1276
A. Demirbas, S. Ceylan, N. Demirbas
Vol 44
(2CH), 126.88 (2CH), 127.92 (2CH), 128.36 (2CH), 128.71
(CH), 135.65 (C), 139.04 (C), 143.17 (C)], 146.90
(triazole-C-3), 153.37 (triazole-C-5), 166.48 (C=O), 181.62
(C=S); ms: m/z (%) 446 (M+, 38), 361 (28), 359 (53), 337
(19), 305 (22), 304 (100), 282 (34), 101 (25). Anal. Calcd.
(%) for C19H20ClN7O2S: C, 51.18; H, 4.52; N, 21.72.
Found: C, 51.19; H, 4.57; N, 21.99.
1-[4-Amino-3-(4-tolyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-
1-yl]acetyl-4-benzyl thiosemicarbazide (2c). This compound
was obtained as colorless needles (yield: 3.54 g, 83.09 %); m.p.
< 300 °C; ir (KBr) (ꢀ, cm-1): 3324-3214 (NH2), 3189 (3NH),
1720 and 1686 (2C=O), 1543 (C=N), 1196 (C=S); 1H nmr
(DMSO-d6, ꢁ ppm): 2.11 (s, CH3), 3.81 (s, benzylic CH2), 4.43
(s, NCH2), 4.70 (s, NHCH2), 5.30 (s, NH2), 7.32 (bs, 9H, arom-
H), 8.58 (bs, NH), 9.49 (bs, NH), 10.35 (s, NH); 13C nmr
(DMSO-d6, ꢁ ppm): 21.65 (CH3), 30.21 (CH2), 38.10-40.60
(NHCH2+DMSO-d6), 46.46 (NCH2), arom-C: [125.31 (2CH),
126.58 (2CH), 127.96 (2CH), 128.33 (2CH), 128.72 (CH),
135.65 (C), 139.04 (C), 139.79 (C)], 146.84 (triazole-C-3),
153.34 (triazole-C-5), 166.46 (C=O), 181.68 (C=S); ms: m/z (%)
426 (M+, 28), 396 (12), 318 (12), 317 (66), 296 (19), 277 (28),
249 (34), 232 (39), 217 (100), 205 (53), 159 (53), 105 (36).
Anal. Calcd. (%) for C20H23N7O2S: C, 56.45; H, 5.45; N, 23.04.
Found: C, 56.39; H, 5.36; N, 22.82.
1-(4-Amino-3-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-
yl)acetyl-4-(3-florophenyl)thiosemicarbazide (3a). This
compound was obtained as colorless needles (yield: 3.59 g,
86.41 %); m.p. 155°C; ir (KBr) (ꢀ, cm-1): 3325-3217 (NH2),
3169 (3NH), 1721 and 1688 (2C=O), 1579 (C=N), 1196 (C=S);
1H nmr (DMSO-d6, ꢁ ppm): 3.80 (s, benzylic CH2), 4.41 (s,
NCH2), 5.38 (s, NH2), 7.20-7.38 (m, 9H, arom-H), 8.61 (bs,
NH), 9.50 (bs, NH), 10.59 (s, NH); 13C nmr (DMSO-d6, ꢁ ppm):
30.22 (CH2), 46.49 (NCH2), arom-C: [126.71 (2CH), 126.80
(2CH), 127.84 (CH), 128.33 (2CH), 128.70 (2CH), 136.69 (C),
138.14 (C), 140.07 (C)], 145.68 (triazole-C-3), 154.38 (triazole-
C-5), 166.35 (C=O), 181.60 (C=S). Anal. Calcd. (%) for
C18H18FN7O2S: C, 52.04; H, 4.37; N, 23.60. Found: C, 52.26; H,
4.38; N, 23.52.
127.74 (CH), 134.16 (C), 138.16.07 (2C), 140.15 (C)], 146.13
(triazole-C-3), 154.62 (triazole-C-5), 166.17 (C=O), 182.05
(C=S). Anal. Calcd. (%) for C19H20FN7O2S: C, 53.14; H, 4.69;
N, 22.83. Found: C, 53.39; H, 4.69; N, 22.72.
1-(4-Amino-3-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-
yl)acetyl-4-benzyl semicarbazide (4a). This compound was
obtained as colorless needles (yield: 2.82 g,71.32 %); m.p.
153°C; ir (KBr) (ꢀ, cm-1): 3314-3207 (NH2), 3107 (3NH), 1721,
1702 and 1684 (3C=O), 1561 (C=N); 1H nmr (DMSO-d6, ꢁ
ppm): 3.67 (s, benzylic CH2), 4.61 (s, NCH2), 4.78 (s, NHCH2),
5.38 (s, NH2), 7.15-7.43 (m, 10H, arom-H), 8.23 (bs, NH), 9.64
(bs, NH), 11.16 (s, NH); 13C nmr (DMSO-d6, ꢁ ppm): 33.36
(CH2), 38.11-40.25 (NHCH2 + DMSO-d6), 46.75 (NCH2), arom-
C: [125.33 (2CH), 125.89 (2CH), 128.17 (2CH), 128.76 (2CH),
129.84 (2CH), 136.65 (C), 138.56 (C)], 144.64 (triazole-C-3),
154.28 (triazole-C-5), 166.46 and 169.13 (2C=O); ms: m/z (%)
395 (M+, 15), 368 (11), 357 (11), 325 (19), 304 (15), 303 (64),
299 (16), 236 (15), 208 (15), 186 (100). Anal. Calcd. (%) for
C19H21N7O3: C, 57.71; H, 5.35; N, 24.80. Found: C, 57.89; H,
5.37; N, 24.80.
1-[4-Amino-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,
4-triazol-1-yl]acetyl-4-benzyl semicarbazide (4b). This
compound was obtained as colorless needles (yield: 3.17 g,
73.75 %); m.p. 173°C; ir (KBr) (ꢀ, cm-1): 3314-3209 (NH2),
3113 (3NH), 1720, 1702 and 1685 (3C=O), 1584 (C=N); 1H nmr
(DMSO-d6, ꢁ ppm): 3.54 (s, benzylic CH2), 4.60 (s, NCH2), 4.74
(s, NHCH2), 5.30 (s, NH2), 7.18-7.32 (m, 9H, arom-H), 8.61 (bs,
NH), 9.36 (bs, NH), 10.71 (s, NH); 13C nmr (DMSO-d6, ꢁ ppm):
33.39 (CH2), 38.10-40.27 (NHCH2 + DMSO-d6), 46.57 (NCH2),
arom-C: [126.25 (CH), 126.13 (3CH), 127.71 (2CH), 128.68
(2CH), 129.76 (CH), 136.65 (C), 138.56 (C), 138.68 (C)],
144.64 (triazole-C-3), 154.31 (triazole-C-5), 166.45 and 168.47
(2C=O); ms: m/z (%) 430 (M+1, 31), 376 (20), 299 (26), 297
(74), 252 (19), 237 (34), 225 (22), 157 (94), 130 (100). Anal.
Calcd. (%) for C19H20ClN7O3: C, 53.09; H, 4.69; N, 22.81.
Found: C, 53.17; H, 4.65; N, 22.70.
General method for the synthesis of compounds 5, 6 and 7.
A solution of corresponding thiosemicarbazide (2 or 3) or
semicarbazide (4) (10 mmol) in 2 N NaOH was refluxed for 3 h.
The resulting solution was cooled to room temperature and
acidified to pH 3-4 with 37% HCl. The precipitate formed was
collected by filtration, washed with water and recrystallized
from ethanol (5b, 6a, 6b, 7a) or dimethyl sulfoxide (1:1) (5a, 5c,
6c).
1-[4-Amino-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,
4-triazol-1-yl]-acetyl-4-(3-florophenyl)thiosemicarbazide
(3b). This compound was obtained as colorless needles (yield:
3.91 g, 86.88 %); m.p. 168°C; ir (KBr) (ꢀ, cm-1): 3325-3219
(NH2), 3157 (3NH), 1720 and 1684 (2C=O), 1609 (C=N), 1195
1
(C=S); H nmr (DMSO-d6, ꢁ ppm): 3.80 (s, benzylic CH2), 4.45
(s, NCH2), 5.27 (s, NH2), 7.21-7.32 (m, 8H, arom-H), 8.61 (bs,
NH), 9.59 (bs, NH), 10.03 (s, NH); 13C nmr (DMSO-d6, ꢁ ppm):
31.60 (CH2), 46.46 (NCH2), arom-C: [126.83 (2CH), 126.90
(2CH), 127.24 (2CH), 128.61 (CH), 128.79 (CH), 134.69 (C),
138.16.07 (C), 139.42 (C), 140.83 (C)], 145.62 (triazole-C-3),
154.21 (triazole-C-5), 166.17 (C=O), 182.03 (C=S). Anal.
Calcd. (%) for C18H17ClFN7O2S: C, 48.05; H, 3.81; N, 21.79.
Found: C, 48.26; H, 3.89; N, 22.01.
1-[4-Amino-3-(4-tolyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-
1-yl]acetyl-4-(3-florophenyl)thiosemicarbazide (3c). This
compound was obtained as colorless needles (yield: 3.72 g,
86.57 %); m.p. 187°C; ir (KBr) (ꢀ, cm-1): 3331-3210 (NH2),
3155 (3NH), 1722 and 1681 (2C=O), 1613 (C=N), 1198 (C=S);
1H nmr (DMSO-d6, ꢁ ppm): 2.04 (CH3), 3.25 (s, benzylic CH2),
4.61 (s, NCH2), 5.31 (s, NH2), 7.17-7.28 (m, 8H, arom-H), 8.87
(bs, NH), 9.41 (bs, NH), 9.75 (s, NH); 13C nmr (DMSO-d6, ꢁ
ppm): 20.13 (CH3), 32.41 (CH2), 46.47 (NCH2), arom-C:
[126.17 (CH), 126.68 (2CH), 127.45 (2CH), 127.37 (2CH),
4-Amino-3-benzyl-1-[4-benzyl-5-mercapto-4H-1,2,4-tria-
zol-3-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one (5a). This
compound was obtained as colorless needles (yield: 2.92 g,
74.11 %); m.p. 235°C; ir (KBr) (ꢀ, cm-1): 3327-3204 (NH2),
2772 (SH), 1720 and 1682 (2C=O), 1618 (C=N), 1256 (C=S);
1H nmr (DMSO-d6, ꢁ ppm): 3.64 (s, benzylic CH2), 4.92 (s,
NCH2), 5.01 (s, NCH2), 5.22 (s, NH2), 7.03-7.33 (m, 10H, arom-
H), 13.97 (s, SH); 13C nmr (DMSO-d6, ꢁ ppm): 29.99 (CH2),
38.49-40.16 (NCH2+DMSO-d6), 45.70 (NCH2), arom-C: [126.14
(2CH), 126.53 (CH), 127.30 (CH), 128.10 (2CH), 128.28 (2CH),
128.65 (2CH), 134.72 (C), 135.37 (C)], 147.37 (triazole-C-3),
147.96 (triazole-C-3'), 152.46 (triazole-C-5), 168.11 (triazole-C-
5'); ms: m/z (%) 394 (M+, 28), 354 (19), 152 (22), 130 (19), 129
(100), 104 (22), 103 (31), 102 (34). Anal. Calcd. (%) for
C19H19N7OS: C, 58.00; H, 4.87; N, 24.92. Found: C, 58.25; H,
4.89; N, 24.76.
4-Amino-3-(4-chlorobenzyl)-1-[(4-benzyl-5-mercapto-4H-
1,2,4-triazol-3-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one