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231 mg) and methyl methacrylate (62) (10.0 mmol, 1.08 mL) accord-
ing to method F. Purification by column chromatography (hexane/EtOAc =
2:1) gave 68 (608 μmol, 133 mg, 61%) as a yellow solid: Rf = 0.4
(hexane/EtOAc = 2:1); 1H NMR (360 MHz, CDCl3) δ 1.49 (s, 3 H),
2.98 (d, J = 13.5 Hz, 1 H), 3.10 (d, J = 13.5 Hz, 1 H), 3.75 (s, 3 H),
7.31 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H); 13C NMR (91
MHz, CDCl3) δ 26.2 (CH3), 45.9 (CH2), 52.9 (CH3), 74.9 (Cq),
110.9 (Cq), 118.8 (Cq), 130.9 (2 × CH), 131.8 (2 × CH), 141.7 (Cq),
(Cq), 133.2 (Cq), 150.8 (Cq), 152.7 (d, JCF = 2.6 Hz, Cq), 156.9 (d, JCF =
0.7 Hz, Cq), 158.9 (d, JCF = 241.7 Hz, Cq); 19F-NMR (338 MHz,
CDCl3) δ −123.1; MS (EI) m/z (%) 325 (15) [M+ + H], 324 (70)
[M+], 199 (15), 198 (100), 183 (28), 155 (15), 83 (13), 44 (25);
HRMS (EI) calcd for C20H17FO3 [M+] 324.1162, found 324.1161.
N,N-Diethyl-2′,5′-dimethoxybiphenyl-4-amine (77). Title
compound was prepared from 30 (1.00 mmol, 277 mg), MnO2
(1.00 mmol, 86.9 mg), and 1,4-dimethoxybenzene (69) (30.0 mmol,
4.14 g) according to method G. Purification by column chromatog-
raphy (hexane/EtOAc = 9:1, desactivated with triethylamine) gave 77
(119 μmol, 34.0 mg, 12%) as a colorless solid: Rf = 0.3 (hexane/
176.2 (Cq); MS (EI) m/z (%) 219 (7) [M+],160 (78) [M+
−
CO2Me], 118 (41), 117 (100), 116 (31), 103 (14), 91 (10), 90 (31),
89 (29), 83 (15), 63 (11); HRMS (EI) calcd for C12H13NO3 [M+]
219.0895, found 219.0895.
1
EtOAc = 9:1); H NMR (360 MHz, CDCl3) δ 1.19 (t, J = 7.1 Hz, 6
2,5-Dimethoxy-4′-nitrobiphenyl (73). Title compound was
prepared from 2 (797 μmol, 200 mg), MnO2 (797 μmol, 69.3 mg),
and 1,4-dimethoxybenzene (69) (23.9 mmol, 3.30 g) according to
method G. Purification by column chromatography (hexane/EtOAc =
19:1 → 4:1) gave 73 (420 μmol, 109 mg, 53%) as a colorless solid:
H), 3.39 (q, J = 7.1 Hz, 4 H), 3.75 (s, 3 H), 3.80 (s, 3 H), 6.72 (d, J =
9.0 Hz, 2 H), 6.77 (dd, J = 3.1 Hz, J = 8.9 Hz, 1 H), 6.90 (dd, J = 6.9
Hz, J = 10.2 Hz, 2 H), 7.43 (d, J = 9.0 Hz, 2 H); 13C NMR (151 MHz,
CDCl3) δ 12.7 (2 × CH3), 44.3 (2 × CH2), 55.8 (CH3), 56.3 (CH3),
111.1 (2 × CH), 111.8 (CH), 112.6 (CH), 116.2 (CH), 125.0 (Cq),
130.3 (2 × CH), 132.0 (Cq), 146.9 (Cq), 150.9 (Cq), 153.8 (Cq); MS
(EI) m/z (%) 286 (11) [M+ + H], 285 (52) [M+], 271 (22), 270
(100), 255 (11), 241 (12), 240 (22), 198 (14), 151 (10), 135 (15), 44
(17); HRMS (EI) calcd for C18H23NO2 [M+] 285.1729, found
285.1729.
1
Rf = 0.4 (hexane/EtOAc = 4:1); H NMR (600 MHz, CDCl3) δ 3.78
(s, 3 H), 3.82 (s, 3 H), 6.90 (dd, J = 0.5 Hz, J = 2.9 Hz, 1 H), 6.92−
6.97 (m, 2 H), 7.69 (d, J = 9.0 Hz, 2 H), 8.26 (d, J = 9.0 Hz, 2 H); 13C
NMR (151 MHz, CDCl3) δ 55.9 (CH3), 56.2 (CH3), 112.8 (CH),
114.6 (CH), 116.6 (CH), 123.2 (2 × CH), 129.2 (Cq), 130.3 (2 ×
CH), 145.2 (Cq), 150.7 (Cq), 153.9 (Cq), one Cq-signal is missing
because of overlapping; MS (EI) m/z (%) 260 (17) [M+ + H], 259
(100) [M+], 244 (15), 227 (16), 199 (10), 198 (67), 197 (17), 183
(31), 155 (22), 127 (17), 83 (10), 44 (10); HRMS (EI) calcd for
C14H13NO4 [M+] 259.0845, found 259.0845.
2,5-Dichloro-4′-nitrobiphenyl (78). Title compound was
prepared from 2 (797 μmol, 200 mg), MnO2 (797 μmol, 69.3 mg),
and 1,4-dichlorobenzene (70) (23.9 mmol, 3.51 g) according to
method G. Purification by column chromatography (hexane/EtOAc =
10:1) gave 78 (287 μmol, 76.5 mg, 36%) as a yellowish solid: Rf = 0.6
1
2,5-Dimethoxybiphenyl-4′-carbonitrile (74). Title compound
was prepared from 63 (1.00 mmol, 233 mg), MnO2 (1.00 mmol,
86.9 mg), and 1,4-dimethoxybenzene (69) (10.0 mmol, 1.38 g) according
to method G. Purification by column chromatography (hexane/EtOAc =
4:1) gave 74 (440 μmol, 105 mg, 44%) as a yellowish solid: Rf = 0.4
(hexane/EtOAc = 10:1); H NMR (600 MHz, CDCl3) δ 7.33−7.36
(m, 2 H), 7.45 (d, J = 9.0 Hz, 1 H), 7.60 (d, J = 8.9 Hz, 2 H), 8.31 (d,
J = 8.9 Hz, 2 H); 13C NMR (151 MHz, CDCl3) δ 123.3 (2 × CH),
129.4 (CH), 130.4 (2 × CH), 130.6 (Cq), 130.8 (CH), 131.4 (CH),
133.1 (Cq), 139.7 (Cq), 144.5 (Cq), 147.6 (Cq); MS (EI) m/z (%) 271
(11), 270 (14), 269 (71), 268 (16) [M+ + H], 267 (100) [M+], 237
(15), 211 (14), 209 (19), 188 (31), 187 (14), 186 (99), 151 (32), 150
(31), 93 (18), 83 (12), 75 (16); HRMS (EI) calcd for C12H7Cl2NO2
[M+] 266.9854, found 266.9856.
1
(hexane/EtOAc = 4:1); H NMR (600 MHz, CDCl3) δ 3.76 (s, 3 H),
3.81 (s, 3 H), 6.87 (dd, J = 0.5 Hz, J = 3.0 Hz, 1 H), 6.92 (td, J = 5.9
Hz, J = 8.9 Hz, 2 H), 7.64 (d, J = 8.7 Hz, 2 H), 7.68 (d, J = 8.7 Hz, 2 H);
13C NMR (151 MHz, CDCl3) δ 55.8 (CH3), 56.2 (CH3), 110.6
(Cq), 112.7 (CH), 114.3 (CH), 116.5 (CH), 119.1 (Cq), 129.5 (Cq),
130.2 (2 × CH), 131.8 (2 × CH), 143.2 (Cq), 150.6 (Cq), 153.9 (Cq);
MS (EI) m/z (%) 240 (17) [M+ + H], 239 (100) [M+], 225 (14), 224
(98), 209 (50), 196 (16), 193 (15), 181 (16), 164 (12), 153 (33), 127
(19), 54 (11), 44 (19); HRMS (EI) calcd for C15H13NO2 [M+]
239.0946, found 239.0947.
4′-Fluoro-2,5-dimethoxybiphenyl (75). Title compound was
prepared from 1 (1.00 mmol, 224 mg), MnO2 (1.00 mmol, 86.9 mg),
and 1,4-dimethoxybenzene (69) (30.0 mmol, 4.14 g) according to
method G. Purification by column chromatography (hexane/EtOAc =
29:1 → 19:1) gave 75 (230 μmol, 53.5 mg, 23%) as a colorless solid:
Rf = 0.4 (hexane/EtOAc = 19:1); 1H NMR (360 MHz, CDCl3) δ 3.75
(s, 3 H), 3.81 (s, 3 H), 6.84−6.94 (m, 3 H), 7.09 (t, JHF = 8.9 Hz, J =
8.9 Hz, 2 H), 7.50 (dd, JHF = 5.5 Hz, J = 8.9 Hz, 2 H); 13C NMR (151
MHz, CDCl3) δ 55.8 (CH3), 56.3 (CH3), 112.7 (CH), 113.1 (CH),
114.9 (d, JCF = 21.3 Hz, 2 × CH), 116.7 (CH), 130.6 (Cq), 131.0 (d,
JCF = 8.0 Hz, 2 × CH), 134.3 (d, JCF = 3.4 Hz, Cq), 150.7 (Cq), 153.8
(Cq), 162.1 (d, J = 246.1 Hz, Cq); 19F-NMR (338 MHz, CDCl3)
δ −118.8; MS (EI) m/z (%) 233 (16) [M+ + H], 232 (100) [M+], 219
(11), 218 (12), 217 (84), 202 (42), 189 (19), 186 (19), 174 (13), 146
(24), 120 (10), 83 (12), 44 (24); HRMS (EI) calcd for C14H13FO2
[M+] 232.0900, found 232.0901.
4′-(4-Fluorophenoxy)-2,5-dimethoxybiphenyl (76). Title
compound was prepared from 12 (1.00 mmol, 316 mg), MnO2
(1.00 mmol, 86.9 mg), and 1,4-dimethoxybenzene (69) (30.0 mmol,
4.14 g) according to method G. Purification by column chroma-
tography (hexane/EtOAc = 6:1) gave 76 (304 μmol, 98.6 mg, 32%) as a
yellowish solid: Rf = 0.5 (hexane/EtOAc = 4:1); 1H NMR (600 MHz,
CDCl3) δ 3.77 (s, 3 H), 3.81 (s, 3 H), 6.85 (dd, J = 3.1 Hz, J = 8.9 Hz,
1 H), 6.89 (d, J = 3.1 Hz, 1 H), 6.91 (d, J = 8.9 Hz, 1 H), 7.00 (d, J =
8.7 Hz, 2 H), 7.04−7.05 (m, 4 H), 7.50 (d, J = 8.7 Hz, 2 H); 13C NMR
(151 MHz, CDCl3) δ 55.8 (CH3), 56.3 (CH3), 112.8 (d, JCF = 22.6
Hz, 2 × CH), 116.2 (CH), 116.4 (CH), 116.7 (CH), 117.6 (2 × CH),
120.8 (d, JCF = 8.3 Hz, 2 × CH), 130.8 (2 × CH), 130.9 (Cq), 132.0
2,4,6-Trimethoxy-4′-nitrobiphenyl (79). Title compound was
prepared from 2 (1.00 mmol, 251 mg), MnO2 (2.00 mmol, 174 mg),
and 1,3,5-trimethoxybenzene (71) (30.0 mmol, 5.05 g) according to
method G. Purification by column chromatography (hexane/EtOAc =
4:1) gave 79 (595 μmol, 172 mg, 59%) as a colorless solid: Rf = 0.4
(hexane/EtOAc = 4:1); 1H NMR (600 MHz, CDCl3) δ 3.74 (s, 6 H),
3.88 (s, 3 H), 6.23 (s, 2 H), 7.51 (d, J = 8.9 Hz, 2 H), 8.22 (d, J = 8.9
Hz, 2 H); 13C NMR (91 MHz, CDCl3) δ 55.4 (CH3), 55.8 (2 × CH3),
90.9 (2 × CH), 110.2 (Cq), 122.7 (2 × CH), 132.2 (2 × CH), 141.8
(Cq), 146.3 (Cq), 158.2 (2 × Cq), 161.6 (Cq); MS (EI) m/z (%) 290
(17) [M+ + H], 289 (100) [M+], 288 (6), 260 (7), 259 (6), 228 (17),
213 (13), 185 (9), 170 (7), 126 (6), 114 (7); HRMS (EI) calcd for
C15H15NO5 [M+] 289.0950, found 289.0950.
2,4,6-Trimethoxybiphenyl-4′-carbonitrile (80). Title com-
pound was prepared from 63 (1.00 mmol, 233 mg), MnO2
(2.00 mmol, 174 mg), and 1,3,5-trimethoxybenzene (71) (15.0 mmol,
2.52 g) according to method G. Purification by column chromatography
(hexane/EtOAc = 4:1 → 3:1) gave 80 (504 μmol, 136 mg, 50%) as a
yellowish solid: Rf = 0.4 (hexane/EtOAc = 4:1); 1H NMR (360 MHz,
CDCl3) δ 3.73 (s, 6 H), 3.87 (s, 3 H), 6.23 (s, 2 H), 7.44 (d, J = 8.6
Hz, 2 H), 7.64 (d, J = 8.6 Hz, 2 H); 13C NMR (91 MHz, CDCl3) δ
55.4 (CH3), 55.8 (2 × CH3), 90.9 (2 × CH), 109.8 (Cq), 110.5 (Cq),
119.4 (Cq), 131.3 (2 × CH), 132.1 (2 × CH), 139.5 (Cq), 158.1 (2 ×
Cq), 161.4 (Cq); MS (EI) m/z (%) 270 (18) [M+ + H], 269 (100)
[M+], 240 (12), 153 (14), 140 (13), 116 (17), 85 (11), 83 (15), 44
(16); HRMS (EI) calcd for C16H15NO3 [M+] 269.1052, found
269.1053.63
4-Nitro-4′-phenoxybiphenyl and 4-Nitro-2′-phenoxybi-
phenyl (81). Compound 81 was prepared from 2 (1.00 mmol,
251 mg), MnO2 (2.00 mmol, 174 mg), and diphenylether (72)
(15.0 mmol, 2.55 g, 2.38 mL) according to method G. Purification
by column chromatography (hexane/EtOAc = 19:1 → 4:1) gave 81
(540 μmol, 157 mg, 54%) as a mixture of ortho and para as colorless
liquids. 4-Nitro-4′-phenoxybiphenyl: Rf = 0.4 (hexane/EtOAc = 19:1); 1H
1530
dx.doi.org/10.1021/jo202406k | J. Org. Chem. 2012, 77, 1520−1532