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J. Agric. Food Chem., Vol. 57, No. 10, 2009
Fan et al.
Scheme 4
Data for 10f. Light yellow crystal. Yield, 90%. mp 271-272 °C.
1H NMR (CDCl3): 3.108 (3H, s, thiadiazole-CH3), 7.247 (1H, s,
thiazole-H), 7.489 (2H, d, 3JHH = 8.6 Hz, benzene-H), 7.740 (2H, d,
3JHH = 8.6 Hz, benzene-H). Anal. Calcd for C13H9ClN4OS2: C,
46.36; H, 2.69; N, 16.63. Found: C, 46.51; H, 2.89; N, 16.63. IR
(KBr pellet press): 3200 (NH, st), 3106, 3065, 3977, 3927, 1666
(CdO, st), 1553, 1471, 1318, 1287, 1087, 1062, 878, 837, 763, 711.
Data for 10g. Light yellow crystal. Yield, 61%. mp 262-263 °C.
1H NMR (CDCl3): 3.082 (3H, s, thiadiazole-CH3), 7.471
Data for 12b. White crystal. Yield, 49%. mp 126-127 °C. 1H NMR
(CDCl3): 3.161 (3H, s, thiadiazole-CH3), 3.913 (3H, s, -OCH3), 7.047
3
3
(2H, d, JHH = 8.9 Hz, CHdCH), 8.056 (2H, d, JHH = 8.9 Hz,
CHdCH). Anal. Calcd for C12H10N4O2S: C, 52.51; H, 3.52; N, 20.45.
Found: C, 52.54; H, 3.67; N, 20.43. IR (KBr pellet press): 3115 (CH, st),
1605, 1496, 1402 (vibration of oxadiazole ring), 1169 (vibration of
C-O-C), 1024, 835.
Data for 12c. White crystal. Yield, 17%. mp 131-132 °C. 1H NMR
(CDCl3): 2.451 (3H, s, CH3), 3.076 (3H, s, thiadaizole-CH3), 7.381
3
3
3
(1H, s, thiazole-H), 7.989 (2H, d, JHH = 8.9 Hz, benzene-H), 8.286
(2H, t, JHH = 3.6 Hz, benzene-H), 7.947 (2H, d, JHH = 2.4 Hz,
benzene-H). Anal. Calcd for C12H10N4OS: C, 55.80; H, 3.90; N, 21.69.
Found: C, 55.98; H, 4.06; N, 21.23. IR (KBr pellet press): 3485 (st),
3412 (st), 1641, 1547, 1394 (vibration of oxadiazole ring), 1053 (vibration
of C-O-C).
3
(2H, d, JHH = 8.9 Hz, benzene-H). Anal. Calcd for C13H9N5O3S2:
C, 44.95; H, 2.61; N, 20.16. Found: C, 44.83; H, 2.51; N, 20.45. IR
(KBr pellet press): 3254 (NH, st), 3116, 2927, 1669 (CdO, st), 1597, 1547,
1508, 1343, 1278, 1205, 1107, 1053, 879, 857, 809, 733.
Data for 10h. White crystal. Yield, 68%. mp 147-148 °C. 1H NMR
Data for 12d. White crystal. Yield, 44%. mp 156-157 °C. 1H NMR
(CDCl3): 3.161 (3H, s, thiadiazole-CH3), 4.008 (3H, s, -OCH3), 7.093-
7.130 (2H, m, benzene-H), 7.550-7.608 (1H, m, benzene-H), 8.062
3
(CDCl3): 1.250 (3H, t, JHH
= 7.5 Hz, CH3), 2.634 (2H, q,
3JHH = 7.5 Hz, CH2), 2.865 (3H, s, thiadiazole-CH3), 6.978 (1H, q,
3JHH = 1.8 Hz, benzene-H), 7.124 (1H, d, 3JHH = 8.2 Hz, CH2), 7.348
(1H, s, benzene-H), 12.369 (1H, br, N-H). Anal. Calcd for
C15H12Cl2N4OS2: C, 45.12; H, 3.03; N, 14.03. Found: C, 45.58;
H, 3.25; N, 13.83. IR (KBr pellet press): 3153 (NH, st), 3068, 2972,
2930, 2875, 1673 (CdO, st), 1545, 1472, 1379, 1323, 1291, 1213,
1103, 1029, 825.
3
(1H, q, JHH = 7.7 Hz, benzene-H). Anal. Calcd for C12H10N4O2S:
C, 52.54; H, 3.67; N, 20.43. Found: C, 52.07; H, 3.89; N, 19.95. IR
(KBr pellet press): 3528 (st), 3448 (st), 3469 (st), 2839 (OCH3, st), 1605,
1525, 1489 (vibration of oxadiazole ring), 1017 (vibration of C-O-C),
1278, 1249, 748.
Data for 12e. White crystal. Yield, 42%. mp 159-160 °C. 1H NMR
(CDCl3): 2.795 (3H, s, CH3), 3.202 (3H, s, thiadiazole-CH3),
7.411-7.460 (1H, m, benzene-H), 7.516-7.569 (2H, m, benzene-H),
Data for 10i. White crystal. Yield, 65%. mp 181-182 °C. 1H NMR
(CDCl3): 0.886 (3H, t, 3JHH = 7.3 Hz, CH3), 1.617 (2H, m, CH2), 2.556
3
3
(2H, t, JHH = 7.5 Hz, CH2), 2.862 (3H, s, thiadiazole-CH3), 6.950
8.138 (1H, d, JHH = 8.3 Hz). Anal. Calcd for C14H11N7OS: C, 51.68;
3
3
(1H, d, JHH = 8.2 Hz, benzene-H), 7.112 (1H, q, JHH = 1.8 Hz,
benzene-H), 7.343 (1H, d, 3JHH = 2.1 Hz, benzene-H), 12.447 (1H, br,
N-H). Anal. Calcd for C16H14Cl2N4OS2: C, 46.49; H, 3.41; N, 13.55.
Found: C, 46.11; H, 3.34; N, 13.29. IR (KBr pellet press): 3137 (NH, st),
3063, 2960, 2932, 2870, 2759, 1735, 1671 (CdO, st), 1630, 1546, 1382,
1319, 1290, 1215, 1102, 1024, 907, 781.
H, 3.41; N, 30.14. Found: C, 51.60; H, 3.40; N, 29.97. IR (KBr pellet
press): 3855, 3746, 3673, 3115 (CH, st), 1648 (CdN, st), 1540, 1510,
1394 (vibration of oxadiazole ring), 1075 (vibration of C-O-C).
Data for 12f. White crystal. Yield, 19%. mp 146-147 °C. 1H NMR
(CDCl3): 3.177 (3H, s, thiadiazole-CH3), 7.557 (1H, d, 3JHH = 8.4 Hz,
3
3
pyridinone-H), 8.381 (1H, dd, J1HH = 8.4 Hz, J2HH = 2.4 Hz,
3
2.16. Preparation of 4-Methyl-1,2,3-thiadiazol-5-carbonyl Hy-
drazine (11). A mixture of ethyl 4-methyl-1,2,3-thiadiazol-5-carboxy-
late (4, 6.9 g, 40 mmol) and hydrazine hydrate (44 mmol) were refluxed
for 10 h. The mixture was then stirred overnight at room temperature.
After evaporation under reduced pressure, the residue was washed with
40 mL of petroleum ether and then filtered to give 4.9 g of a light yellow
solid (11) with a yield of 78% (see ref 21 and Scheme 4).
pyridinone-H), 9.122 (1H, d, JHH = 2.4 Hz, pyridinone-H). Anal.
Calcd for C10H7N5O2S: C, 42.94; H, 2.16; N, 25.04. Found: C, 42.74; H,
2.05; N, 25.33. IR (KBr pellet press): 3035 (CH, st), 1634, 1394 (vibration
of oxadiazole ring), 1104 (vibration of C-O-C).
Data for 12g. White crystal. Yield, 40%. mp 98-100 °C. 1H NMR
3
3
(CDCl3): 0.926 (3H, t, JHH = 7.3 Hz, CH3), 1.668 (2H, q, JHH
=
3
7.5 Hz, CH2), 3.078 (2H, t, JHH = 7.8 Hz, CH2), 3.163 (3H, s,
thiadiazole-CH3), 7.423 (2H, dd, J1HH = 8.7 Hz, J2HH = 1.8 Hz,
benzene-H), 7.519 (2H, d, JHH = 8.5 Hz, benzene-H), 8.154 (1H, s,
3
3
2.17. General Synthetic Procedures for 2-(40-Methyl-10,20,30-
3
thiadiazol)-5-substituted-1,3,4-oxadiazole Derivatives (12a-12n).
pyrazole-H). Anal. Calcd for C17H15ClN6OS: C, 52.78; H, 3.91; N,
21.72. Found: C, 52.50; H, 3.87; N, 21.94. IR (KBr pellet press): 3514,
3441, 3405, 1612, 1394 (vibration of oxadiazole ring), 1060 (vibration of
C-O-C).
A
mixture of 4-methyl-1,2,3-thiadiazol-5-carbonyl hydrazine (11,
5 mmol), aromatic acids or fatty acids (5 mmol), and POCl3 (7.5 mL)
was heated at 120 °C for 6 h. Ice water (80 mL) was added, and then the
mixture was neutralized with concentrated ammonia and extracted with
dichloromethane (3 ꢀ 20 mL). After drying with anhydrous Na2SO4, the
solvent was evaporated off under reduced pressure to give crude
products. These products were purified by column chromatography with
silica gel using ethyl acetate and petroleum ether at a ratio of 1:4 as an
eluent (see Scheme 4).
Data for 12h. White crystal. Yield, 48%. mp 119 °C. 1H NMR
(CDCl3): 2.675 (3H, s, CH3), 3.176 (3H, s, thiadiazole-CH3), 7.315
3
3
(1H, d, JHH = 7.9 Hz, benzene-H), 8.361 (1H, d, JHH = 7.9 Hz,
benzene-H). Anal. Calcd for C11H8ClN5OS: C, 44.72; H, 2.88; N, 23.80.
Found: C, 44.98; H, 2.75; N, 23.84. IR (KBr pellet press): 3056 (CH),
2960, 2924, 1603, 1583 (CdN, st), 1546, 1433, 1402, 1350, 1252, 1216,
1153, 1123, 1087, 1043, 964, 846, 821, 747, 681.
Data for 12a. White crystal. Yield, 25%. mp 135-136 °C. 1H NMR
(CDCl3): 2.400 (3H, s, CH3), 3.100 (3H, s, thiadiazole-CH3), 7.290
Data for 12i. White crystal. Yield, 27%. mp 139-140 °C. 1H NMR
3
3
(2H, d, JHH = 8.0 Hz, benzene-H), 7.935 (2H, d, JHH = 8.3 Hz,
benzene-H). Anal. Calcd for C12H10N4OS: C, 55.80; H, 3.90; N, 21.69.
Found: C, 55.71; H, 4.00; N, 21.62. IR (KBr pellet press): 2922 (CH, st),
1661 (CdN, st), 1548, 1496, 1441 (vibration of oxadiazole ring),
1178 (vibration of C-O-C), 1178, 1060, 950, 821, 730.
(CDCl3): 2.601 (3H, s, CH3), 3.137 (3H, s, CH3), 6.886 (1H, dd, 3J1HH
3.9 Hz, J2HH = 0.9 Hz, H-thiophene), 7.667 (1H, d, JHH = 3.9 Hz,
thiophene-H). Anal. Calcd for C10H8N4OS2: C, 45.44; H, 3.05;
N, 21.20. Found: C, 45.23; H, 2.96; N, 21.25. IR (KBr pellet press):
=
3
3