K. M. Khan et al. / Bioorg. Med. Chem. 19 (2011) 4286–4294
4293
6H, 2xCH3); MS: m/z (rel. abund.%), 254 (M+, 100), 210 (15), 127
(25), 108 (11).
4.1.24. 2-(2-Thienyl)-1,3-benzothiazole (24)
1H NMR: (500 MHz, CD3OD): d 8.18 (m, 1H, H-40), 7.97 (d, 2H,
J4,5/7,6 = 9.0 Hz, H-4/7), 7.72 (dd, 1H, J3 ,5 = 1.5, J3 ,4 = 6.5 Hz, H-30),
0
0
0
0
7.60 (dd, 1H, J5 ,3 = 2.0, J5 ,4 = 6.5 Hz, H-50), 7.51 (dt, 1H, J5,7 = 1.0,
J5(6,4) = 7.5 Hz, H-5), 7.51 (t, 1H, J6(5,7) = 7.5 Hz, H-6); MS: m/z (rel.
abund.%), 216 (M+, 100), 108 (45), 81 (33), 69 (77).
0
0
0
0
4.1.15. 2-(4-Methylphenyl)-1,3-benzothiazole (15)
1H NMR: (500 MHz, CD3OD): d 7.99 (m, 2H, H-4/7), 7.97 (d, 2H,
J2 ,3 /6 ,5 = 8.0 Hz, H-20/60), 7.51 (dt, 1H, J5,7 = 1.0, J5(6,4) = 7.0 Hz, H-
5), 7.41 (dt, 1H, J6,4 = 1.0, J6(7,5) = 7.0 Hz, H-6), 6.90 (d, 2H,
0
0
0
0
J3 ,2 /5 ,6 = 8.0 Hz, H-30/50), 2.42 (s, 3H, CH3); MS: m/z (rel. abund.%),
4.1.25. 2-(4-Chlorophenyl)-1,3-benzothiazole (25)
0
0
0
0
225 (M+, 100), 108 (23), 82 (14), 69 (37).
1H NMR: (500 MHz, CD3OD): d 8.09 (d, 2H, J3 ,2 /5 ,6 = 8.5 Hz, H-
30/50), 8.02 (d, 1H, J4,5 = 7.5 Hz, H-4), 7.93 (d, 1H, J7,6 = 7.5 Hz, H-7),
0
0
0
0
7.55 (d, 2H, J2 ,3 /6 ,5 = 8.5 Hz, H-20/60), 7.53 (m, 1H, H-5), 7.43 (dt,
1H, J6,4 = 1.0, J6(7,5) = 7.5 Hz, H-6); MS: m/z (rel. abund.%), 244 (M+,
64), 210 (8), 108 (65), 69 (100).
0
0
0
0
4.1.16. 2-(1,3-Benzothiazol-2-yl)phenol (16)
1H NMR: (500 MHz, CD3OD): d 8.02 (br d, 1H, J4,5 = 4.5 Hz, H-4),
0
0
8.00 (dd, 1H, J7,5 = 1.0, J7,6 = 5.0 Hz, H-7), 7.84 (dd, 1H, J6 ,4 = 1.5,
J6 ,5 = 8.0 Hz, H-60), 7.55 (dt, 1H, J5’,3’ = 1.0, J5’(4’,6’) = 8.0 Hz, H-50),
7.46 (td, 1H, J4’,6’ = 1.0, J4’(3’,5’) = 8.0 Hz, H-40), 7.40 (td, 1H,
0
0
4.1.26. 2-(3,4-Dichlorophenyl)-1,3-benzothiazole (26)
J5,7 = 1.0, J5(6,4) = 7.5 Hz, H-5), 7.04 (dd, 1H, J3 ,5 = 1.0, J3 ,4 = 8.0 Hz,
H-30), 7.00 (td, 1H, J6,4, = 1.0, J6(5,7) = 7.0 Hz, H-6); MS: m/z (rel.
abund.%), 227 (M+, 90), 199 (100), 108 (37), 69 (99).
1H NMR: (500 MHz, CD3OD): d 8.27 (d, 1H, J2 ,6 = 2.5 Hz, H-20),
0
0
0
0
0
0
8.05 (m, 3H, 4/7 60), 7.70 (d, 1H, J5 ,6 = 8.5 Hz, H-50), 7.55 (dt, 1H,
J5,7 = 1.0, J5(4,6) = 7.0 Hz, H-5), 7.45 (dt, 1H, J6,4 = 1.0, J6(5,7) = 7.0 Hz,
H-6); MS: m/z (rel. abund.%), 279 (M+, 98), 244 (22), 108 (77), 82
(41).
0
0
4.1.17. 2-(3-Chlorophenyl)-1,3-benzothiazole (17)
1H NMR: (500 MHz, CD3OD): d 8.1 (t, 1H, J2 (4 ,6 ) = 2.0 Hz, H-20),
7.99 (m, 3H, H-4/7/40), 7.53 (m, 3H, H-5/50/60), 7.45 (dt, 1H,
J6,4 = 1.5, J6(7,5) = 7.5 Hz, H-6); MS: m/z (rel. abund.%), 245 (M+,
100), 210 (11), 108 (69), 82 (29).
0
0
0
References and notes
1. (a) Carroll, A. R.; Schuer, P. J. J. Org. Chem. 1990, 55, 4426; (b) Gunwardana, G. P.;
Kohmoto, S.; Gunasekera, S. P.; McConnell, O. J.; Koehn, F. E. J. Am. Chem. Soc.
1988, 110, 4856.
2. Hutchinson, I.; Bradshaw, T. D.; Matthews, C. S.; Stevens, M. F. G.; Westwell, A.
D. Bioorg. Med. Chem. Lett. 2003, 13, 471.
3. Hutchinson, I.; Jennings, S. A.; Vishnuvajjala, B. R.; Westwell, A. D.; Stevens, M.
F. G. J. Med. Chem. 2002, 45, 744.
4. Lin, P. Y.; Shi, S. J.; Shu, H. L.; Chen, H. F.; Lin, C. C.; Liu, P. C.; Wang, L. F. Bioorg.
Chem. 2000, 28, 266.
4.1.18. 5-(1,3-Benzothiazol-2-yl)-1,2,4-benzenetriol (18)
Mp 194–196 °C, 1H NMR: (500 MHz, CD3OD): d 7.94 (d, 1H,
J4,5 = 8.0 Hz, H-4), 7.89 (d, 1H, J7,6 = 8.0 Hz, H-7), 7.49 (dt, 1H,
J5,7 = 1.0, J5(4,6) = 8.0 Hz, H-5), 7.38 (td, 1H, J6,4 = 1.0, J6(5,7) = 8.0 Hz,
H-6), 7.14 (s, 1H, H-60), 6.44 (s, 1H, H-30); MS: m/z (rel. abund.%),
259 (M+, 100), 185 (14), 108 (14), 69 (31).
5. Hall, I. H.; Peaty, N. J.; Henry, J. R.; Easmon, J.; Heinisch, G.; Pürstinger, G. Arch.
Pharm. Pharm. Med. Chem. 1999, 332, 115.
6. Beneteau, V.; Besson, T.; Guillard, J.; Leonce, S.; Pfeiffer, B. Eur. J. Med. Chem.
1999, 34, 1053.
7. Bradshaw, T. D.; Wrigley, S.; Shi, D. F.; Schultz, R. J.; Paull, K. D.; Stevens, M. F. G.
Br. J. Cancer 1998, 77, 745.
4.1.19. 2-(3-Pyridinyl)-1,3-benzothiazole (19)
1H NMR: (300 MHz, CD3OD): d 9.27 (d, 1H, J2 ,6 = 3.5 Hz, H-20),
0
0
8.76 (dd, 1H, J6 ,4 = 2.5, J6 ,5 = 8.0 Hz, H-60), 8.47 (td, 1H,
0
0
0
0
8. Tanaka, T.; Umekawa, H.; Saitoh, M.; Ishikawa, T.; Shin, T.; Ito, M.; Itoh, H.;
Kawamatsu, Y.; Sugihara, H.; Hidaka, H. Mol. Pharmacol. 1986, 29, 264.
9. Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J. C.; Boireau, A.; Bour, Y.;
Coléno, M. A.; Doble, A.; Doerflinger, G.; Hu, C. D.; Donat, M. H.; Duchesne, J. M.;
Ganil, P.; Guérémy, C.; Honoré, E.; Just, B.; Kerphirique, R.; Gontier, S.; Hubert,
P.; Laduron, P. M.; Le Blevec, J.; Meunier, M.; Miquet, J. M.; Nemecek, C.;
Pasquet, M.; Piot, O.; Pratt, J.; Rataud, J.; Reibaud, M.; Stutzmann, J. M.;
Mignani, S. J. Med. Chem. 1999, 42, 2828.
10. Benavides, J.; Camelin, J. C.; Mitrani, N.; Flamand, F.; Uzan, A.; Legrand, J. J.;
Guérémy, C.; Le Fur, G. Neuropharmacology 1985, 24, 1085.
11. Mizoule, J.; Meldrum, B.; Mazadier, M.; Croucher, M.; Ollat, C.; Uzan, A.;
Legrand, J. J.; Gueremy, C.; Le Fur, G. Neuropharmacology 1985, 24, 767.
12. Malgouris, C.; Bardot, F.; Daniel, M.; Pellis, J.; Rataud, A.; Uzan, A.; Blanchard, J.
C.; Laduron, P. M. J. Neurosci. 1989, 9, 3720.
J4 (6 ,2 ) = 3.5, J4 ,5 = 6.0 Hz, H-40), 8.19 (d, 1H, J4,5 = 8.7 Hz, H-4),
8.12 (d, 1H, J7,6 = 8.7 Hz, H-7), 7.63 (m, 3H, H-50,5,6); MS: m/z
(rel. abund.%), 212 (M+, 100), 186 (22), 108 (19), 69 (46).
0
0
0
0
0
4.1.20. 2-(4-Pyridinyl)-1,3-benzothiazole (20)
Mp 138–140 °C, 1H NMR: (300 MHz, CD3OD): d 8.79 (m, 2H, H-
20/60), 8.24 (br d, 1H, J4,5 = 7.5 Hz, H-4), 8.15 (br d, 1H, J7,6 = 7.2 Hz,
H-7), 8.02 (m, 2H, H-30/50), 7.63 (dt, 1H, J5,7 = 1.2, J5(4,6) = 7.2 Hz,
H-5), 7.58 (dt, 1H, J6,4 = 1.2, J6(5,7) = 7.2 Hz, H-6); MS: m/z (rel.
abund.%), 212 (M+, 100), 186 (13), 108 (25), 69 (40).
13. Pratt, J.; Rataud, J.; Bardot, F.; Roux, M.; Blanchard, J. C.; Laduron, P. M.;
Stutzmann, J. M. Neurosci. Lett. 1992, 140, 225.
14. Yamazaki, K.; Kaneko, Y.; Suwa, K.; Ebara, S.; Nakazawa, K.; Yasuno, K. Bioorg.
Med. Chem. 2005, 13, 2509.
15. Brantley, E.; Antony, S.; Kohlhagen, G.; Meng, L. H.; Agama, K.; Stinson, S. F.;
Sausville, E. A.; Pommier, Y. Cancer Chemother. Pharmacol. 2006, 58, 62.
16. Lion, C. J.; Matthews, C. S.; Wells, G.; Bradshaw, T. D.; Stevens, M. F. G.;
Westwell, A. D. Bioorg. Med. Chem. Lett. 2006, 16, 5005.
4.1.21. 2-(4-Bromophenyl)-1,3-benzothiazole (21)
1H NMR: (500 MHz, CD3OD): d 8.02 (m, 2H, H-4/7), 7.99 (d, 2H,
J3 ,2 /5 ,6 = 9.0 Hz, H-30/50), 7.70 (d, 2H, J2 ,3 /6 ,5 = 9.0 Hz, H-20/60),
7.53 (dt, 1H, J5,7 = 1.0 Hz, J5(6,4) = 8.0 Hz, H-5), 7.43 (dt, 1H,
J6,4 = 1.0, J6(7,5) = 8.0 Hz, H-6); MS: m/z (rel. abund.%), 291 (M+,
79), 289 (100), 210 (33), 108 (63).
0
0
0
0
0
0
0
0
17. Huang, S.-T.; Hsei, I. J.; Chena, C. Bioorg. Med. Chem. 2006, 14, 6106.
18. Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.; Oda, Y.; Tanzawa, F.;
Iwasaki, S.; Koyama, K.; Furukawa, H.; Kurakata, S.; Sugano, Y. Bioorg. Med.
Chem. Lett. 2005, 15, 3328.
19. Das, J.; Moquin, R. V.; Lin, J.; Liu, C.; Doweyko, A. M.; DeFex, H. F.; Fang, Q.;
Pang, S.; Pitt, S.; Shen, D. R.; Schieven, G. L.; Barrish, J. C.; Wityak, J. Bioorg. Med.
Chem. Lett. 2003, 13, 2587.
20. O’Brien, S. E.; Browne, H. L.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G.;
Laughton, C. A. Org. Biomol. Chem. 2003, 1, 493.
21. Goldfarb, R. H.; Kitson, R. P.; Brunson, K. W.; Yoshino, K.; Hirota, N.; Kirii, Y.;
Kotera, Y.; Inoue, Y.; Ohashi, M. Anticancer Res. 1999, 19, 1663.
22. Grandolini, G.; Ambrogi, V.; Rossi, C.; Tiralti, M. C.; Tuttobello, L. Eur. J. Med.
Chem. 1990, 25, 403.
4.1.22. 2-(4-Ethoxyphenyl)-1,3-benzothiazole (22)
1H NMR: (500 MHz, CD3OD): d 8.00 (m, 2H, H-4/7), 7.95 (d, 2H,
J3 ,2 /5 ,6 = 9.0 Hz, H-30/50), 7.49 (dt, 1H, J5,7 = 1.0 Hz, J5(6,4) = 7.0 Hz,
H-5), 7.38 (dt, 1H, J6,4 = 1.0, J6(7,5) = 7.0 Hz, H-6), 7.95 (d, 2H,
0
0
0
0
J2 ,3 /6 ,5 = 9.0 Hz, H-20/60), 3.01 (q, 2H, J = 7.0 Hz, OCH2), 3.01 (t,
3H, J = 7.0 Hz, CH3); MS: m/z (rel. abund.%), 255 (M+, 68), 227
(100), 198 (25), 108 (28).
0
0
0
0
4.1.23. 2-(2-Fluorophenyl)-1,3-benzothiazole (23)
1H NMR: (400 MHz, CD3OD):
d 8.40 (dt, 1H, J5,7 = 1.6,
23. Chua, M. S.; Shi, D. F.; Wrigley, S.; Bradshaw, T. D.; Hutchinson, I.; Nicholas, P.;
Barret, D. A.; Stanley, L. A.; Stevens, M. F. G. J. Med. Chem. 1999, 42, 381.
24. Hutchinson, I.; Jennings, S. A.; Vishnuvajjala, B. R.; Wetsell, A. D.; Stevens, M. F.
G. J. Med. Chem. 2002, 45, 744.
J5(6,4) = 8.0 Hz, H-5), 8.11 (d, 1H, J4,5 = 8.0 Hz, H-4), 7.93 (d, 1H,
J7,6 = 8.0 Hz, H-7), 7.43 (m, 3H, H-6/30/60), 7.24 (m, 2H, H-40/50);
MS: m/z (rel. abund.%), 229 (M+, 100), 108 (71), 69 (62).
25. Burger, A.; Sawhey, S. N. J. Med. Chem. 1968, 11, 270.
26. Palmer, F. J.; Trigg, R. B.; Warrington, J. V. J. Med. Chem. 1971, 14, 248.