N-heterocyclic carbene catalyzed one-pot synthesis of 2,3- diarylquinoxalines

Article abstract of DOI:10.1055/s-0032-1316687

A one-pot efficient and facile protocol for the direct synthesis of quinoxaline derivatives via tandem N-heterocyclic carbene (NHC)-catalyzed umpolung of aldehydes/oxidation of the benzoins to benzils/condensation of benzils with benzene-1,2-diamines has been developed. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1316687

PAPER
▌2699
paper
N-Heterocyclic Carbene Catalyzed One-Pot Synthesis of
2,3-Diarylquinoxalines
One-Pot Synthesis of 2,3-Diarylquinoxalines
Yang Lin,b Xiaoli Lei,b Qin Yang,a Jiangjun Yuan,a Qiuping Ding,*b Jingshi Xu,a Yiyuan Peng*a,b
a
Key Laboratory of Small Functional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University,
Nanchang, Jiangxi 330022, P. R. of China
b
Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry, Jiangxi Normal University, Nanchang, Jiangxi 330022,
P. R. of China
Fax +86(791)88120396; E-mail: yypeng@jxnu.edu.cn; E-mail: Yiyuanpeng@yahoo.com
Received: 25.04.2012; Accepted after revision: 13.06.2012
tion. Here, we report on the NHC-catalyzed one-pot
synthesis 2,3-diarylquinoxalines from aldehydes and ben-
zene-1,2-diamines, the tandem one-pot reaction including
three steps in a stepwise manner proceeds as follows: (1)
N-heterocyclic carbene (NHC) catalytic umpolung reac-
tion of aromatic aldehyde to form α-hydroxy ketone (ben-
zoin); (2) the synthesis of benzils via subsequent
oxidation of the corresponding α-hydroxy ketones with
catalytic amount of DBU under air atmosphere; and (3)
formation of 2,3-diarylquinoxalines by condensation of
benzils with benzene-1,2-diamines (Scheme 1).
Abstract: A one-pot efficient and facile protocol for the direct syn-
thesis of quinoxaline derivatives via tandem N-heterocyclic carbene
(NHC)-catalyzed umpolung of aldehydes/oxidation of the benzoins
to benzils/condensation of benzils with benzene-1,2-diamines has
been developed.
Key words: N-heterocyclic carbene, quinoxaline, aldehyde, benzo-
in, benzene-1,2-diamine
Quinoxaline derivatives are important nitrogen-contain-
ing heterocyclic compounds and exhibit a wide range of
biological activities, such as antiviral, antibacterial, anti-
inflammatory, and kinase inhibitors.1 Quinoxalines are
also useful intermediates in organic synthesis.2 While
many strategies are available,3 there are two general meth-
ods for the synthesis of quinoxaline derivatives. One is the
double condensation reaction of 1,2-aryldiamines with
1,2-diketones.4 The other method involves a two-step pro-
cedure of tandem oxidation and condensation reaction of
α-hydroxy ketones.5 Many of these methods are efficient,
but suffer from the major drawback such as the separate
preparation of starting materials. Therefore, the discovery
of mild and practicable routes for direct synthesis of qui-
noxaline derivatives continues to attract the attention of
researchers.
(1) NHC, DBU
O
(2) [O]
Ar
Ar
N
N
Ar
H
NH2
NH2
(3)
Scheme 1 Tandem one-pot reaction for synthesis of quinoxalines
Initially, benzaldehyde (1a) and benzene-1,2-diamine
(2a) were selected as a model for this one-pot synthesis of
2,3-diarylquinoxalines. The benzoin condensation reac-
tion was carried out in DMF using DBU as a base under
nitrogen. We first screened several NHC catalysts (Figure
1). When 10 mol% of bulky imidazolium salt derived
NHC (A) was used as the umpolung catalyst, no benzoin
product was detected (Table 1, entry 1). When 10 mol%
thiazolium salt derived NHC (B) was used, after stirring
for 4 hours at 0 °C, all the benzaldehyde was transformed
to the corresponding benzoin. Then, ethyl acetate was
added and the reaction mixture was left open to air and
stirred for 6 hours at 70 °C to convert the benzoin to the
corresponding benzil (TLC monitoring). Finally, ben-
zene-1,2-diamine was added and after 1.5 hours, the prod-
uct 2,3-diphenylquinoxaline (3a) was isolated in 55%
yield (entry 2). When imidazolium salt derived NHC (C)
was used as the NHC catalyst, 2,3-diphenylquinoxaline
was obtained in 85% yield. Furthermore, good isolated
yield was achieved as well when the reaction was cata-
lyzed by NHC derived from triazolium salt (E) (entry 5).
However, the yield decreased to 32%, when the reaction
was carried out at room temperature (entry 6). By screen-
Recently, the powerful catalytic capacities of N-heterocy-
clic carbenes (NHCs) have been demonstrated as promi-
nent organocatalysts for transformations based on
aldehyde umpolung, such as benzoin condensation.6 A
wide variety of structurally diverse thiazolium, imidazoli-
um, and triazolium salts have been developed over the
years and this has resulted in constant improvements in
benzoin condensation reaction.7 Sakaguchi reported that
thiazolium salts (NHC precursors) catalyzed the benzoin
condensation of aldehydes in the presence of DBU and
then oxidation of benzoin to benzil under air atmosphere
by a catalytic amount of DBU.8 We envisaged that benzils
may undergo in situ condensation with benzene-1,2-di-
amines to form 2,3-diarylquinoxalines in a one-pot reac-
SYNTHESIS 2012, 44, 2699–2706
Advanced online publication: 23.07.2012
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DOI: 10.1055/s-0032-1316687; Art ID: SS-2012-H0382-OP
© Georg Thieme Verlag Stuttgart · New York

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Y. Lin et al.
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ing the solvent and the base, DMF was found to be the best
solvent (entries 7–11) and DBU was the best base (entries
12–16) for this one-pot synthesis of 2,3-diphenylquinoxa-
line.
Table 1 NHC-Catalyzed Tandem Reactions of 1a with 2a under Se-
lected Reaction Conditions
1) NHC(10 mol%),
base (20 mol%), solvent, 5 h
2) DBU (10 mol%),
EtOAc, 70 °C, 6 h
H
Ph
Ph
N
O
2
NH2
Cl–
N
HO
+
N
N
3)
, r.t., 2 h
1a
3a
+
N
NH2
S
Cl–
2a (1.5 equiv)
A
Me
B
Entry
Base
Solvent
NHC
Yield (%)a
N+
I–
1
2
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DMF
A
B
C
D
E
C
C
C
C
C
C
C
C
C
C
C
0
55
85
30
80
32
45
78
70
60
50
47
52
50
0
N
Me
DMF
C
F
F
Cl–
3
DMF
HO
H
+
N
F
F
4
DMF
N
S
+
N
F
5
DMF
Cl
H2N
N
N
D
F
B–
N
6b
7
DMF
F
F
O
MeOH
DMSO
THF
F
E
8
Figure 1 NHC catalysts screened
9
In order to evaluate the efficiency of this methodology, we
examined the scope of this one-pot reaction under the op-
timized conditions. First, benzaldehyde (1a) was subject-
ed to condensation with a number of benzene-1,2-
diamines. The results are shown in Table 2 (entries 1–5).
All reactions proceeded smoothly to provide the corre-
sponding products in good yields. For instance, 4-methyl-
benzene-1,2-diamine (2b) reacted with benzaldehyde,
leading to the desired 6-methyl-2,3-diphenylquinoxaline
(3b) in 85% yield (entry 2). Reactions of substrates with
methoxy, chloro, or bromo attached to the benzene ring
afforded the expected products in good yields as well (Ta-
ble 2, entries 3–5). These results indicate that the electron-
ic nature of the substituent on the benzene-1,2-diamines
has no substantial effect on the reaction.
10
11
12
13
14
15
16
CH2Cl2
MeCN
Na2CO3
K2CO3
NaOH
Et3N
DMF
DMF
DMF
DMF
DMF
NaHCO3
30
a Isolated yield based on benzaldehyde.
b At r.t.
also successful in the present catalytic system. High yield
(88%) was obtained when 2-furaldehyde was used as a re-
actant (entry 13). β-Naphthaldehyde was also converted
into the corresponding quinoxaline in 90% yield (entry
14). However, reactions between substituted benzalde-
hydes and 4-methylbenzene-1,2-diamine (2b) gave just
moderate yields (entries 15–17). The aliphatic aldehyde n-
butyraldehyde was also examined; however, here the
NHC catalytic umpolung reaction did not take place (data
not shown in Table 2). On conducting additional experi-
ments with two different aldehydes (such as 1b + 1c and
1b + 1d), only the symmetric diarylquinoxalines (from
self benzoin condensation) were obtained in low yields
(entries 18, 19). The asymmetric diarylquinoxaline based
on the cross benzoin condensation was not detected.
Then, a survey of various aromatic aldehydes was per-
formed and the results are also presented in Table 2. Aro-
matic aldehydes with either moderate electron-donating
or electron-withdrawing groups all gave the correspond-
ing quinoxalines in moderate to good yields. For instance,
a reasonable yield (69%) was obtained when 4-methyl-
benzaldehyde (1b) was used as a reactant (entry 6). Sub-
strates with different functional groups, such as 4-
methoxy, 4-chloro, 4-bromo, or 4-pyrrol-1-yl were readi-
ly accommodated in this protocol (entries 6–8, and 10–
12). However, in the case of hindered 2-chlorobenzalde-
hyde, only trace of the corresponding product 3i was iso-
lated (entry 9). Not even α-hydroxy ketones were
observed in the case of aldehydes possessing strong elec-
tron-withdrawing or electron-donating group such as A plausible catalytic cycle was proposed as illustrated in
NO2, NMe2, and 3,4-dimethoxy (data not shown in Table Scheme 2. The imidazolium salt derived carbene I is gen-
2). These results are similar to the previously reported erated by deprotonation of thiazolium salt C in the pres-
ones by other authors.9 Heteroaromatic aldehydes were ence of the base. Carbene I then reacts with benzaldehyde
Synthesis 2012, 44, 2699–2706
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Synthesis of 2,3-Diarylquinoxalines
2701
to give the intermediate II. Upon proton transfer, interme- Intermediate V, obtained from IV by proton transfer, re-
diate II gives the Breslow intermediate III, which could leases the carbene catalyst I and product benzoin VI to
further react with benzaldehyde to give intermediate IV. complete the catalytic cycle.
Me
N+
I–
H
N
Me
C
Base
Me
ArCHO
N
O
OH
Ar
O
O
O
N
NHC
Me
Ar
I
Ar
Ar
VI
NH2
NH2
Me
N+
O–
R
Me
N+
O–
OH
Ar
N
H
H
Me
II
N
Ar
Ar
Me
N
Ar
Ar
V
R
Me
N
N
OH
Ar
N
III
Me
Me
N+
O–
OH
H
ArCHO
N
Ar
Ar
Me
IV
Scheme 2 Plausible catalytic cycle mechanism for the reaction
Table 2 NHC-Catalyzed One-Pot Synthesis of 2,3-Diarylquinoxaline from Aldehydes
1) NHC, DBU, DMF, 0 °C, N2
O
Ar
Ar
N
N
2) DBU, EtOAc, 70 °C, air
R
NH2
Ar
H
3)
, r.t.
R
1
3
NH2
2
Entry
1
Aldehyde
Diamine
Product
Yield (%)a
NH2
N
CHO
1a
2a
3a
85
NH2
N
NH2
N
N
2
1a
2b
3b
85
NH2
© Georg Thieme Verlag Stuttgart · New York
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Y. Lin et al.
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Table 2 NHC-Catalyzed One-Pot Synthesis of 2,3-Diarylquinoxaline from Aldehydes (continued)
1) NHC, DBU, DMF, 0 °C, N2
O
Ar
Ar
N
N
2) DBU, EtOAc, 70 °C, air
R
NH2
Ar
H
3)
, r.t.
R
1
3
NH2
2
Entry
3
Aldehyde
Diamine
Product
Yield (%)a
NH2
NH2
N
N
OMe
1a
2c
3c
82
MeO
NH2
N
N
Cl
4
5
6
1a
1a
1b
2d
2e
2a
3d
3e
3f
85
80
69
Cl
Br
NH2
NH2
NH2
N
N
Br
N
N
CHO
MeO
N
N
CHO
7
8
1c
2a
2a
2a
2a
3g
3h
3i
83
MeO
MeO
Cl
CHO
N
N
1d
1e
1f
88
Cl
Cl
Cl
Cl
CHO
Cl
N
N
9
trace
Cl
CHO
N
N
Cl
Cl
10
3j
60
Cl
Cl
Cl
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One-Pot Synthesis of 2,3-Diarylquinoxalines
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Table 2 NHC-Catalyzed One-Pot Synthesis of 2,3-Diarylquinoxaline from Aldehydes (continued)
1) NHC, DBU, DMF, 0 °C, N2
O
Ar
Ar
N
N
2) DBU, EtOAc, 70 °C, air
R
NH2
Ar
H
3)
, r.t.
R
1
3
NH2
2
Entry
11
Aldehyde
Diamine
Product
Yield (%)a
Br
Br
CHO
N
N
1g
2a
3k
84
Br
N
N
CHO
N
N
12
1h
2a
3l
78
N
N
N
O
CHO
13
14
1i
1j
2a
2a
3m
3n
88
90
O
O
N
CHO
N
Cl
CHO
N
15
1d
2b
3o
3p
48
45
Cl
N
Cl
Br
CHO
N
N
16
17
1g
1j
2b
2b
Br
Br
N
CHO
3q
3f
53
21
N
18
19
1b + 1c
1b + 1d
2a
2a
3f
3h
11
12
a Isolated yield based on aldehyde 1.
© Georg Thieme Verlag Stuttgart · New York
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1H NMR (400 MHz, CDCl3): δ = 7.31–7.39 (m, 6 H), 7.51 (d, J =
6.4 Hz, 4 H), 7.84 (m, 1 H), 8.03 (d, J = 8.8 Hz, 1 H), 8.36 (d, J =
2.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 123.8, 128.3, 129.0, 129.1, 129.7,
129.8, 130.5, 131.4, 133.5, 138.6, 138.7, 139.9, 141.7, 153.7, 154.2.
In conclusion, we have developed a one-pot efficient and
facile protocol for the direct synthesis of quinoxaline de-
rivatives via tandem N-heterocyclic carbene (NHC)-cata-
lyzed umpolung of aldehydes, oxidation of the benzoins
to benzils, and condensation of the corresponding benzils
with benzene-1,2-diamines. The reactions require only a
catalytic amount of imidazolium salt derived NHC (C)
and base (DBU), and use air as oxidant.
6-Bromo-2,3-diphenylquinoxaline (3e)4c
Yield: 288.9 mg (80%); pale yellow solid; mp 120–122 °C (Lit.4c
mp 120–122 °C).
1H NMR (400 MHz, CDCl3): δ = 7.32–7.40 (m, 6 H), 7.51 (d, J =
6.8 Hz, 4 H), 7.69–7.27 (m, 1 H), 8.11 (d, J = 8.8 Hz, 1 H), 8.17 (d,
J = 2.0 Hz, 1 H).
Unless otherwise stated, all commercial reagents and solvents were
used without additional purification. All solvents were dried and
distilled according to standard procedures. Petroleum ether (PE)
used refers to the fraction boiling at 60–90 °C. Flash column chro-
matography was performed using silica gel (60 Å pore size, 32–63
mm, standard grade). Analytical TLC was performed using glass
plates precoated with 0.25 mm 230–400 mesh silica gel impregnat-
ed with a fluorescent indicator (254 nm). TLC plates were visual-
ized by exposure to ultraviolet light. Organic solutions were
concentrated on a rotary evaporator at 25–35 °C/20 Torr (house
vacuum). NMR spectra are recorded in parts per million from inter-
nal TMS on the δ scale.
13C NMR (100 MHz, CDCl3): δ = 128.0, 128.3, 129.0, 129.1, 129.8,
129.9, 130.4, 130.9, 135.6, 138.6, 138.7, 139.7, 141.4, 153.5, 154.2.
2,3-Bis(p-tolyl)quinoxaline (3f)4d
Yield: 214.2 mg (69%); pale white solid; mp 143–144 °C (Lit.4d mp
143–144 °C).
1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 6 H), 7.15 (d, J = 7.6 Hz,
4 H), 7.42 (d, J = 8.0 Hz, 4 H), 7.73–7.75 (m, 2 H), 8.13–8.16 (m, 2
H).
13C NMR (100 MHz, CDCl3): δ = 21.3, 128.9, 129.9, 129.1, 129.63,
129.74, 130.0, 136.4, 138.7, 141.1, 153.5.
N-Heterocyclic Carbene-Catalyzed One-Pot Synthesis of 2,3-
Diarylquinoxalines; General Procedure
2,3-Bis(4-methoxyphenyl)quinoxaline (3g)4d
Yield: 284.2 mg (83%); pale white solid; mp 149–150 °C (Lit.4d mp
149–150 °C).
1H NMR (400 MHz, CDCl3): δ = 3.71 (d, J = 1.6 Hz, 6 H), 6.78–
6.81 (m, 4 H), 7.40–7.42 (m, 4 H), 7.63–7.65 (m, 2 H), 8.03–8.06
(m, 2 H).
Aldehyde 1 (2 mmol) was allowed to react in the presence of N-het-
erocyclic carbene C (0.1 mmol) and base DBU (0.2 mmol) in DMF
(2 mL) at 0 °C for 5 h under N2 atmosphere. The mixture was al-
lowed to react in the presence of DBU (0.1 mmol) in EtOAc (10
mL) at 70 °C for 6 h under air atmosphere. Finally, benzene-1,2-di-
amine 2 (1 mmol) was added to the reaction mixture at r.t. for 1.5 h
under air atmosphere. The crude reaction mixture was diluted with
EtOAc (15 mL) and washed with H2O (3 × 10 mL). After evapora-
tion of the solvent, the residue was purified by silica gel column
chromatography (PE–EtOAc, 10:1) to afford the title compound 3.
13C NMR (100 MHz, CDCl3): δ = 55.3, 55.6, 113.7, 114.3, 129.0,
129.5, 129.9, 131.2, 131.4, 131.6, 132.0, 141.0, 153.0, 160.1, 164.5.
2,3-Bis(4-chlorophenyl)quinoxaline (3h)4c
Yield: 308.9 mg (88%); white solid; mp 188–189 °C (Lit.4c mp
191–193 °C).
1H NMR (400 MHz, CDCl3): δ = 7.34–7.37 (m, 2 H), 7.39–7.42 (m,
3 H), 7.44–7.48 (m, 3 H), 7.78–7.81 (m, 1 H), 7.90 (d, J = 8.0 Hz, 1
H), 8.02 (d, J = 8.0 Hz, 1 H), 8.15–8.17 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 128.7, 128.8, 128.9, 129.1, 129.2,
129.5, 129.7, 129.9, 130.1, 130.3, 131.1, 131.3, 131.8, 132.7, 135.3,
135.8, 137.2, 140.1, 140.3, 141.2.
2,3-Diphenylquinoxaline (3a)4d
Yield: 239.9 mg (85%); beige solid; mp 125–126 °C (Lit.4d mp
124–125 °C).
1H NMR (400 MHz, CDCl3): δ = 7.29–7.35 (m, 6 H), 7.50–7.52 (m,
4 H), 7.73–7.75 (m, 2 H), 8.16–8.18 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 128.3, 128.8, 129.2, 129.8, 129.9,
139.1, 141.2, 153.4.
6-Methyl-2,3-diphenylquinoxaline (3b)4d
Yield: 251.8 mg (85%); pale yellow solid; mp 137–138 °C (Lit.4d
mp 112–114 °C).
1H NMR (400 MHz, CDCl3): δ = 2.53 (s, 3 H), 7.26–7.32 (m, 6 H),
7.50 (t, J = 6.0, 1.2 Hz, 4 H), 7.53 (d, J = 8.8 Hz, 1 H), 7.92 (s, 1 H),
8.01 (d, J = 8.4 Hz, 1 H).
2,3-Bis(3,4-dichlorophenyl)quinoxaline (3j)
Yield: 252.1 mg (60%); yellow solid; mp 180–182 °C.
IR (KBr): 1642, 1566, 1137, 1070, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.55 (d, J = 1.4 Hz, 2 H), 6.65 (d,
J = 2.4 Hz, 2 H), 7.62 (s, 2 H), 7.71–7.73 (m, 2 H), 8.11–8.13 (m, 2
H).
13C NMR (100 MHz, CDCl3): δ = 111.9, 113.0, 129.0, 130.3, 140.5,
142.5, 144.1, 150.7.
13C NMR (100 MHz, CDCl3): δ = 21.9, 128.0, 128.2, 128.6, 128.7,
129.9, 129.9, 132.3, 139.2, 139.7, 140.4, 141.3, 152.5, 153.3.
6-Methoxy-2,3-diphenylquinoxaline (3c)4a
Yield: 256.1 mg (82%); pale yellow solid; mp 160–162 °C (Lit.4a
mp 160–162 °C).
1H NMR (400 MHz, CDCl3): δ = 3.99 (s, 3 H), 7.32–7.34 (m, 6 H),
7.41–7.44 (m, 2 H), 7.47–7.51 (m, 5 H), 8.06 (d, J = 8.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 55.8, 106.4, 123.4, 128.2, 128.3,
128.5, 128.7, 129.8, 130.1, 137.4, 139.2, 139.29, 142.7, 150.9,
153.3, 160.8.
HRMS (ESI): m/z [M + H]+ calcd for C20H11Cl4N2: 418.9676;
found: 418.9678.
2,3-Bis(4-bromophenyl)quinoxaline (3k)10
Yield: 396.7 mg (84%); pale yellow solid; mp 191–193 °C (Lit.10
mp 189–191 °C).
1H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8.0 Hz, 3 H), 7.50–
7.53 (m, 5 H), 7.55–7.57 (m, 2 H), 7.59–7.60 (m, 1 H), 7.80–7.82
(m, 1 H).
6-Chloro-2,3-diphenylquinoxaline (3d)4d
Yield: 269.2 mg (85%); pale yellow solid; mp 115–116 °C (Lit.4d
mp 122–123 °C).
13C NMR (100 MHz, CDCl3): δ = 123.7, 124.0, 127.9, 129.2, 130.2,
130.4, 131.4, 131.6, 131.9, 132.2, 133.1, 137.7, 141.2, 151.9.
2,3-Bis[4-(1H-pyrrol-1-yl)phenyl]quinoxaline (3l)
Yield: 321.7 mg (78%); white solid; mp 178–180 °C.
Synthesis 2012, 44, 2699–2706
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of 2,3-Diarylquinoxalines
2705
IR (KBr): 1617, 1561, 1122, 1068 cm–1.
Acknowledgment
1H NMR (400 MHz, CDCl3): δ = 6.38 (s, 4 H), 7.16 (d, J = 0.8 Hz,
4 H), 7.40–7.46 (m, 4 H), 7.64 (d, J = 0.8 Hz, 4 H), 7.79–7.81 (m, 2
H), 8.17–8.20 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 110.9, 111.6, 111.8, 18.9, 119.0,
119.1, 119.3, 119.4, 119.8, 120.8, 129.1, 130.2, 130.7, 131.2, 131.7,
135.9, 140.9, 141.2, 152.2.
Financial Support from the National Natural Science Foundation of
China (No. 20962010 and 21162012), Natural Science Foundation
of Jiangxi Province of China, Jiangxi Educational Committee
(GJJ10386), and Foundation for young people (Yang Qin) of
Jiangxi Normal University is gratefully acknowledged.
HRMS (ESI): m/z [M + H]+ calcd for C28H21N4: 413.1766; found:
413.1768.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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r
itmnatr
2,3-Bis(furan-2-yl)quinoxaline (3m)4d
Yield: 230.7 mg (88%); pale brown solid; mp 131–132 °C (Lit.4d
mp 130–131 °C).
References
1H NMR (400 MHz, CDCl3): δ = 6.52–6.54 (m, 2 H), 6.65 (d, J =
3.6 Hz, 2 H), 7.60 (s, 2 H), 7.67–7.70 (m, 2 H), 8.08–8.11 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 76.8, 77.1, 77.5, 111.8, 112.9,
129.0, 130.3, 140.5, 142.5, 144.1, 150.8.
(1) (a) Kim, Y. B.; Kim, Y. H.; Park, J. Y.; Kim, S. K. Bioorg.
Med. Chem. Lett. 2004, 14, 541. (b) He, W.; Meyers, M. R.;
Hanney, B.; Spada, A.; Blider, G.; Galzeinski, H.; Amin, D.;
Needle, S.; Page, K.; Jayyosi Perrone, H. Bioorg. Med.
Chem. Lett. 2003, 13, 3097. (c) Sakata, G.; Makino, K.;
Kuraswa, Y. Heterocycles 1988, 27, 2481. (d) Seitz, L. E.;
Suling, W. J.; Reynolds, R. C. J. Med. Chem. 2002, 45, 5604.
(2) (a) Brown, D. J. The Chemistry of Heterocyclic Compounds,
Quinoxalines: Supplement II; Vol. 61; Wiley: New York,
2004. (b) Brock, E. D.; Lewis, D. M.; Yousaf, T. I.; Harper,
H. H. (The Procter and Gamble Company USA)
2,3-Di(naphthalen-2-yl)quinoxaline (3n)11
Yield: 344.0 mg (90%); yellow solid; mp 187–188 °C (Lit.11 mp
192–193 °C).
1H NMR (400 MHz, CDCl3): δ = 7.50–7.57 (m, 6 H), 7.72 (d, J =
8.8 Hz, 2 H), 7.82–7.86 (m, 6 H), 8.30–8.32 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 126.3, 126.9, 127.1, 127.7, 127.8,
WO9951688, 1999; Chem. Abstr. 1999, 131, 287743.
(c) Dailey, S.; Feast, J. W.; Peace, R. J.; Sage, I. C.; Till, S.;
Wood, E. L. J. Mater. Chem. 2001, 11, 2238. (d) O’Breien,
D.; Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C. Appl.
Phys. Lett. 1996, 69, 881.
128.7, 129.2, 129.8, 130.1, 133.25, 133.28, 136.6, 141.4, 153.4.
2,3-Bis(4-chlorophenyl)-6-methylquinoxaline (3o)12
Yield: 175.3 mg (48%); pale yellow solid; mp 178–180 °C (Lit.12
mp 180–181 °C).
(3) (a) Porter, A. E. A. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R.; Rees, C. W., Eds.; Pergamon:
Oxford, 1984; 157,. (b) Woo, G. H. C.; Snyder, J. K.; Wan,
Z. K. Prog. Heterocycl. Chem. 2002, 14, 279. (c) Brown, D.
J. Quinoxalines: Supplement II, In The Chemistry of
Heterocyclic Compounds; Taylor, E. E. C.; Wipf, P., Eds.;
Wiley: New Jersey, 2004.
1H NMR (400 MHz, CDCl3): δ = 2.60 (s, 3 H), 7.35–7.38 (m, 4 H),
7.47 (d, J = 8.0 Hz, 4 H), 7.58–7.61 (m, 1 H), 7.90 (s, 1 H), 8.01 (d,
J = 0.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 22.0, 123.5, 123.6, 127.9, 128.6,
131.46, 131.47, 131.6, 132.8, 137.8, 139.7, 141.0, 141.3, 150.9,
151.7.
(4) (a) Zhao, Z.; Wisnoski, D. D.; Wolkenberg, S. E.; Leister,
W. H.; Wang, Y.; Lindsley, C. W. Tetrahedron Lett. 2004,
45, 4873. (b) More, S. V.; Sastry, M. N. V.; Wang, C.; Yao,
C. Tetrahedron Lett. 2005, 46, 6345. (c) Cai, J.; Zou, J.; Pan,
X.; Zhang, W. Tetrahedron Lett. 2008, 49, 7386. (d) More,
S. V.; Sastry, M. N. V.; Yao, C. Green Chem. 2006, 8, 91.
(e) Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W.
N.; Bhusare, S. R.; Pawar, R. P. Tetrahedron Lett. 2005, 46,
7183.
(5) (a) Sithambaram, S.; Ding, Y.; Li, W.; Shen, X.; Gaenzler,
F.; Suib, S. L. Green Chem. 2008, 10, 1029. (b) Raw, S. A.;
Wilfred, C. D.; Taylor, J. K. Org. Biomol. Chem. 2004, 2,
788.
2,3-Bis(4-bromophenyl)-6-methylquinoxaline (3p)
Yield: 204.4 mg (45%); yellow solid; mp 183–185 °C.
1H NMR (400 MHz, CDCl3): δ = 2.63 (s, 3 H), 7.34 (d, J = 8.0 Hz,
4 H), 7.38–7.47 (m, 4 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.94 (s, 1 H),
8.05 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 21.9, 128.0, 128.6, 131.1, 132.7,
135.1, 132.7, 135.2, 137.4, 139.7, 141.0, 141.3, 151.0, 151.7.
HRMS (ESI): m/z [M + H]+ calcd for C21H15Br2N2: 452.9602;
found: 452.9621.
2,3-Di(naphthalen-2-yl)-6-methylquinoxaline (3q)
Yield: 210.2 mg (53%); yellow solid; mp 191–193 °C.
(6) Some reviews: (a) Nair, V.; Vellalath, S.; Babu, B. P. Chem.
Soc. Rev. 2008, 37, 2691. (b) Marion, N.; Diez-Gonzalez, S.;
Nolan, S. P. Angew. Chem. Int. Ed. 2007, 46, 2988.
(c) Niemeier, D. O.; Henseler, A. Chem. Rev. 2007, 107,
5606. (d) Christmann, M. Angew. Chem. Int. Ed. 2005, 44,
2632. (e) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004,
37, 534. (f) Nair, V.; Bindu, S.; Sreekumar, V. Angew.
Chem. Int. Ed. 2004, 43, 5130.
IR (KBr): 1641, 1605, 1566, 1475, 1123, 1069 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.60 (s, 3 H), 7.39–7.49 (m, 6 H),
7.59–7.64 (m, 3 H), 7.75 (s, 3 H), 7.99 (s, 1 H), 8.10 (d, J = 8.0 Hz,
1 H), 8.19 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.95, 126.2, 126.74, 126.77,
127.1, 127.6, 127.6, 127.7, 128.1, 128.6, 128.8, 129.7, 129.8, 132.4,
133.2, 136.8, 139.9, 140.6, 141.4, 152.5, 153.2.
(7) (a) Mavis, M. E.; Yolacan, C.; Aydogan, F. Tetrahedron
Lett. 2010, 51, 4509. (b) John, M. D.; Williamson, C.
Tetrahedron Lett. 2005, 46, 7337. (c) Xu, L.; Gao, Y.; Yin,
J.; Li, L.; Xia, C. Tetrahedron Lett. 2005, 46, 5317.
(d) Iwamoto, K.; Kimura, H.; Oike, M.; Sato, M. Org.
Biomol. Chem. 2011, 9, 5948. (e) Iwamoto, K.; Kimura, H.;
Oike, M.; Sato, M. Org. Biomol. Chem. 2008, 6, 912.
HRMS (ESI): m/z [M + H]+ calcd for C29H21N2: 397.1705; found:
397.1706.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2699–2706

2706
Y. Lin et al.
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© Georg Thieme Verlag Stuttgart · New York