Et3N-catalyzed oxidative dehydrogenative coupling of α-unsubstituted aldehydes and ketones with aryl diamines leading to quinoxalines using molecular oxygen as oxidant

Article abstract of DOI:10.1016/j.tet.2012.03.020

A novel Et₃N-catalyzed oxidative dehydrogenative coupling of α-unsubstituted carbonyl compounds with aryl diamines leading to quinoxaline derivatives using molecular oxygen as oxidant has been developed. Six hydrogen dissociations involving 2 sp³ C-H bonds activation are realized under mild conditions in this approach. Plausible mechanism is proposed for this novel Et₃N-catalyzed transformation on the basis of the aboratively designed mechanistic studies including the radical detection by EPR. 2012 Elsevier Science. All rights reserved.

Full text of DOI:10.1016/j.tet.2012.03.020

Supporting Information
Et N-catalyzed Oxidative Dehydrogenative Coupling of α-Unsubstituted
3
Aldehydes and Ketones with Aryl Diamines Leading to Quinoxalines Using
Molecular Oxygen as Oxidant
Chun Zhang, Zejun Xu, Liangren Zhang and Ning Jiao*
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, School of
Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191,
China
jiaoning@bjmu.edu.cn
Supporting Information
Table of Contents
Screening with different catalysts and solvents
EPR Spectras
2
4
Labeling Experiments
9
Synthesis of material
10
Analytical data for compounds 3
11
22
1
13
H NMR and C NMR spectra of those compounds
1

a
Table S1: The reactions of 1a and 2a catalyzed by different catalysts .
H N
2
N
[
Cat.] 10 mol%
O
+
Ph
toluene (2.5 mL)
H N
2
o
N
3aa
Air, 60 C
1
a
2a
b
entry
[cat.] (10 mol %)
Yield %
65
20
7
1
2
3
3
Et N
pyridine
2a
c
4
DEBACO
TEMPO
Li CO
50
14
30
34
59
29
29
24
35
36
32
54
6
5
6
7
8
9
2
3
Na CO
2
3
K CO
2
3
NaOH
KOH
1
0
1
1
NaHCO3
Cs CO
1
1
1
1
1
2
3
4
5
6
2
3
K HPO
2
4
t-BuOH
.
K PO 3H O
3
4
2
None
a
c
o
b
1
a (0.25 mmol), 2a (0.25 mmol), Cat. (0.025 mmol), toluene (2.5 mL), Air (1 atm), 60 C12 h. Isolated yields.
0.0125 mmol catalyst was employed.
2

a
Table S2: The reactions of 1a and 2a in different solvents.
H N
2
N
Et N (10 mol%)
3
O
+
Ph
Solvent (2.5 mL)
H N
2
o
N
3aa
Air, 60 C
1a
2a
b
entry
Solvent (2.5 mL)
toluene
Yield %
65
1
2
3
4
5
6
7
8
9
DMSO
30
DMF
63
CH CH OH
12
3
2
benzene
DCE
63
51
H O
2
Trace
Trace
45
acetone
DMA
1
0
1
1,4-dioxane
37
1
CH CN
64
3
1
1
2
3
CH NO
30
3
2
THF
64
a
o
b
1
a (0.25 mmol), 2a (0.25 mmol), Et
3
N (0.025 mmol), solvent (2.5 mL), Air (1 atm), 60 C, 12 h. Isolated
yields.
3

EPR spectra
EPR measurements. EPR spectra were recorded at room temperature on a Bruker ESP-300
spectrometer operating at 9.7 GHz and a cavity equipped with a Bruker Aquax liquid sample cell.
Typical spectrometer parameters were: scan range, 200 G; field set, 3450 G; time constant, 165
ms; scan time, 60s; modulation amplitude 3.2 G; modulation frequency 100 kHz; receiver gain
4
1
.00*10 ; microwave power, 20 mW. DMPO ( 5-,5-dimethyl-1-pyrroline N-oxide) was
employed as the radical trap.
3 2
In our case, a) When the reaction under the standard conditions (1a, 2a, Et N, DMPO, O ) was
recorded for the EPR spectra (Fig. S1), the signals corresponding to (DMPO–O(H)) can be
obviously assigned. They are classical 4 peaks. The calculated hyperfine splittings are g (2.030),
and α (14.8 G).
b) Definitely, the 4 peaks completely disappeared with the addition of the superoxide dismutase
SOD), which is one of the well known experiments to confirm the presence of superoxide
0
H
(
radical (Fig. S3). Because the signal of hydroxy radical is inexistent at the same time with that of
superoxide radicals ruined by SOD, the Fig. S1 and Fig. S3 could demonstrate that hydroxy
radical derived from the superoxide radicals.
c) When the EPR was tested in the absence of Et
to (DMPO–O(H)) did not appear, which indicates that the hydroxy radical was not produced in
this system. This fact indicates that Et N plays the key role to trigger the formation of the
3
N catalyst (Fig. S4) the signals corresponding
3
superoxide radical and the subsequent hydroxy radical.
d) In the absence of 1a and 2a, the hydroxyl radical was not detected. This result demonstrates
that the hydroxyl radical is an important intermediate of this transformation.
Table S3. The EPR investigations.
signals
product
entry
EPR sample
(DMPO–O(H))
observed
observation
3
standard sample (1a, 2a, Et N ,
1
2
3
yes
no
yes
--
DMPO, O2)
standard sample + SOD
standard sample in the absence
no
trace
of Et N
3
standard sample in the absence
4
no
no
of 1a and 2a
4

EPR spectra of reaction system
50
30
10
-10
-30
-50
H/G
Figure S1: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et N (0.025 mmol), 1a (0.25
3
mmol), 2a (0.3 mmol) in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at
2
6
0 °C for 1 h. 0.01 mL of this reaction solution was taken out into a small tube, followed by the
-2
addition of 0.01 mL DMPO (5*10 M). Then, this mixture was analyzed by EPR. There are
classical 4 peaks the signals corresponding to (DMPO–O(H)). g (2.030), and α (14.8 G).
0
H
EPR spectra of reaction system without DMPO
50
30
10
-10
-30
-50
H/G
Figure S2: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et
3
N (0.025 mmol), 1a (0.25
mmol), 2a (0.3 mmol) in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at
2
6
0 °C for 1 h. 0.01 mL of this reaction solution was taken out into a small tube, then the mixture
was analyzed by EPR.
5

EPR spectra of reaction system with SOD
80
60
40
20
0
-20
-40
-60
-80
H/G
3
Figure S3: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et N (0.025 mmol), 1a (0.25
mmol), 2a (0.3 mmol) in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at
2
6
0
0 °C for 1 h. 0.01 mL of this reaction solution was taken out into a small tube, mixed well with
-
2
-2
.01 mL SOD solvent (1*10 M), followed by the addition of 0.01 mL DMPO (5*10 M). Then,
this mixture was analyzed by EPR.
EPR spectra of reaction system without Et3N
80
60
40
20
0
-20
-40
-60
-80
H/G
Figure S4: EPR spectra (X band, 9.7 GHz, RT) of reaction system: 1a (0.25 mmol), 2a (0.3 mmol)
in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at 60 °C for 1 h. 0.01 mL
2
of this reaction solution was taken out into a small tube, followed by the addition of 0.01 mL
-2
DMPO (5*10 M). Then, this mixture was analyzed by EPR.
6

EPR spectra of reaction system without 1a and 2a
60
40
20
0
-20
-40
-60
H/G
Figure S5: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et N (0.025 mmol) in toluene
3
(
2.5 mL) under O (1 atm). The reaction mixture was stirred at 60 °C for 1 h. 0.01 mL of this
2
reaction solution was taken out into a small tube, followed by the addition of 0.01 mL DMPO
-2
(
5*10 M). Then, this mixture was analyzed by EPR.
EPR spectra of reaction without 2a
60
40
20
0
-20
-40
-60
H/G
Figure S6: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et N (0.025 mmol), 1a (0.25
3
2
mmol), in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at 60 °C for 1 h.
0
.01 mL of this reaction solution was taken out into a small tube, followed by the addition of 0.01
-
2
mL DMPO (5*10 M). Then, this mixture was analyzed by EPR.
7

EPR spectra of reaction system without 1a
60
40
20
0
-20
-40
-60
H/G
Figure S7: EPR spectra (X band, 9.7 GHz, RT) of reaction system: Et N (0.025 mmol), 2a (0.3
3
mmol) in toluene (2.5 mL) under O (1 atm). The reaction mixture was stirred at 60 °C for 1 h.
2
0
.01 mL of this reaction solution was taken out into a small tube, followed by the addition of 0.01
-
2
mL DMPO (5*10 M). Then, this mixture was analyzed by EPR.
8

For the Labeling experiments:
O
Ph
Ph
O
NH2
+
N
Ph
H
Et N (10 mol%)
3
Ph
D
H
O
+
Ph
Ph
toluene (2.5 mL)
NH2
o
N
D
Ph
D
O2 (1 atm), 90
10 min
C
2a
Ph
17% (3ja)
2j-D
0.455 mmol
D%=56%
0
.25 mmol
D
2
j-D
0
.5 mmol
H%:D%= 1.2:1
D%=55%
The 1H-NMR spectra of substrate carbonyl compounds.
5
.02
2
.00
1.99
1
.06
0
.90
10
8
6
4
2
0PPM
The 1H-NMR spectra of recuperated carbonyl compounds.
4
.86
2
.00
2.00
1
.01
0
.89
10
8
6
4
2
0 PPM
9

Experimental section:
General Remarks.
1
All manipulations were conducted with Schlenk tube. H-NMR spectra were recorded on a
Bruker AVIII-400 spectrometers. Chemical shifts (in ppm) were referenced to tetramethylsilane
1
3
(
δ = 0 ppm) in CDCl
3
as an internal standard. C-NMR spectra were obtained by using the same
NMR spectrometers and were calibrated with CDCl
3
(δ = 77.00 ppm). Unless otherwise noted,
materials obtained from commercial suppliers were used without further purification.
Synthesis of material
NaOD (5 mol%)
D O (0.2 mL)
D
D
Ph
2
Ph
Ph
Ph
CD OD (5mL)
3
O
mmol
O
36 hours
1
yield=95%
d%=94%
3 2
Put 1j (1 mmol, 196mg) solved in 5ml CD OD. And then, 0.2 mL NaOD/D O solution (10% in
D
2
O) was added into the reaction system. The mixture was stirred for 36 hours, under room
temperature. And then, concentrating in vacuum the residue was purified by flash
chromatography on a short silica gel (eluent: petroleum ether/ethyl acetate = 20:1) to afford 188
mg (95%, D% = 94%) of 1j-d.
The 1H-NMR spectra of 1j-d.
1
0

Analytical data for compounds 3
N
N
3
aa
1
2
2
):
1
-Phenylquinoxaline.
-phenylacetaldehyde 1a (30 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in
(1 atm). The reaction mixture was stirred at 60 °C for 12 h. After
Typical procedure: Mix Et
3
N
(2.53 mg, 0.025 mmol),
toluene (2.5 mL) under O
2
cooling down to room temperature and concentrating in vacuum, the residue was purified by
flash chromatography on a short silica gel (eluent: petroleum ether/ethyl acetate = 20:1) to afford
1
4
7 mg (91%) of 3aa. 3aa: white solid; H NMR (CDCl
3
, 400 MHz): δ = 9.31 (s, 1H), 8.20-8.10
, 100 MHz): δ = 151.8, 143.3,
42.3, 141.6, 136.8, 130.2, 130.1, 129.6, 129.4, 129.09, 129.08, 127.5 ppm; IR (neat): ν = 3064.0,
13
(
m, 4H), 7.78-7.70 (m, 2H), 7.57-7.48 (m, 3H); C NMR (CDCl
3
1
1
-
1
611.6, 1540.1, 1485.6, 766.2 cm ; Ms (70 ev): m/z (%): 206.3 [M+] (100).
Me
N
N
3ba
2
）：
1
2
-p-Tolylquinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol)，2-p-tolylacetaldehyde 1b
3
(
33.6 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in toluene (2.5 mL) under
1
O
2
(1 atm) at 60 °C for 12 h, afforded 50 mg (90%) of 3ba. 3ba: white solid; H NMR (CDCl
3
,
4
00 MHz): δ = 9.29 (s, 1H), 8.14-8.08 (m, 4H), 7.77-7.69 (m, 2H), 7.35 (d, J = 8.8 Hz, 2H), 2.43
1
3
(
s, 3H); C NMR (CDCl , 100 MHz): δ = 151.7, 143.2, 142.3, 141.4, 140.4, 133.9, 130.1, 129.8,
3
-
1
1
29.5, 129.2, 129.0, 127.4, 21.3 ppm; IR (neat): ν = 2919.2, 1611.4, 1543.2, 1310.8, 752.7 cm ;
Ms (70 ev): m/z (%): 220.3 [M+] (100)..
N
Me
N
3
ca
3
):
2
2
-m-Tolylquinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol)，2-m-tolylacetaldehyde 1c
3
(
33.6 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in toluene (2.5 mL) under
11

1
O
2
(1 atm) at 60 °C for 12 h, afforded 47 mg (85%) of 3ca. 3ca: white solid; H NMR (CDCl
3
,
4
00 MHz): δ = 9.31 (s, 1H), 8.16-8.10 (m, 2H), 8.02 (s, 1H), 7.96 (d, J = 7.6 Hz, 1H), 7.80-7.71
1
3
(
m, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 2.49 (s, 3H); C NMR (CDCl , 100
3
MHz): δ = 152.0, 143.5, 142.3, 141.5, 138.9, 136.7, 130.9, 130.2, 129.6, 129.4, 129.1, 129.0,
-
1
1
28.2, 124.6, 21.5 ppm; IR (neat): ν = 3420.6, 2918.4, 1544.2, 1315.8, 759.6 cm ; Ms (70 ev):
m/z (%): 220.3 [M+] (100).
N
Me
N
3da
4
):
2
2
-o-Tolylquinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol)，2-o-tolylacetaldehyde 1d
3
(
33.6 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in toluene (2.5 mL) under
1
O
2
(1 atm) at 60 °C for 12 h, afforded 42 mg (76%) of 3da. 3da: yellow solid; H NMR (CDCl
3
,
4
7
1
2
00 MHz): δ = 9.01 (s, 1H), 8.16 (d, J = 9.6 Hz, 2H), 7.82-7.77 (m, 2H), 7.57-7.54 (m, 1H),
1
3
.43-7.37 (m, 3H), 2.47 (s, 3H); C NMR (CDCl , 100 MHz): δ = 155.0, 145.9, 142.0,141.1,
3
37.2, 136.6, 131.2, 130.2, 130.0, 129.7, 129.6, 129.4, 129.2, 126.3, 20.3 ppm; IR (neat): ν =
-
1
922.5, 1549.6, 1485.5, 1461.1, 758.5 cm ; Ms (70 ev): m/z (%): 220.3 [M+] (100).
F
N
N
3
ea
5
2
2
):
-(4-Fluorophenyl)quinoxaline. The reaction of Et
-(4-fluorophenyl)acetaldehyde 1e (34.5 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
3
3
N (2.53 mg, 0.025 mmol) ，
2
mmol), in toluene (2.5 mL) under O (1 atm) for at 60 °C 12 h, afforded 46 mg (82%) of 3ea.
1
3
ea: white solid; H NMR (CDCl , 400 MHz): δ = 9.27 (s, 1H), 8.19 (d, J = 5.6 Hz, 1H), 8.17 (d,
3
1
3
J = 5.2 Hz, 1H), 8.11 (t, J = 6 Hz, 2H),7.78-7.70 (m, 2H), 7.23 (d, J = 8.8 Hz, 2H); C NMR
CDCl , 100 MHz): δ = 164.2 (d, J = 250 Hz), 150.6, 142.8, 142.1, 141.4, 132.9, 130.3, 129.5,
29.4 (d, J = 8.5 Hz), 129.1, 116.2 (d, J = 21 Hz) ppm; IR (neat): ν = 3431.6, 2918.6, 1600.9,
(
3
1
1
-
1
514.9, 1229.0 cm ; Ms (70 ev): m/z (%): 224.2 [M+] (100).
1
2

Cl
N
N
3
fa
6
2
2
):
1
-(4-Chlorophenyl)quinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
-(4-chlorophenyl)acetaldehyde 1f (38.5 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) for at 60 °C 12 h, afforded 53.4 mg (89%) of 3fa.
1
3
2
1
8
fa: white solid; H NMR (CDCl , 400 MHz): δ = 9.28 (s, 1H), 8.15-8.10 (m, 4H), 7.80-7.73 (m,
3
1
3
H), 7.52 (d, J = 8.4 Hz, 2H); C NMR (CDCl
3
, 100 MHz): δ = 150.5, 142.9, 142.2, 141.7,
36.5, 135.2, 130.4, 129.7, 129.6, 129.3, 129.2, 128.7 ppm; IR (neat): ν = 3435.7, 1486.4, 1093.5,
-
1
31.1, 753.8 cm ; Ms (70 ev): m/z (%): 240.2 [M+] (100).
Br
N
N
3
ga
7
2
2
):
-(4-Bromophenyl)quinoxaline. The reaction of Et
-(4-bromophenyl)acetaldehyde 1g (50 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
3
3
N
(2.53 mg, 0.025 mmol),
2
mmol), in toluene (2.5 mL) under O (1 atm) for at 60 °C 12 h, afforded 60 mg (84%) of 3ga.
1
3
2
1
1
ga: white solid; H NMR (CDCl , 400 MHz): δ = 9.29 (s, 1H), 8.15-8.08 (m, 4H), 7.81-7.74 (m,
3
1
3
H), 7.69 (d, J = 8.4 Hz, 2H); C NMR (CDCl
3
, 100 MHz): δ = 150.6, 142.8, 142.2, 141.7,
35.7, 132.4, 130.5, 129.8, 129.6, 129.2, 129.0, 125.0 ppm; IR (neat): ν = 3433.5, 2920.8, 1483.6,
-
1
071.7, 760.4 cm ; Ms (70 ev): m/z (%): 284.3 [M+] (100).
OMe
N
N
3
ha
8
):
1
2
-(4-Methoxyphenyl)quinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
2
0
3
-(4-methoxyphenyl)acetaldehyde 1h (37.5 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg,
2
.3 mmol), in toluene (2.5 mL) under O (1 atm) for at 60 °C 12 h, afforded 52 mg (88%) of 3ha.
1
ha: white solid; H NMR (CDCl , 400 MHz): δ = 9.27 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 8.09 (t,
3
1
3
3
J = 8.4 Hz, 2H), 7.75-7.67 (m, 2H), 7.05 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H); C NMR (CDCl , 100
1
3

MHz): δ = 161.4, 151.3, 143.0, 142.2, 141.1, 130.1, 129.3, 129.2, 129.0, 128.9, 128.89, 114.5,
-
1
5
2
5.3 ppm; IR (neat): ν = 3417.4, 1661.2, 1603.2, 1247.3, 1030.0 cm ; Ms (70 ev): m/z (%):
36.2 [M+] (100).
N
N
3ia
9
):
3
2
-(Naphthalen-2-yl)quinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
2
-(naphthalen-2-yl)acetaldehyde 1i (42.5 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 60 °C for 12 h, afforded 56 mg (87 %) of 3ia. 3ia:
1
white solid; H NMR (CDCl , 400 MHz): δ =9.46 (s, 1H), 8.64 (s, 1H), 8.35 (d, J = 8.8 Hz, 1H),
3
8
7
1
1
2
.19 (d, J = 9.2 Hz, 1H), 8.13 (d, J = 6.8 Hz, 1H), 8.02-7.99 (m, 2H), 7.90 (t, J = 4.8 Hz, 1H),
1
3
.81-7.72 (m, 2H), 7.57-7.53 (m, 2H); C NMR (CDCl
3
, 100 MHz): δ = 151.7, 143.5, 142.4,
41.6, 134.1, 134.09, 133.4, 130.3, 129.6, 129.5, 129.2, 129.0, 128.9, 127.8, 127.5, 127.3, 126.7,
-
1
24.5 ppm; IR (neat): ν = 3420.7, 2918.2, 1462.2, 1034.0, 744.7 cm ; Ms (70 ev): m/z (%):
56.4 [M+] (100).
N
Ph
Ph
N
ja
3
1
2
2
0):
4
,3-Diphenylquinoxaline.
3
The reaction of Et N (2.53 mg, 0.025 mmol),
-(naphthalen-2-yl)acetaldehyde 1j (49.5 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 59 mg (84 %) of 3ja.
1
3
ja:white solid; H NMR (CDCl , 400 MHz): δ = 8.17 (dd, J = 6.6 Hz, J = 3.2 Hz, 2H), 7.75
3
1
2
13
(
dd, J
1 2 3
= 6.6 Hz, J = 3.2 Hz, 2H), 7.53-7.51 (m , 4H), 7.35-7.30 (m, 6H); C NMR (CDCl , 100
MHz): δ = 153.4, 141.2, 139.0, 129.9, 129.8, 129.2, 128.7, 128.2 ppm; IR (neat): ν = 3056.4,
-
1
2
922.4, 1441.7, 1346.0, 770.1 cm ; Ms (70 ev): m/z (%): 282.4 [M+] (100).
N
Ph
Ph
N
3
ka
1
2
1
1):
-Benzyl-3-phenylquinoxaline. The reaction of Et
,3-diphenylpropan-2-one 1k (52.6 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3
(1 atm) at 90 °C for 12 h, afforded 58 mg (78 %) of 3ka.
3
N
(2.53 mg, 0.025 mmol),
mmol), in toluene (2.5 mL) under O
2
1
4

1
3
7
1
1
ka: white solid; H NMR (CDCl
.45-7.35 (m, 5H), 7.17-7.11 (m, 3H), 6.98 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H); C NMR (CDCl
00 MHz): δ = 155.4, 154.3, 141.4, 140.9, 138.9, 138.2, 129.7, 129.5, 129.2, 128.9, 128.8,
3
, 400 MHz): δ =8.15-8.11 (m, 2H), 7.76-7.70 (m, 2H),
1
3
3
,
-
1
28.79, 128.4, 128.2, 126.3, 42.2 ppm; IR (neat): ν = 3424.5, 3058.3, 1492.7, 731.8, 698.1 cm ;
+
HRMS m/z (ESI) calcd for C21
H
16
N
2
(M + H) 297.1386, found 297.1383.
N
Ph
N
CF3
3
la
-Phenyl-3-(trifluoromethyl)quinoxaline. The reaction of Et
,1,1-trifluoro-3-phenylpropan-2-one 1l (47 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg,
1
2):
2
3
N (2.53 mg, 0.025 mmol),
1
0
3
7
1
2
.3 mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 60 mg (87 %) of 3la.
1
la: white solid; H NMR (CDCl , 400 MHz): δ = 8.28-8.20 (m, 2H), 7.95-7.86 (m, 2H),
3
1
3
.65-7.63 (m, 2H), 7.55-7.51 (m, 3H); C NMR (CDCl
3
, 100 MHz): δ = 152.6, 142.5, 141.3,
41.0, 139.3, 137.4, 132.6, 131.1, 129.7, 129.5, 129.3, 128.8, 128.3, 121.4 (q, J = 274 Hz) ppm;
-
1
IR (neat): ν = 3058.4, 2919.0, 1545.0, 1337.6, 1196.3 cm ; HRMS m/z (ESI) calcd for
+
C
15
H
9
N
2
F
3
(M + H) 275.0791, found 275.0786.
N
N
Ph
3ab
1
3):
2
-Phenylbenzo[g]quinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
2
-phenylacetaldehyde 1a (30 mg, 0.25 mmol), naphthalene-2,3-diamine 2b (47.46 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 60 °C for 12 h, afforded 49 mg (77 %) of 3ab.
1
3
ab: yellow solid; H NMR (CDCl , 400 MHz): δ = 9.38 (s, 1H), 8.71 (s, 1H), 8.67 (s, 1H), 8.26
3
1
3
(
d, J = 7.2 Hz, 2H), 8.12-8.10 (m, 2H), 7.61-7.54 (m, 5H); C NMR (CDCl
3
, 100 MHz): δ =
1
1
51.8, 144.6, 138.8, 138.2, 136.8, 134.2, 133.7, 130.4, 129.2, 128.5, 128.47, 128.0, 127.7, 127.6,
-
1
26.9, 126.7 ppm; IR (neat): ν = 3054.3, 2918.8, 1551.0, 1443.0, 871.9 cm ; HRMS m/z (ESI)
+
calcd for C18
H
12
N
2
(M + H) 257.1073, found 257.1066.
Cl
N
N
Ph
Cl
3ac
1
4):
5
6
,7-Dichloro-2-phenylquinoxaline. The reaction of Et
3
N (2.53 mg, 0.025 mmol),
1
5

2
-phenylacetaldehyde 1a (30 mg, 0.25 mmol), 4,5-dichlorobenzene-1,2-diamine 2c (53.1 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 60 °C for 12 h, afforded 64 mg (93 %) of 3ac.
1
3
3
1
ac: white solid; H NMR (CDCl , 400 MHz): δ = 9.27 (s, 1H), 8.22-8.14 (m, 4H), 7.57-7.51 (m,
3
1
3
H); C NMR (CDCl
3
, 100 MHz): δ = 152.5, 144.2, 141.0, 140.2, 135.9, 134.9, 133.9, 130.7,
-
1
30.1, 129.7, 129.2, 127.5 ppm; IR (neat): ν = 3435.3, 3049.6, 1538.0, 1461.9, 1443.3 cm ; Ms
(
70 ev): m/z (%): 274.2 [M+] (100).
N
Ph
F
N
Ph
and
F
N
N
3
ad-1
3ad-2
1
5):
6
-Fluoro-2-phenylquinoxaline and 7-Fluoro-2-phenylquinoxaline. The reaction of Et N (2.53
3
mg, 0.025 mmol), 2-phenylacetaldehyde 1a (30 mg, 0.25 mmol), 4-fluorobenzene-1,2-diamine
2
d (37.8 mg, 0.3 mmol), in toluene (2.5 mL) under O
2
(1 atm) at 60 °C for 12 h, afforded 53 mg
1
(
95 %) of 3ad (3ad-1 : 3ad-2 = 4.6 : 1). 3ad-1: white solid; H NMR (CDCl , 400 MHz): δ =
3
9
7
1
2
.28 (s, 1H), 8.18 (d, J = 6.8 Hz, 2H), 8.10 (t, J = 7.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H),
13
.57-7.51 (m, 4H); C NMR (CDCl
3
, 100 MHz): δ = 163.0 (d, J = 250 Hz), 152.4, 143.2 (d, J =
3.1 Hz), 142.6, 142.57, 138.8, 136.4, 131.1 (d, J = 10.3 Hz), 130.5, 129.2, 127.6, 119.8 (d, J =
-
1
.6 Hz), 113.0 (d, J = 21 Hz) ppm; IR (neat): ν = 3418.9, 3055.6, 1619.3, 1491.1, 1199.7 cm ;
+
HRMS m/z (ESI) calcd for C14
H
9
N
2
F (M + H) 225.0823, found 225.0830; 3ad-2: brown solid;
1
H NMR (CDCl
.59-7.53 (m, 4H); C NMR (CDCl
d, J = 13.1 Hz), 139.5, 136.5, 131.7 (d, J = 100 Hz), 130.2, 129.2, 127.4, 120.7 (d, J = 26 Hz),
3
, 400 MHz): δ = 9.32 (s, 1H), 8.19-8.14 (m, 3H), 7.74 (d, J = 8.8 Hz, 1H),
1
3
7
3
, 100 MHz): δ = 162.5 (d, J = 251 Hz), 151.3, 144.1, 142.2
(
-
1
1
12.7 (d, J = 21 Hz) ppm; IR (neat): ν = 3058.1, 1727.1, 1621.1, 1544.7, 1544.7 cm ; HRMS
+
9 2
m/z (ESI) calcd for C14H N F (M + H) 225.0823, found 225.0817;.
N
Ph MeO
and
N
N
Ph
MeO
N
3ae-1
3ae-2
16):
6
-Methoxy-2-phenylquinoxaline and 7-Methoxy-2-phenylquinoxaline. The reaction of Et
3
N
(2.53 mg, 0.025 mmol), 2-phenylacetaldehyde 1a (30 mg, 0.25 mmol),
4
6
-methoxybenzene-1,2-diamine 2e (41.5 mg, 0.3 mmol), in toluene (2.5 mL) under O
2
(1 atm) at
1
0 °C for 12 h, afforded 53 mg (90 %) of 3ae (3ae-1 : 3ae-2 = 1: 5.6). 3ae-1: white solid; H
1
6

NMR (CDCl , 400 MHz): δ = 9.24 (s, 1H), 8.15 (d, J = 6.8 Hz, 2H), 8.03 (d, J = 9.2 Hz, 1H),
3
1
3
7
1
5
.57-7.53 (m, 2H), 7.50 (d, J = 7.2 Hz, 1H), 7.43-7.39 (m, 2H), 3.99 (s, 3H); C NMR (CDCl
3
,
00 MHz): δ = 160.6, 149.6, 143.2, 143.1, 138.4, 137.0, 130.6, 129.7, 129.1, 127.2, 123.5, 106.5,
-
1
5.8 ppm; IR (neat): ν = 3432.5, 2920.1, 1614.3, 1210.4, 1026.2 cm ; HRMS m/z (ESI) calcd
+
1
for C H N O (M + H) 237.1022, found 237.1030. 3ae-2: white solid; H NMR (CDCl , 400
15
12
2
3
MHz): δ = 9.15 (s, 1H), 8.16 (d, J = 6.8 Hz, 2H), 7.98 (d, J = 9.2 Hz, 1H), 7.57-7.48 (m, 3H),
1
3
7
1
1
2
.43-7.27 (m, 2H), 3.97 (s, 3H); C NMR (CDCl , 100 MHz): δ = 161.0, 151.9, 143.9, 140.7,
3
37.7, 137.0, 130.9, 130.0, 129.1, 127.5, 122.8, 106.8, 55.8 ppm; IR (neat): ν = 2959.7, 2930.1,
-
1
+
727.3, 1617.4, 830.4 cm ; HRMS m/z (ESI) calcd for C15
12 2
H N O (M + H) 237.1022, found
37.1014.
Me
N
N
Ph
Ph
3jf
1
7):
-Methyl-2, 3-diphenylquinoxaline.
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 4-methylbenzene-1,2-diamine 2f (36.7 mg, 0.3
4
6
3
The reaction of Et N (2.53 mg, 0.025 mmol),
1
2
mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 69 mg (93 %) of 3jf. 3jf:
1
white solid; H NMR (CDCl , 400 MHz): δ = 8.05 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.58-7.56 (m,
3
1
3
1
1
H), 7.51-7.49 (m, 4H), 7.33-7.28 (m, 6H), 2.59 (s, 3H); C NMR (CDCl
3
, 100 MHz): δ = 153.2,
52.5, 141.2, 140.4, 139.6, 139.2, 132.2, 129.8, 129.75, 128.6, 128.59, 128.5, 128.1, 128.0, 21.8
-
1
ppm; IR (neat): ν = 3421.4, 3054.4, 1728.8, 1343.6, 701.1 cm ; Ms (70 ev): m/z (%): 296.4 [M+]
(
100).
Me
N
Ph
Ph
N
3jg
1
8):
5
-Methyl-2, 3-diphenylquinoxaline. The reaction of Et
3
N (2.53 mg, 0.025 mmol),
1
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 3-methylbenzene-1,2-diamine 2g (36.7 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 65 mg (88 %) of 3jg.
1
3
7
1
jg: white solid; H NMR (CDCl , 400 MHz): δ =7.99 (d, J = 8 Hz, 1H), 7.63-7.51 (m, 6H),
3
1
3
.33-7.28 (m, 6H), 2.84 (s, 3H); C NMR (CDCl
3
, 100 MHz): δ = 152.7, 151.7, 141.1, 140.3,
39.4, 139.3, 137.5, 130.1, 129.8, 129.7, 129.6, 128.6, 128.2, 128.0, 126.9, 17.1 ppm; IR (neat):
1
7

-
1
+
ν = 3414.9, 3053.9, 1345.6, 763.3, 693.1 cm ; HRMS m/z (ESI) calcd for C21
16 2
H N (M + H)
2
97.1386, found 297.1388.
Me
Me
N
N
Ph
Ph
3
jh
1
5
1
0
3
7
1
2
9):
6
,6-Dimethyl-2, 3-diphenylquinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 3,4-dimethylbenzene-1,2-diamine 2h (40.9 mg,
2
.3 mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 66 mg (85 %) of 3jh.
1
jh: white solid; H NMR (CDCl , 400 MHz): δ = 7.90 (d, J = 8.8 Hz, 1H), 7.58-7.50 (m, 5H),
3
1
3
.32-7.27 (m, 6H), 2.78 (s, 3H), 2.51 (s, 3H); C NMR (CDCl
3
, 100 MHz): δ = 151.6, 151.4,
40.1, 139.7, 139.5, 139.45, 137.6, 134.5, 132.8, 130.1, 129.7, 128.5, 128.46, 128.2, 128.0, 125.8,
-
1
0.4, 12.9 ppm; IR (neat): ν = 3059.0, 2919.4, 1561.5, 1443.1, 1342.82 cm ; Ms (70 ev): m/z
(
%): 310.4 [M+] (100).
F
N
N
Ph
Ph
Cl
3
ji
-Chloro-7-fluoro-2, 3-diphenylquinoxaline. The reaction of Et
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 4-chloro-5-fluorobenzene-1,2-diamine 2i (48 mg,
2
6
1
0
3
1
0):
3
N (2.53 mg, 0.025 mmol),
2
.3 mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 64 mg (76 %) of 3ji.
1
ji: white solid; H NMR (CDCl , 400 MHz): δ = 8.23 (d, J = 7.6 Hz, 1H), 7.86 (d, J = 9.6 Hz,
3
1
3
H), 7.51-7.47 (m, 4H), 7.39-7.30 (m, 6H); C NMR (CDCl , 100 MHz): δ = 158.1 (d, J = 253
3
Hz), 154.3, 153.7, 140.5, 140.4, 138.43, 138.4, 138.3, 130.3, 129.8, 129.7, 129.2, 129.1, 128.3,
1
7
25.5 (d, J = 22 Hz), 113.7 (d, J = 21 Hz) ppm; IR (neat): ν = 3420.7, 1468.3, 1338.5, 1214.2,
-
1
+
12 2 1 1
01.1 cm ; HRMS m/z (ESI) calcd for C20H N F Cl (M + H) 335.0746, found 335.0759.
N
Ph
Cl
N
Ph
3
jj
2
1):
-Chloro-2,3-diphenylquinoxaline. The reaction of Et N (2.53 mg, 0.025 mmol),
3
7
6
1
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 4-chlorobenzene-1,2-diamine 2j (42.8 mg, 0.3
(1 atm) at 90 °C for 12 h, afforded 61 mg (77 %) of 3jj. 3jj:
mmol), in toluene (2.5 mL) under O
2
1
8

1
white solid; H NMR (CDCl , 400 MHz): δ = 8.16 (d, J = 2.4 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H),
3
1
3
7
1
1
.68 (dd, J
1 2 3
= 9.2 Hz, J = 2.4 Hz, 1H), 7.52-7.49 (m, 4H), 7.38-7.29 (m, 6H); C NMR (CDCl ,
00 MHz): δ = 154.2, 153.6, 141.4, 139.7, 138.7, 138.6, 135.6, 130.9, 130.4, 129.82, 129.78,
-
1
29.1, 129.0, 128.3, 128.1 ppm; IR (neat): ν = 3431.5, 2917.9, 1341.7, 1060.6, 696.1 cm ; Ms
(
70 ev): m/z (%): 316.3 [M+] (14); 206.3 (100).
N
Ph
Br
N
Ph
3
jk
-Bromo-2,3-diphenylquinoxaline. The reaction of Et
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), 4-bromobenzene-1,2-diamine 2k (56.1 mg, 0.3
2
6
1
2):
7
3
N (2.53 mg, 0.025 mmol),
2
mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 68 mg (75 %) of 3jk.
1
3
jk: white solid; H NMR (CDCl , 400 MHz): δ = 8.35 (d, J = 2 Hz, 1H), 8.02 (d, J = 8.8 Hz,
3
1
3
1
H), 7.82 (dd, J
, 100 MHz): δ = 154.2, 153.7, 141.7, 139.9, 138.7, 138.6, 133.4, 131.4, 130.5, 129.8,
29.7, 129.1, 129.0, 128.29, 128.27, 123.8 ppm; IR (neat): ν = 3431.5, 2917.9, 1341.7, 1060.6,
1 2
= 8.8 Hz, J = 2 Hz, 1H), 7.52-7.49 (m, 4H), 7.39-7.30 (m, 6H); C NMR
(CDCl
3
1
6
-
1
96.1 cm ; Ms (70 ev): m/z (%): 360.3 [M+] (86); 75.2 (100).
N
Ph
MeOOC
N
Ph
3
jl
2
3):
Methyl 2,3-diphenylquinoxaline-6-carboxylate. The reaction of Et N (2.53 mg, 0.025 mmol)，
3
1
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), methyl 3,4-diaminobenzoate 2l (49.9 mg, 0.3
2
mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 60 mg (71 %) of 3jl. 3jl
1
white solid; H NMR (CDCl , 400 MHz): δ = 8.89 (d, J = 1.6 Hz, 1H), 8.35 (dd, J = 8.8 Hz, J =
3
1
2
1
3
1
.6 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.55-7.51 (m, 4H), 7.40-7.32 (m, 6H), 4.01 (s, 3H); C
NMR (CDCl , 100 MHz): δ = 166.3, 155.1, 154.4, 143.1, 140.4, 138.6, 131.9, 131.1, 130.8,
3
1
1
3
29.8, 129.78, 129.4, 129.35, 129.2, 129.1, 128.7, 128.3, 52.5 ppm; IR (neat): ν = 3410.3, 2952.0,
-
1
+
716.2, 1434.0, 700.1 cm ; HRMS m/z (ESI) calcd for C22
16 2 2
H N O (M + H) 341.1285, found
41.1296.
N
N
Ph
Ph
MeO
3je
2
4):
1
9

6
6
-Methoxy-2,3-diphenylquinoxaline. The reaction of Et
3
N (2.53 mg, 0.025 mmol),
1
,2-diphenylethanone 1j (49.1 mg, 0.25 mmol), methyl 4-methoxybenzene-1,2-diamine 2e (41.5
2
mg, 0.3 mmol), in toluene (2.5 mL) under O (1 atm) at 90 °C for 12 h, afforded 76 mg (97 %) of
1
3
je. 3je white solid; H NMR (CDCl
3
, 400 MHz): δ =8.04 (d, J = 8.8 Hz, 1H), 7.52-7.48 (m, 4H),
= 9.2 Hz, J = 2.8 Hz, 1H), 7.34-7.29 (m, 6H), 3.96 (s, 3H);
, 100 MHz): δ = 160.8, 153.3, 150.8, 142.7, 139.2, 139.1, 137.3, 130.8, 130.1,
29.7, 128.6, 128.4, 128.14, 128.12, 123.2, 106.4, 55.7 ppm; IR (neat): ν = 2960.9, 2933.8,
7
.46 (d, J = 2.8 Hz, 1H), 7.40 (dd, J
1
2
1
3
C NMR (CDCl
3
1
1
-
1
727.4, 1616.9, 1483.1 cm ; Ms (70 ev): m/z (%): 312.5 [M+] (100).
Me
N
Ph
Me
N
3am
2
5):
,7-Dimethyl-2-phenylquinoxaline. The reaction of Et
-phenylacetaldehyde 1a (600 mg, 5 mmol), 4,5-dimethylbenzene-1,2-diamine 2m (818 mg, 6
1
6
3
N
(50.6 mg, 0.5 mmol),
2
2
mmol), in toluene (50 mL) under O (1 atm) at 60 °C for 24 h, afforded 1.0062 g (86 %) of 3am.
1
3
1
1
am: white solid; H NMR (CDCl , 400 MHz): δ = 9.20 (s, 1H), 8.15 (d, J = 6.8 Hz, 2H), 7.88 (s,
3
13
H), 7.83 (s, 1H), 7.55-7.46 (m, 3H), 2.48 (s, 6H); C NMR (CDCl
3
, 100 MHz): δ = 150.9,
42.3, 141.2, 140.7, 140.5, 140.0, 137.1, 129.7, 129.0, 128.6, 128.1, 127.3, 20.3, 20.2 ppm; IR
-
1
(
neat): ν = 3418.7, 2965.3, 1727.8, 1537.1, 1484.3 cm ; Ms (70 ev): m/z (%): 234.4 [M+] (100).
O
N
N
and
N
ma-1
N
ma-2
3
3
2
6):
1
1H-Indeno[1,2-b]quinoxaline and 11H-Indeno[1,2-b]quinoxalin-11-one. The reaction of
Et (2.53 mg, 0.025 mmol), 1H-inden-2(3H)-one 1m (33.1 mg, 0.25 mmol),
benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in toluene (2.5 mL) under O
3
N
2
(1 atm) for at 60 °C
1
1
2 h, afforded 22 mg (40%) of 3ma-1 and 32 mg (55%) of 3ma-2. 3ma-1 yellow solid; H NMR
(
CDCl , 400 MHz): δ = 8.24 (t, J = 4.4 Hz, 1H), 8.16 (t, J = 4.4 Hz, 1H), 8.08 (t, J = 4.4 Hz, 1H),
3
13
7
3
.76-7.69 (m, 2H), 7.64 (d, J = 6 Hz, 1H), 7.56-7.5 (m, 2H), 4.13 (s, 2H); C NMR (CDCl , 100
MHz): δ = 159.4, 154.6, 143.5, 142.1, 141.3, 138.0, 131.1, 129.2, 129.0, 128.8, 128.0, 125.8,
-
1
1
22.6, 35.9 ppm; IR (neat): ν = 3418.7, 2922.3, 1613,3, 1333.6, 773.5 cm ; HRMS m/z (ESI)
+
1
10 2 3
calcd for C15H N (M + H) 219.0917, found 219.0924; 3ma-2 yellow solid; H NMR (CDCl ,
2
0

4
00 MHz): δ = 8.21 (d, J = 8.4 Hz, 1H), 8.08-8.04 (m, 2H), 7.89 (d, J = 7.6 Hz, 1H), 7.82-7.70
13
(
m, 3H), 7.58 (t, J = 7.6 Hz, 1H); C NMR (CDCl
3
, 100 MHz): δ = 189.8, 156.5, 149.2, 143.0,
1
3
2
42.5, 141.4, 136.7, 136.6, 132.4, 132.3, 131.5, 130.2, 129.6, 124.6, 122.4 ppm; IR (neat): ν =
-
1
+
434.0, 2918.7, 1729.8, 1568.9, 774.6 cm ; HRMS m/z (ESI) calcd for C15
18 2 1
H N O (M + H)
33.0709, found 233.0707.
Reference:
1
2
3
) Meshram, H. M.; Kumar, G. S.; Ramesh, P.; Reddy, B. C. Tetrahedron Lett. 2010, 51, 2580.
) Cho, C. S.; Oh, S.G. Tetrahedron Lett. 2006, 47, 5633.
) Madhav, B.; Murthy, S. N.; Reddy, V. P.; Rao, K. R.; Nageswar, Y. V. D. Tetrahedron Lett.
009, 50, 6025.
) Mousset, C.; Provot, O.; Hamze, A.; Bignon, J.; Brion, J.-D.; Alami, M. Tetrahedron, 2008, 64,
287.
2
4
4
5
6
7
) Rueping, M.; Tato, F.; Schoepke, F. R. Chem. Eur. J. 2010, 16, 2688.
) Zhou, J.-F.; Gong,; Zhi, S.-J.; Duan, X.-L. Synthetic Commun. 2009, 39, 3743.
) Cai, J.-J.; Zou, J.-P.; Pan, X.-Q.; Zhang, W. Tetrahedron Lett. 2008, 49, 7386.
2
1

S22

S23

S24

S25

S26

S27

S28

S29

S30