[4+2] heterocyclization for efficient formation of substituted quinoxalines through carbon-oxygen bonds cleavage

Article abstract of DOI:10.1002/jhet.2128

A new domino strategy for efficient synthesis of highly functionalized quinoxaline derivatives via [4 + 2] heterocyclization involving ring-opening of oxirane process has been developed. The reaction promoted by Cs₂CO₃ was easy to perform in a simple operation from common and inexpensive starting materials. The bisfunctionalization of quinoxaline framework including C2 benzylation and C3 arylation was readily achieved in domino fashion that involved the cleavage of three C-O bonds of 1,3-diaryl-2,3-epoxypropan-1-one.

Full text of DOI:10.1002/jhet.2128

Month 2014
[4 + 2] Heterocyclization for Efficient Formation of Substituted
Quinoxalines through Carbon–Oxygen Bonds Cleavage
*
*
Man-Su Tu, Hai-Wei Xu, Wei Fan, Bo Jiang, and Shu-Jiang Tu
Key Laboratory of Biotechnology for Medicinal Plant, and School of Chemistry & Chemical Engineering, Jiangsu Normal
University, Xuzhou 211116, People’s Republic of China
*
E-mail: laotu@jsnu.edu.cn
Received August 6, 2013
DOI 10.1002/jhet.2128
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A new domino strategy for efficient synthesis of highly functionalized quinoxaline derivatives via
[4 + 2] heterocyclization involving ring-opening of oxirane process has been developed. The reaction
promoted by Cs2CO3 was easy to perform in a simple operation from common and inexpensive starting
materials. The bisfunctionalization of quinoxaline framework including C2 benzylation and C3 arylation
was readily achieved in domino fashion that involved the cleavage of three C–O bonds of 1,3-diaryl-2,
3-epoxypropan-1-one.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
the transformations green. In recent years, considerable
efforts have been devoted to the development of various
domino reactions toward the formation of heterocycles
[15]. However, the utilization of domino reaction of
1,3-diaryl-2,3-epoxypropan-1-one selectively yielding
2-benzylquinoxalines was seldom documented. We thus
planned an alternative approach to these important
compounds under more concise and efficient conditions.
Recently, our group have developed a series of unique
domino reactions for the construction of useful functional-
ized complex molecules of chemical and pharmaceutical
importance [16]. As a result of our continuous effort on these
domino processes, herein, we would like to disclose another
new Cs2CO3 promoted domino reaction of 1,2-diamines 1
with 1,3-diaryl-2,3-epoxypropan-1-one 2 [17] in ethylene
glycol yielding 2-benzylquinoxalines (Scheme 1). The
unique characteristic of the present domino reaction
demonstrates that the formation of quinoxaline skeleton
with concomitant achievement of its C2 benzylation and
C3 arylation was readily achieved in domino fashion that
involved the cleavage of three C–O bonds of 1,3-diaryl-2,3-
epoxypropan-1-one. The reaction was easy to perform in a
simple operation from common and preformed starting
materials such as 1,3-diaryl-2,3-epoxypropan-1-one, avoiding
the use of oxidizing agent (Scheme 1). This observation is
very useful in organic chemistry.
Quinoxaline and its derivatives are found in a number of
drugs or drug candidates, which represent one of the most
biologically active classes of compounds [1]. They possess a
wide and diverse spectrum of pharmacological properties [2],
such as anticancer [3], antiviral [4], antibiotic (echinomycin),
and anti-inflammatory activities [5]. Furthermore, they are the
potential building blocks for the synthesis of organic semicon-
ductors [6], electroluminescent material [7], dehydroannulenes
[8], and dyes [9]. Consequently, many approaches to various
substituted quinoxalines have been developed. Among these
methods, condensation of 1,2-diamines and 1,2-dicarbonyl
compounds [10], oxidative cyclization of α-hydroxy ketones
[11] or α-haloketones [12] with 1,2-diamines, has been widely
used. Because of the preparation of 1,2-dicarbonyl com-
pounds, α-hydroxy ketones or α-haloketones requires multi-
steps involving benzoic condensation, oxidation reactions or
halogenations, such reactions suffered from narrow substrate
scopes, the use of expensive reagents/additives, or harsh reac-
tion conditions, as well as the difficult experimental/work-up
procedures. In addition, there are some other oxidative
approaches to synthesize quinoxaline derivatives [13]. These
shortcomings may limit the functional group compatibility
and their application. New methodology from simple
substrates and environmentally benign reagents, with high
efficiency, under mild conditions, is still desirable.
Domino reactions, being one of the most effective
methods to improve synthetic efficiency, can implement
reaction cascades and generate high levels of diversity
giving rise to biologically important molecules from
simple substrates [14]. Obviously, such transformations
can avoid time-consuming and costly processes for purifi-
cation of various precursors and isolation of intermediate,
thereby minimizing the generation of waste and rendering
RESULTS AND DISCUSSION
Initial reaction using benzene-1,2-diamine (1a) and a
preformed 1,3-diphenyl-2,3-epoxypropan-1-one (2a) as
simple model substrates in ethylene glycol was investigated
to establish the feasibility of the strategy and to screen the
reaction conditions (Table 1). The reaction in ethylene glycol
© 2014 HeteroCorporation

M.-S. Tu, H.-W. Xu, W. Fan, B. Jiang, and S.-J. Tu
Vol 000
Scheme 1. The synthesis of 2-benzylquinoxalines.
benzene-1,2-diamine 1a was used as a model substrate
(Table 2, entries 1–8), and the results indicated that the
substituents residing in different positions on the aromatic
ring of 2 were all successfully engaged in this reaction
and were readily transformed into the corresponding
substituted quinoxalines 3a–3 h with 82–89% yields. The
bulky o-halogen-substituted 2d, 2 h, 2 k, 2 l, and 2 m were
suitable for these domino reactions. As an extension of the
aforementioned study, we devised various 1,2-diamines 1
to subject with 2 to investigate the possibility of this transfor-
mation. The substituents on the aromatic ring of 1,2-diamines
1 did not hamper the reaction process. Reactions of methyl-
(1b) or chloro-substituted (1c) 1,2-diamines 1 with 1,3-
diaryl-2,3-epoxypropan-1-ones 2 all worked well to provide
the desired substituted quinoxalines in good yields within
short times. The tolerance of functionalities, such as chloro,
bromo in this protocol provides the opportunity of their
various further chemical manipulations in products. It is
worth mentioning that the protocol provides a straightfor-
ward pathway for the rapid generation of 2,3-disubstituted
quinoxalines with concomitant achievement of its C2
benzylation and C3 arylation in a simple operation. More-
over, it also gives a new example for heterocyclization
involved ring-opening of oxirane process in an economical
and atom-efficient fashion, providing a valuable strategy to
discover new bioactive compounds.
at 100°C gave the desired product 3a in 54% yield without
any base (Table 1, entry 1). Next, different bases such as
Et3N, NaOH, and Cs2CO3 were explored. The results are
listed in Table 1. The reaction proceeded to provide the 48%
yield of the expected product 3a in the presence of Et3N at
100°C under microwave heating (Table 1, entry 2). A low
yield (25%) of product 3a was observed using NaOH as a base
promoter (entry 3). The identical reaction promoted by
Cs2CO3 at 100°C generated higher yield of 3a (75%) (entry 4).
Subsequently, different solvents were screened, and it was
found that the reaction proceeded most efficiently in ethylene
glycol than that in DMF, EtOH, and water (entries 4–7).
Gratifyingly, this reaction promoted by Cs2CO3 worked well
in ethylene glycol at an enhanced temperature of 120°C,
which afforded the corresponding product 3a in 86% yield
(entry 8). Further increase of reaction temperature failed to
improve the yield of desired product 3a (entry 9). It is
anticipated that 1 equiv of Cs2CO3 acts as the base,
dehydrating agent, and heterogeneous activator for the
formation of substituted quinoxalines as shown in Scheme 1.
With the aforementioned optimized conditions in hand,
we then proceeded to explore the substrate diversity of this
Cs2CO3 that promoted domino reaction of 1,2-diamines 1
and 1,3-diaryl-2,3-epoxypropan-1-ones 2. The results were
presented in Table 2. At the beginning, we made a search
for the 1,3-diaryl-2,3-epoxypropan-1-one substrate scope,
In all cases, the reaction proceeded at a very fast speed
and can be finished within 14–22 min. The reaction process
is environmentally friendly in which water is a sole by-
product. In most cases, the products that can precipitate
out after the reaction mixture were poured into cold water.
The structural elucidation of the products was determined
1
from its IR, H NMR, 13C NMR, and HRMS spectra.
Table 1
Optimization of reaction conditions.
Entry
Base (equiv.)
Solvent
T (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
-
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
DMF
EtOH
Water
Ethylene glycol
Ethylene glycol
100
100
100
100
100
100
100
120
130
16
16
16
16
18
18
18
16
16
54
48
25
75
61
40
31
86
83
Et3N (1.0)
NaOH (1.0)
Cs2CO3 (1.0)
Cs2CO3 (1.0)
Cs2CO3 (1.0)
Cs2CO3 (1.0)
Cs2CO3 (1.0)
Cs2CO3 (1.0)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Efficient Formation of Quinoxalines
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-S. Tu, H.-W. Xu, W. Fan, B. Jiang, and S.-J. Tu
Vol 000
On the basis of experimental results, a reasonable reaction
mechanism for this domino reaction is postulated in Scheme 2.
First, the nucleophilic addition and elimination between 1,3-
diaryl-2,3-epoxypropan-1-ones 2 and 1,2-diamines 1 occurs,
leading to intermediate A and followed by intramolecular cycli-
zation/ring-opening of oxirane to convert into intermediate B.
The intermediate B then undergoes dehydration and 1,3-H
transfer to afford final 2,3-disubstituted quinoxalines 3.
In conclusion, we have developed a new Cs2CO3 promoted
[4 + 2] heterocyclization of 1,3-diaryl-2,3-epoxypropan-1-ones
that led to efficient construction of quinoxaline skeleton in dom-
ino fashion that involved ring-opening of oxirane process. This
reaction process involves nucleophilic addition/elimination/
cyclization/ring-opening of oxirane sequence. Undoubt-
edly, this domino strategy provides a straightforward path-
way to construct the target molecules in an atom-economic
manner. Other features of this tactic include the mild condi-
tions, convenient one-pot operations, and high bond-forming
efficiency. The resulting quinoxaline derivatives are of
importance for organic and medicinal research, which are
in progress.
EXPERIMENTAL
Microwave irradiation was carried out with Initiator 2.5
Microwave Synthesizers from Biotage, Uppsala, Sweden. The
reaction temperatures were measured by infrared detector during
microwave heating. Melting points were determined in open
capillaries and were uncorrected. IR spectra were recorded on an
FT-IR-tensor 27 spectrometer (Bruker Company, Ettlingen,
1
Germany). H NMR spectra were measured on a DPX 400 MHz
spectrometer (Bruker Company, Ettlingen, Germany) using TMS
as an internal standard and DMSO-d6 as a solvent. HRMS (ESI)
was determined by using the microTOF-Q II HPLC/MS instru-
ment (BRUKER).
General procedure for the synthesis of compound 3 with
microwave irradiation.
Typically, phenyl(3-phenyloxiran-2-
yl)methanone (2a, 1.0 mmol, 0.224g, 1.0 equiv.) was introduced
in a 10-mL InitiatorTM reaction vial, benzene-1,2-diamine (1a,
1.0 mmol, 0.108 g, 1.0 equiv.) and Cs2CO3 (1.0 mmol, 0.326 g,
1.0 equiv.) as well as ethylene glycol (1.5 mL) were then
successively added. Subsequently, the reaction vial was closed
and then pre-stirred for 20 s. The mixture was irradiated (time:
16 min, temperature: 120°C; absorption level: high; fixed hold
Scheme 2. Proposed mechanism for the formation of 3.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Efficient Formation of Quinoxalines
time) until TLC (petroleum ether–acetone, 3:1) revealed that
conversion of the starting material 1a was complete. The
reaction mixture was then cooled at room temperature and then
diluted with cold water (20 mL). The solid product was collected
by Büchner filtration and was purified by re-crystallization from
80% ethanol to afford the desired 2-benzyl-3-phenylquinoxaline
3a as a white solid (mp: 113–115°C).
2-(4-Bromobenzyl)-3-phenylquinoxaline (3f). A white solid;
mp: 142–143°C; 1H NMR (400MHz, DMSO-d6) δ: 8.11–8.08
(m, 2H, ArH), 7.86–7.84 (m, 2H, ArH), 7.59–7.51 (m, 5H, ArH),
7.36 (d, J= 8.4 Hz, 2H, ArH), 6.91 (t, J= 8.4 Hz, 2H, ArH), 4.38 (s,
2H, CH2). IR (KBr, ν, cmÀ1): 3043, 3021, 2952, 1563, 1552, 1524,
1456, 1434, 1353, 1235, 1213, 1071, 1019, 812, 756, 618. HRMS
(ESI): m/z calcd. for C21H16BrN2, 375.0492 [M + H]+; found: 375.0500.
2-(4-Bromobenzyl)-3-(4-methoxyphenyl)quinoxaline (3g). A yellow
solid; mp: 132–133°C; 1H NMR (400 MHz, DMSO-d6) δ: 8.08–8.04
(m, 2H, ArH), 7.84–7.81 (m, 2H, ArH), 7.56 (d, J=8.8Hz, 2H,
ArH), 7.38 (d, J= 8.4 Hz, 2H, ArH), 7.07 (d, J= 8.8 Hz, 2H, ArH),
6.90 (d, J= 8.4 Hz, 2H, ArH), 4.40 (s, 2H, CH2), 3.84 (s, 3H,
OCH3). 13C NMR (100 MHz, DMSO-d6) δ: 160.3, 154.9, 154.5,
140.9, 140.8, 138.2, 131.6, 131.5, 131.1, 131.0, 130.4, 130.3,
129.2, 128.8, 119.9, 114.2, 55.7, 41.4; IR (KBr, ν, cmÀ1):
3045, 3034, 2972, 1594, 1565, 1501, 1474, 1451, 1353, 1234,
1308, 1212, 1082, 1001, 833, 811, 752, 617. HRMS (ESI): m/z
calcd. for C22H18BrN2O, 405.0598 [M + H]+; found: 405.0602.
2-Benzyl-3-phenylquinoxaline (3a).
A white solid; mp:
113–115°C; 1H NMR (400 MHz, DMSO-d6) δ: 8.10 (d,
J = 8.0 Hz, 2H, ArH), 7.85 (d, J = 4.0 Hz, 2H, ArH), 7.57–7.50
(m, 5H, ArH), 7.19–7.13 (m, 3H, ArH), 6.92 (d, J = 6.8 Hz, 2H,
ArH), 4.41 (s, 2H, CH2); 13C NMR (100 MHz, DMSO-d6) δ:
154.9, 154.4, 140.6, 140.3, 138.5, 138.2, 130.1, 129.9, 128.9,
128.8, 128.8, 128.6, 128.4, 128.2, 128.2, 126.2, 41.5; IR (KBr,
ν, cmÀ1): 3031, 3012, 2967, 1578, 1545, 1501, 1480, 1431,
1352, 1234, 1301, 1223, 1091, 1007, 824, 811, 756, 610. HRMS
(ESI): m/z calcd. for C21H17N2, 297.1383 [M + H]+; found: 297.1399.
2-(4-Fluorobenzyl)-3-(4-methoxyphenyl)quinoxaline (3b). A white
1
solid; mp: 99–101°C; H NMR (400 MHz, DMSO-d6) δ: 8.07
2-(2,4-Dichlorobenzyl)-3-phenylquinoxaline (3h).
A white
1
(d, J = 3.2 Hz, 2H, ArH), 7.84–7.82 (m, 2H, ArH), 7.55
solid; mp: 117–119°C; H NMR (400 MHz, DMSO-d6) δ: 8.10
(d, J = 7.6 Hz, 1H, ArH), 7.95 (d, J = 2.4 Hz, 4H, ArH), 7.83–7.81
(m, 2H, ArH), 7.70–7.67 (m, 2H, ArH), 7.54–7.52 (m, 4H, ArH),
7.37–7.34 (m, 1H, ArH), 7.30 (d, J = 8.4 Hz, 1H, ArH), 4.48
(s, 2H, CH2). 13C NMR (100MHz, DMSO-d6) δ: 155.1, 153.5,
140.9, 140.7, 138.7, 136.1 134.6, 133.6, 132.4, 130.6, 130.4,
129.5, 129.4, 129.3, 129.0, 128.8, 127.7, 39.6; IR (KBr, ν, cmÀ1):
3055, 3042, 2970, 1598, 1562, 1506, 1480, 1433, 1354, 1224,
1308, 1203, 1090, 1002, 830, 815, 762, 615. HRMS (ESI): m/z
calcd. for C21H15Cl2N2, 365.0607 [M+ H]+; found: 365.0612.
2-(4-Chlorobenzyl)-3-(4-methoxyphenyl)-6,7-dimethylquinoxaline
(d, J = 8.8 Hz, 2H, ArH), 7.07 (d, J = 8.8 Hz, 2H, ArH), 7.02–
7.00 (m, 4H, ArH), 4.42 (s, 2H, CH2), 3.84 (s, 3H, OCH3). 13
C
NMR (100 MHz, DMSO-d6) δ: 159.8, 154.5, 154.3, 140.3,
134.4, 130.7, 130.5, 130.5, 130.4, 129.9, 129.8, 128.7, 128.3,
115.1, 114.8, 113.7, 55.2, 40.7, 30.6; IR (KBr, ν, cmÀ1): 3040,
3031, 2958, 1591, 1563, 1521, 1476, 1454, 1353, 1235, 1302,
1213, 1076, 1016, 812, 756, 618. HRMS (ESI): m/z calcd. for
C22H18FN2O, 345.1398 [M + H]+; found: 345.1409.
2-(4-Chlorobenzyl)-3-(4-methoxyphenyl)quinoxaline (3c). A white
solid; mp: 125–127°C; 1H NMR (400 MHz, DMSO-d6) δ: 8.09–
8.04 (m, 2H, ArH), 7.84–7.81 (m, 2H, ArH), 7.56 (d, J = 8.8 Hz,
2H, ArH), 7.25 (d, J = 8.4 Hz, 2H, ArH), 7.07 (d, J = 8.8 Hz, 2H,
ArH), 7.01 (d, J = 8.4 Hz, 2H, ArH), 4.43 (s, 2H, CH2), 2.46
(s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ: 160.3,
154.9, 154.5, 140.9, 140.8 137.8, 131.3, 131.1, 131.0, 130.4,
130.3, 129.2, 128.8, 128.7, 114.2, 55.7, 41.4; IR (KBr, ν, cmÀ1):
3046, 3031, 2972, 1591, 1567, 1501, 1471, 1452, 1351, 1237,
1301, 1202, 1085, 1001, 833, 813, 754, 616. HRMS (ESI): m/z
calcd. for C22H18ClN2O, 403.0805 [M+ H]+; found: 403.0813.
1
(3i). A pale yellow solid; mp: 142–144°C; H NMR (400 MHz,
DMSO-d6) δ: 7.82 (d, J= 4.8 Hz, 2H, ArH), 7.53 (d, J= 8.8 Hz, 2H,
ArH), 7.25 (d, J= 8.4 Hz, 2H, ArH), 7.05 (d, J= 8.8 Hz, 2H, ArH),
7.00 (d, J= 8.4 Hz, 2H, ArH), 4.37 (s, 2H, CH2), 3.84 (s, 3H,
OCH3), 2.46 (s, 6H, CH3). 13C NMR (100 MHz, DMSO-d6) δ:
159.7, 153.3, 152.7, 140.1, 140.0, 139.3, 137.6, 130.9, 130.8, 130.5,
130.4, 128.1, 127.6, 127.3, 113.7, 55.2, 40.7, 19.7, 19.7; IR (KBr, ν,
cmÀ1): 3043, 3035, 2954, 1578, 1552, 1524, 1475, 1451, 1343,
1332, 1213, 1072, 1011, 802, 753, 610. HRMS (ESI): m/z calcd. for
C24H22ClN2O, 389.1412 [M + H]+; found: 389.1431.
2-(2-Chlorobenzyl)-3-(4-chlorophenyl)quinoxaline (3d).
A white
solid; mp: 130–131°C; 1H NMR (400 MHz, DMSO-d6) δ:
8.13–8.10 (m, 1H, ArH), 7.98–7.96 (m, 1H, ArH), 7.85–7.83
(m, 2H, ArH), 7.71 (d, J = 8.4 Hz, 2H, ArH), 7.60 (d,
J = 8.4 Hz, 2H, ArH), 7.37–7.35 (m, 1H, ArH), 7.27–7.24 (m,
3H, ArH), 4.50 (s, 2H, CH2). 13C NMR (100 MHz, DMSO-d6)
δ: 154.1, 153.8, 141.1, 140.6, 137.7, 136.8, 134.4, 133.5,
132.3, 131.3, 130.8, 130.5 129.5, 129.3, 128.9, 128.8, 127.5,
40.0; IR (KBr, ν, cmÀ1): 3053, 3032, 2948, 1593, 1562, 1511,
1456, 1456, 1351, 1245, 1301, 1233, 1072, 1046, 815, 756,
611. HRMS (ESI): m/z calcd. for C21H15Cl2N2, 365.0607
[M + H]+; found: 365.0612.
2-(4-Bromobenzyl)-3-(4-chlorophenyl)-6,7-dimethylquinoxaline
(3j).
A yellow solid; mp: 154–155°C; 1H NMR (400 MHz,
DMSO-d6) δ: 7.85 (s, 2H, ArH), 7.62–7.54 (m, 4H, ArH), 7.38
(d, J= 8.4 Hz, 2H, ArH), 6.92 (d, J= 8.4 Hz, 2H, ArH), 4.33 (s, 2H,
CH2), 2.48 (s, 3H, CH3), 2.47 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6) δ: 153.0, 141.2, 140.8, 140.1, 139.7, 138.2, 138.0, 134.1,
131.6, 131.5, 131.4, 128.8, 128.1, 127.8, 119.8, 41.2, 20.3; IR (KBr, ν,
cmÀ1): 3045, 3032, 2965, 1591, 1552, 1500, 1470, 1431, 1351, 1219,
1301, 1210, 1075, 1004, 830, 812, 761, 621. HRMS (ESI): m/z
calcd. for C23H19BrClN2, 437.0412 [M + H]+; found: 437.0408.
2-(4-Bromobenzyl)-6,7-dimethyl-3-phenylquinoxaline
A yellow solid; mp: 133–134°C; 1H NMR (400 MHz,
2-(4-Bromobenzyl)-3-(4-chlorophenyl)quinoxaline (3e).
A
(3k).
1
white solid; mp: 137–138°C; H NMR (400 MHz, DMSO-d6) δ:
8.10 (dd, J = 4.4 Hz, J = 5.2 Hz, 2H, ArH), 7.89–7.85 (m, 2H,
ArH), 7.63–7.56 (m, 4H, ArH), 6.95 (d, J = 8.4 Hz, 2H, ArH),
4.38 (s, 2H, CH2). 13C NMR (100 MHz, DMSO-d6) δ: 154.3,
154.2, 141.1, 140.7, 137.9, 137.7, 134.3, 131.6, 131.5, 131.4,
130.9, 130.5, 129.3, 128.9, 128.8, 119.9, 41.4; IR (KBr, ν,
cmÀ1): 3049, 3034, 2978, 1592, 1567, 1501, 1471, 1452, 1351,
1237, 1301, 1202, 1085, 1001, 833, 811, 752, 615. HRMS
(ESI): m/z calcd. for C21H15BrClN2, 409.0102 [M + H]+; found:
409.0106.
DMSO-d6) δ: 7.85 (s, 1H, ArH) , 7.70 (s, 1H, ArH), 7.67
(d, J= 4.0 Hz, 2H, ArH), 7.52–7.50 (m, 4H, ArH), 7.30
(t, J= 7.2 Hz, 1H, ArH), 7.23–7.22 (m, 1H, ArH), 7.18–7.14
(m, 1H, ArH), 4.44 (s, 2H, CH2), 2.44 (s, 3H, CH3), 2.42 (s, 3H,
CH3). 13C NMR (100 MHz, DMSO-d6) δ: 154.2, 152.6, 140.8,
140.5, 139.9, 139.6, 139.1, 139.0, 132.8, 132.4, 129.4, 128.8,
128.1, 128.0, 127.8, 124.5, 42.4, 20.3, 20.2; IR (KBr, ν, cmÀ1):
3035, 3018, 2951, 1571, 1553, 1523, 1453, 1443, 1352, 1231,
1213, 1076, 1016, 812, 756, 611. HRMS (ESI): m/z calcd. for
C23H20BrN2, 403.0805 [M + H]+; found: 403.0814.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-S. Tu, H.-W. Xu, W. Fan, B. Jiang, and S.-J. Tu
Vol 000
2-(3-Fluorobenzyl)-6,7-dimethyl-3-phenylquinoxaline
6,7-Dichloro-2-(4-chlorobenzyl)-3-phenylquinoxaline
(3l).
A white solid; mp: 105–106°C; 1H NMR (400 MHz,
DMSO-d6) δ: 7.85 (d, J= 4.8 Hz, 2H, ArH), 7.57–7.48 (m, 5H,
ArH), 7.24–7.19 (m, 1H, ArH), 6.99–6.94 (m, 1H, ArH), 6.78–7.72
(m, 2H, ArH), 4.38 (s, 2H, CH2), 2.48 (s, 3H, CH3), 2.47 (s, 3H,
CH3). 13C NMR (100 MHz, DMSO-d6) δ: 161.9(JC1F = 248.1 Hz),
153.7, 152.5, 141.2 (J5CF = 7.5 Hz), 140.5, 140.2, 139.5, 139.3,
138.6, 130.0 (J4CF = 8.4 Hz), 128.9, 128.7, 128.2, 127.6, 127.3,
124.8(J6CF = 2.6 Hz), 115.4(JC2F = 21.2 Hz ), 112.9(JC3F = 20.7 Hz ),
41.0, 19.7; IR (KBr, ν, cmÀ1): 3049, 3035, 2968, 1595, 1568,
1511, 1471, 1454, 1353, 1235, 1301, 1208, 1081, 1012, 830, 810,
751, 612. HRMS (ESI): m/z calcd. for C23H20FN2, 315.1293
(3q).
A brown solid; mp: 139–141°C; 1H NMR (400 MHz,
DMSO-d6) δ: 8.41 (d, J = 7.6 Hz, 2H, ArH), 7.60–7.58 (m, 2H,
ArH), 7.55–7.52 (m, 3H, ArH), 7.23 (d, J = 8.4 Hz, 2H, ArH),
6.96 (d, J = 8.4 Hz, 2H, ArH), 4.40 (s, 2H, CH2). 13C NMR
(100 MHz, DMSO-d6) δ: 156.67, 156.2, 140.0, 139.8, 138.2,
137.1, 133.3, 133.1, 131.5, 131.2, 130.2, 129.9, 129.8, 129.4,
128.8, 128.7, 41.4; IR (KBr, ν, cmÀ1): 3040, 3031, 2958, 1591,
1563, 1521, 1476, 1454, 1353, 1235, 1302, 1213, 1076, 1016,
812, 756, 618. HRMS (ESI): m/z calcd. for C21H14Cl3N2,
399.0214 [M+ H]+; found: 399.0219.
2-(2-Chlorobenzyl)-6,7-dichloro-3-phenylquinoxaline
1
[M + H]+; found: 315.1297.
(3r).
A purple solid; mp: 129–130°C; H NMR (400 MHz,
DMSO-d6) δ: 8.45 (s, 1H, ArH) , 8.28 (s, 1H, ArH) , 7.70–
7.67 (m, 2H, ArH), 7.55–7.54 (m, 3H, ArH), 7.35
(d, J = 4.0 Hz, 1H, ArH), 7.27–7.24 (m, 3H, ArH), 4.50 (s, 2H,
CH2). 13C NMR (100 MHz, DMSO-d6) δ: 156.5, 155.7, 139.9,
139.7, 138.1, 136.5, 133.5, 133.3, 133.0, 132. 3, 130.2, 129.8,
129.7, 129.5, 129.4, 128.9 127.6, 120.7, 117.8, 41.3; IR (KBr,
ν, cmÀ1): 3051, 3034, 2948, 1592, 1561, 1511, 1456, 1457,
1358, 1256, 1301, 1215, 1072, 1017, 830, 751, 631. HRMS
(ESI): m/z calcd. for C21H14Cl3N2, 399.0218 [M + H]+; found:
399.0209.
2-(4-Chlorobenzyl)-3-(4-chlorophenyl)-6,7-dimethylquinoxaline
(3m).
A white solid; mp: 160–162°C; 1H NMR (400 MHz,
DMSO-d6) δ: 7.98 (d, J = 8.4 Hz, 2H, ArH), 7.85 (s, 2H, ArH),
7.58–7.56 (m, 4H, ArH), 7.24 (d, J = 8.4 Hz, 2H, ArH), 7.24
(d, J = 8.4 Hz, 2H, ArH), 7.24 (d, J = 8.4 Hz, 2H, ArH), 7.24
(d, J = 8.4 Hz, 2H, ArH),4.35 (s, 2H, CH2), 2.48 (s, 3H, CH3),
2.47 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ: 153.1,
153.0, 141. 2, 140.8, 140.1, 139.7, 138.0, 137.8, 134.1, 131.4,
131.3, 131.1, 128.8, 128.6, 128.1, 127.8, 41.2, 20.3; IR (KBr,
ν, cmÀ1): 3045, 3034, 2972, 1594, 1565, 1501, 1474, 1451,
1353, 1234, 1308, 1212, 1082, 1001, 833, 811, 752, 617.
HRMS (ESI): m/z calcd. for C23H19Cl2N2, 393.0920 [M + H]+;
found: 393.0928.
Acknowledgments. We are grateful for the financial support from
the NSFC (Nos. 21072163, 21232004, 21272095, and 21102124),
the NSF of Jiangsu Education Committee (11KJB150016), Jiangsu
Science and Technology Support Program (No. BE2011045), and
the Qing Lan Project (12QLG006).
2-(2-Chlorobenzyl)-6,7-dimethyl-3-phenylquinoxaline
(3n).
A pale yellow solid; mp: 129–130°C; 1H NMR (400 MHz,
DMSO-d6) δ: 7.85 (s, 1H, ArH), 7.72 (s, 1H, ArH), 7.67–7.62 (m, 2H,
ArH), 7.54–7.50 (m, 3H, ArH), 7.37–7.33 (m, 1H, ArH), 7.26–7.22
(m, 3H, ArH), 4.45 (s, 2H, CH2), 2.46 (s, 3H, CH3), 2.44 (s, 3H,
CH3). 13C NMR (100 MHz, DMSO-d6) δ: 154.1, 152.6, 140.9,
140.5, 140.0, 139.6, 139.1, 137.2, 133.6, 132.2, 129.5, 129.4, 129.2,
128.8, 128.7, 128.1, 127.8, 127.5, 39.9, 20.2(5), 20.1(8); IR (KBr,
ν, cmÀ1): 3040, 3031, 2958, 1591, 1563, 1521, 1476, 1454, 1353,
1235, 1302, 1213, 1076, 1016, 812, 756, 618. HRMS (ESI): m/z
calcd. for C23H20ClN2, 359.1317 [M + H]+; found: 359.1337.
2-(2-Chlorobenzyl)-3-(4-methoxyphenyl)-6,7-dimethylquinoxaline
(3o). A yellow solid; mp: 151–152°C; 1H NMR (400 MHz,
DMSO-d6) δ: 7.83 (s, 1H, ArH) , 7.68 (s, 1H, ArH), 7.63
(d, J = 8.8 Hz, 2H, ArH), 7.38–7.36 (m, 1H, ArH), 7.27–7.23
(m, 3H, ArH), 7.08 (d, J = 8.8 Hz, 2H, ArH), 4.47 (s, 2H, CH2),
3.84 (s, 3H, OCH3), 2.45 (s, 3H, CH3), 2.42 (s, 3H, CH3). 13C
NMR (100 MHz, DMSO-d6) δ: 160.2, 153.8, 152.6, 140.5,
140.4, 139.7, 139.7, 137.4, 133.6, 132.2, 131.3, 131.0, 129.5,
128.7, 128.1, 127.7, 127.5, 114.2, 55.7, 41.3, 20.2(5), 20.1(5).
IR (KBr, ν, cmÀ1): 3040, 3031, 2958, 1591, 1563, 1521, 1476,
1454, 1353, 1235, 1302, 1213, 1076, 1016, 812, 756, 618.
HRMS (ESI): m/z calcd. for C24H22ClN2O, 389.1417 [M + H]+;
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