A One-pot Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-Dichloroquinoxaline Derivatives Using Silica Gel as an Efficient Catalyst

Article abstract of DOI:10.1002/jhet.3224

An efficient one-pot reaction has been developed for the synthesis of 2,3-dichloroquinoxaline derivatives 3a–n. The reaction was performed in two steps via a silica gel catalyzed tandem process from o-phenylenediamine and oxalic acid, followed by addition of phosphorus oxychloride (POCl₃). A variety of 2,3-dichloroquinoxalines have been obtained in good to excellent overall yields. Eight known compounds 3a–3h were characterized by IR, ¹H-NMR, and mass spectroscopies. Compounds 3i–3n without spectroscopic data were characterized by IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopies.

Full text of DOI:10.1002/jhet.3224

Month 2018
A One-pot Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-
Dichloroquinoxaline Derivatives Using Silica Gel as an Efficient Catalyst
Pei-Ming Zhang,a,b Yao-Wei Li,a,b Jing Zhou,a,b Lin-Ling Gan,a,b Yong-Jie Chen,a,b Zong-Jie Gan,a,b
and Yu Yua,b
*
*
aDepartment of Medicinal Chemistry, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
bChongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China
*
E-mail: gzj@cqmu.edu.cn; yuyu3519@163.com
Received November 17, 2017
DOI 10.1002/jhet.3224
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
An efficient one-pot reaction has been developed for the synthesis of 2,3-dichloroquinoxaline derivatives
3a–n. The reaction was performed in two steps via a silica gel catalyzed tandem process from
o-phenylenediamine and oxalic acid, followed by addition of phosphorus oxychloride (POCl3). A variety
of 2,3-dichloroquinoxalines have been obtained in good to excellent overall yields. Eight known compounds
1
3a–3h were characterized by IR, H-NMR, and mass spectroscopies. Compounds 3i–3n without spectro-
1
scopic data were characterized by IR, H-NMR, 13C-NMR, and mass spectroscopies.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
directly chlorinated by POCl3 to form 2,3-dichloro
quinoxalines in a one-pot reactor without purification. To
the best of our knowledge, silica gel catalyzed, one-pot
synthetic strategies to obtain this important intermediate
are still scarce. This method, with the advantages of easy
work-up and high yield, would provide a potential way
for the industrial synthesis of 2,3-dihydroxyquinoxalines
and 2,3-dichloroquinoxalines (Scheme 1).
2,3-Dihydroxyquinoxalines and 2,3-dichloroquino
xalines are notably one of the most important classes of
nitrogen-containing heterocyclic compounds in synthetic
chemistry because of their practical applications in a
number of fields such as biological and photochemical
[1–3]. For example, they have been employed in the
preparation of different important pharmaceutical
compounds or intermediates such as antipsychotic,
antimicrobial, and anticancer agents [4–9]. To this end,
much attention has been devoted to the synthesis of
substituted quinoxaline and 2,3-dichloroquinoxaline
derivatives. Until now, there are several methods
reported in the literature. Traditionally, condensing o-
phenylenediamine with oxalic acid or diethyl oxalate in
the presence of an acid catalyst (usually HCl) is to date
one of the most employed methods [6–16]. However, a
large amount of concentrated hydrochloric acid was
required in this process. Moreover, the inconvenient
work-up impeded this method for large-scale synthesis.
Therefore, exploring simple, efficient synthetic process is
still desirable.
RESULTS AND DISCUSSION
Initially, the reaction of o-phenylenediamine and oxalic
acid was chosen as a model of the reaction in the
presence of different acids. It was observed that the
methanesulfonic acid in toluene system could afford the
target compound with good yield. Then, much attention
was focused on the optimization of the catalyst with the
aim to discover mild and non-corrosive catalyst; a series
of Lewis acids, molecular sieve, and silica gel were
chosen as the catalyst for the reaction. To our delight, the
results indicated that none of these catalysts except silica
gel could catalyze the reaction (Table 1).
It is noteworthy that silica gel is a widely applied and
practical tool in organic synthesis and its advantages
including inexpensive, readily available, recyclable, and
environment-friendly properties have been well
demonstrated [17–19]. Herein in this article, silica gel is
initially utilized as the catalyst instead of concentrated
HCl to synthesize the substituted 2,3-dihydroxy
quinoxalines under moderate conditions, which is then
With this preliminary and intriguing result in hand, we
tend to further optimize the above model reaction. Firstly,
o-phenylenediamine and oxalic acid in toluene were
heated at 110°C for 5 h without silica gel to test whether
the 2,3-dihydroxyquinoxaline intermediate could be
formed without silica gel, and trace product was detected.
This observation indicated that silica gel is necessary for
the construction of 2,3-dihydroxyquinoxaline intermediate
© 2018 Wiley Periodicals, Inc.

P.-M. Zhang, Y.-W. Li, J. Zhou, L.-L. Gan, Y.-J. Chen, Z.-J. Gan, and Y. Yu
Vol 000
Scheme 1. One-pot synthesis of 2,3-dichloroquinoxalines.
Table 1
Optimization of catalysts for the synthesis of 2,3-dihydroxyquinoxalines.
Entry
Catalyst
Amount of catalyst
Reaction time (h)
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
H2SO4
HAc
20 mol%
20 mol%
20 mol%
100 mol%
100 mol%
100 mol%
100 mol%
100 mol%
100 mol%
100 mol%
100 mol%
100 mol%
300 wt%
3
3
3
3
3
3
3
3
5
5
5
5
5
5
5
Toluene
Toluene
Toluene
Toluene
THF
CH3CN
Dioxane
DMF
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
60
Trace
73
CH3SO3H
CH3SO3H
CH3SO3H
CH3SO3H
CH3SO3H
CH3SO3H
ZnCl2
Cu(OAc)2
FeCl3
AlCl3
86
Trace
Trace
Trace
Trace
—
—
—
—
Trace
90
9
10
11
12
13
14
15
Molecular sieve (4A)
Silica gel (200–300 mesh)b
Silica gel (200–300 mesh)c
300 wt%
300 wt%
88
aIsolated yield.
bPurchased from QinDao HaiYang Chemical Corporation.
cPurchased from Macklin reagent.
Table 2
Table 3
Optimization of model reaction conditions.
Synthesis of 2,3-dichloroquinoxaline derivatives.
Amount
of catalyst
(wt%)
Reaction
time (h)
Yield
(%)a
Entry
Solvent
T (°C)
1
2
3
4
5
6
7
8
—
150
200
300
400
300
300
300
300
300
300
300
300
5
5
5
5
5
5
5
5
5
5
5
5
5
Toluene
Toluene
Toluene
Toluene
Toluene
THF
CH3CN
Dioxane Reflux Trace
DMF
Xylene
Toluene
Toluene
Toluene
110
110
110
110
110
Trace
64
80
91
90
Compounds
Reaction
Yield
(%)a
Entry
R1
R2
R3
time (h)
Reflux Trace
Reflux Trace
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
Cl
F
H
CH3
H
H
H
H
H
H
H
H
H
H
H
CH3
H
H
6
5
5
6
5
5
5
7
7
5
7
7
5
7
90
75
88
75
84
90
70
84
71
73
71
50
76
35
Cl
Br
F
9
110
110
100
90
—
77
70
42
10
11
12
13
CF3
NO2
CN
CH3
Cl
Cl
H
70
Trace
aIsolated overall yield.
9
10
11
12
13
14
CH3
OCH3
(Table 2, entry 1). Next, the effect of solvent and catalyst
loading on the yield of the reaction was also examined.
The results were surmised in Table 2. Toluene seems to be
the best solvent for the processes (Table 2, entry 4 vs.
entries 6–10). And 300 wt% loading of silica gel provided
the maximum yield; higher percentage loading of the
aIsolated overall yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-Dichloroquinoxaline
Derivatives
Scheme 2. Plausible mechanism of the reaction to produce 2,3-dihydroxyquinoxaline.
catalyst increased the yield (Table 2, entry 4 vs. entries 2 and
3). But it should be noted that no significant effect on
reactivity was observed when the amount of silica gel was
raised from 300 to 400 wt% whereas product yield
improved slightly (Table 2, entries 4 and 5). Furthermore,
reaction temperature was also investigated, and the results
showed that reaction temperature played an important role
in this reaction, higher temperature benefited for the
reaction, and 110°C would be the optimal temperature
(Table 2, entry 4 vs. entries 11–13).
Under the optimized conditions, we proceeded to
explore the scope of o-phenylenediamines, and the results
are shown in Table 3. The o-phenylenediamines bearing
electron-donating and electron-withdrawing groups were
tolerated well under the reaction conditions, affording the
desired 2,3-dichloroquinoxalines in good to excellent
overall yields (Table 3, entries 3a–3n). It was noteworthy
that the electron properties of the substituent groups on
the phenyl ring played an important role in the reaction;
o-phenylenediamines containing electron-withdrawing
groups provided the desired 2,3-dichloroquinoxalines in
better yields than those of electron-donating groups
(Table 3, entries 3e and 3f vs. entries 3h, 3k, and 3l);
however, it should be noted that compound 3g bearing
nitrile group gave the corresponding product in relative
low yield; some hydrolytic by-product was detected in
the reaction. Besides, the 4,5-disubstituted-1,2-diamine
showed less reactivity in comparison with that of 3- or 4-
monosubstituted-1,2-dimine and gave corresponding
products in inferior yields (Table 3, entry 3l vs. entries
3h and 3k). In a similar way, the naphthalene compound
1n could also generate the corresponding product 3n in
35% yield (Table 3, entry 3n).
A plausible mechanism to produce 2,3-dihydroxy
quinoxaline was proposed in Scheme 2. Slightly acidic and
mild desiccant nature of silica gel plays an important role
in this reaction. We hypothesize that silica gel may
activate the acid group, thereby generating an electron
deficient carbon. This facilitates the addition of amine to
form intermediate 4. Removal of water with the assistance
of silica gel from intermediate 4 affords intermediate 6.
Finally, the intramolecular lose of H2O from intermediate
6 generates 2,3-dihydroxyquinoxaline via the same
mechanism.
CONCLUSIONS
In summary, a simple method for the synthesis of 2,3-
dichloroquinoxaline from o-phenylenediamine with oxalic
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P.-M. Zhang, Y.-W. Li, J. Zhou, L.-L. Gan, Y.-J. Chen, Z.-J. Gan, and Y. Yu
Vol 000
acid using silica gel as the promotor is reported. Most of
the products are performed in good yields and high
purities. Moreover, considering the advantages of silica
gel, including inexpensive, readily available, recyclable,
and environment-friendly properties, this method shows
great potential for practical use in the synthesis of
quinoxalines and 2,3-dichloroquinoxalines.
with 2.5 L cold water, and 1 L ethyl acetate was added;
the mixture was filtered, and the aqueous layer was
separated and washed with 500 mL ethyl acetate twice.
The organic layer was combined, successively washed by
saturated NaCl aqueous solution, and dried over
anhydrous Na2SO4, filtered and concentrated under
reduced pressure. The residue was recrystallized from
butanol to give 75.4 g of 3a, yield 82.1%.
Characterization data of products. 2,3-Dichloroquino
EXPERIMENTAL
xaline (3a).
White solid, mp 148–150°C; (lit. [16]
148–150°C), IR (KBr, ν, cmꢀ1): 3104, 3042 (CH¼CH),
1557, 1530 (CH¼CH), 1484, 1457 (CH¼CH), 1271, 1179,
1125, 1018, 991, 768, 599, 436; 1H NMR (600 MHz,
CDCl3) (δ, ppm): 7.76–7.84 (m, 2H, Ar-H), 7.99–8.06 (m,
2H, Ar-H); ESI–MS: m/z 198.9 [M+H]+.
All reagents were obtained from Adamas, Tansoole and
used without further purification unless otherwise noted.
Melting points were determined on X-4 microscopic
melting point apparatus and were uncorrected. The IR
spectra (in KBr pellets) were recorded on a Nicolet IS50
spectrometer. 1H NMR spectra were obtained from
solution in CDCl3 and DMSO-d6 with TMS as internal
standard using a Bruker-600 or Bruker-500 MHz
spectrometer. MS spectra were obtained with an
Agilent 6460 QQQ and GCMS-QP2000 instrument.
Silica gel was purchased from QinDao HaiYang
Chemical Corporation and Macklin reagents, 200–300
mesh, AR.
2,3,6-Trichloroquinoxaline (3b).
White solid, mp
140–142°C; (lit. [20] 144°C), IR (KBr, ν, cmꢀ1): 3090,
3068 (CH¼CH), 3038, 1598, 1552 (CH¼CH), 1526,
1469 (CH¼CH), 1283, 1249, 1158, 1125, 1007, 925,
1
888, 832, 583, 465, 437; H NMR (600 MHz, CDCl3) (δ,
ppm): 7.75 (dd, J = 8.9, 2.2 Hz, 1H, Ar-H), 7.97 (d,
J = 8.9 Hz, 1H, Ar-H), 8.02 (d, J = 2.1 Hz, 1H, Ar-H);
EI–MS: m/z 232 [M]+.
2,3-Dichloro-6-bromoquinoxaline (3c). White solid, mp
128–130°C; (lit. [21] 131°C), IR (KBr, ν, cmꢀ1): 3084,
3065 (CH¼CH), 3032, 1597, 1547 (CH¼CH), 1531,
1474 (CH¼CH), 1459, 1281, 1256, 1158, 1128, 1003,
General procedure for the synthesis of compounds
3a–3n.
A mixture of o-phenylenediamine 1a (1 g,
9.2 mmol), oxalic acid (1.28 g, 10.1 mmol), and silica gel
(3 g, 200–300 mesh) was stirred in toluene (15 mL) at
110°C for 5 h. When the reaction was completed
(monitored by TLC), POCl3 (8.4 mL, 92 mmol) and
5 mL DMF were slowly added into the mixture and
stirred at this temperature for another 1 h, then the
reaction was quenched with 50 mL cold water, and
50 mL ethyl acetate was added; the mixture was filtered,
and the aqueous layer was separated and washed with
15 mL ethyl acetate twice. The organic layer was
combined, successively washed by saturated NaCl
aqueous solution, and dried over anhydrous Na2SO4,
filtered and concentrated under reduced pressure. The
residue was purified by column chromatography on silica
gel using petroleum ether as eluent to afford the desired
products (notice: some products can be directly used
without purification).
1
912, 887, 832, 574, 438; H NMR (600 MHz, CDCl3) (δ,
ppm): 7.74–7.95 (m, 2H, Ar-H), 8.19 (d, J = 0.7 Hz, 1H,
Ar-H); EI–MS: m/z 276 [M]+.
2,3-Dichloro-6-fluoroquinoxaline (3d). White solid, mp
145–147°C; (lit. [20] 143–145°C), IR (KBr, ν, cmꢀ1):
3072, 3047 (CH¼CH), 1620, 1560 (CH¼CH), 1532,
1486 (CH¼CH), 1291, 1268, 1203, 1131, 1116, 1000,
1
966, 887, 834, 548, 444; H NMR (600 MHz, DMSO-d6)
(δ, ppm): 7.84 (td, J = 8.9, 2.8 Hz, 1H, Ar-H), 7.89 (dd,
J = 9.2, 2.7 Hz, 1H, Ar-H), 8.12 (dd, J = 9.2, 5.7 Hz,
1H, Ar-H); EI–MS: m/z 216 [M]+.
2,3-Dichloro-6-trifluoromethylquinoxaline (3e).
White
solid, mp 78–80°C; (lit. [22] 81–83°C), IR (KBr, ν,
cmꢀ1): 3086, 3054 (CH¼CH), 1548 (CH¼CH), 1539,
1436 (CH¼CH), 1388, 1318, 1274, 1177, 1123, 1058,
1
999, 932, 903, 849, 660, 614, 439; H NMR (600 MHz,
Large-scale synthesis of compound 3a. To a 2 L three-
necked flask equipped with Dean Stark apparatus was
added o-phenylenediamine 1a (50 g, 0.46 mol), oxalic
acid (64 g, 0.51 mol), silica gel (200 g, 200–300 mesh),
and toluene (800 mL); the mixture was stirred at 110°C
for 4 h, and an extra 200 mL toluene was added during
this section. When the reaction was completed (monitored
by TLC), the mixture was cooled to room temperature,
and then POCl3 (215 mL, 2.30 mol) and 250 mL DMF
were slowly added into the mixture and warm to 110°C
stirred for another 1 h; then the reaction was quenched
DMSO-d6) (δ, ppm): 8.15 (dd, J = 8.8, 1.5 Hz, 1H, Ar-
H), 8.24 (d, J = 8.7 Hz, 1H, Ar-H), 8.45 (s, 1H, Ar-H);
ESI–MS: m/z 267.1 [M+H]+.
2,3-Dichloro-6-nitroquinoxaline (3f).
White solid, mp
148–150°C; (lit. [20] 152–153°C), IR (KBr, ν, cmꢀ1):
3090, 3056 (CH¼CH), 1612, 1574 (CH¼CH), 1526,
1379, 1355, 1276, 1257, 1164, 1126, 1074, 1014, 916,
855, 832, 741, 436; 1H NMR (600 MHz, CDCl3) (δ,
ppm): 8.21 (d, J = 9.2 Hz, 1H, Ar-H), 8.59 (dd, J = 9.2,
2.4 Hz, 1H, Ar-H), 8.93 (d, J = 2.3 Hz, 1H, Ar-H);
EI–MS: m/z 243 [M]+.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-Dichloroquinoxaline
Derivatives
2,3-Dichloro-6-cyanoquinoxaline (3g). White solid, mp
235–237°C; (lit. [20] 239°C), IR (KBr, ν, cmꢀ1): 3072,
3043 (CH¼CH), 2231 (CN), 1552, 1541 (CH¼CH),
1383,1295, 1281, 1260, 1179, 1168, 1125, 1027, 1005,
912, 856, 622, 562, 435; H NMR (600 MHz, CDCl3) (δ,
ppm): 7.99 (dd, J = 8.7, 1.8 Hz, 1H, Ar-H), 8.17 (dd,
(CH¼CH), 1619 (CH¼CH), 1488, 1467 (CH¼CH),
1401, 1300, 1263, 1216, 1184, 1145, 1122, 1021, 998,
833, 622, 540, 444; 1H NMR (600 MHz, CDCl3) (δ,
ppm): 3.96 (s, 3H, OCH3), 7.30 (d, J = 2.7 Hz, 1H,
Ar-H), 7.43 (dd, J = 9.2, 2.7 Hz, 1H, Ar-H), 7.90 (d,
J = 9.2 Hz, 1H, Ar-H); 13C NMR (150 MHz, CDCl3) (δ,
ppm): 55.9, 105.8, 124.2, 129.0, 136.5, 142.3, 142.3,
1
J = 8.7, 0.4 Hz, 1H, Ar-H), 8.42 (dd, J = 1.7, 0.4 Hz,
1H, Ar-H); EI–MS: m/z 223 [M]+.
145.5, 161.7; ESI–MS: m/z 229.0 [M+H]+.
2,3-Dichloro-6-methylquinoxaline (3h). White solid, mp
2,3-Dichlorobenzo[g]quinoxaline (3n). Yellow solid, mp
112–114°C; (lit. [20] 113–114°C), IR (KBr, ν, cmꢀ1):
3065, 3031 (CH¼CH), 1620, 1566 (CH¼CH), 1526,
1492 (CH¼CH), 1295, 1271, 1257, 1185, 1154, 1127,
996, 619, 574, 438; 1H NMR (600 MHz, CDCl3) (δ,
ppm): 2.60 (s, 3H, CH3), 7.63 (d, J = 8.6 Hz, 1H, Ar-H),
7.78 (s, 1H, Ar-H), 7.90 (d, J = 8.5 Hz, 1H, Ar-H); 13C
NMR (150 MHz, CDCl3) (δ, ppm): 21.8, 127.0, 127.6,
133.4, 139.0, 140.6, 142.1, 144.2, 145.1; EI–MS: m/z
212 [M]+.
236–238°C; IR (KBr, ν, cmꢀ1): 1557 (CH¼CH), 1302,
1200, 1155, 1109, 998, 886, 748, 537, 497, 470; 1H
NMR (500 MHz, CDCl3) (δ, ppm): 7.53–7.75 (m, 2H,
Ar-H), 8.04–8.24 (m, 2H, Ar-H), 8.60 (s, 2H, Ar-H); 13C
NMR (125 MHz, CDCl3) (δ, ppm): 126.9, 127.7, 128.5,
134.2, 137.0, 145.1; EI–MS: m/z 248 [M]+.
Acknowledgments. We appreciate the financial support from the
National Natural Science Foundation of China (no. 21701018)
and the Fundamental and Advanced Research Projects of
Chongqing City (no. cstc2017jcyjAX0228).
2,3,6,7-Tetrachloroquinoxaline (3i).
White solid, mp
168–170°C; (lit. [23] 165–168°C), IR (KBr, ν, cmꢀ1):
3078 (CH¼CH), 1773, 1586 (CH¼CH), 1539, 1520,
1451 (CH¼CH), 1398, 1262, 1152, 1100, 1009, 975,
892, 571, 529, 439; 1H NMR (600 MHz, CDCl3) (δ,
ppm): 8.12 (s, 2H, Ar-H); 13C NMR (150 MHz,
CDCl3) (δ, ppm): 128.7, 136.1, 139.1, 146.7; EI–MS: m/z
266 [M]+.
REFERENCES AND NOTES
[1] Ajani, O. O. Eur J Med Chem 2014, 85, 688.
[2] Achelle, S.; Baudequin, C.; Plé, N. Dyes Pigments 2013, 98,
575.
[3] Pereira, J. A.; Pessoa, A. M.; Cordeiro, M. N. D. S.;
Fernandes, R.; Prudencio, C.; Noronha, J. P.; Vieira, M. Eur J Med Chem
2015, 97, 664.
[4] Yang, Y.; Zhang, S.; Wu, B.; Ma, M.; Chen, X.; Qin, X.; He,
M.; Hussain, S.; Jing, C.; Ma, B.; Zhu, C. Chem Med Chem 2012, 7, 823.
[5] Lee, S. H.; Kim, N.; Kim, S. J.; Song, J.; Gong, Y. D.; Kim, S.
Y. J Cancer Res Clin 2013, 139, 1279.
[6] Xia, Q. H.; Hu, W.; Chen, L.; Wu, J. F.; Yang, L.; Han, X. M.;
Shen, Y. M.; Li, Z. Y.; Li, X. Eur J Med Chem 2016, 124, 311.
[7] Bouanane, Z.; Bounekhel, M.; Elkolli, M.; Abrigach, F.;
Khoutoul, M.; Bouyala, R.; Touzani, R.; Hellal, A. J Mol Struct 2017,
1139, 238.
[8] Sekhar, K. V. G. C.; Rao, V. S.; Deuther-Conrad, W.; Sridhar,
D.; Nagesh, H. N.; Kumar, V. S.; Brust, P.; Kumar, M. M. K. Med Chem
Res 2013, 22, 1660.
[9] Nakhi, A.; Rahman, M. S.; Kishore, R.; Meda, C. L.; Deora, G.
S.; Parsa, K. V. L.; Pala, M. Bioorg Med Chem Lett 2012, 22, 6433.
[10] Kotra, V.; Pradeep, K.; Vasanthi, R. Der Pharm Chem 2013, 5,
301.
[11] Engelhart, J. U.; Lindner, B. D.; Tverskoy, O.; Schaffroth, M.;
Rominger, F.; Bunz, U. H. W. J Org Chem 2013, 78, 1249.
[12] Cho, W.; Cho, H.; Lee, C. S.; Lee, B. Y.; Moon, B. J.; Kang, J.
H. Organometallics 2014, 33, 1617.
[13] Madrzak-Litwa; Iwona; Borowiak-Resterna; Aleksandra
Heterocycl Commu 2014, 20, 177.
2,3,6-Trichloro-7-fluoroquinoxaline (3j).
White solid,
mp 155–157°C; IR (KBr, ν, cmꢀ1): 3092, 3041
(CH¼CH), 1777, 1610, 1552 (CH¼CH), 1526, 1477,
1426 (CH¼CH), 1362, 1264, 1236, 1207, 1133, 1011,
1
896, 754, 603, 560, 448; H NMR (600 MHz, CDCl3) (δ,
ppm): 7.76 (d, J = 8.7 Hz, 1H, Ar-H), 8.12 (d,
J = 7.4 Hz, 1H, Ar-H); 13C NMR (150 MHz, CDCl3) (δ,
ppm): 113.2, 127.2, 129.4, 137.5, 139.9,145.9,
146.7,157.9,159.6; EI–MS: m/z 250 [M]+.
2,3-Dichloro-5-methylquinoxaline (3k). White solid, mp
88–90°C; IR (KBr, ν, cmꢀ1): 3050, 3013 (CH¼CH),
1602, 1569, 1528 (CH¼CH), 1471 (CH¼CH), 1378,
1270, 1184, 1142, 1073, 984, 942, 809, 773, 516, 444;
1H NMR (150 MHz, CDCl3) (δ, ppm): 2.75 (s, 3H,
CH3), 7.63 (d, J = 7.1 Hz, 1H, Ar-H), 7.68 (t, J = 7.7 Hz,
1H, Ar-H), 7.88–7.71 (m, 1H, Ar-H); 13C NMR
(150 MHz, CDCl3) (δ, ppm): 17.1, 125.9, 130.9, 131.1,
137.1, 139.9, 140.8, 144.0, 144.9; EI–MS: m/z 212 [M]+.
2,3-Dichloro-6,7-dimethylquinoxaline (3l).
White solid,
mp 178–180°C; IR (KBr, ν, cmꢀ1): 2950 (CH¼CH),
1623, 1547 (CH¼CH), 1519, 1485 (CH¼CH), 1442,
1388, 1260, 1202, 1133, 1022, 988, 877, 861, 575, 442;
1H NMR (150 MHz, CDCl3) (δ, ppm): 2.49 (s, 6H, CH3,
CH3), 7.75 (s, 2H, Ar-H); 13C NMR (150 MHz, CDCl3)
(δ, ppm): 20.4, 127.1, 139.5,142.1, 144.1; ESI–MS: m/z
227.0 [M+H]+.
[14] Li, N.; Yang, F.; Stock, H. A.; Dearden, D. V.; Lamb, J. D.;
Harrison, R. G. Org Biomol Chem 2012, 10, 7392.
[15] Mota, F.; Gane, P.; Hampden-Smith, K.; Allerston, C. K.;
Garthwaite, J.; Selwood, D. L. Bioorg Med Chem 2015, 23, 5303.
[16] Miranda, F. D. S.; Signori, A. M.; Vicente, J.; Souza, B. D.;
Priebe, J. P.; Szpoganicz, B.; Sanches, N.; AdemirNeves, G. Tetrahedron
2008, 64, 5410.
[17] Taniguchi, T.; Dennis, P. Curran Org Lett 2012, 14, 4540.
[18] Molander, G. A.; Cavalcanti, L. N.; Canturk, B.; Pan, P. S.;
Kennedy, L. E. J Org Chem 2009, 74, 7364.
2,3-Dichloro-6-methoxylquinoxaline (3m).
White solid,
mp 154–156°C; IR (KBr, ν, cmꢀ1): 3067, 3013
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P.-M. Zhang, Y.-W. Li, J. Zhou, L.-L. Gan, Y.-J. Chen, Z.-J. Gan, and Y. Yu
Vol 000
[19] Thakare, M. P.; Kumar, P.; Kumar, N.; Pandey, S. K.
Tetrahedron Lett 2014, 55, 2463.
[22] Wright, W. B.; Morton, G. O.; Tomcufcik, A. S. J Heterocyclic
Chem 1979, 16, 1345.
[20] Romer, D. R. J Heterocyclic Chem 2009, 46, 317.
[21] Charles, D. S.; Charlotte, M.; Patricia, B.; M. G. E; Han, L.
W.; Darryl, P. S.; Birgitte, N.; Derek, B.; Karla, F.; Jette, K. S.; Lennart,
B. ACS Chem Nerosci 2015, 6, 845.
[23] Sarges, R.; Howard, H. R.; Browne, R. G.; Lebel, L. A.;
Seymour, P. A.; Koe, B. K. J Med Chem 1990, 33, 2240.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet