mp 160-161 °C; IR (KBr)
ꢀ: 3057, 1618, 1585, 1558, 1539, 1475, 1390, 1341, 1245, 1217,
1204, 1155, 1111, 1072, 1047, 1009, 979, 958, 865, 843, 833,

Nov-Dec 2008
An Efficient Synthesis of Quinoxaline Derivatives Mediated by Stannous Chloride
1801
814, 767, 722 cm-1. 1H nmr (DMSO-d6): 7.44 (d, J = 8.4 Hz, 4H,
ArH), 7.62 (d, J = 8.4 Hz, 4H, ArH), 7.84-7.89 (m, 1H, ArH),
7.98 (dd, 1H, J1 = 2.0 Hz, J2 = 9.2 Hz, ArH), 8.26 (dd, 1H, J1 =
6.0 Hz, J2 =8.8 Hz, ArH). HRMS [Found: m/z 455.9253 (M+),
cacld for C20H11Br2FN2: M, 455.9273].
Gang, Z.; Grace, A. M.; Carlos, H.; Linda, M. G. T. Org. Lett. 2004, 6,
333
[7] Sascha, O.; Rudiger, F. Synlett 2004, 1509.
[8a] Kazunobu, T.; Ryusuke, T.; Tomohiro, O.; Shuichi, M.
Chem. Commun. 2002, 212. [b] Louis, S.; Marc, M. G.; Jory, J. W.;
Joseph, P. B. J. Org. Chem. 2003, 68, 4179.
2,3-Bis(4-bromophenyl)-6-chloroquinoxaline (3u). This
compound was obtained as solid with mp 166-167 °C; IR (KBr)
ꢀ: 3069, 1601, 1585, 1558, 1540, 1487, 1464, 1389, 1339, 1244,
1192, 1177, 1071, 1048, 1009, 975, 921, 877, 842, 829, 817,
[9] Brown, D. J. Quinoxalines: Supplement II. In The Chemistry
of Heterocyclic Compounds; Taylor, E. C.; Wipf, P., Eds.; John Wiley &
Sons: New Jersey, 2004.
[10] Antoniotti, S.; Donach, E. Tetrahedron Lett. 2002, 43, 3971.
[11] Robinson, R. S.; Taylor, R. J. K. Synlett 2005, 1003.
[12a] Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K. Chem. Commun.
2003, 2286. [b] Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K. Org. Biomol.
Chem. 2004, 2, 788.
1
788, 721 cm-1. H nmr (DMSO-d6): 7.44 (d, J = 8.4 Hz, 4H,
ArH), 7.63 (d, J = 8.4 Hz, 4H, ArH), 7.94 (dd, J1 = 1.2 Hz, J2 =
9.2 Hz, 1H, ArH), 8.20 (d, J =8.8 Hz, 1H, ArH). HRMS [Found:
m/z 471.8957 (M+), cacld for C20H11Br2ClN2: M, 471.8977].
[13] Xekoukoulotakis, N. P.; Hadjiantonious, M. C. P.; Maroulis,
A. J. Tetrahedron Lett. 2000, 41, 10299.
Acknowledgement. We are grateful to the “Surpassing
Project” Foundation of Jiangsu Province and the Key Laboratory
of Biotechnology on Medical Plants of Jiangsu Province for
financial support.
[14] Zhao, Z.; Wisnoski, D. D.; Wolkenberg, S. E.; Leister, W.
H.; Wang, Y.; Lindsley, C. W. Tetrahedron Lett. 2004, 45, 4873.
[15a] More, S. V.; Sastry, M. N. V.; Wang, C. C.; Yao, C. F.
Tetrahedron Lett. 2005, 46, 6345. [b] Bhosale, R. S.; Sarda, S. R.;
Ardhapure, S. S.; Jadhav, W. N.; Rhusare, S. R.; Pawar, R. P.
Tetrahedron Lett. 2005, 46, 7183.
[16a] Wu, Z.; Ede, N. J. Tetrahedron Lett. 2001, 42, 8115. [b]
Singh, S. K.; Gupta, P.; Duggineni, S.; Kundu, B. Synlett 2003, 2147. [c]
Attanasi, O. A.; Crescentini, L. D.; Filippone, P.; Mantellini, F.;
Santeusanio, S. Synlett 2003, 1183.
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