PAPER
2-Substituted 4-Biarylyl-1,3-thiazoles
1037
1H NMR (CDCl3): d = 4.25 (s, 1 H, NH), 6.83–6.88 (m, 1 H), 6.88
(s, 1 H, CH), 7.36–7.44 (m, 4 H), 7.51–7.61 (m, 4 H), 9.73 (d, J =
8.4 Hz, 2 H), 7.9 (d, J = 8.4 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 364 (70) [M+ + 2], 363 (85) [M+ + 1],
362 (85) [M+], 328 (35), 251 (60), 212 (50), 152 (100), 120 (40),
106 (45), 87 (35).
MS (EI, 70 eV): m/z (%) = 277 (100) [M+], 202 (30.1), 178 (15.7),
114 (14.4), 89 (15.3), 77 (37), 63 (36.1), 51 (46.8).
Anal. Calcd for C18H15NS: C, 77.94; H, 5.45; N, 5.05. Found: C,
77.89; H, 5.41; N, 5.20.
Butyl (2E)-3-[4-(2-Methylthiazol-4-yl)phenyl]acrylate (27)
Colorless oil; yield: 90%.
Anal. Calcd for C21H15ClN2S: C, 69.51; H, 4.17; N, 7.72. Found: C,
69.44; H, 4.10; N, 7.90.
1H NMR (CDCl3): d = 0.98 (t, J = 7.5 Hz, 3 H, CH3), 1.27 (m, 2 H,
CH2), 1.71 (m, 2 H, CH2), 2.78 (s, 3 H, CH3), 4.23 (t, J = 6.6 Hz, 2
H, CH2O), 6.47 (d, J = 15.9 Hz, 1 H), 7.38 (s, 1 H, CH), 7.58 (d,
J = 8.1 Hz, 2 H), 7.70 (d, J = 15.9 Hz, 1 H), 7.91 (d, J = 8.4 Hz, 2 H).
N-Phenyl-4-[4-(3-thienyl)phenyl]-1,3-thiazol-2-amine (23)
Yellow crystals; mp 123–124 °C.
IR (KBr): 3369, 3108, 3043, 2923, 1599, 1551, 1464 cm–1.
13C NMR (CDCl3): d = 13.7, 19.2, 30.7, 64.4, 113.3, 118.2, 125.9,
126.5, 126.6, 127.2, 128.5, 134.0, 136.1, 144.0, 167.0.
1H NMR (CDCl3): d = 4.24 (s, 1 H, NH), 6.82 (s, 2 H, CH), 7.1–7.12
(m, 1 H), 7.37–7.4 (m, 6 H), 7.52 (d, J = 8.4 Hz, 2 H), 7.73 (d, J =
8.7 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 301 (M+, 84.9), 245 (100), 228 (58.7),
201 (26.9), 149 (20.2), 115 (64.1), 79 (20.6).
13C NMR (CDCl3) d = 102.2, 118.3, 118.4, 121.8, 123.2, 125.9,
126.1, 127.6, 128.6, 129.4, 131.7, 133.4, 140.1, 150.1, 164.9.
Anal. Calcd for C17H19NO2S: C, 67.74; H, 6.35; N, 4.65. Found: C,
67.69; H, 6.45; N, 4.60.
MS (EI, 70 eV): m/z (%) = 334 (35.5) [M+], 330 (100), 329 (70), 214
(46.4), 182 (30.9), 133 (37.3), 89 (76.4).
Acknowledgment
Anal. Calcd for C19H14N2S2: C, 68.23; H, 4.22; N, 8.38. Found: C,
68.12; H, 4.19; N, 8.51.
The authors are very grateful to Prof. Dr Andreas Kirschning of the
Institute of Organic Chemistry of the University of Hannover for
providing sodium tetrachloropalladate and some arylboronic acids.
K.M.D. is deeply indebted to the Alexander von Humboldt Found-
ation for the donation of a CEM Discover Labmate microwave ap-
paratus.
4-(4¢-Methylbiphenyl-4-yl)-N-phenyl-1,3-thiazol-2-amine (24)
Pale yellow crystals; mp 160–162 °C.
IR (KBr): 3378, 3058, 2924, 1596, 1551, 1494 cm–1.
1H NMR (CDCl3) d = 2.43 (s, 3 H, CH3), 4.26 (s, 1 H, NH), 6.85 (s,
1 H, CH), 7.08–7.11 (m, 1 H), 7.36–7.39 (m, 4 H), 7.55 (d, J = 8.4
Hz, 2 H), 7.63 (d, J = 8.1 Hz, 2 H), 7.72 (d, J = 8.4 Hz, 2 H), 7.91
(d, J = 8.1 Hz, 2 H).
13C NMR (CDCl3) d = 21.1, 101.5, 118.4, 123.1, 126.5, 126.7,
127.0, 127.6, 129.4, 129.5, 131.7, 137.1, 140.2, 140.7, 150.7, 164.7.
References
(1) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419.
(2) (a) Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org.
Lett. 2004, 6, 221. (b) Yang, D.; Chen, Y. C.; Zhu, N. Y.
Org. Lett. 2004, 6, 1577. (c) Li, J. H.; Liu, W. J. Org. Lett.
2004, 6, 2809. (d) Colacot, T. J.; Shea, H. A. Org. Lett.
2004, 6, 3731.
(3) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem.
Soc. 1998, 120, 9722. (b) Wolfe, J. P.; Singer, R. A.; Yang,
B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9550.
(c) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000,
122, 4020. (d) Mori, K.; Yamaguchi, K.; Hara, T.;
Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc.
2002, 124, 11572. (e) Yin, J.; Rainka, M. P.; Zhang, X. X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162.
(4) (a) Bedford, R. B.; Cazin, C. S. J.; Hazelwood, S. L. Angew.
Chem. Int. Ed. 2002, 41, 4120. (b) Littke, A. F.; Fu, G. C.
Angew. Chem. Int. Ed. 2002, 41, 4176. (c) Zhang, W.; Shi,
M. Tetrahedron Lett. 2004, 45, 8921.
(5) Alonso, F.; Beletskaya, I. P.; Pages, M. Y. Tetrahedron
2005, 61, 11771.
(6) (a) Larhed, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res.
2002, 35, 717. (b) Desai, B.; Kappe, C. O. Top. Curr. Chem.
2004, 242, 177. (c) Kappe, C. O. Angew. Chem. Int. Ed.
2004, 43, 6250. (d) Hoz, A.; Ortiz, A. D.; Moreno, A. Chem.
Soc. Rev. 2005, 34, 164.
(7) (a) Mingos, D. M. P.; Baghurst, D. R. Chem. Soc. Rev. 1991,
20, 1. (b) Strauss, C. R.; Trainor, R. W. Aust. J. Chem. 1995,
48, 1665. (c) Gabriel, C.; Gabriel, S.; Grant, E. H.; Halstead,
B. S.; Mingos, D. M. P. Chem. Soc. Rev. 1998, 27, 213.
(d) Elander, N.; Jones, J. R.; Lu, S. Y.; Stone-Elander, S.
Chem. Soc. Rev. 2000, 29, 239. (e) Lidström, P.; Tierney, J.;
Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225.
(f) Larhed, M.; Hallberg, A. Drug Discovery Today 2001, 6,
406.
MS (EI, 70 eV): m/z (%) = 342 (54.5) [M+], 206 (30.3), 163 (36.4),
119 (63.6), 89 (42.4), 77 (100), 51 (57.6).
Anal. Calcd for C22H18N2S: C, 77.16; H, 5.30; N, 8.18. Found: C,
77.02; H, 5.39; N, 8.37.
Mizoroki–Heck Cross-Coupling Reactions of 4-(4-Bromophe-
nyl)-2-methyl-1,3-thiazole (5) with Alkenes in Water under
Microwave Heating
Thiazole 5 (1 mmol) and styrene or butyl acrylate (1.5 mmol) were
mixed with TBAB (0.6 mmol), Pd(II) complex 4 (5.5 mg, 1.5
mol%), and KOH (112 mg, 2 mmol) in H2O (3 mL) in a process vial.
The vial was securely capped and the mixture was heated by micro-
wave irradiation at 160 °C and 250 W for 30 min. When the reaction
was almost complete (TLC), the mixture was allowed to cool to r.t..
The mixture was then extracted with EtOAc (3 × 20 mL) and the
combined extracts were dried (MgSO4), filtered, and concentrated
under reduced pressure. The residue was then subjected to column
chromatography (PE–EtOAc. 10:1) to give the corresponding pure
products 26 and 27.
2-Methyl-4-{4-[(E)-2-phenylvinyl]phenyl}-1,3-thiazole
Colorless crystals; yield: 88%; mp 158–160 °C.
IR (KBr): 3111, 3055, 3023, 2921, 1594, 1497 cm–1.
1H NMR (CDCl3): d = 2.79 (s, 3 H, CH3), 7.13–7.16 (m, 2 H), 7.30
(d, J = 16.8 Hz, 1 H), 7.33–7.40 (m, 3 H), 7.53–7.59 (m, 4 H), 7.89
(d, J = 7.8 Hz, 2 H).
13C NMR (CDCl3): d = 19.3, 112.2, 126.5, 126.6, 126.8, 127.6,
128.2, 128.7, 128.8, 133.7, 136.9, 137.3, 154.8, 165.8.
Synthesis 2010, No. 6, 1030–1038 © Thieme Stuttgart · New York