PAPER
Synthesis and Characterization of 4-Hydroxy-1,3-thiazoles
1607
1H NMR (250 MHz, DMSO-d6): d = 11.64 (s, 1 H, OH), 9.08 (s,
1 H), 8.66 (d, J = 4.5 Hz, 1 H), 8.31–8.21 (m, 1 H), 7.72 (d,
J = 8.0 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2 H, PhH), 7.55–7.54 (m,
1 H).
13C NMR (62.5 MHz, DMSO-d6): d = 162.8, 159.6, 157.6, 151.3,
146.6, 133.1, 132.2, 131.4, 129.3, 128.4, 124.7, 119.6, 108.2.
the crude product was filtered off. Recrystallation from EtOH/
CHCl3 gave the pure product.
Yield: 93%; light-yellow crystals; mp 39.8 °C.
IR (ATR): 2916, 2097, 1662, 1533, 1439, 1385, 1258, 1087, 1071,
783, 759, 657 cm–1.
1H NMR (250 MHz, CDCl3): d = 8.60 (d, J = 4.5 Hz, 1 H), 8.13 (d,
J = 7.9 Hz, 1 H), 7.83–7.75 (m, 3 H), 7.42–7.23 (m, 4 H), 4.64 (t,
J = 6.0 Hz, 2 H, CH2CH2CH2Cl), 3.57 (t, J = 6.8 Hz, 2 H,
CH2CH2CH2Cl), 2.19 (m, 2 H, CH2CH2CH2Cl).
13C NMR (62.5 MHz, CDCl3): d = 160.9, 158.4, 151.2, 149.5,
137.8, 131.5, 128.7, 127.3, 126.8, 119.2, 115.1, 67.3, 62.3, 43.2,
32.8.
MS (EI): m/z (%) = 334/332 (53/49) [M+], 201/199 (47/45), 120
(52), 105 (100), 77 (24).
Anal. Calcd for C14H9BrN2OS: C, 50.46; H, 2.72; N, 8.41; Br,
23.98; S, 9.62. Found: C, 50.3; H, 2.62; N, 8.38; Br, 23.69; S, 9.49.
5-(4-Methoxyphenyl)-2-(pyrazin-2-yl)-1,3-thiazol-4-ol (1j)
Yield: 55%; yellow crystals; mp 290 °C.
1H NMR (400 MHz, DMSO-d6): d = 11.57 (s, 1 H, OH), 9.16 (s,
1 H), 8.69–8.66 (m, 2 H), 7.73 (d, J = 8.6 Hz, 2 H), 7.01 (d,
J = 8.6 Hz, 2 H), 4.14 (s, 3 H, CH3).
MS (EI): m/z (%) = 337/338 (95/23), 254 (25), 121 (100), 105 (59).
MS (micro-ESI): m/z (%) = 360 (100) [M + Na+], 338 (18) [M +
H+], 299 (7).
13C NMR (62.5 MHz, DMSO-d6): d = 158.7, 158.6, 156.6, 146.2,
145.6, 144.9, 140.1, 128.2, 124.3, 114.9, 112.6, 55.7.
HRMS (ESI): m/z calcd for C17H15N5NaOS: 360.0895; found:
360.0908.
MS (EI): m/z (%) = 285 (38) [M+], 139 (100), 106 (46), 79 (36).
1,3,5-Tris{[5-phenyl-2-(pyridine-2-yl)thiazol-4-yloxy]meth-
yl}benzene (7)
Yield (44%); light-yellow crystals; mp 168 °C.
Anal. Calcd for C14H11N3O2S: C, 58.93; H, 3.89; N, 14.73; S, 11.24.
Found: C, 58.71; H, 3.84; N, 14.51; S, 11.01.
1H NMR (400 MHz, DMSO-d6): d = 8.58 (d, J = 4.3 Hz, 3 H), 8.08
(d, J = 7.9 Hz, 3 H), 7.79 (d, J = 7.3 Hz, 6 H), 7.78–7.66 (m, 6 H),
7.33–7.16 (m, 12 H), 5.63 (s, 6 H, CH2).
13C NMR (62.5 MHz, DMSO-d6): d = 160.6, 158.7, 151.2, 149.4,
138.1, 136.8, 131.5, 128.7, 127.0, 126.9, 126.8, 124.1, 118.9, 115.2,
71.9.
Synthesis of 4-Alkoxythiazoles 6a and 6c by the Williamson Re-
action; General Procedure
The corresponding thiazole (0.01 mol) was dissolved in DMSO (20
mL) under an argon atmosphere. Upon addition of a solution of aq
KOH (10 M, 0.64 g, 0.01 mol) the colour of the mixture turned to
deep red. Then, the appropriate halide (0.01 mol) was added to the
stirred solution over 5 min. The reaction was monitored by TLC
(CH2Cl2) and, after completion, H2O (40 mL) was added. The crude
product was filtered off and recrystallised from EtOH/CHCl3.
MS (EI): m/z (%) = 876/877 (42/22), 624 (42), 237 (100), 221 (32).
Anal. Calcd for C51H36N6O3S3: C, 69.84; H, 4.14; N, 9.58; S, 10.97.
Found: C, 69.55; H, 4.06; N, 9.40; S, 10.75.
2-[4-(3-Chloropropoxy)-5-phenyl-1,3-thiazol-2-yl]pyridine (6a)
Yield: 63%; yellow crystals; mp 56 °C.
1-[4-(4-Hydroxy-5-methyl-1,3-thiazol-2-yl)phenyl]butane-1,3-
dione (9)
The synthesis followed the general procedure for the alkylation re-
action using 5-phenyl-2-(pyridin-2-yl)-1,3-thiazol-4-ol4 and 1,3,5-
tris(bromomethyl)benzene in a ratio of 1:3.
1H NMR (250 MHz, CDCl3): d = 8.59 (d, J = 4.4 Hz, 1 H), 8.12 (d,
J = 8.2 Hz, 1 H), 7.88–7.72 (m, 3 H), 7.47–7.22 (m, 4 H), 4.71 (t,
J = 5.9 Hz, 2 H, CH2CH2CH2Cl), 3.81 (t, J = 6.4 Hz, 2 H,
CH2CH2CH2Cl), 2.37 (m, 2 H, CH2CH2CH2Cl).
13C NMR (62.5 MHz, CDCl3): d = 160.6, 158.7, 151.1, 149.4,
137.8, 131.6, 128.9, 127.6, 126.9, 118.9, 114.8, 67.0, 62.8, 41.7,
32.3.
Yield: 41%; off-white crystals; mp 236 °C.
1H NMR (250 MHz, DMSO-d6): d = 10.49 (br s, 1 H, OH), 9.01–
7.98 (m, 2 H), 7.9–7.87 (m, 2 H), 6.55 [s, 1 H, CH=C(OH)CH3],
4.28 [s, 1 H, CH=C(OH)CH3], 2.23 (m, 6 H).
13C NMR (62.5 MHz, DMSO-d6): d = 194.3, 181.6, 159.9, 157.1,
138.4, 129.7, 128.3, 125.4, 105.1, 97.5, 26.1, 9.7.
MS (EI): m/z (%) = 330/332 (34/10) [M+], 294 (12), 121 (100).
Anal. Calcd for C17H15ClN2OS: C, 61.72; H, 4.57; Cl, 10.72;
N, 8.47; S, 9.69. Found: C, 61.69; H, 4.60; Cl, 10.44; N, 8.31.
MS (EI): m/z (%) = 275/276 (42/13), 260 (16), 218 (43), 188 (41),
88 (30), 60 (61), 43 (100).
2-[4-Methyl-5-(prop-2-yn-1-yloxy)-1,3-thiazol-2-yl]pyridine
Anal. Calcd for C14H13NO3S: C, 61.07; H, 4.76; N, 5.09; S, 11.65.
Found: C, 60.96; H, 4.76; N, 5.04; S, 11.61.
(6c)
Yield: 71%; yellow crystals; mp 62 °C.
1H NMR (250 MHz, DMSO-d6): d = 8.53–8.53 (m, 1 H), 8.08–8.04
(m, 1 H), 7.78–7.71 (m, 1 H), 7.27–7.22 (m, 1 H), 5.01 (d, J = 2.2
Hz, 2 H), 2.48 (t, J = 2.4 Hz, 1 H), 2.34 (s, 3 H).
13C NMR (62.5 MHz, DMSO-d6): d = 159.8, 158.6, 151.2, 149.1,
136.9, 123.8, 118.8, 111.9, 79.4, 74.5, 57.8, 9.5.
1-{4-[4-(tert-Butyldimethylsilyloxy)-5-methylthiazol-2-yl]phe-
nyl}butane-1,3-dione (10)
Yield: 73%; light-yellow crystals; mp 92 °C.
1H NMR (250 MHz, CDCl3): d = 16.15 [s, 1 H, CH=C(OH)CH3],
7.94–7.92 (m, 4 H), 6.19 [s, 1 H, CH=C(OH)CH3], 2.29–2.22 (m,
6 H), 1.03 [s, 9 H, SiC(CH3)3], 0.33 [s, 6 H, Si(CH3)2].
MS (EI): m/z (%) = 230 (22) [M+], 191 (16), 105 (91), 59 (100).
13C NMR (62.5 MHz, CDCl3): d = 194.0, 182.1, 157.5, 157.0,
137.4, 134.9, 127.5, 125.1, 109.3, 96.7, 25.9, 25.8, 18.1, 9.6, 4.2.
Anal. Calcd for C12H10N2OS: C, 62.59; H, 4.38; N, 12.16; S, 13.92.
Found: C, 62.44; H, 4.22; N, 12.01; S, 13.72.
MS (EI): m/z (%) = 389 (9) [M+], 332 (100), 190 (7), 117 (37).
2-[4-(3-Azidopropoxy)-5-phenyl-1,3-thiazol-2-yl]pyridine (6b)
Compound 6a (1 g, 2.9 mmol) was dissolved in DMF (15 mL) and,
after addition of NaN3 (0.38 g, 5.9 mmol), the mixture was stirred
for 15 h at 60 °C. After cooling to r.t., H2O (40 mL) was added and
Anal. Calcd for C20H27NO3SSi: C, 61.66; H, 6.99; N, 3.60; S, 8.23;
Si, 7.21. Found: C, 61.77; H, 6.75; N, 3.50; S, 8.50; Si, 7.01.
Synthesis 2010, No. 10, 1603–1608 © Thieme Stuttgart · New York