J. Chil. Chem. Soc., 57, Nº 1 (2012)
benzothiophene-2-carboxamide (5d)
4.6.5. 3-Chloro-N-{4-[1-(4-fluorophenyl)-4-methoxyphenyl-4,5-dihydro-
1H-pyrazol-3-yl] phenyl}-1-benzothiophene-2-carboxamide (6f)
1
IR ν (cm-1): 3260 (N-H), 1642 (C=O), 1625 (C=N); H-NMR δ (ppm):
9.89 (s, 1H, CONH), 7.95-7.02 (m, 12H, Ar-H), 3.75 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.5, 156.1, 148.5, 146.8, 141.6, 140.2, 135.9, 133.4, 129.9, 129.4,
128.0, 126.7, 126.0, 124.4, 124.3, 124.1, 122.8, 121.7, 121.1, 82.3, 42.2; MS:
m/z, 477.91 (M+). Anal. calcd. for C H16ClN3O4S: C, 60.31; H, 03.37; N,
08.79; S, 06.71; found: C, 60.25; H, 032.434; N, 08.75; S, 06.68%.
IR ν (cm-1): 3275 (N-H), 1650 (C=O), 1623 (C=N); 1H-NMR δ (ppm):
10.45 (s, 1H, CONH), 8.03-7.29 (m, 16H, Ar-H), 3.75 (s, 3H, OCH3), 2.52 (s,
2H, CH2); 13C-NMR δ (ppm): 161.2, 158.2, 155.1, 151.2, 141.4, 140.2, 139.4,
135.9, 135.8, 133.4, 132.0, 129.9, 129.4, 126.7, 126.6, 124.4, 124.3, 122.8,
121.5, 116.2, 115.1, 114.3, 55.2, 40.6; MS: m/z, 556.04 (M+). Anal. calcd. for
C31H23ClFN3O2S: C, 66.96; H, 04.17; N, 07.56; S, 05.77; found: C, 66.91; H,
04.12; N, 07.51; S, 05.71%.
4.6. General procedure for synthesis of compounds 6a-h.
Exemplary detail for 3-chloro-N-[4-(1,5-diphenyl-4,5-dihydro-1H-
pyrazol-3-yl)phenyl]-1-benzothiophene-2-carboxamide (6a)
4.6.6.
3-Chloro-N-{4-[1-(4-fluorophenyl)-4-chlorophenyl-4,5-dihydro-
1H-pyrazol-3-yl]phenyl}-1-benzothiophene-2-carboxamide (6g)
1
A mixture of compound 3a (2.50 g, 0.006 mol) in DMF (25 mL) and
phenylhydrazine (0.64 g, 0.006 mol) was refluxed for 15 h. The completion
of the reaction was monitored by TLC. The reaction mixture was allowed to
cool down to room temperature and poured into ice cooled water with constant
stirring. The resulting precipitate was filtered, washed with water, dried and
recrystallized from 1,4-dioxane to produce 6a. Compounds 6b-h were prepared
in the same manner.
IR ν (cm-1): 3272 (N-H), 1645 (C=O), 1624 (C=N); H-NMR δ (ppm):
10.35 (s, 1H, CONH), 7.98-7.03 (m, 16H, Ar-H), 2.45 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.7, 155.4, 151.5, 141.3, 141.5, 140.2, 139.4, 135.9, 133.4, 132.3,
132.0, 129.9, 129.4, 128.6, 127.2, 126.7, 124.4, 124.3, 122.8, 121.7, 121.7,
116.3, 116.3, 115.1, 53.2, 40.4; MS: m/z, 560.47 (M+). Anal. calcd. for
C30H20Cl FN3OS: C, 64.29; H, 03.60; N, 07.50; S, 05.72; found: C, 48.08; H,
03.50; N2, 07.00; S, 5.70%.
1
IR ν (cm-1): 3277 (N-H), 1643 (C=O), 1613 (C=N); H-NMR δ (ppm):
10.65 (s, 1H, CONH), 8.18-7.27 (m, 18H, Ar-H), 2.40 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.6, 151.2, 143.8, 141.6, 140.2, 143.5, 135.9, 133.4, 132.0, 129.9,
129.5, 129.5, 129.4, 128.5, 128.5, 126.9, 126.8, 126.7, 124.4, 124.3, 122.8,
121.7, 120.8, 116.7, 53.2, 40.5; MS: m/z, 508.03 (M+). Anal. calcd. for
C30H22ClN3OS: C, 70.92; H, 04.36; N, 08.27; S, 06.31; found: C, 70.89; H,
04.31; N, 08.23; S, 06.27%.
4.6.7. 3-Chloro-N-{4-[1-(4-fluorophenyl)-4-nitrophenyl-4,5-dihydro-1H-
pyrazol-3-yl] phenyl}-1-benzothiophene-2-carboxamide (6h)
1
IR ν (cm-1): 3281 (N-H), 1656 (C=O), 1610 (C=N); H-NMR δ (ppm):
11.43 (s, 1H, CONH), 8.11-6.99 (m, 16H, Ar-H), 2.43 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.2, 155.1, 151.4, 149.6, 145.9, 141.6, 140.2, 139.4, 135.9, 133.4,
132.0, 129.9, 129.4, 126.7, 124.4, 124.3, 123.7, 123.4, 122.8, 121.7, 121.7,
116.3, 115.3, 115.1, 53.7, 40.5; MS: m/z, 571.02 (M+). Anal. calcd. for
C30H20ClFN4O3S: C, 63.10; H, 03.53; N, 09.81; S, 05.62; found: C, 63.07; H,
03.50; N, 09.78; S, 05.60%.
4.6.1.
3-Chloro-N-[4-(1-phenyl-4-methoxyphenyl-4,5-dihydro-1H-
pyrazol-3-yl)phenyl]-1-benzothiophene-2-carboxamide (6b)
1
IR ν (cm-1): 3275 (N-H), 1635 (C=O), 1615 (C=N); H-NMR δ (ppm):
10.38 (s, 1H, CONH), 7.95-7.02 (m, 17H, Ar-H), 3.80 (s, 3H, OCH3), 2.80 (s,
2H, CH2); 13C-NMR δ (ppm): 161.7, 158.3, 151.1, 143.1, 141.1, 140.1, 135.1,
133.1, 132.0, 129.9, 129.5, 129.4, 126.7, 126.6, 124.1, 124.1, 122.2, 121.3,
121.4, 120.8, 116.7, 114.1, 55.8, 53.2, 40.5; MS: m/z, 538.05 (M+); Anal.
calcd. for C31H24ClN3O2S: C, 69.20; H, 04.50; N, 07.81; S, 05.96. Found: C,
69.15; H, 04.44; N, 07.78; S, 05.90%.
4.7. General procedure for synthesis of compounds 7a-d.
Exemplary detail for 3-chloro-N-[4-(5-phenyl-4,5-dihydro-1H-pyrazol-
3-yl)phenyl]-1-benzothiophene-2-carboxamide (7a)
A mixture of compound 3a (2.50 g, 0.006 mol) in 1.4-dioxane (20 mL) and
hydrazine hydrate (0.29 g, 0.006 mol) was refluxed for 10 h. After completion
of reaction, the reaction mixture was cooled, poured into crushed ice and
then neutralized with HCl. The precipitate was filtered, washed with water,
dried and recrystallized from methanol. It was further purified by column
chromatography using a gradient mixture of petroleum ether/ethyl acetate
(80:20) as an eluent to give compound 7a. Compounds 7b-d were prepared in
the same manner.
4.6.2. 3-Chloro-N-[4-(1-phenyl-4-chlorophenyl-4,5-dihydro-1H-pyrazol-
3-yl)phenyl]-1-benzothiophene-2-carboxamide (6c)
1
IR ν (cm-1): 3265 (N-H), 1640 (C=O), 1625 (C=N); H-NMR δ (ppm):
10.22 (s, 1H, CONH), 8.02-7.13 (m, 17H, Ar-H), 2.69 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.4, 151.2, 143.2, 141.2, 141.2, 140.2, 135.9, 133.4, 132.3, 132.0,
129.9, 129.5, 129.4, 128.6, 128.6, 127.2, 126.7, 124.4, 124.3, 122.8, 121.7,
120.8, 116.7, 116.7, 53.4, 40.3; MS: m/z, 542.46 (M+). Anal. calcd. for
C30H21Cl N3OS: C, 66.42; H, 03.90; N, 07.75; S, 05.91; found: C, 66.38; H,
03.89; N2, 7.71; S, 05.89%.
1
IR ν (cm-1): 3240 (N-H), 1650 (C=O), 1626 (C=N); H-NMR δ (ppm):
10.84 (s, 1H, NH), 9.70 (s, 1H, CONH), 8.23-7.01 (m, 13H, Ar-H), 3.45 (s,
2H, CH2); 13C-NMR δ (ppm): 161.0, 151.1, 143.4, 141.3, 140.1, 143.5, 135.9,
133.4, 132.0, 129.9, 129.4, 129.5, 129.5, 128.5, 128.5, 126.9, 126.7, 124.4,
124.3, 122.8, 121.7, 120.8, 116.7, 54.1, 40.8; MS: m/z, 431.93(M+). Anal.
calcd. for C24H18ClN3OS: C, 67.74; H, 04.20; N, 09.73; S, 07.4; found: C,
67.70; H, 04.17; N, 09.70; S, 07.39%.
4.6.3. 3-Chloro-N-[4-(1-phenyl-4-nitrophenyl-4,5-dihydro-1H-pyrazol-3-
yl)phenyl]-1-benzothiophene-2-carboxamide (6d)
1
IR ν (cm-1): 3264 (N-H), 1659 (C=O), 1614 (C=N); H-NMR δ (ppm):
4.7.1.
3-Chloro-N-[4-(4-methoxyphenyl-4,5-dihydro-1H-pyrazol-3-yl)
10.32 (s, 1H, CONH), 8.14-7.87 (m, 17H, Ar-H), 2.71 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.1, 151.2, 149.3, 145.1, 143.8, 141.6, 140.2, 135.9, 133.4, 132.0,
129.9, 129.5, 129.4, 126.7, 124.4, 124.3, 123.7, 123.7, 123.4, 123.4, 122.8,
121.7, 120.8, 116.7, 116.4, 53.1, 40.2; MS: m/z, 553.01 (M+). Anal. calcd. for
C30H21ClN4O S: C, 65.15; H, 03.83; N, 10.13; S, 05.80; found: C, 65.10; H,
03.80; N, 10.310; S, 05.76%.
phenyl]-1-benzoth iophene-2-carboxamide (7b)
IR ν (cm-1): 3245 (N-H), 1660 (C=O), 1616 (C=N); H-NMR δ (ppm):
10.49 (s, 1H, NH), 9.62 (s, 1H, CONH), 8.93-7.60 (m, 12H, Ar-H), 3.91
(s, 2H, OCH ), 3.57 (s, 2H, CH2); 13C-NMR δ (ppm): 161.6, 158.3, 151.3,
141.5, 140.2,3 135.9, 135.8, 133.4, 132.0, 129.9, 129.4, 126.7, 126.6, 124.4,
124.3, 121.7, 114.1, 55.8, 49.9, 42.1; MS: m/z, 461.96 (M+). Anal. calcd. for
C25H20ClN3O S: C, 65.00; H, 04.36; N, 09.10; S, 06.94; found: C, 64.98; H,
04.30; N, 09.203; S, 06.89%.
1
4.6.4.
3-Chloro-N-{4-[1-(4-fluorophenyl)-4-phenyl-4,5-dihydro-1H-
pyrazol-3-yl]phenyl}-1-benzothiophene-2-carboxamide (6e)
IR ν (cm-1): 3250 (N-H), 1642 (C=O), 1595 (C=N); 1H-NMR δ (ppm):
10.40 (s, 1H, CONH), 8.39-7.45 (m, 17H, Ar-H), 2.50 (s, 2H, CH2); 13C-NMR
δ (ppm): 161.9, 155.2, 151.2, 143.1, 141.3, 140.2, 139.4, 135.9, 133.4, 132.0,
129.9, 129.4, 128.5, 126.9, 126.9, 126.7, 124.4, 124.3, 122.4, 121.3, 116.2,
115.1, 53.3, 40.8; MS: m/z, 526.02 (M+). Anal. calcd. for C30H21ClFN3OS: C,
68.50; H, 04.02; N, 07.99; S, 06.10; found: C, 68.48; H, 04.00; N, 07.95; S,
06.05%.
4.7.2.
3-Chloro-N-[4-(4-chlorophenyl-4,5-dihydro-1H-pyrazol-3-yl)
phenyl]-1-benzo thiophene-2-carboxamide (7c)
IR ν (cm-1): 3265 (N-H), 1667 (C=O), 1622 (C=N); H-NMR δ (ppm):
10.75 (s, 1H, NH), 10.11 (s, 1H, CONH), 8.20-7.33 (m, 12H, Ar-H), 2.85 (s,
2H, CH ); 13C-NMR δ (ppm): 161.6, 151.3, 141.2, 140.2, 135.4, 133.2, 132.3,
132.0, 1229.9, 129.4, 128.6, 127.2, 126.7, 124.4, 124.3, 122.8, 121.7, 49.7, 42.5;
MS: m/z, 466.37 (M+). Anal. calcd. for C24H17Cl2N3OS: C, 61.81; H, 03.67; N,
1
1046