Supporting Information
Experimental and spectroscopic data for:
Green oxidations: Titanium dioxide induced
tandem oxidation coupling reactions
Vineet Jeena and Ross S. Robinson*
Department of Chemistry, University of KwaZulu-Natal, Scottsville,
Pietermaritzburg, 3209, South Africa
robinsonr@ukzn.ac.za
General
1H
and
13C
NMR spectra were obtained using a Bruker Avance 400 operating at
either at 400 or 100 MHz using CDCl3 as an internal standard. Data are
expressed in parts per million relative to residual solvent. All J values given in Hz.
Low resolution electron impact (EI) mass spectra were recorded on
Thermofinnigan trace GC, coupled with PolarisQ mass spectra. IR spectra were
recorded on Perkin-Elmer Spectrum One. Absorption maxima are expressed in
wavenumbers (cm−1). Radial chromatography was performed on the Harrison
Research Chromatatron (Model 7924T) with the solvent system delivered by
gravity flow using a 1 mm layer of Merck silica gel (7749).
1
The α-hydroxyketone 1b was synthesized from the corresponding methyl ketone
using the method described by Moriarty et al. [1] PE refers to petroleum ether
with a boiling point range 40–60 °C.
Microwave
All microwave reactions were conducted on a CEM Focused Microwave TM
Synthesis system which uses an infrared sensor located below the microwave
cavity floor to measure temperature.
Temperature/Time Profile for 2-phenylquinoxaline
(3a)
2

Reaction temperature and profile was monitored every minute during a
5 min run.

After the 5 min, the reaction vessel was rapidly cooled to 50 °C by the
instrument.

Once a temperature of 50 °C was reached, the instrument stopped
cooling and released the residual pressure.
General procedure for the synthesis of
quinoxalines (table 2, entries i-vii)
N
N
3a
2-Phenylquinoxaline (3a) 2-Hydroxyacetophenone (0.068 g, 0.50 mmol), ophenylenediamine (0.054 g, 0.50 mmol), TiO2 (0.040 g, 0.50 mmol) and 2,2,6,6Tetramethylpiperidine-1-oxyl (TEMPO) (0.008 g, 0.050 mmol) were added to a
sealed 10 mL CEM Discover® reaction vial equipped with a magnetic stirrer bar.
The reaction vial was irradiated (at 150 W with cooling) for 10 min (2 x 5 min) at
150 °C, after which the vessel was rapidly cooled to 50 °C by the unit. The
reaction mixture was diluted with dichloromethane (DCM) and passed through a
short silica plug. The solvent was removed in vacuo to produce a crude product
3
which was purified using radial chromatography (3 : 1 PE : EtOAc) to produce the
title compound 3a (0.089 g, 87%) as an orange solid: Rf 0.46 (3 : 1 PE : EtOAc);
νmax (neat) 1599, 1541, 1488, 1445, 1305 cm −1; 1H NMR (400 MHz, CDCl3) 7.53–
7.58 (3H, m), 7.78–7.80 (2H, m), 8.16 (2H, m), 8.21 (m, 2H), 9.34 (1H, s); δC
(100 MHz) 127.5, 127.6, 129.2, 129.6, 129.7, 130.2, 130.4, 136.8, 141.4, 142.4,
143.2, 151.9; m/z (EI) 206 (M+). Data consistent with literature [2].
N
N
3b
2-Cyclohexylquinoxaline (3b) Prepared by the procedure given for 3a using 1cyclohexyl-2-hydroxyethanone
1b
[1]
(0.106
g,
0.50
mmol)
and
o-
phenylenediamine (0.054 g, 0.50 mmol). Purified using radial chromatography (2:
1 PE : EtOAc) to produce the title compound 3b (0.064 g, 60%) as a brownish
solid: Rf 0.80 (2 : 1 PE : EtOAc); vmax (neat) 1559, 1491, 1449, 1368 cm−1;
1H
NMR (400 MHz, CDCl3) δH 1.38–2.07 (10H, m), 2.99 (1H, tt, J = 12.0 Hz J =
3.5 Hz), 7.72 (2H, m); 8.07 (2H, m); 8.78 (1H, s); δ C (100 MHz) 25.9, 26.4, 32.3,
45.0, 128.9, 128.9, 129.1, 129.9, 141.4, 142.1, 144.9, 161.1 m/z (EI) 212 (M+).
Data consistent with literature [2].
4
N
N
3c
2,3-Diphenylquinoxaline (3c) Prepared using the procedure given for 3a using
benzoin (0.106 g, 0.50 mmol) and o-phenylenediamine (0.054 g, 0.50 mmol) but
irradiated for 20 min. Purified using radial chromatography (9 : 1 PE : EtOAc) to
give the title compound 3c (0.114 g, 81%) as a yellow solid: Rf 0.59 (9 : 1 PE :
EtOAc); νmax (neat) 1596, 1514, 1448, 1346 cm−1; 1H NMR (400 MHz, CDCl3) δH
7.34–7.36 (6H, m), 7.52–7.54 (4H, m), 7.78 (2H, m), 8.19 (2H, m); δC (100 MHz)
128.2, 128.8, 129.2, 129.8, 129.9, 139.1, 141.2, 153.5; m/z (EI) 282 (M+). Data
consistent with literature [2].
N
N
3d
1,2,3,4-Tetrahydrophenazine (3d) Prepared using the procedure given for 3a
using
2-hydroxycyclohexanone
dimer
(0.057
g,
0.500
mmol)
and
o-
phenylenediamine (0.054 g, 0.50 mmol). Purified using radial chromatography
(1 : 1 PE : EtOAc) to give the title compound 3d (0.810 g, 88%) as a white solid:
Rf 0.54 (1 : 1 PE : EtOAc); νmax (neat) 1459, 1423, 1384, 1330, 1291, 1238 cm −1;
1H
NMR (400 MHz, CDCl3) δH 2.04 (4H, m), 3.16 (4H, m), 7.65 (2H, m), 7.97 (2H,
5
m); δC (100 MHz) 22.8, 33.2, 128.3, 128.9, 141.2, 154.1; m/z 184 (M+). Data
consistent with literature [3].
N
N
N
3e
2-/3-Phenylpyrido[2,3-b]pyrazine (3e) Prepared using the procedure given for
3a
using
2-hydroxyacetophenone
and
2,3-diaminopyridine
2b
(0.054g,
0.50 mmol) but irradiated for 20 min. Purified using radial chromatography
(EtOAc) to give the title compound 3e (0.087 g, 83%) as a brown solid, as a
mixture of regioisomers with 3-phenylpyrido[2,3-b]pyrazine predominating: Rf
0.70 (EtOAc); νmax (neat) 1645, 1561, 1457, 1419, 1363, 1327 cm −1; 1H NMR
(400 MHz) 3-phenylpyrido[2,3-b]pyrazine δH 7.55–7.60 (3H, m), 7.69 (1H, dd, J
= 8.3 Hz, J = 4.2 Hz), 8.32–8.35 (2H, m), 8.48 (1H, dd, J = 8.3 Hz, J = 1.8 Hz),
9.18 (1H, dd, J = 4.1 Hz, J = 1.8 Hz), 9.45 (1H, s); δC (100 MHz) 124.7, 128.0,
129.1,
131.0,
135.7,
136.7,
138.1,
144.3,
150.8,
153.4;
154.4.
2-
phenylpyrido[2,3-b]pyrazine δH (400 MHz) 7.53–7.60 ( 3H, m), 7.73 (1H, dd, J =
8.4 Hz, J = 4.2 Hz), 8.21–8.24 (2H, m), 8.51 (1H, dd, J = 8.4 Hz J = 1.8 Hz), 9.17
(1H, dd J = 4.1 Hz J = 1.8 Hz), 9.55 (1H, s); δC (100 MHz) 125.5, 127.6, 129.2,
130.7, 135.8, 137.5, 138.5, 146.2, 150.4, 152.9, 154.6; m/z 207 (M+). Data
consistent with literature [2].
6
N
N
N
3f
2,3-Diphenylpyrido[2,3-b]pyrazine (3f) Prepared using the procedure given for
3a using benzoin (0.106g, 0.50mmol) and 2,3-diaminopyridine (0.054 g,
0.50 mmol) but irradiated for 20 min. Purified using radial chromatography (9:1
DCM:EtOAc) to produce the title compound 3f (0.076 g, 54%) as a yellow solid Rf
0.30 (9:1 DCM:EtOAc); νmax (neat) 1588, 1545, 1430, 1382, 1328 cm −1; 1H NMR
(400 MHz) δH 7.31–7.41 (6H, m), 7.56 (2H, d, J = 7.8 Hz), 7.64 (2H, d, J = 7.8
Hz), 7.74–7.76 (1H, dd, J = 8.4 Hz J = 4.1 Hz), 8.55–8.57 (1H, d, J = 8.2 Hz),
9.19 (1H, d, J = 4.2 Hz); δC (100 MHz) 125.2, 128.2, 128.5, 129.4, 129.6, 129.8,
130.3, 136.2, 138.0, 138.5, 149.4, 153.6, 155.0, 156.6; m/z 283 (M+). Data
consistent with literature [4].
N
N
N
3g
6,7,8,9-Tetrahydropyrido[2,3-b]quinoxaline (3g) Prepared using the procedure
given for 3a using 2-hydroxycyclohexanone dimer (0.057 g, 0.50 mmol), 2,3diaminpyridine (0.054 g, 0.50 mmol) but irradiated for 20 min. Purified using
radial chromatography (9:1 DCM: EtOAc) to produce the title compound 3g
7
(0.052 g, 56%) as a purple solid Rf 0.40 (9:1 DCM:EtOAc); νmax (neat) 2926,
2858, 1459, 1425, 1380, 1327, 1261 cm −1; 1H NMR (400 MHz) δH 2.05 (4H, m),
3.22 (2H, m), 3.25 (2H, m), 7.59–7.62 (1H, dd, J = 8.3 Hz J = 4.2 Hz), 8.30–8.33
(1H, dd, J = 8.3 Hz J = 1.6 Hz), 9.05 (1H, dd, J = 3.9 Hz J = 1.5 Hz) δC (100
MHz) 22.4, 22.6, 33.1, 33.4, 124.3, 136.1, 137.2, 150.1, 152.8, 155.7, 157.9; m/z
185 (M+). Compound has been previously reported [5].
References:
1. Moriarty, R. M.; Berglund, B. A.; Penmasta, R. Tetrahedron Lett. 1992, 33,
6065–6068. doi:10.1016/S0040-4039(00)60007-2
2. Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K. Org. Biomol. Chem. 2004, 2,
788–796. doi:10.1039/b315689c
3. Petukhov, P. A.; Tkachev, A. V. Tetrahedron. 1997, 53, 9761–9768.
doi:10.1016/S0040-4020(97)00623-6
4. Mohsenzadeh, F.; Aghapoor, K.; Darabi, H. R. J. Braz. Chem. Soc. 2007,
18, 297–303. doi:10.1590/S0103-50532007000200009.
5. Antoniotti, S.; Duňach, E. Tetrahedron Lett. 2002, 43, 3971–3973.
doi:10.1016/S0040-4039(02)00715-3
8
15
200
14
13
N
180
12
11
160
10
140
9
8
120
7
77.32
77.00
76.68
16
151.90
143.19
142.35
141.44
136.75
130.35
130.23
129.68
129.61
129.17
127.62
127.53
N
N
3a
10
6
100
5
80
9
4
3
60
8
2
1
40
7
0
-1
20
ppm
-2
-3 ppm
N
3a
0
ppm
9
9.340
8.221
8.217
8.204
8.200
8.197
8.189
8.185
8.168
8.165
8.154
8.134
8.130
7.802
7.783
7.774
7.581
7.576
7.566
7.562
7.548
7.531
N
200
2.986
2.066
2.040
2.037
2.032
1.952
1.943
1.927
1.919
1.912
1.743
1.734
1.711
1.704
1.505
1.473
1.378
3b
3.0
14
13
N
180
7.5
12
11
160
10
140
9
8
120
7
6
100
5
4
80
3
2
60
32.32
26.38
25.88
15
8.0
45.00
16
8.5
144.91
142.07
141.37
129.88
129.06
128.94
128.92
9.0
161.06
8.776
8.089
8.086
8.078
8.073
8.069
8.065
8.058
8.056
8.053
7.744
7.740
7.724
7.720
7.716
7.700
7.696
N
2.5
2.0
1
40
1.5 ppm
ppm
0
-1
20
-2
-3 ppm
N
3b
0
ppm
10
15
200
14
13
180
12
11
N
160
141.24
139.10
129.92
129.84
129.21
128.79
128.24
16
153.47
N
N
3c
10
140
9
8
120
7
6
100
5
8.2
8.0
7.8
7.6
7.4
4
3
2
1
0
80
60
40
ppm
-1
20
-2
-3 ppm
N
3c
0
ppm
11
8.202
8.193
8.185
8.177
7.789
7.780
7.773
7.764
7.540
7.537
7.527
7.522
7.517
7.360
7.354
7.350
7.335
200
4.0
N
N
180
12
11
160
7.5
10
140
9
8
120
7
6
100
5
4
80
3.5
3
60
3.0
2
1
40
22.80
13
33.20
8.0
128.91
128.34
14
141.23
15
154.14
16
2.061
2.053
2.044
2.036
2.027
3.185
3.168
7.984
7.975
7.968
7.959
7.952
7.679
7.671
7.663
7.655
7.647
7.639
N
N
3d
ppm
2.5
2.0
0
-1
20
1.5
ppm
-2
-3 ppm
3d
0
ppm
12
16
170
15
N
165
14
160
13
155
150
12
145
138.49
138.09
137.48
136.72
135.82
135.65
130.95
130.65
129.19
129.11
127.97
127.61
125.55
124.66
N
146.17
144.26
154.59
154.38
153.37
152.86
150.76
150.36
9.547
9.454
9.192
9.188
9.182
9.177
8.517
8.500
8.493
8.488
8.472
8.467
8.352
8.347
8.332
8.328
8.231
8.227
8.211
8.208
7.730
7.719
7.710
7.700
7.689
7.679
7.604
7.600
7.596
7.583
7.565
7.552
N
N
3e
9.5
11
140
10
135
9
130
8
125
120
9.0
7
6
115
5
110
105
8.5
4
100
8.0
N
N
3e
3
2
95
90
85
7.5
1
0
80
-1
75
70
ppm
-2
65
-3 ppm
60
ppm
13
N
16
15
N
N
200
156.59
154.96
153.59
149.43
138.46
137.97
136.18
130.31
129.82
129.56
129.38
128.45
128.18
125.15
9.5
14
13
180
12
11
160
10
9
140
8
120
7
6
100
5
8.568
8.547
7.760
7.749
7.739
7.729
7.650
7.630
7.572
7.552
7.413
7.394
7.385
7.372
7.368
7.351
7.332
7.314
9.190
9.180
N
N
3f
9.0
4
80
8.5
3
2
60
8.0
1
40
7.5
0
-1
20
7.0
-2
0
ppm
-3 ppm
N
ppm
14
N
N
200
8
180
7
160
140
8.0
6
120
7.5
5
100
ppm
4
80
3.5
3
60
3.0
40
22.61
22.40
9
8.5
33.43
33.07
9.0
124.26
N
137.23
136.06
157.86
155.66
152.83
150.10
2.064
2.055
2.047
3.253
3.184
7.623
7.612
7.602
7.591
8.325
8.321
8.305
8.300
9.055
9.051
9.045
9.041
N
N
3g
2.5
2
20
ppm
1
0 ppm
N
3g
0
ppm
15