3.2. Synthetic Procedures
3.2.1. 2-Cyano-N-(4-sulfamoylphenyl)acetamide (3)
A mixture of
1 (3.44 g, 20 mmol) and 3,5-dimetyl-1-cyanoacetyl Pyrazole (
2) (3.26 g, 20 mmol) in dioxane (20 mL) was refluxed for 3 h. The reaction mixture was poured into crushed ice. The resulting precipitate was filtrated off, dried, and crystallized from DMF/MeOH (1:3) to give
3; Yield (70%), mp 248 °C (from DMF/MeOH) (lit. mp 230 °C) [
31]; IR (KBr) ν
max: 3337, 3236, 3102 (NH, NH
2), 2269 (C≡N), 1687 (C=O) cm
−1; 1H-NMR (DMSO-
d6): δ 3.96 (s, 2H, CH
2), 7.29 (s, 2H, D
2O-exchangeable NH
2), 7.77 (d, 2H,
J = 9 Hz), 7.80 (d, 2H,
J = 9 Hz), 10.63 (s, 1H, D
2O-exchangeable NH). MS
m/
z (%): 241 (M
+ + 2, 0.7), 240 (M
+ + 1, 5.8), 239 (M
+, 12.7), 238 (100), 222 (34.9), 172 (25.3), 159 (29.7), 132 (19.1), 108 (47.3), 92 (46.3), 90 (25.1), 75 (15.9). Anal. Calcd for C
9H
9N
3O
3S (239.25): C, 45.18; H, 3.79; N, 17.56; S, 13.40. Found: C, 45.11; H, 3.70; 65, N, 17.42; S, 13.30%.
3.2.2. N-[4-(Aminosulfonyl)phenyl]-3-aryl-2-cyanoacrylamide (5a–c)
General Procedure: To a solution of cyanoacetanilide 3 (0.239 g, 1 mmol) and the appropriate aromatic aldhyeds (1 mmol) in dioxane (20 mL), was added few drops of piperidine and the reaction mixture was refluxed for 6 h. The solid product so formed was filtered off, washed with EtOH and then recrystallized from proper solvent to give 5a–c.
3.2.3. 2-Cyano-3-phenyl-N-(4-sulfamoylphenyl)prop-2-enamide (5a)
Yield (45%), mp 322 °C (from dioxane/ethanol); IR (KBr) νmax: 3362, 3316, 3262 (NH, NH2), 2220 (C≡N), 1680 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.29 (s, 2H, D2O-exchangeable NH2), 7.63 (d, 2H, J = 9 Hz), 7.80 (d, 2H, J = 9 Hz), 7.81–7.83 (m, 5H, ArH), 8.32 (s, 1H, olefinicH), 10.70 (s, 1H, D2O-exchangeable NH). MS m/z (%): 327 (M+, 18.2), 128 (40.4), 104 (10.7), 156 (100), 77 (23.9); Anal. Calcd for C16H13N3O3S (327.35): C, 58.70; H, 4.00; N, 12.84; S, 9.80. Found: C, 58.65; H, 3.88; N, 12.72; S, 9.77%.
3.2.4. 2-Cyano-3-(4-methoxyphenyl)-N-(4-sulfamoylphenyl)prop-2-enamide (5b)
Yield (90%), mp 292 °C (from dioxane/ethanol); IR (KBr) νmax: 3312, 3266, 3106 (NH, NH2), 2218 (C≡N), 1682 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.87 (s, 3H, OCH3), 7.19 (d, 2H, J = 9 Hz), 7.27 (s, 2H, D2O-exchangeable NH2), 7.82–7.83 (m, 4H, ArH), 8.04 (d, 2H, J = 9 Hz), 8.24 (s, 1H, olefinicH), 10.56 (s, 1H, D2O-exchangeable NH); MS m/z (%): 357 (M+, 11.3), 199 (0.3), 187 (12.6), 186 (100), 158 (19.2), 77 (7.6); Anal. Calcd for C17H15N3O4S (357.38): C, 57.13; H, 4.23; N, 11.76; S, 8.97. Found: C, 57.00; H, 4.18; N, 11.55; S, 8.67%.
3.2.5. 2-Cyano-3-(4-chlorophenyl)-N-(4-sulfamoylphenyl)prop-2-enamide (5c)
Yield (63%), mp 286 °C (from dioxane/ethanol); IR (KBr) νmax: 3388, 3329, 3262 (NH, NH2), 2218 (C≡N), 1688 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.37 (s, 2H, D2O-exchangeable NH2), 7.76 (d, 2H, J = 9 Hz), 7.91–8.07 (m, 4H, ArH), 8.10 (d, 2H, J = 9 Hz), 8.39 (s, 1H, olefinicH), 10.78 (s, 1H, D2O-exchangeable NH); MS m/z (%): 361 (M+, 19.4), 191 (17.3), 190 (100), 162 (27.9), 127 (29.6), 123 (4.6), 111 (5.8), 99 (5.2), 75 (13.8); Anal. Calcd for C16H12ClN3O3S (361.80): C, 53.11; H, 3.34; Cl, 9.80; N, 11.61; S, 8.86. Found: C, 53.01; H, 3.29; Cl, 9.72; N, 11.51; S, 8.76%.
3.2.6. Synthesis of Pyridines 7a–c
Method A: A mixture of 5 (10 mmol) and malononitrile (0.66 g, 10 mmol) in ethanol (30 mL) containing piperidine (0.5 mL) was heated under reflux for 3 h. After cooling, the precipitate was filtered off, washed with ethanol and then recrystallized from the proper solvent to give 7a–c.
Method B: Equimolar amounts of 3 (10 mmol) and the appropriate 2-(arylidene)-malononitrile (namely 2-(benzylidene)-malononitrile, 2-(4-methoxybenzylidene)-malononitrile, and 2-(4-chloro benzylidene)-malononitrile) (10 mmol) in ethanol (30 mL) was treated with piperidine (0.5 mL) and the reaction mixture was heated under reflux for 3 h. After cooling, the precipitate was filtered off, washed with ethanol and then recrystallized from the proper solvent to give 7a–c.
Method C: A mixture of 3 (10 mmol), the appropriate aldehyde (namely benzaldehyde, p-anisaldehyde, and p-chlorobenzaldehyde) (10 mmol), piperidine (10 mmol), and malononitrile (0.66 g, 10 mmol) in ethanol (30 mL) was heated under reflux for 3 h. After cooling, the precipitate was filtered off, washed with ethanol and then recrystallized from the proper solvent to give 7a–c.
3.2.7. 4-(6-Amino-3,5-dicyano-2-oxo-4-phenylpyridin-1(2H)-yl)benzenesulfonamide (7a)
Yield (54%), mp 316 °C (from dioxane/ethanol); IR (KBr) νmax: 3458, 3332, 3212 (NH, NH2), 2216 (C≡N), 1672 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.50 (s, 2H, D2O-exchangeable NH2), 7.51–7.58 (m, 7H, ArH, NH2), 7.60 (d, 2H, J = 9 Hz), 8.01 (d, 2H, J = 9 Hz); MS m/z (%): 392 (M+ + 1, 10.7), 391 (M+, 7.8), 237 (7.8), 155 (9.2), 129 (8.7), 81 (46.5), 69 (100). Anal. Calcd for C19H13N5O3S (391.40): C, 58.30; H, 3.35; N, 17.89; S, 8.19. Found: C, 58.20; H, 3.34; N, 17.86; S, 8.15%.
3.2.8. 4-[6-Amino-3,5-dicyano-4-(4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]benzenesulfonamide (7b)
Yield (56%), mp 350 °C (from dioxane/ethanol); IR (KBr) νmax: 3311, 3208, 3078 (NH, NH2), 2214 (C≡N), 1659 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.88 (s, 3H, OCH3), 7.12 (s, 2H, D2O-exchangeable NH2), 7.50–7.52 (m, 6H, ArH, NH2), 7.62 (d, 2H, J = 9 Hz), 8.00 (d, 2H, J = 9 Hz); 13C-NMR: δ 55.3, 66.3, 75.4, 87.8, 114.0, 116.5, 120.1, 126.5, 127.7, 129.7, 132.7, 136.8, 145.3, 156.9, 159.5, 161.1; MS m/z (%): 422 (M+ + 1, 15.1), 421 (M+, 3.9), 336 (11.2), 265 (12.9), 229 (15.1), 195 (13.6), 185 (34.8), 157 (22.6), 82 (34.4), 55.1 (100). Anal. Calcd for C20H15N5O4S (421.43): C, 57.00; H, 3.59; N, 16.62; S, 7.61. Found: C, 56.98; H, 3.53; N, 16.55; S, 7.58%.
3.2.9. 4-[6-Amino-4-(4-chlorophenyl)-3,5-dicyano-2-oxopyridin-1(2H)-yl]benzenesulfonamide (7c)
Yield (60%), mp > 300 °C (from dioxane/ethanol); IR (KBr) νmax: 3348, 3208, 3097 (NH, NH2), 2219 (C≡N), 1661 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.51 (s, 2H, D2O-exchangeable NH2), 7.56–7.59 (m, 4H, ArH), 7.69 (d, 2H, J = 9 Hz), 8.01 (d, 2H, J = 9 Hz), 8.10 (s, 2H, D2O-exchangeable NH2); MS m/z (%): 427 (M+ + 2, 46.3), 426 (M+ + 1, 46.0), 425 (M+, 100), 397 (38.0), 313 (22.4), 269 (18.4), 156 (25.8), 132 (28.2), 111 (27.3), 106 (22.4), 91 (41.4), 80 (29.1), 77 (55.2). Anal. Calcd for C19H12ClN5O3S (425.84): C, 53.59; H, 2.84; Cl, 8.33; N, 16.45; S, 7.53. Found: C, 53.46; H, 2.80; Cl, 8.30; N, 16.42; S, 7.50%.
3.2.10. 4-(3-Cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzenesulfonamide (10)
To a mixture of cyanoacetanilide 3 (1.20 g, 5 mmol) and acetylacetone (0.50 g, 1mmol) in dioxane (20 mL), triethylamine (0.5 mL) was added and the reaction mixture was refluxed for 8 h. On cooling, the separated solid was filtered, washed with ethanol and crystallized from DMF to afford the corresponding 4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzenesulfonamide (10). Yield (64%), mp > 300 °C (from DMF); IR (KBr) νmax: 3314, 3174, 3083 (NH, NH2), 2223 (C≡N), 1648 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 1.98 (s, 3H, CH3), 2.40 (s, 3H, CH3), 6.49 (s, 1H, pyridineH), 7.52–7.57 (m, 4H, ArH, NH2), 7.99 (d, 2H, J = 9 Hz, ArH); MS m/z (%): 303 (M+, 51.9), 302 (100), 274 (10.6), 223 (21.5), 171 (0.9), 156 (2.8), 78 (23.6), 50 (20.6). Anal. Calcd for C14H13N3O3S (303.33): C, 55.43; H, 4.32; N, 13.85; S, 10.57. Found: C, 55.33; H, 4.28; N, 13.78; S, 10.52%.
3.2.11. 2-Imino-N-(4-sulfamoylphenyl)-2H-chromene-3-carboxamide (11)
A mixture of equimolar amounts of 3 (1.20 g, 5 mmol) and salicyaldehyde (0.61 g, 5 mmol) in 1,4-dioxane (25 mL) containing a catalytic amount of piperidine was heated under reflux for 2 h. The solid product formed was collected by filtration and recrystallized from dioxane/ethanol (3:1) to give 11. Yield (90%), mp 294 °C (from dioxane/ethanol); IR (KBr) νmax: 3318, 3244 (NH, NH2), 1680 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.25 (s, 2H, D2O-exchangeable NH2), 7.32 (d, 2H, J = 9 Hz, ArH), 7.58–7.63 (m, 4H, ArH), 7.83 (d, 2H, J = 9 Hz, ArH), 8.58 (s, 1H, CH), 9.29 (s, 1H, D2O-exchangeable NH), 13.11 (s, 1H, D2O-exchangeable NH); MS m/z (%): 344 (M+ + 1, 4.8), 343 (M+, 13.5), 172 (86.5), 156 (62.9), 143 (99.1), 65 (100). Anal. Calcd for C16H13N3O4S (343.35): C, 55.97; H, 3.82; N, 12.24; S, 9.34. Found: C, 55.90; H, 3.80; N, 12.20; S, 9.31%.
3.2.12. 2-Oxo-N-(4-sulfamoylphenyl)-2H-chromene-3-carboxamide (12)
Method A: To a solution of 3 (1.20 g, 5 mmol) in acetic acid (30 mL) containing 0.5 g of fused sodium acetate, salicyaldehyde (0.61 g, 5 mmol) was added. The mixture was heated under reflux for 2 h. After cooling, the formed product was collected by filtration and recrystallized from DMF to give 12.
Method B: The iminochromene derivatives 11 (0.86 g, 2.5 mmol) was dissolved in boiling dioxane (40 mL) and treated with 5 mL HCl. The reaction mixture was heated under reflux for 2 h. Left to cool, the obtained product was filtered off, washed with cold water, and air-dried. Yield (86%), mp > 300 °C (from DMF); IR (KBr) νmax: 3362, 3258, 3108 (NH, NH2), 1698 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.30 (s, 2H, D2O-exchangeable NH2), 7.57 (d, 2H, J = 9 Hz, ArH), 7.79–7.89 (m, 4H, ArH), 8.03 (d, 2H, J = 9 Hz, ArH), 8.92 (s, 1H, CH), 10.88 (s, 1H, D2O-exchangeable NH); 13C-NMR: δ 114.9, 118.7, 119.8, 124.3, 126.9, 130.2, 134.6, 139.1, 141.2, 142.1, 153.5, 155.4, 160.2, 161.2; MS m/z (%): 345 (M+ + 1, 3.6), 344 (M+, 10.1), 224 (2.8), 173 (100), 118 (5.8), 101 (47.3), 90 (14.6), 80 (14.2), 76 (6.5), 64 (47.0). Anal. Calcd for C16H12N2O5S (344.34): C, 55.81; H, 3.51; N, 8.14; S, 9.31. Found: C, 55.76; H, 3.45; N, 8.10; S, 9.29%.
3.2.13. Coupling of N-[4-(Aminosulfonyl)phenyl]-2-cyanoacetamide (3) with the Appropriate Diazonium Salt of Aromatic Amines
General procedure: To a cold solution of cyanoacetanilide
3 (1.20 g, 5 mmol) in pyridine (20 mL), was added the appropriate diazonium salt of aromatic amine (4-methylaniline or 4-methoxyaniline or aniline or 4-chloroaniline or methyl 2-aminobenzoate) (5 mmol) [prepared according to literature procedures] [
32]. The addition was carried out portion wise with stirring at 0–5 °C over a period of 30 min. After complete addition, the reaction mixture was stirred for a further 4 h then kept in an ice chest for 12 h and finally diluted with water. The precipitated solid was collected by filtration, washed with water, dried and finally recrystallized from the proper solvent to afford the corresponding coupling products
13a–
e.
3.2.14. 2-Cyano-2-[2-(4-methylphenyl)hydrazinylidene]-N-(4-sulfamoylphenyl)ethanamide (13a)
Yield (94%), mp 288 °C (from dioxane); IR (KBr) νmax: 3325, 3226, 3186 (NH, NH2), 2214 (C≡N),1664 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 2.30 (s, 3H, CH3), 7.20 (s, 2H, D2O-exchangeable NH2), 7.22–7.64 (m, 4H, ArH), 7.81 (d, 2H, J = 9 Hz, ArH), 7.92 (d, 2H, J = 9 Hz, ArH), 10.13 (s, 1H, D2O-exchangeable NH), 11.93 (s, 1H, D2O-exchangeable NH); MS m/z (%): 358 (M+ + 1, 8.7), 357 (M+, 45.0), 198 (6.4), 186 (23.8), 172 (87.8), 134 (10.9), 119 (19.9), 106 (47.9), 91 (100), 77 (52.1), 65 (38.3). Anal. Calcd for C16H15N5O3S (357.38): C, 53.77; H, 4.23; N, 19.60; S, 8.97. Found: C, 53.71; H, 4.20; N, 19.55; S, 8.87%.
3.2.15. 2-Cyano-2-[2-(4-methoxyphenyl)hydrazinylidene]-N-(4-sulfamoylphenyl)ethanamide (13b)
Yield (95%), mp 274 °C (from dioxane); IR (KBr) νmax: 3336, 3227 (NH, NH2), 2212 (C≡N), 1662 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.77 (s, 3H, OCH3), 7.00 (d, 2H, J = 9 Hz, ArH), 7.25 (s, 2H, D2O-exchangeable NH2), 7.69 (d, 2H, J = 9 Hz, ArH), 7.81 (d, 2H, J = 8.7 Hz, ArH), 7.92 (d, 2H, J = 8.7 Hz, ArH), 10.10 (s, 1H, D2O-exchangeable NH), 11.95 (s, 1H, D2O-exchangeable NH); MS m/z (%): 374 (M+ + 1, 8.7), 373 (M+, 24.3), 270 (5.8), 175 (21.4), 172 (39.8 ), 129 ( 22.3), 122 (100), 107 (38.8), 92 (38.8), 77 (47.6). Anal. Calcd for C16H15N5O4S (373.38): C, 51.47; H, 4.05; N, 18.76; S, 8.59. Found: C, 51.36; H, 4.00; N, 18.69; S, 8.52%.
3.2.16. 2-Cyano-2-(2-phenylhydrazinylidene)-N-(4-sulfamoylphenyl)ethanamide (13c)
Yield (92%), mp > 300 °C (from dioxane); IR (KBr) νmax: 3367, 3269, 3240 (NH, NH2), 2218 (C≡N), 1680 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.26 (s, 2H, D2O-exchangeable NH2), 7.38–7.79 (m, 5H, ArH), 7.82 (d, 2H, J = 9 Hz, ArH), 7.93 (d, 2H, J = 9 Hz, ArH), 10.17 (s, 1H, D2O-exchangeable NH), 11.98 (s, 1H, D2O-exchangeable NH); MS m/z (%): 343 (M+, 36.8), 206 (21.1), 198 (18.4), 172 (68.4), 145 (50.0), 118 (31.6), 108 (36.8), 91 (84.2), 80 (50.0), 77 (76.3), 60 (100). Anal. Calcd for C15H13N5O3S (343.36): C, 52.47; H, 3.82; N, 20.40; S, 9.34. Found: C, C, 52.45; H, 3.78; N, 20.38; S, 9.30%.
3.2.17. 2-[2-(4-Chlorophenyl)hydrazinylidene]-2-cyano-N-(4-sulfamoylphenyl)ethanamide (13d)
Yield (95%), mp > 300 °C (from dioxane); IR (KBr) νmax: 3360, 3232, 3190 (NH, NH2), 2216 (C≡N), 1668 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 7.26 (s, 2H, D2O-exchangeable NH2), 7.47 (d, 2H, J = 9 Hz), 7.74–7.82 (m, 4H, ArH), 7.92 (d, 2H, J = 9 Hz), 10.22 (s, 1H, D2O-exchangeable NH), 12.04 (s, 1H, D2O-exchangeable NH); MS m/z (%): 379 (M+ + 2, 17.9), 378 (M+ + 1, 12.5), 377 (M+, 39.3), 296 (26.8), 238 (12.5 ), 206 (41.1), 182 (32.1), 172 (96.4), 156 (51.8), 125 (57.1), 111 (53.6), 106 (30.4), 90 (69.6), 77 (21.4), 64 (100). Anal. Calcd for C15H12ClN5O3S (377.80): C, 47.69; H, 3.20; Cl, 9.38; N, 18.54; S, 8.49. Found: C, 47.61; H, 3.15; Cl, 9.27; N, 18.49; S, 8.43%.
3.2.18. Methyl 4-[2-(1-Cyano-2-oxo-2-{(4-sulfamoylphenyl)amino}ethylidene)hydrazinyl]benzoate (13e)
Yield (95%), mp > 300 °C (from dioxane); IR (KBr) νmax: 3340, 3231, 3148 (NH, NH2) 2211 (C≡N), 1687 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.94 (s, 3H, CH3), 7.24 (s, 2H, D2O-exchangeable NH2), 7.31–7.94 (m, 4H, ArH), 8.03 (d, 2H, J = 9 Hz), 8.32 (d, 2H, J = 9 Hz), 10.43 (s, 1H, D2O-exchangeable NH), 12.49 (s, 1H, D2O-exchangeable NH); MS m/z (%): 402 (M+ + 1, 3.0), 401 (M+, 12.8), 170 (11.7), 133 (100), 90 (34.1), 92 (20.2), 77 (21.2), 65 (12.7). Anal. Calcd for C17H15N5O5S (401.39): C, 50.87; H, 3.77; N, 17.45; S, 7.99. Found: C, 50.81; H, 3.65; N, 17.40; S, 7.92%.
3.2.19. Synthesis of Aminopyrazoles 14a,b
To a solution of the compound 13a,b (5 mmol) in dioxane (20 mL), hydrazine hydrate (80%, 1.0 mL, 5 mmol) was added and the reaction mixture was refluxed for 6 h and allowed to cool. The solid product obtained was filtered, washed with EtOH and dried. Recrystallization from dioxane afforded 14a,b.
3.2.20. 4-({5-Amino-4-[(4-methylphenyl)diazenyl]-1H-pyrazol-3-yl}amino)benzenesulfonamide (14a)
Yield (40%), mp 240 °C (from dioxane); IR (KBr) νmax: 3459, 3367, 3345, 3208 (NH, NH2), 2920, 2859 (aliphaticCH) cm−1; 1H-NMR (DMSO-d6): δ 2.29 (s, 3H, CH3), 5.18 (s, 2H, D2O-exchangeable NH2), 7.23 (d, 2H, J = 9 Hz), 7.42 (d, 2H, J = 9 Hz), 7.49 (s, 2H, D2O-exchangeable NH2), 7.75–7.90 (m, 4H, ArH), 9.86 (s, 1H, D2O-exchangeable NH), 13.65 (s, 1H, D2O-exchangeable NH); 13C-NMR: δ 20.5, 99.4, 117.0, 119.5, 126.4, 129.5, 132.9, 137.9, 141.8, 145.1, 151.5, 165.7; MS m/z (%): 372 (M+ + 1, 14.6), 356 (20.8), 217 ( 31.3 ), 201 (16.7), 156 ( 31.3 ), 126 ( 22.9), 123 (58.3), 107 (50.0), 106 (100), 90 (50.0), 77 (54.2). Anal. Calcd for C16H17N7O2S (371.41): C, 51.74; H, 4.61; N, 26.40; S, 8.63. Found: C, 51.70; H, 4.58; N, 26.20; S, 8.59%.
3.2.21. 4-({5-Amino-4-[(4-methoxyphenyl)diazenyl]-1H-pyrazol-3-yl}amino)benzenesulfonamide (14b)
Yield (72%), mp 200 °C (from dioxane); IR (KBr) νmax: 3436, 3351, 3259 (NH, NH2), 1658 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.77 (s, 3H, OCH3), 5.03 (s, 2H, D2O-exchangeable NH2), 7.00 (d, 2H, J = 9 Hz), 7.21 (s, 2H, D2O-exchangeable NH2), 7.49 (d, 2H, J = 9 Hz), 7.77–7.81 (m, 4H, ArH), 9.70 (s, 1H, D2O-exchangeable NH), 13.20 (s, 1H, D2O-exchangeable NH); MS m/z (%): 389 (M+ + 2, 35.4), 388 (M+ + 1, 40.2), 387 (M+, 38.4), 250 (31.7 ), 216 (40.2), 196 (53.0 ), 171 (45.1), 155 (31.7), 122 (33.5), 108 (34.8), 95 (40.2), 69 (100). Anal. Calcd for C16H17N7O3S (387.41): C, 49.60; H, 4.42; N, 25.31; S, 8.28. Found: C, 49.58; H, 4.40; N, 25.30; S, 8.20%.
3.2.22. 4-Amino-3-phenyl-N-(4-sulfamoylphenyl)-2-thioxo-2,3-dihydro-1,3-thiazole-5-carboxamide (15)
To a solution of cyanoacetamide 3 (1.20 g, 5 mmol) in DMF containing triethylamine (1 mL), elemental sulfur (0.16 g, 5 mmol) and phenyl isothiocyanate (0.68 mL, 5 mmol) were added. The reaction mixture was heated at 60 °C for 2 h with continous stirring and then poured into a beaker containing an ice-water mixture with few drops of HCl. The solid product so formed was filtered off, washed with EtOH and dried. Recrystallization from dioxane afforded compound 15. Yield (60%), mp > 300 °C (from DMF); IR (KBr) νmax: 3397, 3210 (NH, NH2), 1671 (C=O), 1335, 1217 (C=S) cm−1; 1H-NMR (DMSO-d6): δ 3.42 (s, 2H, D2O-exchangeable NH2), 7.19 (s, 2H, D2O-exchangeable NH2), 7.50 (d, 2H, J = 9 Hz), 7.55–7.88 (m, 5H, ArH), 7.96 (d, 2H, J = 9 Hz), 8.45 (s, 1H, D2O-exchangeable NH); MS m/z (%) 406 (M+, 0.9), 402 (5.7), 172 (14.3), 156 (8.6), 129 (11.4), 114 (11.4), 109 (17.1), 82 (32.9), 76 (44.3), 63 (100). Anal. Calcd for C16H14N4O3S3 (406.50): C, 47.27; H, 3.47; N, 13.78; S, 23.66. Found: C, 47.21; H, 3.44; N, 13.71; S, 23.59%.
3.2.23. 3,5-Diamino-4-cyano-N-(4-sulfamoylphenyl)thiophene-2-carboxamide (16)
To a solution of compound 3 (1.20 g, 5 mmol) in dioxane (25 mL) containing triethylamine (1.00 mL), malononitrile (0.33 g, 5 mmol) was added followed by the addition of an equimolar amount of elemental sulfur (0.16 g, 5 mmol). The reaction mixture was heated under reflux for 5 h, then cooled and neutralized by pouring onto ice/water mixture containing few drops of hydrochloric acid. The solid product formed was collected by filtration and crystallized from dioxane. Yield (86%), mp > 300 °C (from dioxane); IR (KBr) νmax: 3743, 3316 (NH, NH2), 2209 (C≡N), 1635 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 3.45 (s, 4H, D2O-exchangeable 2NH2), 7.26 (s, 2H, D2O-exchangeable NH2), 7.50–7.92 (m, 4H, ArH), 11.36 (s, 1H, D2O-exchangeable NH); MS m/z (%): 338 (M+ + 1, 44.9), 337 (M+, 47.2), 295 (47.2), 278 (45.7), 181 (49.6), 156 (53.5), 150 (51.9), 122 (51.2), 105 (64.6), 80 (48.8), 58 (100.0). Anal. Calcd for C12H11N5O3S (337.37): C, 42.72; H, 3.29; N, 20.76; S, 19.01. Found: C, 42.68; H, 3.21; N, 20.66; S, 18.96%.
3.2.24. Synthesis of 18, 19 and 20
Compound 3 (1.20 g, 5 mmol) was added to a stirred solution of potassium hydroxide (0.26 g, 5 mmol) in DMF (20 mL). After stirring for 30 min, phenyl isothiocyanate (0.68 g, 5 mmol) was added to the resulting mixture. Stirring was continued for 6 h, and then chloroacetone or 3-(2-bromoacetyl)- 2H-chromen-2-one or methyl iodide, (5 mmol) was added portion wise over a period of 30 min. After the addition was complete, the reaction mixture was stirred for an additional 12 h, during which the reactant dissolved and a yellow product precipitated. The solid product was filtered off, washed with EtOH and dried. Recrystallization from proper solvent afforded 18, 19 and 20.
3.2.25. N-[4-(Aminosulfonyl)phenyl]-2-cyano-2-(4-methyl-3-phenyl-1,3-thiazol-2(3H)-ylidene)acet- amide (18)
Yield (95%), mp 272 °C (from Dioxane) (lit. mp 260–262 °C) [
31]; IR (KBr) ν
max: 3294, 3196, 3107 (NH, NH
2), 2178 (C≡N), 1605 (C=O) cm
−1;
1H-NMR (DMSO-
d6): δ 1.86 (s, 3H, CH
3), 6.98 (s, 1H, thiazole-CH), 7.17 (s, 2H, D
2O-exchangeable NH
2), 7.49 (d, 2H,
J = 9 Hz), 7.57 (d, 2H,
J = 9 Hz), 7.60–7.70 (m, 5H, ArH), 9.02 (s, 1H, D
2O-exchangeable NH);
13C-NMR (DMSO-
d6): δ 14.2, 66.3, 106.9, 115.9, 119.3, 126.2, 128.9, 129.6, 130.6, 136.6, 137.5, 138.3, 142.4, 165.1, 166.5; MS
m/
z (%): 412 (M
+, 10.1), 332 (2.1), 241 (100), 214 (35.3), 198 (19.2), 172 (6.9), 118 (19.9), 90 (38.3), 77 (43.2). Anal. Calcd for C
19H
16N
4O
3S
2 (412.48): C, 55.32; H, 3.91; N, 13.58; S, 15.55. Found: C, 55.30; H, 3.88; N, 13.51; S, 15.50%.
3.2.26. 2-Cyano-2-[4-(2-oxo-2H-chromen-4-yl]-3-phenyl-1,3-thiazol-2(3H)-ylidene)-N-(4-sulfamoyl- phenyl)ethanamide (19)
Yield (55%), mp 280 °C (from Dioxane); IR (KBr) νmax: 3367, 3310 and 3235 (NH, NH2), 3060 (aromatic CH), 1713 (C=O), 1635 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 1.01 (s, 3H, J = 7.2 Hz, CH3), 4.04 (q, 2H, J = 7.2 Hz, CH2), 7.08–7.13 (m, 5H, ArH), 7.21 (d, 2H, J = 9 Hz), 7.39–7.44 (m, 7H, ArH and NH2), 7.63 (d, 2H, J = 9 Hz), 9.54 (s, 1H, D2O-exchangeable NH), 9.73 (s, 1H, D2O-exchangeable NH); 13C-NMR: δ 70.9, 95.3, 115.4, 115.8, 118.0, 119.6, 120.9, 124.8, 125.8, 126.3, 128.4, 128.8, 129.3, 129.5, 132.7, 137.0, 138.0, 142.1, 143.0, 153.2, 158.4, 164.7, 171.3; MS m/z (%): 521 (M+, 26.3), 322 (15.8), 218 (100.0), 199 (15.8), 77 (86.0). Anal. Calcd for C27H18N4O5S2 (542.58): C, 59.77; H, 3.34; N, 10.33; S, 11.82. Found: C, 59.75; H, 3.30; N, 10.31; S, 11.79%.
3.2.27. 2-Cyano-3-(methylsulfanyl)-3-(phenylamino)-N-(4-sulfamoylphenyl)prop-2-enamide (20)
Yield (95%), mp 204 °C (from EtOH) (lit. mp 220–222 °C) [
33]; IR (KBr) ν
max: 3410, 3339, 3243, 3119 (NH, NH
2), 2194 (C≡N), 1628 (C=O) cm
−1;
1H-NMR (DMSO-
d6): δ 2.49 (s, 3H, CH
3), 7.18 (s, 2H, D
2O-exchangeable NH
2), 7.31–7.41 (m, 5H, ArH), 7.67 (d, 2H,
J = 9 Hz), 7.79 (d, 2H,
J = 9 Hz), 9.65 (s, 1H, D
2O-exchangeable NH), 9.91 (s, 1H, D
2O-exchangeable NH); MS
m/
z (%): 389 (M
+ + 1, 63.0), 388 (M
+, 10.9), 341 (58.7), 294 (100), 249 (56.5), 223 (67.4), 208 (68.5), 197 (58.7), 185 (25.0), 182 (59.8), 140 (76.1), 92 (17.4). Anal. Calcd for C
17H
16N
4O
3S
2 (388.46): C, 52.56; H, 4.15; N, 14.42; S, 16.51. Found: C, 52.50; H, 4.12; N, 14.45; S, 16.48%.
3.2.28. 2-Cyano-2-(1,3-dithian-2-ylidene)-N-(4-sulfamoylphenyl)acetamide (22)
To a stirred suspension of finely powdered potassium hydroxide (0.26 g, 5 mmole) in dry DMF (20 mL) cyanoacetamide 3 (1.20 g, 5 mmole) was added, the resulted mixture was cooled at 10 °C in an ice bath, then carbon disulfide (5 mmol) was added slowly over the course of 10 min. After addition was complete, stirring of the reaction mixture was continued for additional 2 h. Then dibromopropane (5 mmol) was added to the mixture while cooling (~15 °C) and stirring for 1 h. The mixture was then poured into crushed ice and the resulting precipitate was filtrated off, dried and crystallized from the proper solvent to give 22. Yield (95%), mp 278 °C (from Dioxane); IR (KBr) νmax: 3314, 3241, 3107 (NH, NH2), 2209 (C≡N), 1653 (C=O) cm−1; 1H-NMR (DMSO-d6): δ 2.18 (m, 2H, J = 6.80 Hz, CH2), 3.04 (t, 2H, J = 6.6 Hz, CH2), 3.19 (t, 2H, J = 6.6 Hz, CH2), 7.25 (s, 2H, D2O-exchangeable NH2), 7.75 (m, 4H, ArH), 10.29 (s, 1H, D2O-exchangeable NH); 13C-NMR: δ 22.5, 29.2, 98.5, 115.6, 119.8, 126.5, 139.0, 141.3, 159.8, 177.3; MS m/z (%): 356 (M+ + 1, 2.9), 355 (M+, 14.8), 237 (0.2), 183 (100), 129 (2.3), 118 (1.2), 110 (27.6), 80 (18.1). Anal. Calcd for C13H13N3O3S3 (355.45): C, 43.93; H, 3.69; N, 11.82; S, 27.06. Found: C, 43.85; H, 3.57; N, 11.78; S, 27.00%.