The Journal of Organic Chemistry
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121.1, 118.6, 113.1, 52.6, 25.8, 12.0; 19F NMR (282 MHz, CDCl3) δ
−57.3; HRMS (ESI) calcd for C13H16BrF3O2N (M + H)+ 354.03110
(79Br) and 356.02917 (81Br), found 354.03129 and 356.02938,
respectively.
yield: H NMR (300 MHz, CDCl3) δ 7.76−7.64 (m, 1H), 7.64−7.48
(m, 4H), 7.38−7.22 (m, 3H), 7.01 (dd, J = 5.0, 3.8 Hz, 2H); 13C NMR
(75 MHz, CDCl3) δ 165.4, 139.2, 137.8, 133.9, 133.8, 133.4, 131.0,
130.2, 128.7, 127.7, 123.3.
N-(2-Bromo-3,4,5-trimethoxyphenyl)cyclohexanecarboxamide
3-(2-Bromophenyl)-1,1-diethylurea (1s). Prepared by the reaction
with 2-bromophenyl isocynate (1 g, 5 mmol) and diethylamine (0.58
mL, 5.6 mmol) in toluene at 80 °C for 6 h; purified by column
chromatography (PE:EA ratio of 8) that gave the product in 94% yield
(1i). White solid, purified by column chromatography (PE:EA ratio of
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6), 70% yield: mp 131−134 °C; H NMR (300 MHz, CDCl3) δ 7.97
(s, 1H), 7.70 (s, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.81 (s, 3H), 2.34−
2.21 (m, 1H), 2.04−1.92 (m, 2H), 1.88−1.76 (m, 2H), 1.69−1.16 (m,
6H); 13C NMR (75 MHz, CDCl3) δ 174.3, 152.8, 150.4, 139.0, 132.0,
101.0, 99.5, 77.0, 61.1, 61.0, 56.0, 46.6, 29.6, 25.6, 25.5; HRMS (ESI)
calcd for C16H23BrO4N (M + H)+ 372.08050 (79Br) and 374.07864
(81Br), found 372.08065 and 374.07865, respectively.
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as a colorless liquid: H NMR (300 MHz, CDCl3) δ 8.2 (dd, J = 8.3,
1.6 Hz, 1H), 7.4 (dd, J = 8.0, 1.5 Hz, 1H), 7.3−7.1 (m, 1H), 7.0 (s,
1H), 6.9−6.7 (m, 1H), 3.3 (q, J = 7.2 Hz, 4H), 1.2 (t, J = 7.6, 6H); 13C
NMR (75 MHz, CDCl3) δ 153.6, 136.9, 131.5, 127.9, 122.9, 120.6,
112.6, 112.6, 41.5, 13.6.
N-(2-Bromophenyl)adamantane-1-carboxamide (1j).25 White
solid, purified by column chromatography (PE:EA ratio of 15), 83%
N-(2-Bromo-4-chlorophenyl)cyclohexanecarboxamide (1v). Yel-
low solid, further purified by column chromatography (PE:EA ratio of
1
1
yield: H NMR (300 MHz, CDCl3) δ 8.33 (dd, J = 8.3, 1.6 Hz, 1H),
10), 76% yield: H NMR (300 MHz, CDCl3) δ 8.26 (d, J = 8.9 Hz,
7.91 (s, 1H), 7.43 (dd, J = 8.0, 1.5 Hz, 1H), 7.25−7.15 (m, 1H), 6.92−
6.81 (m, 1H), 2.02 (d, J = 3.2 Hz, 3H), 1.92 (d, J = 2.9 Hz, 6H), 1.68
(t, J = 2.9 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 176.0, 135.7, 132.0,
128.3, 124.7, 121.6, 113.6, 42.0, 39.2, 36.3, 28.0.
1H), 7.59 (s, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.24−7.16 (m, 1H), 2.30−
2.17 (m, 1H), 2.00−1.87 (m, 2H), 1.84−1.72 (m, 2H), 1.70−1.60 (m,
1H), 1.54−1.37 (m, 2H), 1.34−1.14 (m, 3H); 13C NMR (75 MHz,
CDCl3) δ 174.2, 134.5, 131.5, 129.1, 128.4, 122.4, 113.4, 46.5, 29.6,
25.6; HRMS (ESI) calcd for C13H16BrClON (M + H)+ 316.00983
(79Br) and 318.00764 (81Br), found 316.0099 and 318.00781,
respectively.
N-(2-Bromophenyl)benzamide (1k).26 White solid, further purified
by column chromatography (PE:EA ratio of 20), 85% yield: 1H NMR
(300 MHz, CDCl3) δ 8.56 (dd, J = 8.3, 1.6 Hz, 1H), 8.47 (s, 1H),
8.02−7.85 (m, 2H), 7.62−7.47 (m, 4H), 7.42−7.32 (m, 1H), 7.09−
6.95 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 155.8, 147.5, 144.6,
135.3, 132.2, 128.3, 125.1, 121.5, 115.6, 113.3, 112.6.
General Procedure (GP) for the Carbonylative Cyclization of
1 To Form 2. To an oven-dried Schlenk (10 mL) tube were added 1
(0.25 mmol), Pd(OAc)2 (2.24 mg, 10 μmol), XantPhos (8.67 mg, 15
μmol), paraformaldehyde (37.5 mg, 1.25 mmol), and KOAc (49 mg,
0.5 mmol). Then the Schlenk tube was vacuumed and purged with
argon three times before 1 mL of toluene was added. After being
stirred at 110 or 120 °C for 18 h, the mixture was cooled to room
temperature.
N-(2-Bromophenyl)-4-chlorobenzamide (1l).26 White solid, with-
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out further purification, 86% yield: H NMR (300 MHz, CDCl3) δ
8.49 (dd, J = 8.1, 1.6 Hz, 1H), 8.39 (s, 1H), 7.92−7.72 (m, 2H), 7.63−
7.28 (m, 4H), 7.09−6.94 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
164.1, 138.5, 135.5, 132.8, 132.2, 129.2, 128.5, 128.5, 125.5, 121.8,
113.8.
2-(tert-Butyl)-4H-benzo[d][1,3]oxazin-4-one (2a).10b Prepared
according to the GP and purified as a white solid in 86% yield (43.6
N-(2-Bromophenyl)-4-methoxybenzamide (1m).26 White solid,
1
1
mg): H NMR (300 MHz, CDCl3) δ 8.19−8.11 (m, 1H), 7.79−7.71
without further purification, 87% yield: H NMR (300 MHz, CDCl3)
(m, 1H), 7.59−7.53 (m, 1H), 7.50−7.42 (m, 1H), 1.38 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 168.1, 160.0, 146.5, 136.2, 128.2, 127.9,
126.8, 116.7, 37.9, 27.6.
δ 8.54 (dd, J = 8.3, 1.6 Hz, 1H), 8.39 (s, 1H), 7.94−7.86 (m, 2H), 7.57
(dd, J = 8.0, 1.5 Hz, 1H), 7.41−7.32 (m, 1H), 7.04−6.95 (m, 3H),
3.88 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.7, 162.7, 136.0,
132.2, 129.0, 128.5, 126.8, 125.0, 121.6, 114.1, 113.6, 55.5.
2-Methyl-4H-benzo[d][1,3]oxazin-4-one (2b).10b Prepared accord-
ing to the GP and purified by column chromatography (PE:EA ratio of
N-(2-Bromophenyl)-4-(tert-butyl)benzamide (1n).27 White solid,
further purified by column chromatography (PE:EA ratio of 15), 80%
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30) as a colorless thick oil in 45% yield (18.2 mg): H NMR (300
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MHz, CDCl3) δ 8.18 (dd, J = 7.9, 1.6 Hz, 1H), 7.79 (dd, J = 8.1, 7.3,
1.6 Hz, 1H), 7.57−7.45 (m, 2H), 2.47 (s, 3H).
yield: H NMR (300 MHz, CDCl3) δ 8.60−8.52 (m, 1H), 8.47 (s,
1H), 7.92−7.84 (m, 2H), 7.61−7.50 (m, 3H), 7.41−7.31 (m, 1H),
7.05−6.96 (m, 1H), 1.37 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
165.1, 155.8, 135.9, 132.2, 131.7, 128.5, 126.9, 125.9, 125.0, 121.6,
113.6, 35.0, 31.1.
2-(Trifluoromethyl)-4H-benzo[d][1,3]oxazin-4-one (2c).10b Pre-
pared according to the GP and purified by column chromatography
(PE:EA ratio of 40) as a colorless thick oil in 36% yield (19.6 mg): 1H
NMR (300 MHz, CDCl3) δ 8.29 (dd, J = 7.9, 1.5, 0.6 Hz, 1H), 7.94
(dd, J = 8.1, 1.5 Hz, 1H), 7.79 (d, J = 8.1, 0.8 Hz, 1H), 7.74−7.65 (m,
1H).
N-(2-Bromophenyl)-4-fluorobenzamide (1o).26 White solid, fur-
ther purified by column chromatography (PE:EA ratio of 20), 78%
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yield: H NMR (300 MHz, CDCl3) δ 8.50 (dd, J = 8.2, 1.6 Hz, 1H),
2-Pentyl-4H-benzo[d][1,3]oxazin-4-one (2d).10b Prepared accord-
ing to the GP and purified by column chromatography (PE:EA ratio of
8.39 (s, 1H), 8.03−7.86 (m, 2H), 7.57 (dd, J = 8.0, 1.5 Hz, 1H), 7.43−
7.30 (m, 1H), 7.25−7.11 (m, 2H), 7.08−6.95 (m, 1H). 13C NMR (75
MHz, CDCl3) δ 166.7, 164.1, 163.4, 135.6, 132.2, 130.7 (d, J = 3.3
Hz), 129.5 (d, J = 9.0 Hz), 128.5, 125.4, 121.8, 116.1, 115.9, 113.8.
130.7.
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40) as a colorless oil in 69% yield (37.6 mg): H NMR (300 MHz,
CDCl3) δ 8.22−8.13 (m, 1H), 7.83−7.72 (m, 1H), 7.60−7.43 (m,
2H), 2.74−2.59 (m, 2H), 1.83 (t, J = 7.6 Hz, 2H), 1.48−1.26 (m, 4H),
0.98−0.79 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 163.3, 159.9,
146.5, 136.4, 128.4, 128.1, 126.5, 116.8, 34.8, 31.2, 25.8, 22.3, 13.9.
2-(tert-Butyl)-7-methyl-4H-benzo[d][1,3]oxazin-4-one (2e). Pre-
pared according to the GP and purified by column chromatography
(PE:EA ratio of 30) as a white solid in 84% yield (45.6 mg): 1H NMR
(300 MHz, CDCl3) δ 8.06 (d, J = 8.1 Hz, 1H), 7.39 (dt, J = 1.6, 0.8
Hz, 1H), 7.29 (dd, J = 8.1, 1.8, 0.7 Hz, 1H), 2.48 (s, 3H), 1.39 (s, 9H);
13C NMR (75 MHz, CDCl3) δ 168.4, 160.2, 147.8, 146.6, 129.3, 128.1,
126.9, 126.9, 114.2, 37.9, 27.7, 22.0; HRMS (ESI) calcd for
C13H16O2N (M + H)+ 218.11756, found 218.11758.
2-(tert-Butyl)-6,8-difluoro-4H-benzo[d][1,3]oxazin-4-one (2f).
Yellowish white solid, prepared according to the GP and purified by
column chromatography (PE:/EA ratio of 20) in 66% yield (39.5 mg):
mp 81−82 °C; 1H NMR (300 MHz, CDCl3) δ 7.59 (ddd, J = 7.6, 2.8,
1.6 Hz, 1H), 7.27−7.18 (m, 1H), 1.34 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 168.4 (d, J = 2.5 Hz), 162.2 (d, J = 10.8 Hz), 158.8 (dd, J =
11.2, 3.4 Hz), 155.3 (d, J = 11.8 Hz), 111.7 (q, J = 27.0, 22.6 Hz),
N-(2-Bromophenyl)-2,4,6-trimethylbenzamide (1p). White solid,
purified by column chromatography (PE:EA ratio of 20), 85% yield:
mp 107−109 °C; 1H NMR (300 MHz, CDCl3) δ 8.52 (dd, J = 8.2, 1.6
Hz, 1H), 7.76 (s, 1H), 7.57 (dd, J = 8.0, 1.5 Hz, 1H), 7.44−7.34 (m,
1H), 7.08−7.00 (m, 1H), 6.95−6.88 (m, 2H), 2.40 (s, 6H), 2.33 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 168.7, 139.0, 135.5, 134.6, 134.3,
132.3, 128.4, 128.4, 125.5, 122.4, 113.7, 21.1,19.2; HRMS (ESI) calcd
for C16H17BrON (M + Na)+ 340.03075 (79Br) and 342.02884 (81Br),
found 340.03083 and 340.02890, respectively.
N-(2-Bromophenyl)furan-2-carboxamide (1q).28 1H NMR (300
MHz, CDCl3) δ 8.60 (s, 1H), 8.41 (dd, J = 8.3, 1.6 Hz, 1H), 7.51−
7.38 (m, 2H), 7.24 (t, J = 8.9, 1H), 7.16 (dd, J = 3.6, 0.8 Hz, 1H), 6.89
(ddd, J = 8.0, 7.4, 1.6 Hz, 1H), 6.47 (dd, J = 3.5, 1.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 155.8, 147.5, 144.6, 135.3, 132.2, 128.3,
125.1, 121.5, 115.6, 113.3, 112.6.
N-(2-Bromophenyl)thiophene-2-carboxamide (1r).29 White solid,
further purified by column chromatography (PE:EA ratio of 15), 84%
E
dx.doi.org/10.1021/jo5020118 | J. Org. Chem. XXXX, XXX, XXX−XXX