Nov-Dec 2007
Synthesis of 2-Substituted Benzimidazoles by Iodine-Mediated Condensation of Orthoesters
1511
2-Butylbenzimidazole (3d). This compound was obtained
as pale yellow solid; ir (KBr): 3414, 2929, 1622, 1534, 1417,
1274, 1153, 1101, 1029, 930, 880, 751 cm-1; 1H nmr (400 MHz,
CDCl3): ꢀ 0.90 (t, J = 7.2 Hz, 3H), 1.39 (sext, J = 7.2 Hz, 2H),
1.83 (quin, J = 7.2 Hz, 2H), 2.92 (t, J = 7.2 Hz, 2H), 7.19-7.23
(m, 2H), 7.53-7.56 (m, 2H), 9.01 (s, 1H); 13C NMR (100 MHz,
CDCl3) ꢀ 13.67, 22.41, 29.06, 30.43, 114.58, 122.07, 138.59,
155.62; ESI-MS: 175 (M+1)+; Anal. Calcd. for C11H14N2: C,
75.82; H, 8.10; N, 16.08. Found: C, 75.96; H, 8.31; N, 15.92.
4-Methylbenzimidazole (3e). This compound was obtained
as pale yellow solid; ir (KBr): 3414, 2990, 2926, 1616, 1485,
115.00, 130.99, 137.32, 154.90; ESI-MS: 203 (M+1)+. Anal.
Calcd. for C13H18N2: C, 77.18; H, 8.97; N, 13.85. Found: C,
77.32; H, 9.05; N, 13.69.
4-Chlorobenzimidazole (3m). This compound was
obtained as yellow solid; ir (KBr): 3442, 1626, 1582, 1461,
1
1287, 1150, 1056, 952, 908, 878, 799, 732 cm-1; H nmr (400
MHz, CDCl3): ꢀ 7.19 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz,
1H), 7.58 (s, 1H), 8.15 (s, 1H), 12.26 (s, 1H); ESI-MS: 153
(M+1)+.
2-Methyl-5-chlorobenzimidazole (3n). This compound
was obtained as yellow solid; ir (KBr): 3415, 2971, 1624, 1545,
1400, 1278, 1059, 921, 804 cm-1; 1H nmr (400 MHz, CDCl3): ꢀ
2.62 (s, 3H), 7.18 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H),
7.50 (s, 1H), 8.49 (s, 1H); ESI-MS: 167 (M+1)+.
1
1450, 1400, 1297, 1249, 1168, 948 cm-1; H nmr (400 MHz,
CDCl3): ꢀ 2.02 (s, 3H), 7.10 (d, J = 8.0 Hz, 1H), 7.20 (t, J = 8.0
Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 8.14 (s, 1H), 10.90 (s, 1H);
13C NMR (100 MHz, CDCl3) ): ꢀ 17.39, 112.74, 123.26, 123.55,
126.18, 136.96, 137.86, 140.34; ESI-MS: 133 (M+1)+; Anal.
Calcd. for C8H8N2: C, 72.70; H, 6.10; N, 21.20. Found: C, 72.98;
H, 6.25; N, 21.05.
5-Nitrobenzimidazole (3o). This compound was obtained
as yellow solid; ir (KBr): 3483, 2814, 1623,1590, 1513, 1464,
1408, 1374, 1300, 1263, 1240, 1067, 952, 896, 741 cm-1; 1H nmr
(400 MHz, DMSO-d6): ꢀ 7.78 (d, J = 8.4 Hz, 1H), 8.12 (d, J =
8.4 Hz, 1H), 8.52 (s, 1H), 8.58 (s, 1H); ESI-MS: 164 (M+1)+.
2-Methyl-5-nitrobenzimidazole (3q). This compound was
obtained as yellow solid; ir (KBr): 3561, 2923, 1684, 1627,
2-Ethyl-4-methylbenzimidazole (3f). This compound was
obtained as pale yellow solid; ir (KBr): 3340, 2716, 2606, 1572,
1413, 1225, 1159, 1024, 865 cm-1; 1H nmr (400 MHz, CDCl3): ꢀ
1.42 (t, J = 7.6 Hz, 3H), 2.60 (s, 3H), 3.08 (q, J = 7.6 Hz, 2H),
7.08 (d, J = 8.0 Hz, 1H), 7.17 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 8.0
Hz, 1H), 10.00 (s, 1H); 13C NMR (100 MHz, CDCl3) ): ꢀ 12.83,
17.37, 22.62, 112.12, 122.76, 123.36, 124.87, 137.45, 137.50,
155.75; ESI-MS: 161 (M+1)+; Anal. Calcd. for C10H12N2: C,
74.97; H, 7.55; N, 17.48. Found: C, 75.05; H, 7.68; N, 17.26.
5-Methylbenzimidazole (3g). This compound was obtained
as pale yellow solid; ir (KBr): 3413, 3016, 2802, 1619, 1476,
1444, 1281, 1248, 1164, 1001, 880, 808 cm-1; 1H nmr (400 MHz,
CDCl3): ꢀ 2.47 (s, 3H), 7.12 (d, J = 7.2 Hz, 1H), 7.44 (s, 1H),
7.56 (d, J = 7.2 Hz, 1H), 8.04 (s, 1H), 9.04 (s, 1H); ESI-MS: 133
(M+1)+.
1
1593, 1516, 1471, 1356, 1216, 1065, 1022, 942, 879 cm-1; H
nmr (400 MHz, CDCl3): ꢀ 2.70 (s, 3H), 7.78 (d, J = 8.4 Hz, 1H),
8.19 (d, J = 8.4 Hz, 1H), 8.48 (s, 1H); ESI-MS: 178 (M+1)+.
2-Butyl-5-nitrobenzimidazole (3s). This compound was
obtained as yellow solid; ir (KBr): 3354, 2959, 1627, 1594,
1
1513, 1471, 1410, 1342, 1066, 1008, 882 cm-1; H nmr (400
MHz, DMSO-d6): ꢀ 0.89 (t, J = 7.2 Hz, 6H), 1.42 (sext, J = 7.2
Hz, 4H), 1.89 (quin, J = 7.2 Hz, 4H), 3.03 (t, J = 7.2 Hz, 4H),
7.59 (d, J = 8.4 Hz, 4H), 8.18 (d, J = 8.4 Hz, 4H), 8.48 (s, 2H),
11.02 (s, 2H); 13C NMR (100 MHz, DMSO-d6) ): ꢀ 13.85,
22.62, 29.44, 30.29, 111.89, 114.38, 118.68, 138.46, 142.90,
143.64, 160.39; ESI-MS: 220 (M+1)+. Anal. Calcd. for
C11H13N3O2: C, 60.26; H, 5.98; N, 19.17; Found: C, 60.42; H,
6.05; N, 19.02.
2,5-Dimethylbenzimidazole (3h). This compound was
obtained as pale yellow solid; ir (KBr): 3417, 2913, 2774, 1630,
1553, 1483, 1401, 1281, 1143, 1029, 881, 804 cm-1; 1H nmr (400
MHz, CDCl3): ꢀ 2.44 (s, 3H), 2.61 (s, 3H), 7.03 (d, J = 8.4 Hz,
1H), 7.31 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 9.41 (s, 1H); ESI-
MS: 147 (M+1)+.
2,2'-Dibutyl-1H,1'H-5,5-bibenzimidazolyl (5). This
compound was obtained as colorless solid, mp 241-242°; ir
(KBr): 3415, 2930, 1728, 1630, 1575, 1542, 1415, 1276, 1085,
1
1026, 810 cm-1; H nmr (400 MHz, CD3OD): ꢀ 0.97 (t, J = 7.2
Hz, 6H), 1.41 (sext, J = 7.2 Hz, 4H), 1.81 (quin, J = 7.2 Hz, 4H),
2.88 (t, J = 7.2 Hz, 4H), 7.47 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4
Hz, 2H), 7.69 (s, 2H); 13C nmr (100 MHz, CD3OH): ꢀ 14.88,
22.19, 28.35, 30.24, 112.36, 114.44, 121.99, 136.71, 156.40;
ESI-MS: 347 (M+1)+; Anal. Calcd. for C22H26N4: C, 76.27; H,
7.56; N, 16.17. Found: C, 76.08; H, 7.40; N, 16.36.
2-Ethyl-5-methylbenzimidazole (3i). This compound was
obtained as pale yellow solid; ir (KBr): 3426, 2972, 2730, 1632,
1549, 1411, 1317, 1276, 1140, 1069, 1040, 971, 863, 807 cm-1; 1H
nmr (400 MHz, CDCl3): ꢀ 1.42 (t, J = 7.6 Hz, 3H), 2.44 (s, 3H),
2.95 (q, J = 7.6 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 7.32 (s, 1H),
7.44 (d, J = 8.4 Hz, 1H), 8.43 (s, 1H); ESI-MS: 161 (M+1)+.
5,6-Dimethylbenzimidazole (3j). This compound was
obtained as pale yellow solid; ir (KBr): 3467, 2758, 1712, 1470,
Acknowledgement. We thank the Science Foundation from
Hebei Normal University (L20061314), the Nature Science
Foundation of Hebei Province (B2005000151) and the Natural
Science Foundation of Hebei Education Department (2006318)
for financial support.
1
1445, 1406, 1335, 1304, 1268, 1157, 1025, 998, 961 cm-1; H
nmr (400 MHz, CDCl3): ꢀ 2.37 (s, 6H), 7.42 (s, 2H), 7.95 (s,
1H), 8.23 (s, 1H); ESI-MS: 147 (M+1)+.
2,5,6-Trimethylbenzimidazole (3k). This compound was
obtained as pale yellow solid; ir (KBr): 3378, 2919, 1632, 1540,
REFERENCES
1
1452, 1389, 1306, 1231, 1161, 1022, 1000, 854 cm-1; H nmr
(400 MHz, CDCl3): ꢀ 2.31 (s, 6H), 2.68 (s, 3H), 7.35 (s, 2H);
ESI-MS: 161 (M+1)+.
[1a] Pozharskii, A. F.; Garnovskii, A. D; Simonov, A. M. Russ.
Chem. Rev. 1966, 35, 122; [b] Valdez, J.; Cedillo, R.; Hernández-
Campos, A.; Yépez, L.; Hernández-Luis, F.; Navarrete-Vázquez, G.;
Tapia, A.; Cortés, R.; Hernándezc, M.; Castilloa, R. Bioorg. Med. Chem.
Lett. 2002, 12, 2221; [c] Zarrinmayeh, H.; Nunes, A. M.; Ornstein, P. L.;
Zimmerman, D. M.; Arnold, B.; Schober, D. A.; Gackenheimer, S. L.;
Bruns, R. F.; Hipskind, P. A.; Britton, T. C.; Cantrell, B. E.; Gehlert, D.
R. J. Med. Chem. 1998, 41, 2709; [d] LaPlante, S. R.; Jakalian, A.;
Aubry, N.; Bousquet, Y.; Ferland, J.-M.; Gillard, J.; Lefebvre, S.;
2-Butyl-5,6-dimethylbenzimidazole (3l). This compound
was obtained as pale yellow solid; ir (KBr): 3452, 2959, 2929,
1630, 1539, 1440, 1305, 1195, 1160, 1085, 1020, 997, 976, 847
1
cm-1; H nmr (400 MHz, CDCl3): ꢀ 0.86 (t, J = 7.6 Hz, 3H),
1.37 (sext, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.6 Hz, 2H), 2.33 (s,
6H), 2.91 (t, J = 7.6 Hz, 2H), 7.32 (s, 2H), 10.49 (s, 1H); 13C
NMR (100 MHz, CDCl3): ꢀ 13.93, 20.49, 22.64, 29.26, 30.71,