Med Chem Res
General procedure for synthesis of 4′-methyl-2′,4-diphenyl-
2,5′-bithiazole (5a)
129.1 (CH, C-2′, C-6′), 130.2 (C, C-1′), 130.5 (CH, C-4′),
133.2 (C, C-1′), 152.2 (C, thiazole C-4), 154.9 (C, thiazole
C-4′), 158.8 (C, thiazole C-2), 162.8 (C, C-4), 166.9 (C,
thiazole C-2′); LC-MS m/z: 353.0 (M + H)+.
In the mixture of 4-methyl-2-phenylthiazol-5-carbothiomide
(0.85 mmol) in 8 mL ethanol, 2-bromo-1-phenylethanone
(0.71 mmol) was added and reaction mixture was reflux for
2 h. After completion of reaction (TLC) the product was
filtered and washed with ethanol.
4′-Methyl-2′-phenyl-4-(p-tolyl)-2,5′-bithiazole (5e) Yield
68 %, m.p. 96–98 °C; 1H NMR (500 MHz, CDCl3) δ: 2.41,
(s, 3H, Ar–CH3), 2.80 (s, 3H, thiazole-CH3), 7.26 (d, J =
9.0 Hz, 2H, Ar–H), 7.47–7.49 (m, 3H, Ar–H), 7.52 (s, 1H,
thiazole-H), 7.86 (d, J = 9.0 Hz, 2H, Ar–H), 7.99–8.01 (m,
2H, Ar–H); 13C NMR (125 MHz, CDCl3) δ: 17.7 (CH3,
thiazole-CH3), 21.5 (CH3, ArCH3), 112.6 (CH, thiazole C-
4), 126.6 (CH, C-2, C-6), 126.8 (C, thiazole C-5′), 128.5
(CH, C-3′, C-5′), 128.8 (CH, C-3, C-5), 129.5 (CH, C-4′),
129.8 (CH, C-2′, C-6′), 130.6 (C, C-1), 134.0 (CH, C-1′),
140.7 (C, C-4), 152.0 (C, thiazole C-4), 155.6 (C, thiazole
C-4′), 158.8 (C, thiazole C-2), 167.1 (C, thiazole C-2′); LC-
MS m/z: 349.1 (M + H)+.
2′-(4-Fluorophenyl)-4′-methyl-4-phenyl-2,5′-bithiazole
(5f) Yield 60%, m.p. 58–60 °C; 1H NMR (200 MHz,
CDCl3) δ: 2.82 (s, 3H, thiazole-CH3), 7.15 (t, J = 9.0 Hz,
2H, Ar–H), 7.47–7.49 (m, 3H, Ar–H), 7.51 (s, 1H, thia-
zole), 7.88–7.90 (m, 2H, Ar–H), 7.99–8.02 (m, 2H, Ar–H);
13C NMR (50 MHz, CDCl3) δ: 17.7 (CH3, thiazole-CH3),
112.2 (CH, thiazole C-4), 115.7 (CH, C-3′, C-5′), 126.6 (C,
thiazole C-5′), 127.1 (CH, C-3, C-5), 128.3 (CH, C-2′, C-
6′), 129.1 (CH, C-2, C-6), 130.0 (C, C-1′), 130.5 (CH, C-4),
133.2 (C, C-1), 152.1 (C, thiazole C-4), 154.8 (C, thiazole
C-4′), 159.8 (C, thiazole C-2), 162.9 (C, C-4′), 166.9 (C,
thiazole C-2′); LC-MS m/z: 353.0 (M + H)+.
4′-Methyl-2′,4-diphenyl-2,5′-bithiazole (5a) Yield 70%,
1
m.p. 112–114 °C; H NMR (500 MHz, CDCl3) δ: 2.82 (s,
3H, thiazole-CH3), 7.47–7.49 (m, 3H, Ar–H), 7.51 (s, 1H,
thiazole-H), 7.54–7.55 (m, 3H, Ar–H), 7.85–7.87 (m, 2H,
Ar–H), 7.99–8.01 (m, 2H, Ar–H); 13C NMR (125 MHz,
CDCl3) δ: 17.2 (CH3, thiazole-CH3), 113.1 (CH, thiazole C-
4), 126.6 (CH, C-2, C-6), 127.2 (CH, C-4), 128.2 (CH, C-3′,
C-5′), 129.4 (CH, C-3, C-5), 130.5 (CH, C-4′), 131.4 (CH,
C-2′, C-6′), 131.9 (C, C-1), 133.0 (C, C-1′), 152.0 (C,
thiazole C-4), 154.6 (C, thiazole C-4′), 158.5 (C, thiazole C-
2), 166.7 (C, thiazole C-2′); LC-MS m/z: 335.1 (M + H)+.
4-(4-Bromophenyl)-4′-methyl-2′-phenyl-2,5′-bithiazole
1
(5b) Yield 60%, m.p. 152–154 °C; H NMR (500 MHz,
CDCl3) δ: 2.82 (s, 3H, thiazole-CH3), 7.47–7.49 (m, 3H,
Ar–H), 7.51 (s, 1H, thiazole-H), 7.58 (d, J = 8.6 Hz, 2H,
Ar–H), 7.85 (d, J = 8.6 Hz, 2H, Ar–H), 7.99–8.01 (m, 2H,
Ar–H); 13C NMR (125 MHz, CDCl3) δ: 17.7 (CH3,
thiazole-CH3), 112.9 (CH, thiazole C-4), 122.5 (C, C-4),
126.6 (CH, C-2, C-6), 127.0 (C, thiazole C-5′), 128.1 (CH,
C-3′, C-5′), 129.0 (CH, C-2′, C-6′), 130.5 (CH, C-4′), 131.9
(CH, C-3, C-5), 132.8 (C, C-1), 133.2 (C, C-1′), 152.1 (C,
thiazole C-4), 154.6 (C, thiazole C-4′), 158.8 (C, thiazole C-
2), 166.8 (C, thiazole C-2′); LC-MS m/z: 413.1 (M + H)+,
m/z: 415.1 (M + H + 2)+.
4-(4-Chlorophenyl)-4′-methyl-2′-phenyl-2,5′-bithiazole
(5c) Yield 65%; m.p. 158–160 °C; 1H NMR (400 MHz,
CDCl3) δ: 2.83 (s, 3H, thiazole-CH3), 7.44 (d, J = 8.6 Hz,
2H, Ar–H), 7.47–7.49 (m, 3H, Ar–H), 7.52 (s, 1H, thiazole-
H), 7.93 (d, J = 8.6 Hz, 2H, Ar–H), 8.00–8.02 (m, 2H,
Ar–H); 13C NMR (100 MHz, CDCl3) δ: 17.7 (CH3,
thiazole-CH3), 112.8 (CH, thiazole C-4), 126.6 (CH, C-2,
C-6), 126.9 (C, thiazole C-5′), 127.8 (CH, C-3′, C-5′), 129.0
(CH, C-3, C-5), 129.1 (CH, C-2′, C-6′), 130.5 (CH, C-4′),
132.5 (C, C-1), 133.2 (C, C-1′), 134.2 (C, C-4), 152.2 (C,
thiazole C-4), 154.7 (C, thiazole C-4′), 158.8 (C, thiazole C-
2), 166.9 (C, thiazole C-2′); LC-MS m/z: 369.0 (M + H)+,
m/z: 371.0 (M + H + 2)+.
4-(4-Chlorophenyl)-2′-(4-fluorophenyl)-4′-methyl-2,5′-
1
bithiazole (5g) Yield 70%, m.p. 78–80 °C; H NMR (500
MHz, CDCl3) δ: 2.82 (s, 3H, thiazole-CH3), 7.16 (t, J = 9.0
Hz, 2H, Ar–H), 7.42 (d, J = 8.6 Hz, 2H, Ar–H), 7.50 (s, 1H,
thiazole-H), 7.90 (d, J = 8.6 Hz, 2H, Ar–H), 7.98–8.01 (m,
2H, Ar–H); 13C NMR (125 MHz, CDCl3) δ: 17.7 (CH3,
thiazole-CH3), 112.6 (CH, thiazole C-4), 115.9 (CH, C-3′,
C-5′), 126.6 (C, thiazole C-5′), 127.1 (CH, C-2, C-6), 128.3
(CH, C-2′, C-6′), 129.3 (CH, C-3, C-5), 130.5 (C, C-1′),
133.2 (C, C-1), 134.2 (C, C-4), 152.0 (C, thiazole C-4),
155.0 (C, thiazole C-4′), 158.7 (C, thiazole C-2), 162.8 (C,
C-4′), 166.9 (C, thiazole C-2′); LC-MS m/z: 387.0 (M +
H)+, m/z: 389.0 (M + H + 2)+.
4-(4-Fluorophenyl)-2′-(4-fluorophenyl)-4′-methyl-2,5′-
1
bithiazole (5h) Yield 66%, m.p. 80–82 °C; H NMR (500
MHz, CDCl3) δ: 2.82 (s, 3H, thiazole-CH3), 7.16 (t, J = 9.0
Hz, 2H, Ar–H), 7.50 (s, 1H, thiazole-H), 7.54 (d, J = 8.6
Hz, 2H, Ar–H), 7.84 (d, J = 8.6 Hz, 2H, Ar–H), 7.98–8.01
(m, 2H, Ar–H); 13C NMR (125 MHz, CDCl3) δ: 17.7 (CH3,
thiazole-CH3), 112.8 (CH, thiazole C-4), 115.8 (CH, C-3′,
C-5′), 122.9 (C, C-4), 126.7 (C, thiazole C-5′), 127.2 (CH,
C-2, C-6), 128.3 (CH, C-2′, C-6′), 130.4 (C, C-1′), 132.7 (C,
C-1), 133.2 (CH, C-3, C-5), 152.1 (C, thiazole C-4), 154.7
(C, thiazole C-4′), 158.8 (C, thiazole C-2), 162.8 (C, C-4′),
4-(4-Fluorophenyl)-4′-methyl-2′-phenyl-2,5′-bithiazole
(5d) Yield 65%, m.p. 40–42 °C; 1H NMR (500 MHz,
CDCl3) δ: 2.84 (s, 3H, thiazole-CH3), 7.16 (t, J = 9.0 Hz,
2H, Ar–H), 7.47–7.49 (m, 3H, Ar–H), 7.50 (s, 1H, thiazole-
H), 7.96–7.99 (m, 2H, Ar–H), 8.00–8.02 (m, 2H, Ar–H);
13C NMR (125 MHz, CDCl3) δ: 17.8 (CH3, thiazole-CH3),
112.3 (CH, thiazole C-4), 115.7 (CH, C-3, C-5), 126.6 (CH,
C-3′, C-5′), 127.1 (C, thiazole C-5′), 128.3 (CH, C-2, C-6),