The Journal of Organic Chemistry
Note
1
(trifluoromethyl)benzamide 2g as a white solid: Mp 186−187 °C; H
NMR (400 MHz, CDCl3) δ 7.58 (dd, J = 3.6, 8.0 Hz, 1H), 7.63 (d, J =
8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 8.17 (s, 1H), 8.56
(dd, J = 1.6, 8.8 Hz, 1H), 8.87 (brs, 1H), 8.93 (dd, J = 1.6, 3.6 Hz, 1H);
13C{1H} NMR (100 MHz, CD2Cl2) δ 123.0, 124.1 (q, J = 272.3 Hz),
carried out under a 2.5 mA constant current condition for 4.5 h. Column
chromatography (silica gel 60 N, 150:1 CH2Cl2/Et2O) afforded 42.3 mg
(58% yield) of 2-chloro-N-(5,7-dichloro-8-quinolinyl)-4-methoxyben-
zamide 2j and 8.8 mg (11% yield) of 2,6-dichloro-N-(5,7-dichloro-8-
quinolinyl)-4-methoxybenzamide 3j as white solids.
2-Chloro-N-(5,7-dichloro-8-quinolinyl)-4-methylbenzamide (2j).
Mp 173−175 °C; H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 7.19
125.6, 127.7 (q, J = 3.7 Hz), 128.5, 128.7 (q, J = 3.0 Hz), 129.7 (q, J =
33.3 Hz), 130.1, 130.8, 130.9, 131.7, 133.6, 135.8 (q, J = 1.4 Hz), 136.0,
144.1, 151.7, 163.4; IR (KBr) 3219, 1669, 1586, 1517, 1487, 1334, 1262,
1188, 1116, 923, 906, 859, 828, 811, 782 cm−1; HRMS (ESI-TOF)
Calcd for [M + Na]+ (C17H8Cl3F3N2Na1O1) m/z 440.9552, Found
440.9548.
1
(d, J = 6.8 Hz, 1H), 7.33 (s, 1H), 7.55 (dd, J = 4.0, 8.4 Hz, 1H), 7.76 (s,
1H), 7.85 (d, J = 7.6 Hz, 1H), 8.55 (dd, J = 1.6, 8.8 Hz, 1H), 8.91−8.93
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 21.2, 122.3, 125.2, 127.9,
128.4, 129.1, 130.3, 130.9, 131.0, 131.1, 131.3, 131.5, 133.2, 142.8, 143.7,
150.9, 164.1; IR (KBr) 3201, 3162, 2993, 1656, 1608, 1541, 1524, 1484,
1452, 1389, 1380, 1355, 1311, 1284, 1266, 1150, 1138, 1041, 946, 929,
885, 866, 824, 810, 784, 766 cm−1; HRMS (ESI-TOF) Calcd for [M +
Na]+ (C17H11Cl3N2Na1O1) m/z 386.9835, Found 386.9816.
Electrochemical Chlorination of Benzamide 5h. General
procedure B was followed with 69.4 mg (0.20 mmol) of benzamide
5h and 3.6 mg (0.020 mmol) of palladium chloride. The reaction was
carried out under a 2.5 mA constant current condition for 4.5 h. Column
chromatography (silica gel 60 N, 80:1 CH2Cl2/Et2O) afforded 43.0 mg
(56% yield) of 2-chloro-N-(5,7-dichloro-8-quinolinyl)-4-methoxyben-
zamide 2h as a yellow solid and 8.1 mg (10% yield) of 2,6-dichloro-N-
(5,7-dichloro-8-quinolinyl)-4-methoxybenzamide 3h as a white solid.
2-Chloro-N-(5,7-dichloro-8-quinolinyl)-4-methoxybenzamide
(2h). Mp 141 °C (decompose); 1H NMR (400 MHz, CDCl3) δ 3.88 (s,
3H), 6.91 (dd, J = 2.4, 8.6 Hz, 1H), 7.02 (d, J = 2.4 Hz, 1H), 7.56 (dd, J =
4.3, 8.6 Hz, 1H), 7.76 (s, 1H), 7.96 (d, J = 8.2 Hz, 1H), 8.55 (dd, J = 1.6,
8.2 Hz, 1H), 8.92 (dd, J = 1.6, 4.3 Hz, 1H), 9.00 (brs, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 55.8, 113.0, 115.9, 122.3, 125.2, 126.1,
128.4, 129.0, 130.2, 131.2, 132.8, 133.1, 133.2, 143.8, 150.9, 162.0,
163.7; IR (KBr) 1653, 1603, 1563, 1524, 1496, 1484, 1453, 1314, 1296,
1277, 1236, 1138, 1042, 1030, 948, 927, 886, 860, 842, 811, 783 cm−1;
HRMS (ESI-TOF) Calcd for [M + Na]+ (C17H11Cl3N2Na1O2) m/z
402.9784, Found 402.9769.
2,6-Dichloro-N-(5,7-dichloro-8-quinolinyl)-4-methylbenzamide
(3j). Mp 225−226 °C; 1H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 7.18
(s, 2H), 7.57 (dd, J = 4.3, 8.6 Hz, 1H), 7.78 (s, 1H), 7.56 (d, J = 8.2 Hz,
1H), 8.91−8.95 (m, 2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 20.2,
123.2, 124.8, 127.7, 128.5, 129.3, 131.2, 131.3, 131.8, 132.7, 133.5, 141.6,
144.8, 152.0, 162.2; IR (KBr) 1686, 1597, 1577, 1499, 1459, 1386, 1374,
1273, 1146, 1136, 950, 885, 844, 813, 806, 781 m cm−1; HRMS (ESI-
TOF) Calcd for [M + Na]+ (C17H10Cl4N2Na1O1) m/z 420.9445, Found
420.9429.
Electrochemical Chlorination of Benzamide 5k. General
procedure B was followed with 79.1 mg (0.20 mmol) of benzamide
5k and 3.6 mg (0.020 mmol) of palladium chloride. The reaction was
carried out under a 2.5 mA constant current condition for 9 h. Column
chromatography (silica gel 60 N, 10:1 CH2Cl2/Et2O) afforded 64.4 mg
(75% yield) of 2-chloro-N-(5,7-dichloro-8-quinolinyl)-4-methylslufo-
nylbenzamide 2k and 7.2 mg (8% yield) of 2,6-dichloro-N-(5,7-
dichloro-8-quinolinyl)-4-methylslufonylbenzamide 3k as white solids.
2-Chloro-N-(5,7-dichloro-8-quinolinyl)-4-(methylsulfonyl)-
benzamide (2k). Mp 213-214 °C; 1H NMR (400 MHz, CDCl3) δ 3.11
(s, 3H), 7.59 (dd, J = 4.4, 8.8 Hz, 1H), 7.77 (s, 1H), 7.95 (d, J = 7.6 Hz,
1H), 8.05−8.09 (m, 2H), 8.57 (dd, J = 1.6, 8.8 Hz, 1H), 8.80 (brs, 1H),
8.93 (dd, J = 0.80, 4.0 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
43.2, 123.4, 125.0, 125.8, 127.5, 128.3, 129.8, 130.3, 131.3, 131.4, 132.2,
132.9, 140.7, 143.1, 144.9, 152.4, 164.2; IR (KBr) 3232, 1683, 1524,
1485, 1375, 1305, 1151, 1095, 947, 823, 809, 763 m cm−1; HRMS (ESI)
Calcd for [M + Na]+ (C17H11Cl3N2Na1O3S1) m/z 450.9454, Found
450.9475.
2,6-Dichloro-N-(5,7-dichloro-8-quinolinyl)-4-(methylsulufonyl)-
benzamide (3k). Mp 315−316 °C (decompose); 1H NMR (400 MHz,
DMSO-d6) δ 3.42 (s, 3H), 7.80 (dd, J = 3.9, 8.2 Hz, 1H), 8.10−8.11 (m,
3H), 8.62 (dd, J = 1.6, 8.6 Hz, 1H), 9.09 (dd, J = 1.6, 4.3 Hz, 1H), 11.21
(s, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 42.9, 123.3, 124.9,
126.6, 127.7, 129.6, 130.6, 131.7, 132.8, 132.8, 140.6, 143.2, 144.6, 152.1,
161.0; IR (KBr) 3235, 3201, 1681, 1604, 1589, 1530, 1485, 1380, 1373,
1307, 1292, 1284, 1277, 1161, 1145, 1136, 1110, 978, 972, 953, 908, 878,
860, 832, 811, 757 cm−1; HRMS (DART-TOF) Calcd for [M + H]+
(C17H11Cl4N2O3S1) m/z 462.9245, Found 462.9218.
Electrochemical Chlorination of Benzamide 5l. General
procedure B was followed with 72.2 mg (0.20 mmol) of benzamide 5l
and 3.6 mg (0.020 mmol) of palladium chloride. The reaction was
carried out under a 2.5 mA constant current condition for 12 h. Column
chromatography (silica gel 60 N, 80:1 CH2Cl2/Et2O) afforded 47.2 mg
(60% yield) of 2-chloro-N-(5,7-dichloro-8-quinolinyl)-4-nitrobenza-
mide 2l and 4.3 mg (5% yield) of 2,6-dichloro-N-(5,7-dichloro-8-
quinolinyl)-4-nitrobenzamide 3l as white solids.
2,6-Dichloro-N-(5,7-dichloro-8-quinolinyl)-4-methoxybenzamide
1
(3h). Mp 204−206 °C; H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H),
6.93 (s, 2H), 7.57 (dd, J = 4.4, 8.8 Hz, 1H), 7.77 (s, 1H), 8.55 (dd, J = 1.2,
8.4 Hz, 1H), 8.74 (brs, 1H), 8.92 (dd, J = 1.6, 4.8 Hz, 1H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 56.2, 114.0, 123.2, 124.8, 127.7, 129.0,
129.2, 131.4, 131.8, 132.4, 132.7, 144.8, 152.0, 160.0, 162.1; IR (KBr)
1679, 1598, 1557, 1503, 1485, 1468, 1298, 1272, 1247, 1138, 1056,
1037, 957, 883, 866, 824, 816, 781 cm−1; HRMS (ESI-TOF) Calcd for
[M + Na]+ (C17H10Cl4N2Na1O2) m/z 436.9394, Found 436.9376.
Electrochemical Chlorination of Benzamide 5i. General
procedure B was followed with 74.6 mg (0.20 mmol) of benzamide 5i
and 3.6 mg (0.020 mmol) of palladium chloride. The reaction was
carried out under a 2.5 mA constant current condition for 7 h. Column
chromatography (silica gel 60 N, 200:1 CH2Cl2/Et2O) afforded 45.0 mg
(55% yield) of 4-(tert-butyl)-2-chloro-N-(5,7-dichloro-8-quinolinyl)-
benzamide 2i and 25.9 mg (29% yield) of 4-(tert-butyl)-2,6-dichloro-N-
(5,7-dichloro-8-quinolinyl)benzamide 3i as white solids.
4-(tert-Butyl)-2-chloro-N-(5,7-dichloro-8-quinolinyl)benzamide
(2i). Mp 134−135 °C; 1H NMR (400 MHz, CDCl3) δ 1.36 (s, 9H), 7.42
(dd, J = 2.0, 8.2 Hz, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.55 (dd, J = 4.3, 8.6
Hz, 1H), 7.76 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 8.55 (dd, J = 1.6, 8.6 Hz,
1H), 8.91 (dd, J = 1.6, 4.3 Hz, 1H), 8.97 (brs, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 31.0, 35.0, 122.3, 124.2, 125.2, 127.8, 128.4, 129.1,
130.3, 130.8, 130.9, 131.2, 131.5, 133.2, 143.7, 150.8, 156.1, 164.1; IR
(KBr) 3169, 2964, 2871, 1668, 1605, 1586, 1508, 1481, 1385, 1361,
1309, 1256, 1137, 1041, 946, 930, 883, 859, 837, 794, 778 cm−1; HRMS
(ESI-TOF) Calcd for [M + Na]+ (C20H17Cl3N2Na1O1) m/z 429.0304,
Found 429.0311.
4-(tert-Butyl)-2,6-dichloro-N-(5,7-dichloro-8-quinolinyl)-
benzamide (3i). Mp 245−246 °C; 1H NMR (400 MHz, CDCl3) δ 1.34
(s, 9H), 7.39 (s, 2H), 7.56 (dd, J = 3.9, 8.6 Hz, 1H), 7.77 (s, 1H), 8.55
(dd, J = 1.2, 8.2 Hz, 1H), 8.76 (brs, 1H), 8.92 (dd, J = 1.6, 4.3 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 30.9, 35.2, 122.4, 125.1, 125.5,
128.6, 129.1, 130.1, 130.1, 132.2, 132.9, 133.2, 143.5, 150.7, 155.2,
162.1; IR (KBr) 2965, 1682, 1596, 1578, 1499, 1457, 1375, 1260, 1136,
951, 886, 867 cm−1; HRMS (ESI-TOF) Calcd for [M + Na]+
(C20H16Cl4N2Na1O1) m/z 462.9914, Found 462.9912.
Electrochemical Chlorination of Benzamide 5j. General
procedure B was followed with 66.2 mg (0.20 mmol) of benzamide 5i
and 3.6 mg (0.020 mmol) of palladium chloride. The reaction was
2-Chloro-N-(5,7-dichloro-8-quinolinyl)-4-nitrobenzamide (2l). Mp
232−233 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.77 (dd, J = 4.4, 8.8
Hz, 1H), 7.98 (d, J = 6.4 Hz, 1H), 8.10 (s, 1H), 8.35−8.41 (m, 2H), 8.59
(dd, J = 0.80, 8.8 Hz, 1H), 9.10 (dd, J = 1.2, 4.0 Hz, 1H), 10.98 (brs, 1H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 122.4, 123.3, 124.8, 125.0,
127.4, 129.8, 130.4, 131.2, 131.5, 132.2, 132.9, 141.8, 144.8, 148.5, 152.4,
163.9; IR (KBr) 1680, 1519, 1347, 952, 886, 875 cm−1; HRMS (ESI-
TOF) Calcd for [M + Na]+ (C16H8Cl3N3Na1O3) m/z 417.9529, Found
417.9518.
G
J. Org. Chem. XXXX, XXX, XXX−XXX