Logic design and synthesis of quinoxalines via the integration of iodination/oxidation/cyclization sequences from ketones and 1,2-diamines

Article abstract of DOI:10.1016/j.tet.2012.09.056

A novel protocol for the synthesis of quinoxalines has been developed from simple ketones and 1,2-diamines. This process underwent a logic approach to bis-substituted quinoxalines via a consecutive iodination/Kornblum oxidation/cyclization in the presence of I₂/CuO/DMSO and to mono-substituted quinoxalines via an iodination/cyclization/aromatization in the presence of I₂/CuO/K₃PO₄·3H ₂O.

Full text of DOI:10.1016/j.tet.2012.09.056

Tetrahedron 68 (2012) 9598e9605
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Logic design and synthesis of quinoxalines via the integration of iodination/
oxidation/cyclization sequences from ketones and 1,2-diamines
,
a,
Mi Lian a, Qi Li a, Yanping Zhu a, Guodong Yin b , Anxin Wu
*
*
a Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, China
b Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Hubei Normal University, Huangshi 435002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2012
Received in revised form 9 September 2012
Accepted 11 September 2012
Available online 17 September 2012
A novel protocol for the synthesis of quinoxalines has been developed from simple ketones and 1,2-
diamines. This process underwent a logic approach to bis-substituted quinoxalines via a consecutive
iodination/Kornblum oxidation/cyclization in the presence of I2/CuO/DMSO and to mono-substituted
quinoxalines via an iodination/cyclization/aromatization in the presence of I2/CuO/K3PO4$3H2O.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Quinoxaline
I2/CuO
One-pot reaction
1,2-Diamines
Logic design
1. Introduction
Quinoxaline is a common nitrogen-containing heterocyclic
compound, which has wide applications in pharmaceutical chem-
istry, in fields, such as anticancer,1 antiviral,2 and antibacterial.3
Quinoxaline and its derivatives can also act as important syn-
thetic intermediates.4 Due to these significant properties, a variety
of methods have been reported for the synthesis of quinoxalines.
The most common methods are derived by the condensation of 1,2-
diamines with two-carbon synthons, such as 1,2-diketone,5 oxalic
acid,6 aldehyde,7 ketones,8 diazenyl butenes,9 epoxides,10 alkyne,11
vicinal diols12 or diazoketone13 (Scheme 1).
In previous studies, we discovered that deoxybenzoin (1a) could
be oxidized to benzil (B) via an intermediate 2-iodo-1,2-
diphenylethanone (A)14 (Scheme 2a). In addition, it is well known
that 2,3-diphenylquinoxaline (3aa) could be obtained when the
benzil condensed with o-phenylenediamine (2a) (Scheme 2b).5a
Here, we present a new method for the synthesis of quinoxalines
via consecutive iodination/oxidation/cyclization sequences in one
pot from simple ketones and 1,2-diamines based on a logic design
(Scheme 2c).
* Corresponding authors. Tel./fax: þ86 27 67867773 (A.W.); tel./fax: þ86 714
6515602 (G.Y.); e-mail addresses: gdyin@hbnu.edu.cn (G. Yin), chwuax@mail.cc-
nu.edu.cn (A. Wu).
Scheme 1. Methods for the synthesis of quinoxalines.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.056

M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
9599
data). Methyl substituted 1,2-diamines gave the corresponding
products 3ab and 3ac in 82% and 81% yields, respectively. The
reactions between chloro-substituted 1,2-diamines and 1a pro-
vided slightly lower yields of 3ad and 3ae. Notably, even electron-
deficient bromo- and nitro-substituted 1,2-diamines were also
shown to be excellent substrates (3af and 3ag). When 3,30,4,40-
tetraamino-1,10-biphenyl was employed, the bis-quinoxaline
product 2,20,3,30-tetraphenyl-6,60-biquinoxaline (3ah) was iso-
lated in 36% yield.
Next, the variations of substituents on the aromatic ring in the
carbonyl compounds were also tested (Table 2). It was established
that the conditions were mild enough to be compatible with
a range of functional groups. The electron-neutral (CH3) and
electron-rich (OCH3) substituted ketones all reacted with 1,2-
diamines efficiently to give the desired products 3baebe in
75e84% yields. Substrates containing the electron-withdrawing
group (Cl and Br) worked well in this transformation, and the
corresponding products 3bf and 3bg were obtained in 81% and
80% yields, respectively. When propiophenone was subjected to
standard conditions, furnishing 3bh in 67% yield. It was found
that the substrate containing hydroxyl group (OH) was also
suitable for the reaction resulting in the iodinated product 3bi in
41% yield.
Scheme 2. Approaches to benzil and 2,3-diphenylquinoxaline.
2. Results and discussions
Firstly, deoxybenzoin (1a) (1.0 mmol) was treated with I2
(1.1 mmol) and CuO (1.1 mmol) in DMSO (3 mL) at 100 ꢀC for 4 h.
After the disappearance of the starting material, o-phenylenedi-
amine (2a) (3.0 mmol) was added and stirred for another 1 h and
the desired product 2,3-diphenylquinoxaline (3aa) was obtained
in 85% yield. Then we set out to explore the generality of this
sequential process with various 1,2-diamines. The results in-
dicated that this method was workable for 1,2-diamines with
electron-withdrawing or electron-donating substituents on the
aromatic backbone (Table 1). We furnished the expected qui-
noxalines 3aaeag in appreciable yields ranging from 62% to 85%,
while the configurations of 3aa and 3ae were unambiguously
clarified by X-ray crystallographic analysis (see Supplementary
Table 2
Scopes of 1,2-diamines and ketonesa,b
Table 1
One-pot synthesis of quinoxalines from 1,2-diamines and deoxybenzoina,b
Furthermore, the reaction substrates were extended to aryl
methyl ketones for the synthesis of mono-substituted quinoxalines.
However, when acetophenone (4a) was treated with o-phenyl-
enediamine under above-mentioned standard conditions, un-
expected (1H-benzo[d]imidazol-2-yl)(phenyl)methanone (5a) was
the main product (69% yield) and 2-phenylquinoxaline (6aa) was
only isolated in 19% yield (Scheme 3). So that, the present trans-
formation is unsuitable for aryl methyl ketone substrates under
above-mentioned standard conditions. We next explore new routes
to synthesis of mono-substituted quinoxalines with high
chemoselectivity.

9600
M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
Table 3
One-pot synthesis of 6 from methyl ketones and o-phenylenediaminea,b
Scheme 3. Synthesis of compounds 5a and 6aa acetophenone.
It was been reported that
a-bromination ketones could react
with 1,2-diamines to deliver quinoxaline.8fei Therefore, we are
attempted to a two-step one-pot synthesis of mono-substituted
quinoxalines via iodinated ketones. It was found that the re-
action was well performed to generate 2-iodo-1-phenylethanone
in situ in the presence of I2 and CuO at refluxing methanol in the
first step.15 Subsequently, o-phenylenediamine and base were
added to optimize the reaction conditions in second step. The
experimental results indicated that the basicity had a great effect
on the yield of 6aa. K3PO4$3H2O was proved to be superior to other
bases, such as K2CO3, Cs2CO3, DBU, DABCO, Et3N, KH2PO4, NaH2
-
PO4$2H2O, Na2HPO4$12H2O, Na3PO4$12H2O, and Zn3(PO4)2$4H2O.
No expected product was observed using piperidine or pyridine.
Compound 6aa was isolated in highest yield (80%) at 40 ꢀC in the
presence of K3PO4$3H2O. The yield of 6aa obviously decreased
with increasing or reducing the reaction temperature (see
Supplementary data).
Based on the successful synthesis of 6aa, the optimized condi-
tions were then applied to other aryl methyl ketones (Table 3).
When the substrates bearing electron-donating substituted groups
on the phenyl ring, the corresponding products 6abeae were ob-
tained in 80e86% yields. In addition, the structure of 6ac was
confirmed by X-ray diffraction analysis (see Supplementary data).
The substrates bearing electron-withdrawing substituted groups
also provided the products 6afeai in good yields (63e72%). Much
to our satisfaction, the substrates containing sterically hindered
naphthyl ring, hydroxyl group (eOH), substituted amino group
(eNR2), and heterocycles (furan, thiophene, benzofuran, and 3-
indole), 6ajeaq were also obtained in satisfied yields (63e81%).
Then we explored the scopes of a series of 1,2-diamines to in-
vestigate the effect of substituents on the reactivity and regiose-
lectivity (Table 4). 4,5-Dimethylbenzene-1,2-diamine and 4-
methylbenzene-1,2-diamine gave the corresponding products
6baebd in good yields (71e83%). Substrates containing electron-
withdrawing groups (eCl, eBr) furnished the corresponding
6beebg in moderate to good yields (50e74%). It should be notable
that, unsymmetrical 1,2-diamines resulted in two isomers of 6bd,
6bf, 6bg with the ratio of 1:1 to 2:3.
We presented a possible pathway of consecutive iodination/
oxidation/cyclization sequences for the synthesis of quinoxalines
(Scheme 4). The ketone was converted into the corresponding a-
(0.10 mmol), iodine (0.11 mmol), and CuO (0.11 mmol) at 100 ꢀC in
DMSO-d6 (0.5 mL). The reaction was monitored at different time
points during the reaction course. The characteristic peak of iodo-
phenylethanone A appeared after 1 h. Intermediate A was con-
sumed completely after 6 h and converted to benzil B quantita-
tively. After addition of 1,2-diamine (0.30 mmol), the
corresponding peaks of quinoxaline 3aa were observed. The ex-
perimental proved that A and B were the possible intermediates.
iodinated intermediates 2-iodo-1,2-diphenylethanone A (R¼Ph) or
2-iodo-1-phenylethanone C (R¼H) in the presence of I2 and CuO.
On the one hand, intermediate A underwent Kornblum oxidation to
give benzil B.14 Subsequently, I2 catalyzed the condensation re-
action of B and 1,2-diamine (2a) to afford the desired quinoxaline
3aa.5a On the other hand, intermediate C15 was reacted with 2a
undergoing intermolecular nucleophilic substitution and conden-
sation reaction to form D,8c,g which underwent an oxidative aro-
matization step to give quinoxaline 6aa.
3. Conclusion
To confirm the reaction process, the reactions of intermediates
were carried out (Scheme 5). When iodo-phenylethanone (A) was
stirred in DMSO and then 1,2-diamine (2a) was added, the target
product 3aa was obtained in 80% yield in the presence of iodine and
DMSO (Scheme 5a). Benzil (B) was reacted with 2a to give 3aa in
96% yield (Scheme 5b).
In summary, a novel and convenient one-pot protocol for the
synthesis of quinoxaline derivatives has been developed from
simple ketones and 1,2-diamines. This process underwent a logic
approach to bis-substituted quinoxalines (3) via a consecutive io-
dination/Kornblum oxidation/cyclization in the presence of I2/CuO/
DMSO and to mono-substituted quinoxalines (6) via an iodination/
cyclization/aromatization in the presence of I2/CuO/K3PO4$3H2O.
The plausible reaction mechanism was also discussed by control
experimental and 1H NMR spectroscopic monitoring.
Moreover, monitoring of the reaction by 1H NMR (400 MHz)
further demonstrated this plausible pathway (Fig. 1). We set up the
reaction in the NMR tube that contained deoxybenzoin (1a)

M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
9601
Table 4
Scopes of methyl ketones and 1,2-diaminesa,b
Fig. 1. 1H NMR spectroscopic monitoring of the present reaction.
4. Experimental section
4.1. General procedure for the synthesis of compound 3
(using 2,3-diphenylquinoxaline 3aa as an example)
A stirred solution of deoxybenzoin 1a (196 mg, 1.0 mmol), CuO
(88 mg, 1.1 mmol), and iodine (279 mg, 1.1 mmol) was heated at
100 ꢀC for 4 h in DMSO (3 mL), after the disappearance of the
starting material (TLC), 1,2-diamine 2a (324 mg, 3.0 mmol) was
added and stirred for another 1 h. Then the reaction mixture was
poured into 50 mL brine and the aqueous layer was extracted with
EtOAc (3ꢁ50 mL). The extract was washed with Na2S2O3 solution,
dried over anhydrous Na2SO4 then the solvent was removed under
reduced pressure. The residue was purified by column chroma-
tography on silica gel using petroleum ether/EtOAc as the eluent to
give the expected products 3aa as the yellow solid (240 mg, 85%
yield).
4.2. General procedure for the synthesis of compound 6
(using 2-phenylquinoxaline 6aa as an example)
Scheme 4. The plausible pathway of the present reaction.
A mixture of acetophenone 4a (120 mg, 1.0 mmol), iodine
(254 mg, 1.0 mmol), and CuO (88 mg, 1.1 mmol) in anhydrous
methanol (10 mL) was heated at reflux, after disappearance of the
reactant (1e12 h, monitored by TLC), 1,2-diamines 2a (108 mg,
1.0 mmol) and K3PO4$3H2O (266 mg, 1.0 mmol) was added and the
mixture was stirred for 12 h at 40 ꢀC. The solvent was removed
under reduced pressure, and 50 mL water was added to mixture,
extracted with EtOAc three times (3ꢁ50 mL). The extract was
washed with Na2S2O3, dried over anhydrous Na2SO4, and concen-
trated in vacuo. The residue was purified by column chromatog-
raphy on silica gel using petroleum ether/EtOAc as the eluent to
give the expected products 6aa as pale yellow solid, (80% yield).
4.3. Characterization data
4.3.1. 2,3-Diphenylquinoxaline (3aa).8l Yield 85%, yellow solid; mp
117e119 ꢀC; IR (KBr, cmꢂ1): 3059, 1634, 1477, 1441, 1346, 1076, 1058,
Scheme 5. Control experimental.

9602
M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
770, 698; 1H NMR (CDCl3, 600 MHz):
d
(ppm) 8.18e8.20 (m, 2H),
129.8, 129.5, 128.9, 128.3, 127.4; EI-MS: m/z 562.5 (M, 100), 355.3
(61), 280.6 (84), 228.9 (56), 215.2 (47), 178.0 (55), 150.1 (98).
7.77e7.79 (m, 2H), 7.52 (d, J¼7.2 Hz, 4H), 7.33e7.38 (m, 6H); 13C
NMR (CDCl3, 100 MHz):
d (ppm) 153.4, 141.1, 138.9, 129.9, 129.8,
129.1, 128.8, 128.2; HRMS (APCI): m/z [MþH]þ calcd for C20H14N2:
4.3.9. 2-Phenyl-3-(p-tolyl)quinoxaline (3ba).8l Yield 82%, yellow
solid; mp 112e114 ꢀC; IR (KBr, cmꢂ1): 3053, 2923, 1613, 1554, 1512,
1476, 1442, 1394, 1345, 1055, 1019, 975, 755, 698; 1H NMR (CDCl3,
283.1230; found: 283.1231.
4.3.2. 6-Methyl-2,3-diphenylquinoxaline (3ab).8l Yield 82%, white
solid; mp 110e112 ꢀC; IR (KBr, cmꢂ1): 3056, 2940, 1618, 1486, 1444,
400 MHz):
(m, 2H), 7.41 (d, J¼8.0 Hz, 2H), 7.32 (m, 3H), 7.11 (d, J¼7.6 Hz, 2H),
2.33 (s, 3H); 13C NMR (CDCl3, 100 MHz):
(ppm) 153.4, 141.2, 141.0,
d (ppm) 8.14e8.16 (m, 2H), 7.69e7.71 (m, 2H), 7.52e7.54
1200, 1057, 1022, 809, 773, 701; 1H NMR (CDCl3, 400 MHz):
d
(ppm)
d
8.06 (d, J¼8.8 Hz, 1H), 7.95 (s, 1H), 7.60 (d, J¼7.6 Hz, 1H), 7.51 (d,
139.2, 138.8, 136.1,129.8, 129.7, 129.1,129.0, 128.7,128.2, 21.3; HRMS
J¼6.8 Hz, 4H), 7.33 (d, J¼6.4 Hz, 6H), 2.61 (s, 3H); 13C NMR (CDCl3,
(APCI): m/z [MþH]þ calcd for C21H16N2: 297.1386; found: 297.1387.
100 MHz):
d (ppm) 153.3, 152.5, 141.2, 140.5, 139.6, 139.1, 132.3,
129.8, 128.7, 128.6, 128.2, 128.0, 21.9; HRMS (APCI): m/z [MþH]þ
4.3.10. 6,7-Dimethyl-2-phenyl-3-(p-tolyl)quinoxaline (3bb). Yield
84%, white solid; mp 132e134 ꢀC; IR (KBr, cmꢂ1): 3031, 2971, 2936,
2916, 1728, 1609, 1476, 1447, 1415, 1340, 1207, 1056, 1020, 867, 699;
calcd for C21H16N2: 297.1386; found: 297.1387.
4.3.3. 6,7-Dimethyl-2,3-diphenylquinoxaline (3ac).8l Yield 81%, yel-
low solid; mp 175e176 ꢀC; IR (KBr, cmꢂ1): 3038, 2970, 2928, 2852,
1630, 1548, 1445, 1414, 1344, 1209, 1023, 870, 761, 700; 1H NMR
1H NMR (CDCl3, 400 MHz):
d
(ppm) 7.91 (s, 2H), 7.51 (d, J¼6.4 Hz,
2H), 7.39 (d, J¼7.6 Hz, 2H), 7.33e7.34 (m, 3H), 7.12 (d, J¼7.6 Hz,
2H), 2.50 (s, 6H), 2.35 (s, 3H); 13C NMR (CDCl3, 100 MHz):
(ppm)
d
(CDCl3, 400 MHz):
d
(ppm) 7.93 (s, 2H), 7.50 (d, J¼6.0 Hz, 4H),
152.4, 140.4, 140.3, 140.2, 139.5, 138.4, 136.4, 129.7, 128.9, 128.4,
128.2, 21.3, 20.4; HRMS (APCI): m/z [MþH]þ calcd for C23H20N2:
325.1699; found: 325.1700.
7.32e7.33 (m, 6H), 2.52 (s, 6H); 13C NMR (CDCl3, 100 MHz):
d
(ppm)
152.4, 140.5, 140.1, 139.3, 129.8, 128.5, 128.2, 20.5; HRMS (APCI): m/z
[MþH]þ calcd for C22H18N2: 311.1543; found: 311.1544.
4.3.11. 6,7-Dichloro-2-phenyl-3-(p-tolyl)quinoxaline (3bc). Yield
75%, yellow solid; mp 134e136 ꢀC; IR (KBr, cmꢂ1): 3065, 3032,
2919, 2856, 1610, 1536, 1441, 1388, 1336, 1256, 1191, 1108, 1058,
4.3.4. 6-Chloro-2,3-diphenylquinoxaline (3ad).8l Yield 66%, white
solid; mp 117e120 ꢀC; IR (KBr, cmꢂ1): 3053, 1605, 1550, 1468, 1444,
1341, 1069, 831, 802, 768, 695; 1H NMR (CDCl3, 400 MHz):
d
(ppm)
1021, 960, 886, 831, 692; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 8.26
(s, 2H), 7.51 (d, J¼6.8 Hz, 2H), 7.33e7.41 (m, 5H), 7.14 (d, J¼7.6 Hz,
2H), 2.37 (s, 3H); 13C NMR (CDCl3, 100 MHz):
(ppm) 154.4, 139.9,
8.16e8.16 (m, 1H), 8.08e8.10 (m, 1H), 7.67e7.70 (m, 1H), 7.51 (d,
J¼7.2 Hz, 4H), 7.31e7.39 (m, 6H); 13C NMR (CDCl3, 100 MHz):
d
d
(ppm) 154.2, 153.5, 141.4, 139.6, 138.6, 138.5, 135.6, 130.9, 130.3,
139.7, 139.5, 138.5, 135.4, 134.3, 134.1, 129.7, 129.2, 129.1, 128.3,
21.4; HRMS (APCI): m/z [MþH]þ calcd for C21H14Cl2N2: 365.0607;
found: 365.0609.
129.8, 129.7, 129.0, 128.9, 128.2, 128.0; HRMS (APCI): m/z [MþH]þ
calcd for C20H13ClN2: 317.0840; found: 317.0841.
4.3.5. 6,7-Dichloro-2,3-diphenylquinoxaline (3ae). Yield 62%, yel-
low solid; mp 154e156 ꢀC; IR (KBr, cmꢂ1): 3047, 2961, 2926, 2854,
1586, 1533, 1492, 1439, 1334, 1259, 1188, 1066, 1021, 881, 768, 697;
4.3.12. 2,3-Bis(4-methoxyphenyl)quinoxaline (3bd).8l Yield 83%,
yellow solid; mp 147e148 ꢀC; IR (KBr, cmꢂ1): 3006, 2960, 2840,
1607, 1512, 1464, 1394, 1348, 1288, 1244, 1174, 1028, 830, 765; 1H
1H NMR (CDCl3, 600 MHz):
d
(ppm) 8.29 (s, 2H), 7.50 (d, J¼7.8 Hz,
NMR (CDCl3, 400 MHz): d (ppm) 8.11e8.14 (m, 2H), 7.70e7.73 (m,
4H), 7.39 (d, J¼6.6 Hz, 2H), 7.35 (t, J¼7.2 Hz, 4H); 13C NMR (CDCl3,
2H), 7.50 (d, J¼8.4 Hz, 4H), 6.87 (d, J¼8.8 Hz, 4H), 3.82 (s, 6H); 13C
100 MHz):
d
(ppm) 154.4, 139.9, 138.3, 134.4, 129.7, 129.3, 128.3;
NMR (CDCl3, 100 MHz): d (ppm) 160.1, 153.0, 141.0, 131.6, 131.2,
HRMS (APCI): m/z [MþH]þ calcd for C20H12Cl2N2: 351.0450; found:
129.5, 128.9, 113.7, 55.3; HRMS (APCI): m/z [MþH]þ calcd for
351.0451.
C22H18N2O2: 343.1441; found: 343.1441.
4.3.6. 6-Bromo-2,3-diphenylquinoxaline (3af). Yield 80%, yellow
solid; mp 118e120 ꢀC; IR (KBr, cmꢂ1): 3045, 1592, 1546, 1468, 1444,
1390, 1340, 1184, 1060, 1024, 975, 914, 829, 801, 767, 695; H NMR
4.3.13. 2,3-Bis(4-methoxyphenyl)-6,7-dimethylquinoxaline (3be).-
Yield 83%, yellow solid; mp 123e125 ꢀC; IR (KBr, cmꢂ1): 2931,
2835, 1605, 1512, 1457, 1419, 1342, 1296, 1248, 1174, 1027, 970, 833;
1
(CDCl3, 400 MHz):
d
(ppm) 8.36e8.37 (m, 1H), 8.03e8.05 (m, 1H),
1H NMR (CDCl3, 400 MHz):
d
(ppm) 7.86 (s, 2H), 7.46 (d, J¼8.8 Hz,
7.84 (q, J¼7.2 Hz, 1H), 7.51 (d, J¼7.2 Hz, 4H), 7.32e7.40 (m, 6H); 13C
4H), 6.85 (d, J¼8.8 Hz, 4H), 3.80 (s, 6H), 2.47 (s, 6H); 13C NMR
NMR (CDCl3, 100 MHz):
d
(ppm) 154.2, 153.7, 141.7, 139.9, 138.6,
(CDCl3, 100 MHz): d (ppm) 159.8, 151.9, 138.9, 131.9, 131.1, 127.9,
138.5, 133.5, 131.4, 130.5, 129.8, 129.7, 129.1, 129.0, 128.3, 123.8;
HRMS (APCI): m/z [MþH]þ calcd for C20H13BrN2: 361.0335; found:
361.0335.
113.6, 55.2, 20.3; HRMS (APCI): m/z [MþH]þ calcd for C24H22N2O2:
371.1754; found: 371.1754.
4.3.14. 2-(4-Chlorophenyl)-3-phenylquinoxaline (3bf).8l Yield 81%,
white solid; mp 136e138 ꢀC; IR (KBr, cmꢂ1): 3056, 2927, 1727, 1589,
1492, 1476, 1441, 1399, 1344, 1089, 1056, 1013, 977, 843, 804, 765,
4.3.7. 6-Nitro-2,3-diphenylquinoxaline (3ag).8l Yield 83%, yellow
solid; mp 184e186 ꢀC; IR (KBr, cmꢂ1): 3090, 3056, 1614, 1520, 1399,
1341, 1055, 1025, 812, 769, 700; 1H NMR (CDCl3, 400 MHz):
d
(ppm)
699; 1H NMR (CDCl3, 400 MHz):
d (ppm) 8.16e8.20 (m, 2H),
9.09e9.09 (m, 1H), 8.54 (q, J¼6.8 Hz, 1H), 8.30e8.32 (m, 1H),
7.78e7.81 (m, 2H), 7.45e7.52 (m, 4H), 7.35e7.40 (m, 3H), 7.32 (d,
7.55e7.58 (m, 4H), 7.36e7.45 (m, 6H); 13C NMR (CDCl3, 100 MHz):
J¼8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz):
d (ppm) 153.2, 152.1,
d
(ppm) 156.2, 155.5, 147.7, 143.4, 139.8, 137.9, 137.9, 130.6, 129.8,
141.1, 138.7, 137.4, 135.1, 131.2, 130.2, 130.2, 129.7, 129.2, 129.1, 129.0,
128.5, 128.5; HRMS (APCI): m/z [MþH]þ calcd for C20H13ClN2:
317.0840; found: 317.0841.
129.7,129.5, 128.4,125.5,123.2; HRMS (APCI): m/z [MþH]þ calcd for
C20H13N3O2: 328.1081; found: 328.1082.
4.3.8. 2,20,3,30-Tetraphenyl-6,60-biquinoxaline (3ah).5d Yield 36%,
yellow solid; mp >300 ꢀC; IR (KBr, cmꢂ1): 3056, 1613, 1553, 1476,
1444, 1390, 1344, 1190, 1058, 830, 802, 767, 697; 1H NMR (CDCl3,
4.3.15. 2-(4-Bromophenyl)-3-phenylquinoxaline (3bg).8l Yield 80%,
white solid; mp 146e147 ꢀC; IR (KBr, cmꢂ1): 3055, 1584, 1535, 1478,
1441, 1396, 1343, 1220, 1071, 1054, 1009, 976, 840, 803, 765, 700; 1H
400 MHz):
d
(ppm) 8.60 (s, 2H), 8.33 (s,1H), 8.31 (s,1H), 8.25 (s,1H),
NMR (CDCl3, 400 MHz):
d
(ppm) 8.19 (s, 2H), 7.80 (d, J¼6.4 Hz, 2H),
8.23 (s, 1H), 7.57 (d, J¼6.8 Hz, 8H), 7.37 (d, J¼6.8 Hz, 12H); 13C NMR
7.50 (q, J¼8.0 Hz, 4H), 7.39e7.42 (m, 5H); 13C NMR (CDCl3,
(CDCl3, 100 MHz):
d
(ppm) 154.1, 153.7, 141.4, 141.2, 140.9, 138.9,
100 MHz): d (ppm) 153.2, 152.1, 141.2, 141.1, 138.7, 137.9, 131.5, 130.2,

M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
9603
130.2, 129.7, 129.2, 129.1, 129.0, 128.5, 123.5; HRMS (APCI): m/z
[MþH]þ calcd for C20H13BrN2: 361.0335; found: 361.0336.
8.10 (t, J¼8.6 Hz, 2H), 7.69e7.77 (m, 4H), 7.04 (d, J¼8.4 Hz, 1H), 4.34
(s, 4H); 13C NMR (CDCl3, 100 MHz):
(ppm) 151.0, 145.6, 143.9,
142.9, 142.1, 141.1, 130.0, 129.3, 129.0, 128.9, 120.7, 117.8, 116.4, 64.5,
64.2. HRMS (ESI): m/z [MþH]þ calcd for C16H13N2O2: 265.0973;
found: 265.0972.
d
4.3.16. 2-Methyl-3-phenylquinoxaline (3bh).5g Yield 67%, red oil; IR
(KBr, cmꢂ1): 3059, 3031, 2923, 1561, 1482, 1444, 1396, 1374, 1343,
1249, 1220, 1191, 1129, 1005, 764, 700; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 8.04e8.12 (m, 2H), 7.64e7.74 (m, 4H), 7.47e7.53 (m, 3H),
4.3.24. 2-(4-Bromophenyl)quinoxaline (6af).8i Yield 72%, pale yel-
low solid; mp: 134e137 ꢀC; IR (KBr, cmꢂ1): 1586, 1538, 1484, 1124,
2.77 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d
(ppm) 154.7, 152.3, 141.0,
140.8, 138.8, 129.6, 129.1, 128.8, 128.8, 128.4, 128.1, 24.3; HRMS
1072, 1046; 1H NMR (CDCl3, 400 MHz):
d (ppm) 9.29 (s, 1H),
(APCI): m/z [MþH]þ calcd for C15H12N2: 221.1073; found: 211.1074.
8.06e8.14 (m, 4H), 7.75e7.81 (m, 2H), 7.68 (d, J¼8.4 Hz, 2H); 13C
NMR (CDCl3, 100 MHz):
d (ppm) 150.6, 142.7, 142.15, 141.6, 135.5,
4.3.17. 4-(3-Phenylquinoxalin-2-yl)benzene-1,3-diol (3bi). Yield
41%, yellow solid; mp 189e192 ꢀC; IR (KBr, cmꢂ1): 3100, 3057,
1614, 1600, 1568, 1531, 1431, 1398, 1328, 1308, 1218, 1138, 1025,
132.3, 130.5, 129.8, 129.5, 129.1, 128.9, 124.9; HRMS (ESI): m/z
[MþH]þ calcd for C14H10BrN2: 285.0023; found: 285.0022.
874, 757, 698; 1H NMR (CDCl3, 600 MHz):
d
(ppm) 8.13 (d,
4.3.25. 2-(4-Chlorophenyl)quinoxaline (6ag).8i Yield 70%, yellow
solid; mp: 131e134 ꢀC; IR (KBr, cmꢂ1): 3451, 3056, 1538, 1486, 1312,
J¼7.8 Hz, 1H), 8.00 (d, J¼7.8 Hz, 1H), 7.75e7.78 (m, 2H), 7.62e7.62
(m, 2H), 7.46 (s, 3H), 6.97 (d, J¼9.0 Hz, 1H), 6.25 (d, J¼9.0 Hz, 1H),
1094; 1H NMR (CDCl3, 400 MHz):
d (ppm) 9.29 (s, 1H), 8.11e8.16 (m,
5.81 (s, 2H); 13C NMR (CDCl3, 100 MHz):
d
(ppm) 159.7, 157.7,
4H), 7.74e7.81 (m, 2H), 7.53 (d, J¼8.4 Hz, 2H); 13C NMR (CDCl3,
153.2, 150.4, 140.1, 139.6, 136.9, 132.9, 130.0, 130.9, 130.0, 129.3,
129.1, 128.9, 126.7; HRMS (APCI): m/z [MþH]þ calcd for
C20H13IN2O2: 441.0094; found: 441.0094.
150 MHz): d (ppm) 150.4, 142.7, 142.1, 141.5, 136.4, 135.0, 130.4,
129.7, 129.5, 129.3, 129.0, 128.6; HRMS (ESI): m/z [MþH]þ calcd for
C14H10ClN2: 241.0528; found: 241.0527.
4.3.18. (1H-Benzo[d]imidazol-2-yl)(phenyl)methanone (5a).16 Yield
69%, white solid; mp 212e215 ꢀC; IR (KBr, cmꢂ1): 3443, 1656, 1429,
4.3.26. 2-(3,4-Dichlorophenyl)quinoxaline (6ah). Yield 65%, pale
green solid; mp: 187e189 ꢀC; IR (KBr, cmꢂ1): 1537, 1477, 1312, 1145,
1316, 1260, 919; 1H NMR (DMSO-d6, 400 MHz):
d
(ppm) 13.57 (s,
1H), 8.64 (d, J¼7.6 Hz, 2H), 7.94 (s,1H), 7.66e7.77 (m, 4H), 7.40e7.44
(m, 2H); 13C NMR (DMSO-d6, 100 MHz):
(ppm) 183.5, 147.9, 143.2,
1028; 1H NMR (CDCl3, 400 MHz):
d (ppm) 9.29 (s, 1H), 8.35 (s, 1H),
8.14 (t, J¼6.8 Hz, 2H), 8.04 (d, J¼8.4 Hz, 1H), 7.77e7.84 (m, 2H), 7.64
d
(d, J¼8.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz):
d (ppm) 149.2, 142.6,
135.6, 134.1, 133.56, 130.9, 130.8, 128.4, 125.9, 123.1, 121.3, 112.8, MS
(ES, 70 eV) m/z: 222 (53), 194 (100), 105 (49), 77 (44).
142.4, 142.1, 141.8, 136.6, 133.6, 131.1, 130.7, 130.1, 129.6, 129.3, 129.2,
126.4; HRMS (ESI): m/z [MþH]þ calcd for C14H9Cl2N2: 275.0135;
found: 275.0137.
4.3.19. 2-Phenylquinoxaline (6aa).8i Yield 80%, pale yellow solid;
mp 70 ꢀC; IR (KBr, cmꢂ1): 3061, 1544, 1487, 1445, 1313, 1029; 1H
4.3.27. 2-([1,10-Biphenyl]-4-yl)quinoxaline (6ai).8i Yield 63%, pale
yellow solid; mp: 130e133 ꢀC; IR (KBr, cmꢂ1): 3060, 1538, 1484,
NMR (CDCl3, 400 MHz):
7.74e7.81 (m, 2H), 7.51e7.60 (m, 3H); 13C NMR (CDCl3, 100 MHz):
(ppm) 151.8, 143.3, 141.5, 136.7, 130.3, 130.2, 129.6, 129.5, 129.2,
d (ppm) 9.34 (s, 1H), 8.12e8.21 (m, 4H),
1419, 1316, 1053; 1H NMR (CDCl3, 400 MHz):
d (ppm) 9.36 (s, 1H),
d
8.28 (d, J¼8.4 Hz, 2H), 8.11e8.17 (m, 2H), 7.80 (s, 1H), 7.78 (s, 1H),
129.1, 127.5.
7.71e7.76 (m, 2H), 7.68 (s, 1H), 7.66 (s, 1H), 7.48 (t, J¼7.4 Hz, 2H),
7.39 (t, J¼7.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz):
d (ppm) 151.3,
4.3.20. 2-(p-Tolyl)quinoxaline (6ab).8i Yield 83%, yellow solid; mp
91e93 ꢀC; IR (KBr, cmꢂ1): 3055, 1613, 1545, 1310, 1046; 1H NMR
143.2, 142.9, 142.3, 141.5, 140.1, 135.5, 130.3, 129.5, 129.5, 129.1,
128.9, 127.9, 127.8, 127.1; HRMS (APCI): m/z [MþH]þ calcd for
C20H15N2: 283.1231; found: 283.1230.
(CDCl3, 400 MHz):
d
(ppm) 9.30 (s, 1H), 8.09e8.14 (q, J¼6.4 Hz, 4H),
7.70e7.78 (m, 2H), 7.36 (d, J¼8.0 Hz, 2H), 2.44 (s, 3H); 13C NMR
(CDCl3, 100 MHz):
d
(ppm) 151.8, 143.2, 142.3, 141.4, 140.5, 133.9,
4.3.28. 2-(Naphthalen-1-yl)quinoxaline (6aj).8i Yield 69%, dark
130.2, 129.9, 129.5, 129.3, 129.0, 127.4, 21.4; HRMS (ESI): m/z
yellow solid; mp: 136 ꢀC; IR (KBr, cmꢂ1): 3045, 1542, 1487, 1183,
[MþNa]þ calcd for C15H12N2Na: 243.0893; found: 243.0893.
1111; 1H NMR (CDCl3, 600 MHz):
d (ppm) 9.17 (s, 1H), 8.22 (t,
J¼9.3 Hz, 2H), 8.17 (d, J¼8.4 Hz, 1H), 8.01 (d, J¼7.8 Hz, 1H), 7.96 (d,
4.3.21. 2-(4-Methoxyphenyl)quinoxaline (6ac).8i Yield 85%, pale
yellow solid; mp 97e98 ꢀC; IR (KBr, cmꢂ1): 1602, 1537, 1437, 1182,
J¼7.8 Hz, 1H), 7.83 (s, 2H), 7.78 (d, J¼6.6 Hz, 1H), 7.64 (t, J¼7.5 Hz,
1H), 7.52e7.57 (m, 2H); 13C NMR (CDCl3, 100 MHz):
d (ppm) 154.2,
1031; 1H NMR (400 MHz, CDCl3):
d
(ppm) 9.28 (s, 1H), 8.17 (d,
146.6, 142.1, 141.3, 135.0, 134.0, 130.4, 130.1, 129.9, 129.6, 129.2,
128.6, 128.5, 128.3, 127.2, 126.3, 125.4, 125.0; HRMS (ESI): m/z
[MþH]þ calcd for C18H13N2: 257.1072; found: 257.1073.
J¼8.8 Hz, 2H), 8.10 (t, J¼8.9 Hz, 2H), 7.68e7.77 (m, 2H), 7.07 (d,
J¼8.8 Hz, 2H), 3.89 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d (ppm)
161.3, 151.3, 143.0, 142.2, 141.1, 130.1, 129.3, 129.1, 129.0, 128.9, 114.5,
55.3; HRMS (ESI): m/z [MþNa]þ calcd for C15H12N2ONa: 259.0841;
found: 259.0842.
4.3.29. 2-(Naphthalen-2-yl)quinoxaline (6ak). Yield 66%, dark yel-
low solid; mp: 138 ꢀC; IR (KBr, cmꢂ1): 3042, 1547, 1491, 1308, 1197;
1H NMR (CDCl3, 600 MHz):
d (ppm) 9.45 (s, 1H), 8.63 (s, 1H), 8.34 (d,
4.3.22. 2-(2,4-Dimethoxyphenyl)quinoxaline (6ad). Yield 86%, pale
white solid; mp 54e56 ꢀC; IR (KBr, cmꢂ1): 2954, 1616, 1509, 1276,
J¼8.4 Hz, 1H) 8.18 (d, J¼8.0 Hz, 1H), 8.13 (d, J¼8.4 Hz, 1H), 7.99 (t,
J¼7 Hz, 2H), 7.88e7.90 (m, 1H), 7.72e7.80 (m, 2H), 7.53e7.56 (m,
1207, 1160, 1128; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 9.35 (s, 1H),
2H); 13C NMR (CDCl3, 100 MHz):
d (ppm) 151.6, 143.4, 142.3, 141.5,
8.11 (t, J¼9.2 Hz, 2H), 7.91e7.94 (m, 1H), 7.73e7.74 (m, 2H), 6.67 (d,
134.0, 134.0, 133.3, 130.3, 129.5, 129.1, 129.0, 128.8, 127.7, 127.4,
127.2, 126.6, 124.4; HRMS (APCl): m/z [MþH]þ calcd for C18H13N2:
257.1075; found: 257.1073.
J¼8.4 Hz, 1H), 6.61 (s, 1H), 3.90 (s, 6H); 13C NMR (CDCl3, 100 MHz):
d
(ppm) 162.4, 158.5, 151.7, 147.1, 142.5, 140.5, 132.4, 129.5, 129.1,
128.9, 119.1, 105.7, 98.5, 55.4, 55.3; HRMS (ESI): m/z [MþH]þ calcd
for C16H15N2O2: 267.1130; found: 267.1128.
4.3.30. 4-(Quinoxalin-2-yl)phenol (6al).8g Yield 78%, white solid;
mp: 208e209 ꢀC; IR (KBr, cmꢂ1): 3070, 3013,1608,1589,1492,1442,
4.3.23. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)quinoxaline (6ae).
Yield 82%, yellow solid; mp 144e147 ꢀC; IR (KBr, cmꢂ1): 1514, 1435,
1272, 1168; 1H NMR (DMSO-d6, 400 MHz):
d (ppm) 10.14 (s, 1H),
9.53 (br s, 1H), 8.24e8.26 (m, 2H), 8.08e8.09 (m, 2H), 7.81e7.87 (m,
1323, 1292, 1053; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 9.25 (s, 1H),
2H), 7.02 (d, J¼8.0 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz):
d (ppm)

9604
M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
159.7, 150.9, 143.4, 141.4, 140.5, 130.3, 129.1, 129.0, 128.8, 128.7,
126.9, 115.9; HRMS (ESI): m/z [MþH]þ calcd for C14H11N2O:
223.0866; found: 223.0866.
100 MHz): d (ppm) 161.1,150.6, 142.1,141.1,140.6, 140.1,139.5, 129.6,
128.7, 128.4, 128.0, 114.4, 55.4, 20.4, 20.3; HRMS (APCI): m/z
[MþH]þ calcd for C17H17N2O: 265.1337; found: 265.1335.
4.3.31. 4-(4-(Quinoxalin-2-yl)phenyl)morpholine (6am). Yield 81%,
yellow crystals; mp: 220e223 ꢀC; IR (KBr, cmꢂ1): 2964, 2863, 2841,
1606, 1533, 1444, 1382, 1247, 1121; 1H NMR (CDCl3, 400 MHz):
4.3.38. 2-(4-Chlorophenyl)-6,7-dimethylquinoxaline (6bc). Yield
71%, pale yellow solid; mp: 157e160 ꢀC; IR (KBr, cmꢂ1): 2972,
2914, 1485, 1440, 1212, 1088, 1010; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 9.28 (s, 1H), 8.16 (d, J¼8.8 Hz, 2H), 8.06e8.11 (m, 2H),
d
(ppm) 9.19 (s, 1H), 8.11 (d, J¼7.6 Hz, 2H), 7.88 (s, 1H), 7.85 (s, 1H),
7.67e7.76 (m, 2H), 7.04 (d, J¼8.4 Hz, 2H), 3.90 (d, J¼4 Hz, 4H), 3.30
7.52 (d, J¼7.6 Hz, 2H), 2.51 (s, 6H); 13C NMR (CDCl3, 100 MHz):
(d, J¼4.8 Hz, 4H); 13C NMR (CDCl3, 100 MHz):
d
(ppm) 152.5, 151.4,
d (ppm) 149.7, 141.9, 141.1, 140.5, 136.1, 135.5, 129.3, 128.6, 128.1,
143.0, 142.3, 141.0, 130.1, 129.2, 129.0, 128.8, 128.5, 127.4, 115.1, 66.7,
48.2; HRMS (ESI): m/z [MþH]þ calcd for C18H18N3O: 292.1446;
found: 292.1444.
20.43; HRMS (APCI): m/z [MþH]þ calcd for C16H14ClN2: 269.0842;
found: 269.0840.
4.3.39. 7-Methyl-2-phenylquinoxaline and 6-methyl-2-phenylquino-
xaline (6bd). Yield 83%, white solid; mp: 106e109 ꢀC; IR (KBr,
cmꢂ1): 3055, 2916, 1541, 1492, 1307, 1027; 1H NMR (CDCl3,
4.3.32. 2-(Furan-2-yl)quinoxaline (6an).8i Yield 65%, pale yellow
solid; mp: 131e136 ꢀC; IR (KBr, cmꢂ1): 3136, 3116, 1612, 1552, 1497,
1297, 1225, 1126, 1082; 1H NMR (CDCl3, 600 MHz):
d
(ppm) 9.24 (s,
400 MHz):
8.00e8.05 (m, 1H), 7.87e7.92 (m, 1H), 7.51e7.61 (m, 4H), 2.6 (s, 3H);
13C NMR (CDCl3, 100 MHz):
(ppm) 151.7, 150.9, 143.2, 142.4, 142.3,
d
(ppm) 9.25e9.27 (m, 1H), 8.17 (d, J¼6.8 Hz, 2H),
1H), 8.09 (d, J¼7.8 Hz, 1H), 8.06 (d, J¼8.4 Hz, 1H), 7.75 (t, J¼7.4 Hz,
1H), 7.70 (d, J¼7.2 Hz, 1H), 7.68 (s, 1H), 7.31 (d, J¼3 Hz, 1H), 6.62 (s,
d
1H); 13C NMR (CDCl3, 100 MHz):
d
(ppm) 151.4, 145.0, 143.7, 141.9,
141.5, 140.7, 140.6, 140.1, 140.0, 140.0, 136.8, 132.6, 131.8, 130.0,
129.9, 129.1, 128.5, 128.4, 127.9, 127.4, 127.3, 21.8.
141.1, 130.3, 129.2, 129.1, 112.4, 111.7; HRMS (APCI): m/z [MþNa]þ
calcd for C12H8N2NaO: 219.0530; found: 219.0529.
4.3.40. 6,7-Dichloro-2-phenylquinoxaline (6be).17 Yield 50%, pale
yellow crystals; mp: 155e157 ꢀC. IR (KBr, cmꢂ1): 3050, 1463, 1444,
4.3.33. 2-(Thiophen-2-yl)quinoxaline (6ao).8i Yield 63%, pale yel-
low solid; mp: 116e117 ꢀC; IR (KBr, cmꢂ1): 3120, 3058, 1547, 1427,
1315, 1178, 1108; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 9.29 (s, 1H),
8.23 (s, 1H), 8.20 (s, 1H), 8.15e8.17 (m, 2H), 7.56 (m, 3H); 13C NMR
(CDCl3, 100 MHz): (ppm) 152.5, 144.2, 141.0, 140.2, 135.9, 133.9,
1320, 1054; 1H NMR (CDCl3, 600 MHz):
d (ppm) 9.21 (s, 1H), 8.05 (d,
J¼3.6 Hz, 2H), 7.84 (s, 1H), 7.72 (d, J¼8.4 Hz, 1H), 7.68 (d, J¼8.4 Hz,
d
1H), 7.53 (d, J¼4.2 Hz, 1H), 7.18 (br s, 1H); 13C NMR (CDCl3,
130.7, 130.1, 129.7, 129.2, 127.5.
100 MHz):
d (ppm) 147.3, 142.0, 141.7, 141.2, 130.4, 130.2, 129.8,
129.1, 129.0, 128.4, 126.9; HRMS (APCI): m/z [MþH]þ calcd for
4.3.41. 7-Chloro-2-phenylquinoxaline and 6-chloro-2-phenyl-qui-
noxaline (6bf). Yield 64%, pale yellow solid; mp: 100e102 ꢀC; IR
(KBr, cmꢂ1): 3049, 1482, 1450, 1317, 1074; 1H NMR (CDCl3,
C12H9N2S: 213.0483; found: 213.0481.
4.3.34. 2-(Benzofuran-2-yl)quinoxaline (6ap). Yield 66%, yellow
solid; mp: 173e175 ꢀC; IR (KBr, cmꢂ1): 3058, 1583, 1545, 1310,
400 MHz):
8.02e8.13 (m, 2H), 7.66e7.72 (m, 2H), 7.55e7.58 (m, 3H); 13C NMR
(CDCl3, 100 MHz): (ppm) 152.4, 151.8, 144.1, 143.3, 142.6, 141.7,
d
(ppm) 9.29e9.30 (m, 1H), 8.17 (d, J¼7.2 Hz, 2H),
1259, 1173, 1128, 1047; 1H NMR (CDCl3, 400 MHz):
d
(ppm) 9.41 (s,
d
1H), 8.17 (d, J¼8 Hz, 1H), 8.11 (d, J¼7.9 Hz, 1H), 7.75e7.81 (m, 2H),
140.8, 140.0, 136.3, 136.2, 136.0, 135.2, 131.3, 130.8, 130.5, 130.4,
130.4, 130.3, 129.2, 128.4, 128.0, 127.5, 127.4.
7.66e7.73 (m, 3H), 7.41 (t, J¼7.6 Hz, 1H), 7.30 (t, J¼7.4 Hz, 1H); 13C
NMR (CDCl3, 100 MHz):
d (ppm) 155.8, 152.8, 143.9, 142.5, 142.1,
141.7, 130.6, 129.9, 129.4, 129.2, 128.2, 126.3, 123.6, 122.0, 111.9,
107.9; HRMS (APCI): m/z [MþH]þ calcd for C16H11N2O: 247.0868;
found: 247.0866.
4.3.42. 7-Bromo-2-phenylquinoxaline and 6-bromo-2-phenyl-qui-
noxaline (6bg). Yield 72%, pale yellow solid; white solid; mp:
96e97 ꢀC; IR (KBr, cmꢂ1): 3045, 1597, 1478, 1135; 1H NMR (CDCl3,
400 MHz):
2H), 7.94e8.00 (m, 1H), 7.78e7.84 (m, 1H), 7.55 (m, 3H); 13C NMR
(CDCl3,100 MHz): (ppm)152.4,144.0,143.5,140.3,136.2,133.8,133.0,
d
(ppm) 9.30 (s, 1H), 8.27e8.32 (m, 1H), 8.17 (d, J¼6.5 Hz,
4.3.35. 2-(1H-Indol-3-yl)quinoxaline (6aq).17 Yield 72%, brown
solid; mp: 206e208 ꢀC; IR (KBr, cmꢂ1): 3255,1553,1446,1170,1133;
d
1H NMR (DMSO-d6, 400 MHz):
d
(ppm) 11.97 (s, 1H), 9.55 (s, 1H),
131.8, 131.4, 130.9, 130.5, 130.4, 130.4, 129.4, 129.2, 127.6, 127.5, 124.3.
8.84e8.87 (1H, m), 8.67 (s, 1H), 8.12 (d, J¼8.4 Hz, 1H), 8.05 (d,
J¼8.0 Hz, 1H), 7.82 (q, J¼7.2 Hz, 1H), 7.69e7.74 (m, 1H), 7.56e7.58
Acknowledgements
(1H, m), 7.29e7.31 (m, 2H); 13C NMR (DMSO-d6, 100 MHz):
d (ppm)
151.0, 144.4, 142.0, 139.5, 137.2, 137.0, 130.0, 128.8, 128.5, 127.7,
125.6, 122.8, 122.5, 121.0, 113.0, 112.0; HRMS (ESI): m/z [MþNa]þ
calcd for C16H11N3Na: 268.0846; found: 268.0845.
Prof. A.W. thanks the National Natural Science Foundation of
China (Grants 20872042 and 21032001). Dr. G.Y. thanks the Na-
tional Natural Science Foundation of China (Grants 20902035 and
21102042). We are also grateful to Dr. Xianggao Meng for his help
with X-ray diffraction analysis.
4.3.36. 6,7-Dimethyl-2-phenylquinoxaline (6ba). Yield 76%, pale
yellow crystals; mp: 130e131 ꢀC; IR (KBr, cmꢂ1): 3059, 3035, 2967,
1538, 1485, 1450,1312,1212,1024,1001; 1H NMR (CDCl3, 400 MHz):
Supplementary data
d
(ppm) 9.16 (s, 1H), 8.12 (d, J¼7.2 Hz, 2H), 7.83 (s, 1H), 7.78 (s, 1H),
7.43e7.52 (m, 3H), 2.42 (s, 6H); 13C NMR (CDCl3, 100 MHz):
d
(ppm)
1H NMR, 13C NMR, and HRMS spectra for all compounds, X-ray
crystal structures of compounds 3aa, 3ae and 6ac are available. Sup-
plementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.09.056. ThesedataincludeMOL files and
InChiKeys of the most important compounds described in this article.
150.5, 142.0, 140.8, 140.4, 140.2, 139.7, 136.7, 129.5, 128.8, 128.3,
127.8, 127.0, 20.11; HRMS (APCI): m/z [MþH]þ calcd for C16H15N2:
235.1231; found: 235.1230.
4.3.37. 2-(4-Methoxyphenyl)-6,7-dimethylquinoxaline (6bb). Yield
80%, yellow solid; mp: 127e129 ꢀC; IR (KBr, cmꢂ1): 2974, 1605,
1487, 1437, 1292, 1252, 1183, 1029; 1H NMR (CDCl3, 400 MHz):
References and notes
d
(ppm) 9.19 (s, 1H), 8.14 (d, J¼7.6 Hz, 2H), 7.87 (s, 1H), 7.83 (s, 1H),
1. (a) Lee, S.-B.; Park, Y. I.; Dong, M.-S.; Gong, Y.-D. Bioorg. Med. Chem. Lett. 2010,
20, 5900e5904; (b) Baffert, F.; Regnier, C. H.; De Pover, A.; Pissot-Soldermann,
7.08 (d, J¼8.0 Hz, 2H), 3.9 (s, 3H), 2.5 (s, 6H); 13C NMR (CDCl3,
ꢀ

M. Lian et al. / Tetrahedron 68 (2012) 9598e9605
9605
ꢁ
C.; Tavares, G. A.; Blasco, F.; Brueggen, J.; Chene, P.; Drueckes, P.; Erdmann, D.;
2508e2510; (d) Robinson, R. S.; Taylor, R. J. K. Synlett 2005, 1003e1005; (e)
Paul, S.; Basu, B. Tetrahedron Lett. 2011, 52, 6597e6602; (f) Das, B.; Ven-
kateswarlu, K.; Suneel, K.; Majhi, A. Tetrahedron Lett. 2007, 48, 5371e5374; (g)
Meshram, H. M.; Kumar, G. S.; Ramesh, P.; Reddy, B. C. Tetrahedron Lett. 2010, 51,
2580e2585; (h) Meshram, H. M.; Ramesh, P.; Kumar, G. S.; Reddy, B. C. Tetra-
hedron Lett. 2010, 51, 4313e4316; (i) Madhav, B.; Narayana Murthy, S.; Prakash
Reddy, V.; Rama Rao, K.; Nageswar, Y. V. D. Tetrahedron Lett. 2009, 50,
6025e6028; (j) Cho, C. S.; Ren, W. X.; Shim, S. C. Tetrahedron Lett. 2007, 48,
4665e4667; (k) Padmavathy, K.; Nagendrappa, G.; Geetha, K. V. Tetrahedron
Lett. 2011, 52, 544e547; (l) Qi, C.; Jiang, H.; Huang, L.; Chen, Z.; Chen, H. Syn-
thesis 2011, 387e396; (m) Chang, M.-Y.; Lee, T.-W.; Hsu, R.-T.; Yen, T.-L. Synthesis
2011, 3143e3151.
Furet, P.; Gerspacher, M.; Lang, M.; Ledieu, D.; Nolan, L.; Ruetz, S.; Trappe, J.;
Vangrevelinghe, E.; Wartmann, M.; Wyder, L.; Hofmann, F.; Radimerski, T. Mol.
Cancer Ther. 2010, 9, 1945e1955.
2. El Ashry, E. S.; Abdel-Rahman, A. A.; Rashed, N.; Rasheed, H. A. Pharmazie 1999,
54, 893e897 Afdsafdsf.
3. Badran, M.; Abouzid, K.; Hussein, M. Arch. Pharm. Res. 2003, 26, 107e113.
4. (a) Castro, P. P.; Zhao, G.; Masangkay, G. A.; Hernandez, C.; Gutierrez-Tunstad, L.
M. Org. Lett. 2004, 6, 333e336; (b) Sessler, J. L.; Maeda, H.; Mizuno, T.; Lynch, V.
M.; Furuta, H. J. Am. Chem. Soc. 2002, 124, 13474e13479.
5. (a) Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W. N.; Bhusare, S. R.;
Pawar, R. P. Tetrahedron Lett. 2005, 46, 7183e7186; (b) Dhakshinamoorthy, A.;
Kanagaraj, K.; Pitchumani, K. Tetrahedron Lett. 2011, 52, 69e73; (c) Guo, W.; Jin,
H.; Chen, J.; Chen, F.; Ding, J.; Wu, H. J. Brazil. Chem. Soc. 2009, 20, 1674e1679;
(d) More, S. V.; Sastry, M. N. V.; Wang, C.-C.; Yao, C.-F. Tetrahedron Lett. 2005, 46,
6345e6348; (e) More, S. V.; Sastry, M. N. V.; Yao, C.-F. Green Chem. 2006, 8,
91e95; (f) Naskar, S.; Paira, P.; Paira, R.; Mondal, S.; Maity, A.; Hazra, A.; Sahu,
K. B.; Saha, P.; Banerjee, S.; Luger, P.; Webe, M.; Mondal, N. B. Tetrahedron 2010,
66, 5196e5203; (g) Tingoli, M.; Mazzella, M.; Panunzi, B.; Tuzi, A. Eur. J. Org.
Chem. 2011, 2011, 399e404; (h) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.;
Shankar, K. S. Synthesis 2008, 3787e3792; (i) Zhao, Z.; Wisnoski, D. D.; Wol-
kenberg, S. E.; Leister, W. H.; Wang, Y.; Lindsley, C. W. Tetrahedron Lett. 2004, 45,
4873e4876.
6. Ali, M.; Ismail, M.; El-Gaby, M.; Zahran, M.; Ammar, Y. Molecules 2000, 5,
864e873.
7. Zhang, C.; Xu, Z.; Zhang, L.; Jiao, N. Tetrahedron 2012, 68, 5258e5262.
8. (a) Akkilagunta, V. K.; Reddy, V. P.; Kakulapati, R. R. Synlett 2010, 2571e2574;
(b) Kim, S. Y.; Park, K. H.; Chung, Y. K. Chem. Commun. 2005, 1321e1323; (c) Pan,
F.; Chen, T.-M.; Cao, J.-J.; Zou, J.-P.; Zhang, W. Tetrahedron Lett. 2012, 53,
9. Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini, F.; Santeusanio, S.
Helv. Chim. Acta 2001, 84, 2379e2386.
~
10. (a) Antoniotti, S.; Dunach, E. Tetrahedron Lett. 2002, 43, 3971e3973; (b) Kamal
Nasar, M.; Ranjith Kumar, R.; Perumal, S. Tetrahedron Lett. 2007, 48, 2155e2158.
11. (a) Chandrasekhar, S.; Reddy, N. K.; Kumar, V. P. Tetrahedron Lett. 2010, 51,
3623e3625; (b) Wang, W.; Shen, Y.; Meng, X.; Zhao, M.; Chen, Y.; Chen, B. Org.
Lett. 2011, 13, 4514e4517.
12. Cho, C. S.; Oh, S. G. Tetrahedron Lett. 2006, 47, 5633e5636.
13. Martin, L. J.; Marzinzik, A. L.; Ley, S. V.; Baxendale, I. R. Org. Lett. 2011, 13,
320e323.
14. Yin, G. D.; Zhou, B. H.; Meng, X. G.; Wu, A. X.; Pan, Y. J. Org. Lett. 2006, 8,
2245e2248.
15. Yin, G. D.; Gao, M.; She, N. F.; Hu, S. L.; Wu, A. X.; Pan, Y. J. Synthesis 2007,
3113e3116.
16. Ge, Y. Q.; Jia, J.; Yang, H.; Tao, X. T.; Wang, J. W. Dyes Pigments 2011, 88, 344e349.
17. Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki, A.; Bohmer, F. D. J. Med. Chem.
1996, 39, 2170e2177.