186
W. Mo, Y. Shi, J. He, B. Li, H. Peng, and H. He
Vol 53
Synthesis of compounds
phenoxyacetic acids 5 and substituted phenoxyacetyl chlorides 6
were prepared according to the literature [22].
5
and 6.
Substituted
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-
phenoxyacetamide (8f). Yellow solid, yield 46%, mp 141.8–
142.8°C; IR (KBr): υ 3228, 3062, 2904, 1726, 1674, 1601, 1533,
1501, 1373, 1174, 1095, 759 cmꢀ1 1H-NMR (CDCl3, TMS,
400 MHz): δ 1.40 (t, 3H, J =7.0Hz, CH3), 4.39 (q, 2H, J=7.2Hz,
CH2), 4.77 (s, 2H, OCH2), 6.96–7.38 (m, 5H, ArH), 10.02 (s, 1H,
NH); EI-MS (70 eV): m/z 375 (M+1), 374 (M+); Elemental Anal.
Calcd (%) for C15H13F3N2O4S: C, 48.13; H, 3.50; N, 7.48; Found:
C, 47.91; H, 3.18; N, 7.57.
;
General synthesis of title compounds 7a–e and 8f–r.
A
solution of substituted phenoxyacetyl chlorides 6 (1.2 mmol) in
dry dichloromethane (5 mL) was added dropwise under vigorous
stirring to a mixture of the corresponding thiazole 3 and 4
(1.0 mmol) and triethylamine (1.2mmol) in dichloromethane
(10 mL). Then the mixture was stirred for 0.5–2.5 h at room
temperature, washed with 10% HCl, then with saturated aqueous
NaHCO3 solution and brine sequentially, dried over magnesium
sulfate, and evaporated to give the target compounds as oil or
solid. Purification was performed with column chromatography
(acetone/petroleum ether 1:6).
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2,4-
dichlorophenoxy)acetamide (8g).
mp 190.0–190.3°C; IR (KBr): υ 3215, 3065, 2923, 1718, 1678,
1550, 1530, 1482, 1375, 1295, 1183, 741 cmꢀ1 1H-NMR
White solid, yield 76%,
;
(CDCl3, TMS, 400MHz): δ 1.40 (t, 3H, J=7.2Hz, CH3), 4.39 (q,
2H, J=7.1Hz, CH2), 4.80 (s, 2H, OCH2), 6.90–7.48 (m, 3H,
ArH), 10.02 (s, 1H, NH); EI-MS (70 eV): m/z 443 (M+1), 442
(M+); Elemental Anal. Calcd (%) for C15H11Cl2F3N2O4S: C,
40.65; H, 2.50; N, 6.32; Found: C, 39.95; H, 2.74; N, 6.15.
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2-
N-(4-Methyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2,4-dichloro-
phenoxy)acetamide (7a). White solid, yield 77%, mp 210.1–
210.8°C; IR (KBr): υ 3219, 3070, 2985, 2925, 1717, 1665,
1547, 1481, 1370, 1275, 1105, 807cmꢀ1 1H-NMR (CDCl3,
;
TMS, 400 MHz): δ 1.37 (t, 3H, J = 8.0 Hz, CH3), 2.67 (s, 3H,
CH3), 4.33 (q, 2H, J = 8.0 Hz, CH2), 4.76 (s, 2H, OCH2),
6.90-7.46 (m, 3H, ArH); EI-MS (70eV): m/z 393 (M+4), 391 (M
+2), 389 (M+); Elemental Anal. Calcd (%) for C15H14Cl2N2O4S:
C, 46.28; H, 3.63; N, 7.20; Found: C, 45.95; H, 3.26; N, 7.44.
N-(4-Methyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2-chloro-4-
fluorophenoxy)acetamide (7b).
207.8–208.2°C. IR (KBr): υ 3196, 3063, 2984, 2939, 1719, 1664,
1553, 1491, 1372, 1261, 1088, 811cmꢀ1 1H-NMR (CDCl3,
TMS, 400MHz):δ 1.37 (t, 3H, J =8.0 Hz, CH3), 2.67 (s, 3H,
CH3), 4.34 (q, 2H, J = 8.0 Hz, CH2), 4.75 (s, 2H, OCH2), 6.96-
7.23 (m, 3H, ArH); EI-MS (70 eV): m/z 375 (M+2), 373 (M+);
Elemental Anal. Calcd (%) for C15H14ClFN2O4S: C, 48.33; H,
3.79; N, 7.51; Found: C, 48.04; H, 3.55; N, 7.52.
methyl-4-chlorophenoxy)acetamide (8h).
White solid, yield
48%, mp 198.7–199.1°C; IR (KBr): υ 3226, 3060, 3060, 2929,
1
1723, 1681, 1526, 1490, 1373, 1293, 1178, 806cmꢀ1; H-NMR
(CDCl3, TMS, 400 MHz): δ 1.40 (t, 3H, J = 8.0Hz, CH2CH3),
2.34 (s, 3H, CH3), 4.40 (q, 2H, J = 8.0Hz, CH2), 4.77 (s, 2H,
OCH2), 6.72–7.21 (m, 3H, ArH), 9.79 (s, 1H, NH); EI-MS
(70 eV): m/z 424 (M+2), 422 (M+); Elemental Anal. Calcd (%) for
C16H14ClF3N2O4S: C, 45.45; H, 3.34; N, 6.63; Found: C, 45.26;
H, 3.09; N 6.41.
White solid, yield 58.0%, mp
;
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(3-
methyl-4-chlorophenoxy)acetamide (8i).
White solid, yield
56%, mp 165.5–166.5°C; IR (KBr): υ 3214, 3059, 2998, 1728,
1
1680, 1549, 1531, 1480, 1374, 1292, 1169, 764cmꢀ1; H-NMR
(CDCl3, TMS, 400MHz): δ 1.40 (t, 3H, J = 8.0Hz, CH3), 2.38 (s,
3H, CH3), 4.40 (q, 2H, J = 8.0 Hz, CH2), 4.74 (s, 2H, OCH2),
6.73–7.32 (m, 3H, ArH), 9.99 (s, 1H, NH); EI-MS (70eV): m/z
424 (M+2), 422 (M+); Elemental Anal. Calcd (%) for
C16H14ClF3N2O4S: C, 45.45; H, 3.34; N, 6.63; Found: C, 45.63;
H, 3.02; N, 6.26.
N-(4-Methyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(4-methylphenoxy)
acetamide (7c). Yellow solid, yield 53.0%, mp 179.7–180.3°C. IR
(KBr): υ 3222, 3056, 2982, 2931, 1725, 1661, 1613, 1552, 1511,
1372, 1242, 1089, 815 cmꢀ1
;
1H-NMR (CDCl3, TMS,
400 MHz): δ 1.37 (t, 3H, J = 8.0 Hz, CH3), 2.31 (s, 3H,
Ph-CH3), 2.66 (s, 3H, CH3), 4.34 (q, 2H, J = 8.0 Hz, CH2), 4.70
(s, 2H, OCH2), 6.85 (d, 2H, J = 8.0 Hz, ArH,), 7.13 (d, 2H,
J = 8.0 Hz, ArH,); EI-MS (70 eV): m/z 336(M+2), 335 (M+1),
334 (M+); Elemental Anal. Calcd (%) for C16H18N2O4S: C,
57.47; H, 5.43; N, 8.38; Found: C, 57.35; H, 5.15; N, 8.39.
N-(4-Methyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(4-methoxyphenoxy)
acetamide (7d). White solid, yield 67.1%, mp 187.5–188.5°C. IR
(KBr): υ 3237, 3089, 2982, 2907, 1726, 1658, 1534, 1508, 1370,
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2-
chloro-4-fluorophenoxy)acetamide (8j).
88%, mp 189.5–189.8°C; IR (KBr): υ 3207, 3064, 3003, 1722,
1674, 1530, 1493, 1376, 1319, 1183, 805 cmꢀ1 1H-NMR
White solid, yield
;
(CDCl3, TMS, 400 MHz): δ 1.39 (t, 3H, J = 7.2Hz, CH3), 4.40 (q,
2H, J = 7.1Hz, CH2), 4.78 (s, 2H, OCH2), 6.94–7.23 (m, 3H,
ArH), 10.17 (s, 1H, NH); EI-MS (70eV): m/z 429 (M+2), 427
(M+); Elemental Anal. Calcd (%) for C15H11ClF4N2O4S: C,
42.21; H, 2.60; N, 6.56; Found: C, 42.42; H, 2.48; N, 6.34.
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2,3-
1231, 1091, 818 cmꢀ1 1H-NMR (CDCl3, TMS, 400 MHz): δ
;
1.37 (t, 3H, J = 8.0 Hz, CH3), 2.67 (s, 3H, CH3), 3.78 (s, 3H,
Ph-OCH3), 4.33 (q, 2H, J = 8.0 Hz, CH2), 4.68 (s, 2H, OCH2),
6.86-6.93 (m, 4H, ArH); EI-MS (70 eV): m/z 352 (M+2), 351
(M+1), 350 (M+); Elemental Anal. Calcd (%) for
C16H18N2O5S: C, 54.85; H, 5.18; N, 7.99; Found: C, 54.66; H,
5.02; N, 7.70.
dimethylphenoxy)acetamide (8k).
mp 176.6–177.1°C; IR (KBr): υ 3227, 3061, 2987, 1729, 1686,
1582, 1536, 1474, 1375, 1262, 1179, 772 cmꢀ1 1H-NMR
White solid, yield 88%,
;
(CDCl3, TMS, 400MHz): δ 1.40 (t, 3H, J = 7.0Hz, CH3), 2.26 (s,
3H, Ph-CH3), 2.31 (s, 3H, Ph-CH3), 4.40 (q, 2H, J = 7.2Hz, CH2),
4.76 (s, 2H, OCH2), 6.66–7.10 (m, 3H, ArH), 9.84 (s, 1H, NH);
EI-MS (70 eV): m/z 404 (M+2), 403 (M+1), 402 (M+); Elemental
Anal. Calcd (%) for C17H17F3N2O4S: C, 50.74; H, 4.26; N, 6.96;
Found: C, 50.69; H, 4.24; N, 6.74.
N-(4-Methyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(4-fluorophenoxy)
acetamide (7e). Yellow solid, yield 68.0%, mp 178.4–179.4°C. IR
(KBr): υ 3203, 3059, 2981, 2938, 1722, 1654, 1558, 1505, 1375,
1250, 1096, 829 cmꢀ1 1H-NMR (CDCl3, TMS, 400 MHz): δ
;
1.37 (t, 3H, J = 8.0 Hz, CH3), 2.67 (s, 3H, CH3), 4.34 (q, 2H,
J = 8.0 Hz, CH2), 4.71 (s, 2H, OCH2), 6.91–7.06 (m, 4H, ArH);
EI-MS (70 eV): m/z 340 (M+2), 339 (M+1), 338 (M+);
Elemental Anal. Calcd (%) for C15H15FN2O4S: C, 53.25; H,
4.47; N, 8.28; Found: C, 53.36; H, 4.32; N, 7.93.
N-(4-Trifluoromethyl-5-ethoxycarbonyl-thiazol-2-yl)-2-(2-
chlorophenoxy)acetamide (8l).
191.0–191.8°C; IR (KBr): υ 3216, 3062, 2982, 2938, 1725, 1662,
1552, 1491, 1372, 1243, 1083, 822 cmꢀ1 1H-NMR (CDCl3,
TMS, 400 MHz): δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 4.40 (q, 2H,
White solid, yield 59%, mp
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet