The Journal of Organic Chemistry
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830, 776, 754, 718, 698 cmꢀ1; 1H NMR (CDCl3, 400 MHz) δ 9.54 (br s,
1H), 7.20ꢀ7.27 (m, 5H), 7.01 (d, 2H, J = 8.8 Hz), 7.00 (d, 1H, J = 2.9
Hz), 6.72 (d, 2H, J = 9.0 Hz), 3.74(s, 3H), 3.58 (s, 3H), 3.00 (s, 3H) ppm;
13C NMR (CDCl3, 100 MHz) δ 162.1, 158.2, 136.0, 130.6, 129.8, 128.2,
128.0, 127.4, 126.9, 125.6, 121.5, 119.1, 113.8, 61.2, 55.4, 34.9 ppm. Anal.
Calcd for C20H20N2O3: C, 71.41; H, 5.99; N, 8.33. Found: C, 71.52; H,
5.89; N, 8.48.
N-Methoxy-N-methyl-4-(40-(methylthio)phenyl)-3-phenyl-
1H-pyrrole-2-carboxamide (8e). White crystals (ethyl acetate):
78% yield; mp 153ꢀ154 °C; Rf = 0.19 (1:1 ethyl acetate/petroleum
ether); IR (ATR, neat) 3233, 2923, 1623, 1600, 1557, 1541, 1522, 1473,
1424, 1381, 1264, 1176, 1145, 1087, 1075, 1023, 972, 937, 863, 839, 817,
757, 739, 695 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 9.60 (br s, 1H),
7.20ꢀ7.31 (m, 5H), 7.00ꢀ7.09 (m, 4H), 7.03 (d, 1H, J = 2.8 Hz), 3.58
(s, 3H), 3.02 (s, 3H), 2.43 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ
162.1, 135.9, 135.4, 132.0, 130.5, 129.1, 128.3, 127.9, 127.0, 126.7, 125.3,
121.7, 119.5, 61.2, 35.0, 16.2 ppm. Anal. Calcd for C20H20N2O2S: C,
68.16; H, 5.72; N, 7.95; S, 9.10. Found: C, 68.25; H, 5.76; N, 7.97;
S, 9.03.
4-(40-Fluorophenyl)-N-methoxy-N-methyl-3-phenyl-1H-
pyrrole-2-carboxamide (8f). White crystals (ethyl acetate): 69%
yield; mp 152ꢀ153 °C; Rf (1:1 ethyl acetate/petroleum ether) = 0.24;
IR (ATR, neat) 3221, 3007, 2936, 2160, 1625, 1602, 1552, 1529, 1504,
1480, 1602, 1552, 1529, 1504, 1480, 1443, 1473, 1386, 1302, 1274,
1220, 1179, 1165, 1144, 1100, 1090, 1079, 1019, 999, 972, 939, 920,
867, 840, 814, 778, 756, 720, 702 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
δ 9.72 (br s, 1H), 7.26ꢀ7.30 (m, 3H), 7.19ꢀ7.21 (m, 2H), 7.01ꢀ7.06
(m, 3H), 6.86ꢀ6.90 (m, 2H), 3.59 (s, 3H), 3.02 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 162.1, 161.7 (d, JCꢀF = 245 Hz), 135.3,
131.0 (d, JCꢀF = 3.8 Hz), 130.5, 130.2 (d, JCꢀF = 7.5 Hz), 128.3, 127.9,
127.1, 125.0, 121.7, 119.4, 115.3 (d, JCꢀF = 21 Hz), 61.2, 35.0 ppm.
Anal. Calcd for C19H17FN2O2: C, 70.36; H, 5.28; N, 8.64. Found: C,
70.08; H, 5.42; N, 8.40.
4-(40-Chlorophenyl)-N-methoxy-N-methyl-3-phenyl-1H-
pyrrole-2-carboxamide (8g). White crystals (ethyl acetate): 66%
yield; mp 175ꢀ176 °C; Rf (1:1 ethyl acetate/petroleum ether) = 0.23;
IR (ATR, neat) 3315, 2937, 1639, 1599, 1823, 1437, 1438, 1420, 1381,
1323, 1227, 1180, 1136, 1094, 1068, 1016, 998, 967, 940, 912, 864,
798, 776, 762, 747, 720 cmꢀ1; 1H NMR (CDCl3, 400 MHz) δ 9.62 (br
s, 1H), 7.09ꢀ7.28 (m, 9H), 7.06 (d, 2H, J = 2.8 Hz), 3.60 (s, 3H), 3.02
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 162.4, 135.5, 135.1, 130.5,
128.7, 128.3, 128.2, 127.7, 126.9, 126.1, 125.6, 121.7, 119.8, 61.1, 35.2
ppm. Anal. Calcd for C19H17ClN2O2: C, 66.96; H, 5.03; N, 8.22.
Found: C, 66.83; H, 5.03; N, 8.26.
136.9, 136.0, 132.1, 131.9, 131.0, 129.1, 127.6, 126.8, 126.3, 125.3, 121.6,
119.5, 61.3, 34.9, 16.2, 15.9 ppm. Anal. Calcd for C21H22N2O2S2: C,
63.29; H, 5.56; N, 7.03; S, 16.09. Found: C, 63.06; H, 5.66; N, 6.86;
S, 16.04.
N-Methoxy-N-methyl-4-(40-(methylsulfonyl)phenyl)-3-
phenyl-1H-pyrrole-2-carboxamide (8j). White crystals (ethyl
acetate); general method #3 (95% yield) from 8c; modification of
general method #4 (40% yield) that involved 1.0 equiv of isocyanide 12,
1.2 equiv of nitroalkene 11j, and 1.5 equiv of DBU; mp 203ꢀ205 °C; Rf
(2:1 ethyl acetate/petroleum ether) = 0.29; IR (ATR, neat) 3360, 2927,
1644, 1595, 1548, 1492, 1474, 1416, 1376, 1313, 1291, 1279, 1156, 1126,
1089, 1005, 996, 957, 937, 864, 843, 799, 783, 753, 724, 703 cmꢀ1; 1H
NMR (CDCl3, 400 MHz) δ 9.80 (br s, 1H), 7.72 (d, 2H, J = 8.8 Hz),
7.19ꢀ7.32 (m, 7H), 7.14 (d, 1H, J = 3.1 Hz), 3.58 (s, 3H), 3.05 (s, 3H),
3.03 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 161.7, 141.1, 137.7,
134.8, 130.4, 129.0, 128.6, 128.3, 127.54, 127.48, 124.0, 122.4, 120.2,
61.3, 44.8, 34.7 ppm. Anal. Calcd for C20H20N2O4S: C, 62.48; H, 5.24;
N, 7.29; S, 8.34; Found: C, 62.51; H, 5.14; N, 7.31; S, 8.60.
N-Methoxy-N-methyl-3-(40-(methylsulfonyl)phenyl)-4-
phenyl-1H-pyrrole-2-carboxamide (8k). White crystals (EtOH);
general method #3 (69% yield) from 8e; general method #4 (65% yield);
mp 202ꢀ203 °C; Rf (2:1 ethyl acetate/petroleum ether) = 0.17; IR
(ATR, neat) 3275, 1603, 1548, 1471, 1435, 1383, 1302, 1147, 1088, 955,
937, 863, 835, 768, 695 cmꢀ1; 1H NMR (CDCl3, 400 MHz) δ 9.76 (br s,
1H), 7.83 (d, 2H, J = 8.6 Hz), 7.44 (d, 2H, J = 8.6 Hz), 7.19ꢀ7.21 (m,
3H), 7.05 (d, 1H, J = 3.1 Hz), 7.01ꢀ7.03 (m, 2H), 3.69 (s, 3H), 3.23 (s,
3H), 3.07 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 160.9 141.9,
138.5, 134.1, 131.6, 128.8, 128.7, 127.9, 127.1, 126.7, 126.6, 121.5, 119.7,
61.9, 44.9, 33.9 ppm. Anal. Calcd for C20H20N2O4S: C, 62.48; H, 5.24;
N, 7.29; S, 8.34; Found: C, 62.58; H, 5.32; N, 7.36; S, 8.29.
N-Methoxy-N-methyl-4-(40-nitrophenyl)-3-phenyl-1H-
pyrrole-2-carboxamide (8m). Yellow crystals (EtOH); 64%
yield; mp 219ꢀ220.5 °C; Rf (1:1 ethyl acetate/petroleum ether) = 0.23; IR
(ATR, neat) 3213, 1592, 1499, 1430, 1393, 1330, 1148, 1079, 1013, 966,
938, 857, 758, 745, 727 cmꢀ1; 1H NMR (CDCl3, 400 MHz) δ 9.86 (br s,
1H), 8.03 (d, 2H, J = 8.8 Hz), 7.31ꢀ7.35 (m, 3H), 7.18ꢀ7.22 (m, 4H),
7.16 (d, 1H, J = 3.2 Hz), 3.58 (s, 3H), 3.06 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3) δ 161.7, 146.0, 142.3, 134.8, 130.4, 128.7, 128.6, 128.2,
127.6, 123.8, 123.7, 122.5, 120.4, 61.3, 34.7 ppm. Anal. Calcd for
C19H17N3O4: C, 64.95; H, 4.88; N, 11.96; Found: C, 65.04; H, 4.77;
N, 12.06.
N-Methoxy-N-methyl-4-(30-nitrophenyl)-3-phenyl-1H-
pyrrole-2-carboxamide (8n). Yellow amorphous solid: 60%
yield; mp 196ꢀ199 °C; Rf (2:1 ethyl acetate/petroleum ether) = 0.61; IR
(ATR, neat) 3207, 1612, 1556, 1534, 1512, 1478, 1440, 1392, 1346, 1302,
1231, 1179, 1147, 1086, 1072, 1016, 1000, 974, 956, 915, 904, 864, 804,
778, 756, 734, 700 cmꢀ1; 1H NMR (CDCl3, 400 MHz) δ 9.78 (br s, 1H),
8.03ꢀ8.04 (m, 1H), 7.97ꢀ8.00 (m, 1H), 7.28ꢀ7.32 (m, 4H), 7.19ꢀ7.22
(m, 2H), 7.16 (d, 2H, J = 3.1 Hz), 3.59 (s, 3H), 3.08 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 161.7, 148.5, 136.9, 134.7, 134.6, 130.4,
129.1, 128.6, 128.3, 127.5, 123.7, 123.1, 122.2, 121.0, 119.9, 61.3, 34.7
ppm. Anal. Calcd for C19H17N3O4: C, 64.95; H, 4.88; N, 11.96; Found: C,
64.67; H, 4.97; N, 11.85.
N-Methoxy-3,4-bis(40-methoxyphenyl)-N-methyl-1H-pyrrole-
2-carboxamide (8h). White crystals (EtOH); 82% yield; mp
167ꢀ168 °C; Rf (2:1 ethyl acetate/petroleum ether) = 0.43; IR
(ATR, neat) 3223, 1608, 1534, 1512, 1436, 1380, 1284, 1244, 1177,
1
1140, 1025, 1000, 971, 932, 877, 829, 817, 791, 756 cmꢀ1; H NMR
(CDCl3, 400 MHz) δ 9.42 (br s, 1H), 7.14 (d, 2H, J = 8.8 Hz), 7.03 (d,
2H, J = 8.8 Hz), 6.98 (d, 1H, J = 2.9 Hz), 6.84 (d, 2H, J = 8.8 Hz), 6.75 (d,
2H, J = 8.8 Hz), 3.81 (s, 3H), 3.77 (s, 3H), 3.63 (s, 3H), 3.04 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 162.2, 158.7, 158.2, 131.7, 129.8,
127.84, 127.76, 127.6, 125.6, 121.3, 119.1, 113.9, 61.3, 55.45, 55.41, 35.1
ppm. Anal. Calcd for C21H22N2O4: C, 68.84; H, 6.05; N, 7.65. Found: C,
68.64; H, 6.03; N, 7.76.
General Method. Synthesis of Pyrrole-2-carboxaldehydes
9. A modification of our previously reported literature procedure was
followed.19 To a 0 °C stirred solution of LiAlH4 (1.5 mmol) in THF
(5 mL) was added a solution of pyrrole-2-carboxamide 8 (1.0 mmol) in
THF (5 mL) dropwise via addition funnel. The yellow reaction solution
was stirred at 0 °C for 1 h. The reaction solution was diluted with ether
(15 mL), and then 6.0 equiv of KHSO4 (1.2 g, 8.4 mmol) in H2O
(15 mL) was added dropwise via addition funnel. The aqueous layer was
extracted with ether (3 ꢁ 15 mL), and the combined organic layers were
washed with 5% citric acid (50 mL), sat. NaHCO3 (50 mL), and brine
(50 mL) and then dried over Na2SO4. Removal of the solvent in vacuo
N-Methoxy-3,4-bis(40-(methylthio)phenyl)-N-methyl-1H-
pyrrole-2-carboxamide (8i). White crystals (ethyl acetate); 75%
yield; mp 169ꢀ170 °C; Rf (1:1 ethyl acetate/petroleum ether) = 0.16;
IR (ATR, neat) 3274, 1617, 1559, 1519, 1472, 1423, 1382, 1321, 1259,
1188, 1146, 1103, 1088, 1031, 1015, 973, 934, 861, 834, 824, 813, 759,
738, 715 cmꢀ1 1H NMR (CDCl3, 400 MHz) δ 9.53 (br s, 1H),
;
7.09ꢀ7.17 (m, 6H), 7.01ꢀ7.03 (m, 3H), 3.62 (s, 3H), 3.08 (s, 3H),
2.49 (s, 3H), 2.45 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 162.0,
8210
dx.doi.org/10.1021/jo2013516 |J. Org. Chem. 2011, 76, 8203–8214