9
1220, 1157, 820, 740 cm-1; 1H NMR (400 MHz, CDCl ) δ: 1.01
(t, J = 7.2 Hz, 3H), 1.86 (sextet, J = 7.6 Hz, 2H), 2.81 (t, J = 7.6
Special thanks to Prof. Dr. Frederick W.H. Beamish, Faculty of
ACCEPTED MANUSCRIPT
3
Science, Burapha University, for his comments and English
correction.
Hz, 2H), 5.31 (s, 2H), 6.96-7.04 (m, 4H), 7.16-7.28 (m, 3H), 7.77
(d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.95, 21.00,
29.42, 46.19, 109.32, 115.90 (d, JCF = 21.0 Hz), 119.26, 122.08,
122.33, 127.76 (d, JCF = 8.0 Hz), 131.71 (d, JCF = 3.0 Hz),
135.10, 142.52, 155.11, 162.22 (d, JCF = 245.0 Hz); HRMS
(APCI) m/z [M+H]+ calcd C17H17FN2 269.1454, found 269.1454.
References and notes
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Manakova, E.; Grazulis, S.; Tumkevicius, S.; Matulis, D. Bioorg.
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4.3.26. 1-Chloropropyl-2-isobutyl-5-fluorobenzimidazole (5xa)
As a yellow oil (94.1 mg, 35%); Rf = 0.20 (20% EtOAc/n-
hexane); IR (KBr): νmax 2959, 1625, 1597, 1484, 1445, 1409,
1
1367, 1134, 959, 853, 796 cm-1; H NMR (400 MHz, CDCl3)
δ: 1.04 (d, J = 6.8 Hz, 6H), 2.26 (pentet, J = 6.8 Hz, 2H), 2.28-
2.38 (m, 1H), 2.77 (d, J = 7.2 Hz, 2H), 3.55 (t, J = 6.0 Hz, 2H),
4.32 (t, J = 6.8 Hz, 2H), 6.99 (td, J = 9.2, 2.4 Hz, 1H), 7.24-7.29
(m, 1H), 7.40 (dd, J = 9.2, 2.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ: 22.54, 28.03, 32.23, 36.19, 40.52, 41.39, 105.05 (d, JCF
= 24.0 Hz), 109.27 (d, JCF = 10.0 Hz), 110.13 (d, JCF = 26.0 Hz),
131.18, 143.05 (d, JCF = 12.0 Hz), 155.90, 159.20 (d, JCF = 235.0
Hz); HRMS (APCI) m/z [M+H]+ calcd C14H18ClFN2 269.1221,
found 269.1229.
4.3.27. 1-Chloropropyl-2-isobutyl-6-fluorobenzimidazole (5xb)
As a yellow oil (91.4 mg, 34%); Rf = 0.17 (20% EtOAc/n-
hexane); IR (KBr): νmax 2959, 2928, 1624, 1599, 1481, 1467,
1446, 1407, 1367, 1176, 1135, 959, 830, 809 cm-1; 1H NMR (400
MHz, CDCl3) δ: 1.04 (d, J = 6.8 Hz, 6H), 2.25 (pentet, J = 6.4
Hz, 2H), 2.28-2.38 (m, 1H), 2.76 (d, J = 7.6 Hz, 2H), 3.55 (t, J =
6.4 Hz, 2H), 4.28 (t, J = 7.2 Hz, 2H), 6.98 (td, J = 9.6, 2.4 Hz,
1H), 7.04 (dd, J = 8.8, 2.4 Hz, 1H), 7.64 (dd, J = 8.8, 4.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ: 22.58, 28.02, 32.10, 36.17,
40.59, 41.40, 95.98 (d, JCF = 27.0 Hz), 110.08 (d, JCF = 25.0 Hz),
110.08 (d, JCF = 25.0 Hz), 134.80 (d, JCF = 13.0 Hz), 138.96,
155.06 (d, JCF = 3.0 Hz), 159.33 (d, JCF = 238.0 Hz); HRMS
(APCI) m/z [M+H]+ calcd C14H18ClFN2 269.1221, found
269.1221.
4. (a) Taha, M.; Ismail, N. H.; Imran, S.; Selvaraj, M.; Rashwan, H.;
Farhanah, F. U.; Rahim, F.; Kesavanarayanan, K. S.; Ali, M.
Bioorg. Chem., 2015, 61, 36-44; (b) Paramashivappa, R.; Kumar,
P. P.; Rao, P. V. S.; Rao, A. S. Bioorg. Med. Chem. Lett., 2003,
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McClure, K.; Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.;
Crawford, S.; Pandit, C. R.; Karlsson, L.; Breitenbucher, J. G. J.
Med. Chem., 2005, 48, 1873-1885; (d) Achar, K. C. S.; Hosamani,
K. M.; Seetharamareddy, H. R. Eur. J. Med. Chem., 2010, 45,
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Bhirud, S. B.; Mane, R. B. Eur. J. Med. Chem., 2006, 41, 599-
604; (f) Gardiner, J. M.; Loyns, C. R.; Burke, A.; Khan, A.;
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Patil, A.; Ganguly, S.; Surana, S. Rasayan J. Chem., 2008, 1, 447-
460; (h) Tunçbilek, M.; Kiper, T.; Altanlar, N. Eur. J. Med.
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Bioorg. Med. Chem., 2006, 14, 8271-8279; (j) Ajani, O. O.;
Aderohunmu, D. V.; Olorunshola, S. J.; Ikpo, C. O.; Olanrewaju,
I. O. Orient. J. Chem., 2016, 32, 109-120; (k) Alasmary, F. A. S.;
Snelling, A. M.; Zain, M. E.; Alafeefy, A. M.; Awaad, A. S.;
Karodia, N. Molecules, 2015, 20, 15206-15223; (l) Yoon, Y. K.;
Ali, M. A.; Wei, A. C.; Choon, T. S.; Ismail, R. Eur. J. Med.
Chem., 2015, 93, 614-624; (m) Fuchigami, T.; Yamaguchi, H.;
Ogawa, M.; Biao, L.; Nakayama, M.; Haratake, M.; Magata, Y.
Bioorg. Med. Chem., 2010, 18, 7497-7506.
4.3.28. 2-(2-Furyl)-1-propargylbenzimidazole (5y)
As a yellow solid (164.2 mg, 74%); m.p. 79-81 oC; Rf = 0.28
(20% EtOAc/n-hexane); IR (KBr): νmax 3210, 3009, 2919, 2118,
1608, 1511, 1457, 1389, 1335, 1022, 734 cm-1; H NMR (400
1
MHz, CDCl3) δ: 2.37 (t, J = 1.6 Hz, 1H), 5.27 (d, J = 2.0 Hz,
2H), 6.64 (brt, J = 1.2 Hz, 1H), 7.30-7.40 (m, 3H), 7.51 (d, J =
8.0 Hz, 1H), 7.68 (brs, 1H), 7.82 (d, J = 6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ: 34.54, 73.66, 77.20, 109.78, 112.21,
113.82, 119.64, 123.47, 123.66, 134.65, 141.99, 143.17, 144.42,
144.56; HRMS (APCI) m/z [M+H]+ calcd C14H10N2O 223.0871,
found 223.0871.
4.3.29. 2-(2-Furyl)-1-phenylbenzimidazole (5z)
As a white solid (179.3 mg, 65%); m.p. 131-133 oC; Rf = 0.34
(20% EtOAc/n-hexane); IR (KBr): νmax 3031, 1619, 1514, 1450,
1424, 1227, 1026, 736 cm-1; 1H NMR (400 MHz, CDCl3) δ: 6.56
(dd, J = 3.2, 1.6 Hz, 1H), 7.14 (d, J = 6.8 Hz, 2H), 7.23-7.34 (m,
7H), 7.58 (brs, 1H), 7.84 (d, J = 8.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ: 48.21, 109.92, 111.99, 112.66, 119.81, 122.84,
123.19, 126.16, 127.66, 128.83, 135.68, 136.29, 143.02, 143.98,
144.37, 145.15; HRMS (APCI) m/z [M+H]+ calcd C18H14N2O
275.1184, found 275.1189.
5. (a) Sadig, J. E. R.; Foster, R.; Wakenhut, F.; Willis, M. C. J. Org.
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Acknowledgments
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Shiraishi, Y.; Sugano, Y.; Tanaka, S.; Hirai, T. Angew. Chem. Int.
Financial support was provided by the Research Grant of
Burapha University through National Research Council of
Thailand (Grant nos. 147/2560 and 162/2561) and the Center of
Excellence for Innovation in Chemistry (PERCH-CIC) and