1134
Vol. 55, No. 8
N, 19.69.
206—208 °C; IR (KBr): 3198, 3087, 2980, 1676, 1553, 1490, 1422, 1371,
1
4-Cyanobenzaldehyde Thiosemicarbazone (7e): White powder from 1272, 1091; H-NMR (DMSO-d6) d: 1.24 (3H, t, Jꢃ7.1 Hz), 2.45 (3H, s),
CH2Cl2/EtOH; yield 96%; mp 225—226 °C; IR (KBr): 3418, 3249, 3151,
4.18 (2H, q, Jꢃ7.1 Hz), 7.47 (2H, d, Jꢃ8.5 Hz), 7.68 (2H, d, Jꢃ8.5 Hz),
8.05 (1H, s), 12.49 (1H, s); 13C-NMR (DMSO-d6) d: 14.67, 17.39, 60.49,
109.56, 128.61, 129.27, 133.35, 134.56, 143.46, 158.29, 162.23, 169.51;
3013, 2220, 1601, 1535, 1503, 1464, 1361, 1295, 1099 cmꢁ1 1H-NMR
;
(DMSO-d6) d: 7.83 (2H, d, Jꢃ8.4 Hz), 8.00 (2H, d, Jꢃ8.4 Hz), 8.05 (1H, s),
8.20 (1H, s), 8.34 (1H, s), 11.63 (1H, s); FAB-MS m/z (%): 205 (MꢄꢄH); FAB-MS m/z (%): 326 (Mꢄꢄ2ꢄH), 324 (MꢄꢄH); Anal. Calcd for
Anal. Calcd for C9H8N4S: C, 52.93; H, 3.95; N, 27.43. Found: C, 52.85; H, C14H14N3O2ClS: C, 51.93; H, 4.36; N, 12.98. Found: C, 51.96; H, 4.38; N,
3.91; N, 27.44.
12.95.
4-Methyl-2-[Nꢀ-(4-cyanobenzylidene)hydrazino]thiazole-5-carboxylic
Pyridine-2-carbaldehyde Thiosemicarbazone (7f): Yellow powder from
CH2Cl2/EtOH; yield 71%; mp 199—201 °C; IR (KBr): 3417, 3244, 3156,
Acid Ethyl Ester (8e): Yellow powder from CH2Cl2/EtOH; yield 71%; mp
1611, 1525, 1468 cmꢁ1
;
1H-NMR (DMSO-d6) d: 7.35 (1H, dd, Jꢃ8.0, 227—228 °C; IR (KBr): 3187, 3085, 2980, 2225, 1678, 1556, 1427, 1376,
1
5.2 Hz), 7.80 (1H, t, Jꢃ8.0 Hz), 8.07 (1H, s), 8.15 (1H, s), 8.25 (1H, d, 1277, 1093; H-NMR (DMSO-d6) d: 1.25 (3H, t, Jꢃ6.9 Hz), 2.48 (3H, s),
Jꢃ8.0 Hz), 8.33 (1H, s), 8.54 (1H, d, Jꢃ5.2 Hz), 11.62 (1H, s); FAB-MS m/z 4.18 (2H, q, Jꢃ6.9 Hz), 7.75—7.93 (4H, m), 8.09 (1H, s), 11.82 (1H, s);
(%): 181 (MꢄꢄH); Anal. Calcd for C7H8N4S: C, 46.65; H, 4.47; N, 31.09. 13C-NMR (DMSO-d6) d: 14.44, 17.11, 60.40, 110.35, 111.57, 118.89,
Found: C, 46.64; H, 4.44; N, 31.02.
127.31, 132.88, 138.61, 142.39, 158.82, 161.92, 169.26; FAB-MS m/z (%):
Furan-2-carbaldehyde Thiosemicarbazone (7g): White powder from 315 (MꢄꢄH); Anal. Calcd for C15H14N4O2S: C, 57.31; H, 4.49; N, 17.82.
CH2Cl2/EtOH; yield 66%; mp 189—190 °C; IR (KBr): 3412, 3219, 3138,
Found: C, 57.27; H, 4.49; N, 17.80.
1
3016, 1608, 1582, 1528, 1475, 1343, 1277, 1093 cmꢁ1; H-NMR (DMSO-
4-Methyl-2-(Nꢀ-pyridin-2-ylmethylene-hydrazino)thiazole-5-carboxylic
Acid Ethyl Ester (8f): White power from CH2Cl2/EtOH; yield 82%; mp
229—231 °C; IR (KBr): 3147, 3040, 2987, 2939, 1685, 1563, 1474, 1426,
d6) d: 6.60 (1H, dd, Jꢃ3.9, 1.9 Hz), 6.95 (1H, d, Jꢃ3.9 Hz), 7.61 (1H, s),
7.79 (1H, d, Jꢃ1.9 Hz), 7.95 (1H, s), 8.19 (1H, s), 11.41 (1H, s); FAB-MS
m/z (%): 170 (MꢄꢄH); Anal. Calcd for C6H7N3OS: C, 42.59; H, 4.17; N, 1370, 1324, 1308, 1283, 1096; 1H-NMR (DMSO-d6) d: 1.28 (3H, t,
24.83. Found: C, 42.38; H, 4.11; N, 24.81.
Thiophene-2-carbaldehyde Thiosemicarbazone (7h): Yellow powder from 7.80—8.00 (2H, m), 8.10 (1H, s), 8.60 (1H, d, Jꢃ4.4 Hz), 12.71 (1H, s);
CH2Cl2/EtOH; yield 68%; mp 185—186 °C; IR (KBr): 3412, 3229, 3145,
13C-NMR (DMSO-d6) d: 14.65, 17.67, 60.60, 110.87 120.04, 124.51,
3018, 2983, 1611, 1578, 1536, 1509, 1475, 1278, 1100 cmꢁ1
Jꢃ7.1 Hz), 2.50 (3H, s), 4.22 (2H, q, Jꢃ7.1 Hz), 7.40 (1H, t, Jꢃ4.7 Hz),
;
1H-NMR 137.26, 144.37, 149.92, 153.11, 159.57, 162.18, 169.45; FAB-MS m/z (%):
(DMSO-d6) d: 7.09 (1H, dd, Jꢃ4.9, 3.9 Hz), 7.43 (1H, d, Jꢃ3.9 Hz), 7.53
(1H, s), 7.63 (1H, d, Jꢃ4.9 Hz), 8.18 (1H, s), 8.23 (1H, s), 11.43 (1H, s);
FAB-MS m/z (%): 186 (MꢄꢄH); Anal. Calcd for C6H7N3S2: C, 38.90; H,
3.81; N, 22.68. Found: C, 38.88; H, 3.72; N, 22.70.
291 (MꢄꢄH); Anal. Calcd for C13H14N4O2S: C, 53.78; H, 4.86; N, 19.30.
Found: C, 53.57; H, 4.82; N, 19.13.
4-Methyl-2-(Nꢀ-furan-2-ylmethylene-hydrazino)thiazole-5-carboxylic
Acid Ethyl Ester (8g): Yellow crystals from CH2Cl2/EtOH; yield 56%; mp
Cyclization of Aromatic Aldehyde Thiosemicarbazones (7a—h) with 194—196 °C; IR (KBr): 3208, 3097, 2980, 1668, 1561, 1528, 1410, 1371,
Ethyl 2-Chloroacetoacetate (2a) To the solution of 4-methylbenzalde- 1318, 1277, 1091; 1H-NMR (DMSO-d6) d: 1.26 (3H, t, Jꢃ7.3 Hz), 2.49
hyde thiosemicarbazone (7a, 386 mg, 2 mmol) in absolute ethanol (6 ml),
(3H, s), 4.19 (2H, q, Jꢃ7.3 Hz), 6.63 (1H, dd, Jꢃ3.3, 1.5 Hz), 6.89 (1H, d,
sodium acetate (492 mg, 6 mmol) was slowly added. Acetic acid (1 ml) was Jꢃ3.3 Hz), 7.83 (1H, d, Jꢃ1.5 Hz), 9.97 (1H, s), 12.4 (1H, s); 13C-NMR
added as a catalyst and then ethyl 2-chloroacetoacetate (2a, 494 mg, 3 mmol)
(DMSO-d6) d: 14.41, 17.08, 60.27, 109.08, 112.36, 113.49, 134.77, 145.19,
was slowly added to the above solution. The mixed solution was heated at 149.27, 157.85, 162.02, 168.99; FAB-MS m/z (%): 280 (MꢄꢄH); Anal.
70 °C for about 9 h until the reaction was completed. The system was then Calcd for C12H13N3O3S: C, 51.60; H, 4.69; N, 15.04. Found: C, 51.60; H,
allowed to reach room temperature. The precipitating solid was collected by 4.68; N, 15.07. X-Ray analytical data are listed in Table 1. Further details
filtration and washed with ice-cold water and cold ethanol. The collected have been deposited at the Cambridge Crystallographic Data Center and al-
solid (451 mg) was recrystallized from dichloromethane/ethanol to afford located the deposition number CCDC 615373.
376 mg (1.24 mmol) of 4-methyl-2-[Nꢀ-(4-methylbenzylidene)hydrazino]thi-
4-Methyl-2-(Nꢀ-thiophen-2-ylmethylene-hydrazino)thiazole-5-carboxylic
azole-5-carboxylic acid ethyl ester (8a) as yellow powder in a yield of 62%. Acid Ethyl Ester (8h): Yellow crystals from CH2Cl2/EtOH; yield 70%; mp
The chemical and physical spectral characteristics of these products 8a—h 209—210 °C; IR (KBr): 3191, 3096, 2984, 1665, 1561, 1515, 1413, 1369,
are given below.
1314, 1268, 1091; 1H-NMR (DMSO-d6) d: 1.26 (3H, t, Jꢃ7.2 Hz), 2.46
4-Methyl-2-[Nꢀ-(4-methylbenzylidene)hydrazino]thiazole-5-carboxylic (3H, s), 4.19 (2H, q, Jꢃ7.2 Hz), 7.12 (1H, dd, Jꢃ5.1, 3.7 Hz), 7.42 (1H, d,
Acid Ethyl Ester (8a): Yellow powder from CH2Cl2/EtOH; yield 62%; mp Jꢃ3.7 Hz), 7.63 (1H, d, Jꢃ5.1 Hz), 8.28 (1H, s), 12.42 (1H, s); 13C-NMR
189—191 °C; IR (KBr): 3192, 3101, 2980, 1664, 1567, 1524, 1429, 1367, (DMSO-d6) d: 14.47, 17.00, 60.30, 108.70, 128.10, 128.68, 130.35, 138.98,
1
1273, 1091; H-NMR (DMSO-d6) d: 1.25 (3H, t, Jꢃ7.2 Hz), 2.32 (3H, s),
2.45 (3H, s), 4.18 (2H, q, Jꢃ7.2 Hz), 7.23 (2H, d, Jꢃ8.0 Hz), 7.56 (2H, d,
140.19, 157.57, 162.03, 168.72; FAB-MS m/z (%): 296 (MꢄꢄH); Anal.
Calcd for C12H13N3O2S2: C, 48.80; H, 4.44; N, 14.23. Found: C, 48.74; H,
Jꢃ8.0 Hz), 8.03 (1H, s), 12.37 (1H, s); 13C-NMR (DMSO-d6) d: 14.46, 4.45; N, 14.05. X-Ray analytical data are listed in Table 1. Further details
17.25, 21.17, 60.21, 109.15, 126.80, 129.59, 131.47, 139.76, 144.64, have been deposited at the Cambridge Crystallographic Data Center and al-
158.36, 162.08, 169.34; FAB-MS m/z (%): 304 (MꢄꢄH); Anal. Calcd for located the deposition number CCDC 615372.
C15H17N3O2S: C, 59.39; H, 5.65; N, 13.85 Found: C, 59.28; H, 5.64; N,
13.81.
Cyclization of Aromatic Aldehyde Thiosemicarbazones (7a—h) with
2-Bromoacetophenone (2b) Sodium acetate (492 mg, 6 mmol) was slowly
4-Methyl-2-[Nꢀ-(4-methoxybenzylidene)hydrazino]thiazole-5-carboxylic added to an iced-cold solution of 4-methylbenzaldehyde thiosemicarbazone
Acid Ethyl Ester (8b): Yellow powder from CH2Cl2/EtOH; yield 65%; mp (7a, 386 mg, 2 mmol) in absolute ethanol (2 ml). Acetic acid (0.5 ml) was
182—184 °C; IR (KBr): 3166, 3056, 2923, 2837, 1699, 1604, 1581, 1512, added as a catalyst and then 2-bromoacetophenone (2b, 418 mg, 2.1 mmol)
1432, 1372, 1310, 1257, 1082; 1H-NMR (DMSO-d6) d: 1.25 (3H, t, was slowly added to the above solution. The mixed solution was stirred at
Jꢃ7.1 Hz), 2.45 (3H, s), 3.79 (3H, s), 4.18 (2H, q, Jꢃ7.1 Hz), 6.99 (2H, d, 0 °C for about 5 h until the reaction was completed. The precipitate was col-
Jꢃ8.4 Hz), 7.61 (2H, d, Jꢃ8.4 Hz), 8.02 (1H, s), 12.32 (1H, s); 13C-NMR
lected by filtration and washed with ice-cold water and cold ethanol. The
(DMSO-d6) d: 14.49, 17.28, 55.45, 60.21, 108.93, 114.53, 126.80, 128.45, collected solid (573 mg) was recrystallized from dichloromethane/ethanol to
144.56, 158.36, 160.87, 162.13, 169.34; FAB-MS m/z (%): 320 (MꢄꢄH); afford 498 mg (1.70 mmol) of 4-phenyl-2-[Nꢀ-(4-methylbenzylidene)hy-
Anal. Calcd for C15H17N3O3S: C, 56.41; H, 5.37; N, 13.16. Found: C, 56.39; drazino]thiazole (9a) as a reddish orange powder in a yield of 85%. The
H, 5.33; N, 13.16.
chemical and physical spectral characteristics of these products 9a—h are
4-Methyl-2-(Nꢀ-benzylidene-hydrazino)thiazole-5-carboxylic Acid Ethyl given below.
Ester (8c): Yellow powder from CH2Cl2/EtOH; yield 50%; mp 194—197 °C;
4-Phenyl-2-[Nꢀ-(4-methylbenzylidene)hydrazino]thiazole (9a): Reddish
orange powder from CH2Cl2/EtOH; yield 85%; mp 195—196 °C; IR (KBr):
IR (KBr): 3193, 3099, 2978, 1664, 1562, 1528, 1423, 1369, 1274, 1090; 1H-
NMR (DMSO-d6) d: 1.27 (3H, t, Jꢃ6.9 Hz), 2.46 (3H, s), 4.21 (2H, q, 3279, 3109, 3026, 2916, 1555, 1510, 1479, 1344, 1268, 1129, 1050,
Jꢃ6.9 Hz), 7.42—7.50 (3H, m), 7.67—7.72 (2H, m), 8.09 (1H, s), 12.47 711 cmꢁ1 1H-NMR (DMSO-d6) d: 2.32 (3H, s), 7.23 (2H, d, Jꢃ8.0 Hz),
;
(1H, s); 13C-NMR (DMSO-d6) d: 14.46, 17.24, 60.26, 109.31, 126.83,
128.99, 129.94, 134.18, 144.52, 158.25, 162.06, 169.39; FAB-MS m/z (%):
7.28—7.40 (4H, m), 7.54 (2H, d, Jꢃ8.0 Hz), 7.85 (2H, d, Jꢃ8.3 Hz), 8.00
(1H, s), 12.08 (1H, s); 13C-NMR (DMSO-d6) d: 21.16, 103.68, 125.70,
290 (MꢄꢄH); Anal. Calcd for C14H15N3O2S: C, 58.11; H, 5.23; N, 14.52. 126.42, 127.68, 128.77, 129.60, 131.91, 134.91, 139.12, 141.57, 150.72,
Found: C, 58.05; H, 5.16; N, 14.45.
4-Methyl-2-[Nꢀ-(4-chlorobenzylidene)hydrazino]thiazole-5-carboxylic 69.60; H, 5.15; N, 14.32. Found: C, 69.60; H, 5.29; N, 14.23.
Acid Ethyl Ester (8d): Yellow powder from CH2Cl2/EtOH; yield 77%; mp 4-Phenyl-2-[Nꢀ-(4-methoxybenzylidene)hydrazino]thiazole (9b): Brown
168.49; FAB-MS m/z (%): 294 (MꢄꢄH); Anal. Calcd for C17H15N3S: C,