March 2016
Isothiocyanate in Heterocyclic Synthesis
491
8.1 (d, 1H, J = 8.6 Hz) 12.40 (br. s, 2H, 2NH, exchangeable); 13
C
264 (M+., 7), 263 (5), 248 (10), 202 (77), 146 (63), 119 (69), 97
(50), 57 (100); Anal. Calcd. for C11H12N4O2S (264.30): C, 49.99;
H, 4.58; N, 21.20. Found C, 49.79; H, 4.62; N, 20.91%.
NMR (DMSO-d6) ar-C [113.57 (2CH), 123.33 (2CH and
C―CONH), 123.42 (3CH), 124 (1CH), 129.17 (1CH), 131.49
(C―N imide), 132.11 (2C), 132.39 (2CH), 132.77 (CH), 136.04
(2C)], 149.29 (C¼N), 165.47 (CO), 167.62 (2CO); MS (70 eV)
m/z (%): 382 (M+., 4), 278 (3), 265 (20), 251 (8), 250 (38), 223
(18), 222 (6), 186 (22), 160 (100), 132 (25), 104 (44), 76 (48);
Anal. Calcd. for C22H14N4O3 (382.37): C, 69.10; H, 3.69; N,
14.65. Found C, 69.14; H, 3.42; N, 14.69%.
N-(2-phenylhydrazinecarbonothioyl)-2-(1,3-dioxisoindolin-2-yl)
benzamide (11). The solution of isothiocyanate 1 (3 mmole) in
dry acetonitrile (30 mL) and phenyl hydrazine (3 mmole) was
stirred for 1 h at room temperature. The precipitated yellow
solid product was filtered off and recrystallized from toluene.
79% yield; mp 233–235°C; IR (KBr) υ: 3311, 3209 (NH),
1
N-(benzo[d]oxazol-2-yl)-2-(1,3-dioxisoindolin-2-yl)benzamide (6b).
Compound 5b (1mmole) was fused at 225–235°C on a sand bath,
H2S gas was evolved during fusion. The evolution of H2S gas
was ceased after 20 min. A solid product was obtained, cooled
to room temperature and recrystallized from ethanol to give
brown crystals of compound 6b. 77% yield, mp 226–228; IR
(KBr) υ: 3120 (NH), 1778, 1697, 1638 (C¼O), 1597 (C¼N),
1764, 1705, 1680 (C¼O), 1228 (C¼S) HNMR (DMSO-d6) δ:
7.10–8.10 (m, 13H, ArH), 8.67, 11.4, 11.8 (br. s, 3H, NH,
exchangeable); 13C NMR (DMSO-d6) ar-C [116.79 (2CH),
120.13 (1CH), 123.31 (CCONH), 123.48 (2CH), 127.74 (1CH),
128.16 (1CH), 129.04 (2CH), 130.27 (1CH), 130.38 (C―N
imide), 131.55 (2C), 134.39 (2CH), 136.71 (1CH), 149.09
(C―NHNHCS)], 165.98 (2CO), 166.14 (CO), 169.88 (CS); MS
(70 eV) m/z (%):416 (M+., 0), 339 (M+. –Ph, 4), 268 (18), 267
(100), 250 (4), 238 (1), 223 (49), 195 (21), 169 (2), 167 (6), 119
(2), 104 (6), 76 (6); Anal. Calcd. for C22H16N4O3S (416.45): C,
63.45; H, 3.87; N, 13.45. Found C, 63.74; H, 3.70; N, 13.68%.
2-(2-(2-Phenyl-5-thioxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)phenyl)
1
767 δ4H; HNMR (DMSO-d6) δ: 7.56 (t, 2H, J = 7.5, 7.2 Hz),
7.75 (t, 2H, J = 7.8 Hz), 7.82 (d, 2H, J = 7.8 Hz), 7.90 (t, 1H,
J = 7.2, 8.1 Hz), 7.96 (d, 1H, J = 7.5 Hz), 8.05 (d, 2H,
J = 7.2 Hz), 8.18 (d, 2H, J = 7.2 Hz), 12.50 (br. s, 1H, NH,
exchangeable); 13C NMR (DMSO-d6) ar-C [122.57 (3CH),
124.81 (1CH + C―CO), 127.24 (2CH), 128.20 (3CH), 129.50
(C―N imide), 133.80 (2CH), 134.36 (1CH), 135.37 (2C),
135.67 (C―N¼C), 146.35 (C―O)], 149.98 (C¼N), 157.24
(CO), 163.68 (2CO); MS (70eV) m/z (%): 383 (M+., 2), 368 (6),
340 (32), 323 (12), 294 (16), 250 (76), 248 (100), 220 (94), 134
(10), 118 (9), 90 (23); Anal. Calcd. for C22H13N3O4 (383.36): C,
68.93; H, 3.42; N, 10.96. Found C, 69.00; H, 3.18; N, 10.58%.
4-(2-Aminobenzoyl)thiosemicarbazide (8). 78% yield; colorless
crystals; mp 171–173°C (ethanol); IR (KBr) υ: 3372, 3263, 3178
(NH), 1644 (C¼O), 1286 (C¼S); 1HNMR (DMSO-d6) δ: 4.48
(br.s, 4H, NH2, exchangeable), 7.09–7.25 (m, 2H, Ar―H), 7.36–7.56
(m, 2H, Ar―H), 8.59 (br. s, 2H, NH, exchangeable); MS
(70 eV) m/z (%): 210 (M+., 1), 196 (25), 195 (13), 194 (100),
192 (81), 152 (18), 138 (22), 120 (63), 91 (65); Anal. Calcd.
for C8H10N4OS (210.26): C, 45.70; H, 4.79; N, 26.65. Found
C, 45.47; H, 4.66; N, 26.43%.
isoindoline-1,3-dione (12).
88% yield; yellow crystals; mp
248–250°C (ethanol); IR (KBr) υ: 3328 (NH), 1772, 1712
(C¼O), 1225 (C¼S); 1HNMR (DMSO-d6) δ: 7.42–8.84 (m,
11H, ArH), 7.92 (d, 1H, J = 6.4 Hz), 8.16 (d, 1H, J = 6.5 Hz),
7.96 (br. s, 1H, NH, exchangeable); 13C NMR (DMSO-d6) ar-C
[117.01 (C―C¼N), 123.73 (2CH), 124.96 (1CH), 127.07 (1CH),
127.89 (1CH), 128.13 (1CH), 128.79 (2CH), 129.36 (1CH),
130.26 (1CH), 130.34 (C―N imide), 131.01 (2C), 131.54 (1CH),
132.24(2CH) 137.26 (C―NNHCS)], 159.12 (C¼N), 165.97
(2CO), 172.96 (CS); MS (70 eV) m/z (%): 398 (M+., 4.), 397 (2),
292 (4), 279 (3.0), 267 (1), 223 (1), 165 (5), 146 (1), 119 (19), 105
(1), 92 (9); 34 (100); Anal. Calcd. for C22H14N4O2S (398.44): C,
66.32; H, 3.54; N, 14.06. found C, 66.42; H, 3.32; N, 14.12%.
2-(2-(2,2-Dimethyl-4-phenyl-5-thioxo-2,3,4,5-tetrahydro-1,3,4,6-
oxatriazepin-7-yl)phenyl)isoindoline-1,3-dione (13). 73% yield;
yellow crystals; mp 186–188°C (ethanol); IR (KBr) υ: 3210
1
1-Ethoxy carbonyl-4-(2-aminobenzoyl)thiosemicarbazide (9).
67% yield; colorless crystals; mp 176–178°C (ethanol); IR (KBr)
υ: 3292, 3220, 3178 (NH), 2988 (CH aliph.), 1723, 1703 (C¼O),
(NH), 1775, 1715, (C¼O), 1220 (C¼S); HNMR (DMSO-d6) δ:
1.5 (s, 3H, CH3), 2.1 (s, 3H, CH3) 7.06–8.10 (m, 13H, ArH), 6.5
(br. s, 1H, NH, exchangeable); 13C NMR (DMSO-d6) 26.19
(CH3), 30.64(CH3), 69.42 (C(CH3)2), ar-C [123.11 (2CH), 123.41
(2CH), 124.70 (1CH), 125.86 (1CH), 128.49 (1CH), 128.99
(2CH), 130.23 (1CH), 130.99 (2C), 131.18 (1CH), 131.63 (2CH),
131.93 (C―N imide), 134.46 (C―N azepine), 139 (C―C azepine],
166.95 (C¼N), 169.91 (2CO), 173.81 (CS); MS (70 eV) m/z (%):
412 (M+ ꢀ CS, 1), 398 [(M+ ꢀ NCS) or (M+ ꢀ (CH3)2CO), 1], 366
(17), 268 (15), 267 (85), 234 (1), 222 (30), 179 (58), (5), 146 (11),
76 (100); Anal. Calcd. for C25H20N4O3S (456.52): C, 65.77; H,
4.42; N, 12.27. Found C, 65.84; H, 3.94; N, 12.24%.
1239 (C¼S), 755 δ4H
;
1HNMR (DMSO-d6) δ: 1.18 (t, 3H,
CH3, J = 7.5 Hz, 7.2 Hz), 4.04 (q, 2H, CH2, J = 7.2 Hz), 7.53
(d, 1H, J = 7.8 Hz), 7.62 (t, 1H, J = 7.8 Hz, J = 7.2 Hz), 7.77
(t, 1H, J = 7.5 Hz, J = 7.8 Hz), 8.04 (d, 1H, J = 7.8 Hz), 9.15
(br. s, 2H, NH2, exchangeable) 7.48, 7.82, 13.06 (br. s, 3H, NH,
exchangeable); MS (70 eV) m/z (%): 282 (M+., 1), 267 (40), 250
(5), 223 (33), 195 (13), 179 (32), 163 (100), 117 (19), 104 (83),
76 (22); Anal. Calcd. for C11H14N4O3S (282.32): C, 46.80; H,
5.00; N, 19.85. Found C, 46.53; H, 4.83; N, 19.76%.
2-Amino-N-(5-ethoxy-1,3,4-thiadiazol-2-yl)benzamide (10).
The solution of compound 9 (0.5 g) in ethanol (30 mL) and 3 M
hydrochloric acid (5 mL) was refluxed for 3 h. A solid product
was obtained during reflux, was filtered off while hot and
recrystallized from ethanol to give compound 10; 88% yield;
pale yellow crystals; mp 265–267°C; IR (KBr) υ: 3138 (NH),
2918, 2849 (CH aliph.), 1683 (CO), 768 δ4H; 1HNMR (DMSO-d6)
δ: 1.39 (t, 3H, CH3, J = 7.5 Hz, 6.3 Hz), 4.55 (q, 2H, CH2,
J = 7.2 Hz, 6.9 Hz), 7.11–8.22 (m, 4H, Ar―H), 9.45 (br. s, 2H,
NH2, exchangeable) 11.10 (br. s, 1H, NH, exchangeable); 13C
NMR (DMSO-d6) 14.39 (CH3), 61.27 (CH2), ar-C [115.27 (CH),
116.93 (CCO), 124.32 (1CH), 126.51 (1CH), 129.01 (1CH), 135
(C―NH2),], 152.41 (2C¼N), 161.08 (CO); MS (70eV) m/z (%):
2-(2-(5-Oxo-2-phenyl-2,5-dihydro-1H-1,2,4-triazol-3-yl)phenyl)
isoindoline-1,3-dione (17).
To the solution of compound 12
(3 mmole) in acetone 30 mL, ethyl chloroacetate (3 mmole) and
a catalytic amount of K2CO3 (0.3 g) were added. The reaction
mixture was refluxed for 10 h, and then filtered while hot.
Acetone was evaporated to leave a solid product of compound
17. 76% Yield; yellow crystals; mp 154–156°C (ethanol); IR
(KBr) υ: 3316 (NH), 1782, 1759, 1724 (C¼O), 1601 (C¼N),
1
750, 689 δ5H; HNMR (DMSO-d6) δ: 6.72 (d, 2H, J = 8.4 Hz),
6.79 (t, 2H, J = 7.0, 7.2 Hz), 7.16 (t, 3H, J = 8.4, 7.8 Hz), 7.90–
7.97 (m, 6H, ArH), 8.56 (br. s, 1H, NH, exchangeable); MS
(70 eV) m/z (%): 382 (M+., 7), 368 (3), 353 (5), 325 (73), 281
(25), 250 (21), 238 (48), 104 (56), 91 (97), 77 (100); Anal.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet