The Journal of Organic Chemistry
Article
(m, 2H), 7.65−7.63 (m, 1H), 7.48−7.43 (m, 2 H); 13C NMR (75
MHz, CDCl3) δ 146.6, 141.9, 139.9, 127.3, 126.8, 126.0, 124.3, 123.2.
3-(2-Nitrophenyl)thiophene (4j). Yellow oil (86 mg, 42% yield):
1H NMR (300 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 1H), 7.61−7.55
(m, 1H), 7.51−7.42 (m, 2H), 7.38−7.33 (m, 2H), 7.08 (d, J = 4.8 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 137.0, 132.1, 131.7, 130.7, 128.1,
127.4, 126.2, 123.9, 123.5; HRMS (ESI) calcd. for C10H7NO2S [M +
H+] 206.0276, found 206.0277.
2-(4-Nitrophenyl)thiophene (5i).26 White solid (102 mg, 50%
1
yield): H NMR (300 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz, 2H), 7.75
(d, J = 8.4 Hz, 2H), 7.49−7.42 (m, 3H), 7.17−7.15 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 146.6, 141.6, 140.6, 128.7, 127.7, 126.0,
125.7, 124.4.
2-(2-Nitrophenyl)thiophene (5j). Yellow oil (80 mg, 39% yield):
1H NMR (300 MHz, CDCl3) δ 7.76−7.72 (m, 2H), 7.60−7.54 (m,
2H), 7.49−7.40 (m, 2H), 7.09−7.07 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 149.5, 141.7, 137.1, 132.3, 131.9, 128.6, 128.4, 127.7, 127.1,
123.5; HRMS (ESI) calcd. for C10H7NO2S [M + H+] 206.0276, found
206.0274.
2-(Thiophen-3-yl)pyrimidine (4k).6a White solid (146 mg, 90%
yield): 1H NMR (300 MHz, CDCl3) δ 8.73 (d, J = 5.1 Hz, 2H), 8.30−
8.28 (m, 1H), 7.90−7.87 (m, 1H), 7.40−7.36 (m, 1H), 7.14−7.10 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 161.9, 157.2, 141.5, 127.9, 127.3,
126.1, 118.6.
2-(Thiophen-2-yl)pyrimidine (5k).6a White solid (138 mg, 90%
yield): 1H NMR (300 MHz, CDCl3) δ 8.71 (d, J = 4.5 Hz, 2H), 8.03−
8.01 (m, 1H), 7.49 (d, J = 4.5 Hz, 1H), 7.16−7.10 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 161.4, 157.1, 143.0, 129.8, 128.9, 128.3, 118.4.
5-(Thiophen-2-yl)pyrimidine (5l).6j White solid (138 mg, 85%
5-(Thiophen-3-yl)pyrimidine (4l).6j White solid (135 mg, 83%
yield): 1H NMR (300 MHz, CDCl3) δ 9.15 (s, 1H), 8.96 (s, 2H), 7.61
(s, 1H), 7.53−7.50 (m, 1H), 7.42−7.40 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 157.0, 154.0, 134.9, 129.3, 127.7, 125.2, 122.4.
2-(Thiophen-3-yl)thiazole (4m).6b Light yellow oil (148 mg, 89%
1
yield): H NMR (300 MHz, CDCl3) δ 9.13 (s, 1H), 8.96 (s, 2H),
7.46−7.42 (m, 2H), 7.19−7.16 (m, 1H); 13C NMR (75 MHz, CDCl3)
δ 157.2, 153.4, 143.4, 136.1, 128.5, 127.2, 125.2.
1
yield): H NMR (300 MHz, CDCl3) δ 7.86 (s, 1H), 7.82 (s, 1H),
2-(Thiophen-2-yl)thiazole (5m).27 White solid (145 mg, 87%
yield): 1H NMR (300 MHz, CDCl3) δ 7.77 (s, 1H), 7.53 (s, 1H), 7.40
(d, J = 4.5 Hz, 1H), 7.27−7.25 (m, 1H), 7.10−7.07 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 161.9, 143.2, 137.2, 127.8, 127.6, 126.5,
118.0; HRMS (ESI) calcd. for C7H5NS2 [M + H+] 167.9942, found
167.9944.
7.59−7.57 (m, 1H), 7.41−7.39 (m, 1H), 7.28−7.25 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 163.2, 143.2, 135.6, 126.7, 126.1, 123.7,
118.0; HRMS (ESI) calcd. for C7H5NS2 [M + H+] 167.9942, found
167.9943.
3-(Thiophen-3-yl)quinoline (4n).6i Brown solid (192 mg, 91%
1
yield): H NMR (300 MHz, CDCl3) δ 9.21 (d, J = 2.4 Hz, 1H), 8.29
3-(Thiophen-2-yl)quinoline (5n).6j White solid (188 mg, 89%
yield): 1H NMR (300 MHz, CDCl3) δ 9.21 (s, 1H), 8.29 (s, 1H), 8.10
(d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.70 (t, J = 7.5 Hz, 1H),
7.59−7.51 (m, 2H), 7.41 (d, J = 4.5 Hz, 1H), 7.18−7.17 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 148.3, 147.0, 140.4, 131.0, 129.1, 129.0,
128.2, 127.6, 127.3, 127.0, 125.9, 124.2.
(s, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.73−7.66
(m, 2H), 7.59−7.48 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 149.4,
147.1, 138.8, 132.0, 130.9, 129.2, 128.8, 128.7, 128.1, 127.8, 127.1,
126.1, 121.7.
2-(4-Methoxyphenyl)thiophene (5a).23 White solid (175 mg, 92%
yield): 1H NMR (300 MHz, CDCl3) δ 7.54 (d, J = 8.1 Hz, 2H), 7.25−
7.20 (m, 2H), 7.06−7.03 (m, 1H), 6.92 (d, J = 8.1 Hz, 2H), 3.84 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 159.1, 143.9, 127.9, 127.3, 127.2,
123.8, 122.0, 114.2, 55.3.
2-(4-Dimethylamino-phenyl)thiophene (5o). Blue liquid (128 mg,
63% yield): 1H NMR (300 MHz, CDCl3) δ 7.43−7.40 (m, 1H), 7.31−
7.28 (m, 1H), 7.19−7.11 (m, 2H), 7.07−7.00 (m, 1H), 6.96−6.90 (m,
2H), 2.52 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 150.9, 141.5, 129.5,
128.9, 128.0, 126.1, 126.0, 124.8, 122.9, 119.6, 44.0; HRMS (ESI)
calcd. for C12H13NS [M + H+] 203.0769, found 203.0765.
Methyl 2-(thiophen-2-yl)benzoate (5p).5a Yellow oil (126 mg,
2-(3-Methoxyphenyl)thiophene (5b).24 Yellow oil (140 mg, 74%
yield): 1H NMR (300 MHz, CDCl3) δ 7.30−7.26 (m, 4H), 7.23−7.21
(m, 1H), 7.15 (s, 1H), 7.06 (s, 1H), 6.86−6.83 (m, 1H), 3.85 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 159.9, 144.2, 135.7, 129.9, 127.9, 124.9,
123.3, 118.6, 112.9, 111.7, 55.3; HRMS (ESI) calcd. for C11H10SO [M
+ H+] 191.0531, found 191.0530
1
58% yield): H NMR (300 MHz, CDCl3) δ 7.61 (d, J = 7.5 Hz, 1H),
7.37 (d, J = 3.6 Hz, 2H), 7.29−7.22 (m, 2H), 6.96−6.93 (m, 2H), 3.62
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 169.0, 141.9, 134.0, 131.5,
131.0, 130.9, 129.3, 127.6, 127.1, 126.1, 125.8, 52.1.
2-(4-Tolyl)thiophene (5c).24 White solid (163 mg, 94% yield): H
1
NMR (300 MHz, CDCl3) δ 7.50 (d, J = 7.8 Hz, 2 H), 7.26−7.23 (m,
2H), 7.20 (d, J = 7.8 Hz, 2H), 7.07−7.05 (m, 1H), 2.36 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 144.5, 137.2, 131.6, 129.5, 127.9, 125.8,
124.2, 122.5, 21.1.
General Procedures for the Coupling Reaction of Aryl
Bromides with Pyridylaluminums Catalyzed by Pd(OAc)2 and
(o-Tolyl)3P. Under a dry argon atmosphere, Pd(OAc)2 (0.02 mmol)
and (o-tolyl)3P (0.04 mmol) were mixed in 2 mL of toluene at room
temperature, and the mixture was stirred for 10 min, followed by an
addition of aryl bromide (1.00 mmol) and heteroarylaluminum
reagent (1.3 mmol). After stirring for 5 h, the mixture was diluted with
dichloromethane, passed through a filter, and concentrated. The crude
product was purified by column chromatography (petroleum ether/
ethyl acetate = 10/1) to give the corresponding products 8 or 9.
3-(4-Methoxyphenyl)pyridine (8a).2m White solid (177 mg, 96%
2-(2-Tolyl)thiophene (5d).23 Colorless oil (139 mg, 80% yield): 1H
NMR (300 MHz, CDCl3) δ 7.42−7.39 (m, 1H), 7.35−7.32 (m, 1H),
7.26−7.22 (m, 3H), 7.10−7.06 (m, 2H), 2.42 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 143.0, 136.0, 134.1, 130.7, 130.4, 127.7, 127.0, 126.3,
125.9, 125.1, 21.1; HRMS (ESI) calcd. for C11H10S [M + H+]
175.0582, found 175.0580.
2-Mesitylthiophene (5e).24 Colorless oil (172 mg, 85% yield): H
1
1
NMR (300 MHz, CDCl3) δ 7.35 (dd, J = 6.8, 1.6 Hz, 1H), 7.10−7.08
(m, 1H), 6.93−6.83 (m, 2 H), 6.79 (d, J = 3.3, 1.6 Hz, 1H), 2.32 (s, 3
H), 2.11 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ 141.4, 138.3, 137.8,
131.0, 128.0, 127.0, 126.4, 125.2, 21.1, 20.7.
yield): H NMR (300 MHz, CDCl3) δ 8.81 (s, 1H), 8.54 (d, J = 3.0
Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.35−7.31
(m, 1H), 7.02 (d, J = 8.4 Hz, 1H), 3.86 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ. 159.8, 148.0, 147.8, 136.4, 133.9, 128.2, 123.5, 114.5, 55.4.
3-(3-Methoxyphenyl)pyridine (8b).28 Yellow oil (175 mg, 95%
yield): 1H NMR (300 MHz, CDCl3) δ 8.85−8.84 (m, 1 H), 8.61−8.58
(m, 1 H), 7.89−7.84 (m, 1H), 7.43−7.33 (m, 2H), 7.19−7.15 (m, 1
H), 7.12−7.10 (m, 1H), 6.93−6.98 (m, 1H), 3.88 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ. 159.8, 148.3, 148.0, 138.9, 136.1, 134.0, 129.8,
123.2, 119.2, 113.0, 112.6, 55.0.
2-Phenylthiophene (5f).9a Colorless oil (152 mg, 95% yield): H
1
NMR (300 MHz, CDCl3) δ 7.62 (d, J = 7.2 Hz, 2H), 7.41−7.34 (m,
2H), 7.31−7.25 (m, 3H), 7.11−7.07 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 144.3, 134.3, 128.8, 128.0, 127.4, 125.9, 124.8, 123.0.
4-Thiophen-2-yl-benzonitrile (5g).20 White solid (170 mg, 92%
yield): 1H NMR (300 MHz, CDCl3) δ 7.72−7.64 (m, 4H), 7.43−7.38
(m, 2H), 7.14−7.12 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 138.6,
132.7, 128.5, 127.0, 126.0, 125.1, 118.8, 110.5; HRMS (ESI) calcd. for
C11H7NS [M + H+] 186.0378, found 186.0379.
3-(4-Methylphenyl)-pyridine (8c).2m Yellow solid (160 mg, 95%
yield): 1H NMR (300 MHz, CDCl3) δ 8.78−8.76 (m, 1 H), 8.51−8.48
(m, 1 H), 7.85−7.80 (m, 1 H), 7.47−7.44 (m, 2 H), 7.37−7.25 (m, 3
H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 148.2, 138.0, 136.4
134.9, 134.1, 129.8, 126.9, 123.5, 21.1.
2-Thiophen-2-yl-benzonitrile (5h).25 Yellow oil (174 mg, 94%
yield): 1H NMR (300 MHz, CDCl3) δ 7.73−7.58 (m, 4H), 7.42−7.34
(m, 2H), 7.16−7.13 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 139.2,
137.2, 134.0, 133.7, 132.8, 129.4, 128.0, 127.3, 127.1, 118.7, 109.6.
3-(2-Methylphenyl)-pyridine (8d).3 Colorless oil (155 mg, 92%
1
yield): H NMR (300 MHz, CDCl3) δ 8.57 (s, 2H), 7.61 (d, J = 6.0
236
dx.doi.org/10.1021/jo4024123 | J. Org. Chem. 2014, 79, 230−239