Arch. Pharm. Chem. Life Sci. 2014, 347, 923–935
Benzimidazole Endowed with Oxadiazole as COX-2 Inhibitor
931
7.30 (m, 4H, Ar–H), 4.90 (s, 2H, CH2), 4.84 (s, 2H, CH2), 3.97 (br,
1-((5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
2H, NH2, D2O exchangeable), 2.85 (s, 2H, CH2); 13C NMR (CDCl3):
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5j)
Solid, cyan; yield: 69%; m.p. (°C): 149–152; IR (KBr) cmꢃ1: 2993
–
(d ppm) 164, 160 (2C, oxadiazole), 157 (C N, pyrimidine),
–
–
149 (C N, benzimidazole), 133–116 (Ar–C), 45 (CH2), 43
–
–
(Ar–H), 2990, 2882 (C–H, CH ), 1643 (C N benzimidazole), 1571
–
2
–
(CH2NH2), 29 (CH2); ESI MS (m/z): 354 [MþH]þ. Anal. calcd. for
C16H15N7OS: C: 54.38, H: 4.28, N: 27.74; Found: C: 54.19, H: 4.29,
N: 27.83%.
–
(C N pyrimidine), 1558 (C C), 1353 (C–N), 1227 (Ar–F), 1126
–
–
1
(C–O–C); H NMR (CDCl3): (d ppm) 8.72 (2H, d, J ¼ 2.8 Hz, pyr-H4,
pyr-H6), 7.04 (1H, t, pyr-H5), 7.79–7.27 (m, 8H, Ar–H), 4.95 (s, 2H,
CH2), 4.32 (s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 166, 160 (2C,
–
–
–
–
oxadiazole), 155 (C N, pyrimidine), 145 (C N, benzimidazole),
1-((5-Phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-
132–112 (Ar–C), 49 (CH2), 32 (CH2); ESI MS (m/z): 419 [MþH]þ. Anal.
calcd. for C21H15FN6OS: C: 60.28, H: 3.61, N: 20.08; Found: C: 60.08,
H: 3.62, N: 19.99%.
ylthio)methyl)-1H-benzo[d]imidazole (5f)
Solid, brown; yield: 68%; m.p. (°C): 219–222; IR (KBr) cmꢃ1: 2986
–
–
(Ar–H), 2861 (C–H, CH ), 1647 (C N benzimidazole), 1577 (C N
–
–
2
–
pyrimidine), 1568 (C C), 1352 (C–N), 1134 (C–O–C); 1H NMR
–
1-((5-(2-Nitrophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
(CDCl3): (d ppm) 9.08 (2H, d, J ¼ 2.8 Hz, pyr-H4, pyr-H6), 7.09 (1H, t,
pyr-H5), 7.88–7.28 (m, 9H, Ar–H), 4.38 (s, 2H, CH2), 4.19 (s, 2H,
CH2); 13C NMR (CDCl3): (d ppm) 162, 161 (2C, oxadiazole), 159
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5k)
Powder, gray; yield: 62%; m.p. (°C): 256–258; IR (KBr) cmꢃ1: 3018
–
–
(C N, pyrimidine), 141 (C N, benzimidazole), 134–116 (Ar–C), 48
–
–
–
–
–
(Ar–H), 2883 (C–H, CH ), 1672 (C N benzimidazole), 1566 (C N
–
2
–
(CH2), 33 (CH2); ESI MS (m/z): 401 [MþH]þ. Anal. calcd. for
C21H16N6OS: C: 62.98, H: 4.03, N: 20.99; Found: C: 63.11, H: 4.04,
N: 20.92%.
pyrimidine), 1548 (C C), 1532, 1460 (NO ), 1356 (C–N), 1125
–
2
1
(C–O–C); H NMR (CDCl3): (d ppm) 8.92 (2H, d, J ¼ 3.6 Hz, pyr-H4,
pyr-H6), 7.01 (1H, t, pyr-H5), 7.83–7.25 (m, 8H, Ar–H), 4.81 (s, 2H,
CH2), 4.33 (s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 168, 163 (2C,
–
–
–
–
oxadiazole), 157 (C N, pyrimidine), 148 (C–NO ), 141 (C N,
2
1-((5-(2-Chlorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
benzimidazole), 137–115 (Ar–C), 42 (CH2), 35 (CH2); ESI MS (m/z):
445 [MþH]þ. Anal. calcd. for C21H15N7O3S: C: 56.62, H: 3.39,
N: 22.01; Found: C: 56.80, H: 3.38, N: 21.94%.
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5g)
Solid powder, dark brown; yield: 60%; m.p. (°C): 275–277; IR (KBr)
cmꢃ1: 2999 (Ar–H), 2882 (C–H, CH ), 1664 (C N benzimidazole),
–
–
2
–
–
1582 (C N pyrimidine), 1565 (C C), 1380 (C–N), 1129 (C–O–C),
–
–
755 (Ar–Cl); 1H NMR (CDCl3): (d ppm) 8.77 (2H, d, J ¼ 2.4 Hz, pyr-H4,
pyr-H6), 7.12 (1H, t, pyr-H5), 7.83–7.08 (m, 8H, Ar–H), 4.99 (s, 2H,
CH2), 4.12 (s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 170, 163 (2C,
1-((5-(4-Nitrophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5l)
Solid powder, dark brown; yield: 67%; m.p. (°C): 165–167; IR (KBr)
cmꢃ1: 3015 (Ar–H), 2887 (C–H, CH ), 1669 (C N benzimidazole),
–
–
–
–
oxadiazole), 152 (C N, pyrimidine), 148 (C N, benzimidazole),
–
–
2
–
–
134 (C–Cl), 131–112 (Ar–C), 44 (CH2), 36 (CH2); ESI MS (m/z): 435
[MþH]þ. Anal. calcd. for C21H15ClN6OS: C: 58.00, H: 3.48, N: 19.32;
Found: C: 58.22, H: 3.49, N: 19.26%.
1570 (C N pyrimidine), 1553 (C C), 1536, 1458 (NO ), 1360 (C–N),
–
–
2
1131 (C–O–C); 1H NMR (CDCl3): (d ppm) 8.85 (2H, d, J ¼ 2.4 Hz, pyr-
H4, pyr-H6), 7.21 (1H, t, pyr-H5), 7.85–7.36 (m, 8H, Ar–H), 4.76 (s,
2H, CH2), 4.23 (s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 165, 162 (2C,
–
–
–
–
oxadiazole), 151 (C N, pyrimidine), 147 (C–NO ), 140 (C N,
2
1-((5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
benzimidazole), 137–119 (Ar–C), 49 (CH2), 40 (CH2); ESI MS (m/z):
445 [MþH]þ. Anal. calcd. for C21H15N7O3S: C: 56.62, H: 3.39,
N: 22.01; Found: C: 56.52, H: 3.40, N: 22.08%.
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5h)
Powder, brown; yield: 69%; m.p. (°C): 133–136; IR (KBr) cmꢃ1: 2995
–
–
–
(Ar–H), 2870 (C–H, CH ), 1664 (C N benzimidazole), 1579 (C N
–
2
–
pyrimidine), 1567 (C C), 1353 (C–N), 1128 (C–O–C), 761 (Ar–Cl);
–
1H NMR (CDCl3): (d ppm) 8.79 (2H, d, J ¼ 3.4 Hz, pyr-H4, pyr-H6),
7.18 (1H, t, pyr-H5), 7.82–7.32 (m, 8H, Ar–H), 4.95 (s, 2H, CH2), 4.33
(s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 169, 162 (2C, oxadiazole),
2-(5-((2-((Pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-
1-yl)methyl)-1,3,4-oxadiazol-2-yl)phenol (5m)
Powder, dark green; yield: 72%; m.p. (°C): 242–244; IR (KBr) cmꢃ1
:
–
–
–
–
–
–
156 (C N, pyrimidine), 148 (C N, benzimidazole), 137 (C–Cl),
3356 (Ar–O–H), 2995 (Ar–H), 2870 (C–H, CH ), 1664 (C N
2
138–113 (Ar–C), 49 (CH2), 30 (CH2); ESI MS (m/z): 435 [MþH]þ. Anal.
calcd. for C21H15ClN6OS: C: 58.00, H: 3.48, N: 19.32; Found: C:
57.80, H: 3.47, N: 19.38%.
–
–
benzimidazole), 1568 (C N pyrimidine), 1539 (C C), 1375
–
–
(C–N), 1097 (C–O–C); 1H NMR (CDCl3): (d ppm) 8.68 (2H, d,
J ¼ 2.8 Hz, pyr-H4, pyr-H6), 7.10 (1H, t, pyr-H5), 7.71–7.26 (m, 8H,
Ar–H), 5.33 (s, 1H, OH, D2O exchangeable), 4.91 (s, 2H, CH2), 3.96
(s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 170, 161 (2C, oxadiazole),
1-((5-(2-Fluorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-2-
–
–
–
157 (C–OH), 156 (C N, pyrimidine), 140 (C N, benzimidazole),
–
((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazole (5i)
Solid powder, greenish; yield: 63%; m.p. (°C): 186–189; IR (KBr)
134–118 (Ar–C), 50 (CH2), 41 (CH2); ESI MS (m/z): 417 [MþH]þ. Anal.
calcd. for C21H16N6O2S: C: 60.56, H: 3.87, N: 20.18; Found: C: 60.80,
H: 3.88, N: 20.10%.
cmꢃ1: 3013 (Ar–H), 2905, 2880 (C–H, CH ), 1667 (C N benzimid-
–
–
2
–
–
azole), 1568 (C N pyrimidine), 1554 (C C), 1359 (C–N), 1224 (Ar–
–
–
F), 1144 (C–O–C); 1H NMR (CDCl3): (d ppm) 8.41 (2H, d, J ¼ 3.4 Hz,
pyr-H4, pyr-H6), 6.96 (1H, t, pyr-H5), 7.79–7.22 (m, 8H, Ar–H), 4.55
(s, 2H, CH2), 4.14 (s, 2H, CH2); 13C NMR (CDCl3): (d ppm) 163, 159
4-(5-((2-((Pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-
1-yl)methyl)-1,3,4-oxadiazol-2-yl)phenol (5n)
Solid, gray; yield: 70%; m.p. (°C): 212–214; IR (KBr) cmꢃ1: 3358 (Ar–
–
–
–
(2C, oxadiazole), 155 (C N, pyrimidine), 140 (C N, benzimid-
–
–
O–H), 2980 (Ar–H), 2854 (C–H, CH ), 1660 (C N benzimidazole),
azole), 136–116 (Ar–C), 45 (CH2), 37 (CH2); ESI MS (m/z): 419
[MþH]þ. Anal. calcd. for C21H15FN6OS: C: 60.28, H: 3.61, N: 20.08;
Found: C: 60.50, H: 3.62, N: 20.15%.
–
2
1
–
–
1568 (C N pyrimidine), 1533 (C C), 1379 (C–N), 1120 (C–O–C); H
–
–
NMR (CDCl3): (d ppm) 8.74 (2H, d, J ¼ 2.4 Hz, pyr-H4, pyr-H6), 7.17
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