General procedure for the synthesis of compounds 7–31
To a well-stirred solution of 6 (0.2 g, 0.64 mmol) in glacial acetic acid (35 ml) buffered with anhydrous sodium acetate (1.83 mmol), the respective aryl aldehyde (1.28 mmol) was added. The solution was refluxed for 24–72 h and then poured into ice-cold water. The precipitate was filtered and recrystallized from ethanol to give compounds 7–31 (All the compounds were recrystallized from ethanol except compounds 11, 12, 13, 18, 19 and 20 that were recrystallized in ethyl acetate).
2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)-5-benzylidenethiazolidin-4-one (7). Yield: 90%. M.p. 292–293 °C. IR (KBr): 3164 (NH), 1712 (C = O), 1562, 1353 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.17 (bs, 1H, NH); 7.91 (bs, 1H, furan); 7.82 (s, 1H, = CH); 7.67–7.53 (m, 6H, aromatic, furan). MS (m/z, %): 399 (M+, 5), 368 (42), 236 (14), 212 (13), 134 (65), 111 (20), 97 (36), 83 (45), 69 (60), 57 (100). Anal. Calcd. For C16H9N5O4S2: C, 48.12; H, 2.27; N, 17.54, Found: C, 48.43; H, 2.06; N, 17.23.
5-(4-Methylbenzylidene)-2-[5-(5-nitro-furan-2-yl)-[1,3,4]thiadiazol-2-ylimino]-thiazolidin-4-one (8). Yield: 68%. M.p. 306–308 °C. IR (KBr): 3138 (NH), 1714 (C = O), 1562, 1349 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.08 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.75 (s, 1H, = CH); 7.56 (bs, 3H, aromatic, furan); 7.38 (bs, 2H, aromatic); 2.36 (s, 3H, CH3). MS (m/z, %): 413 (M+, 18), 148 (100), 82 (16), 69 (12), 57 (18). Anal. Calcd. For C17H11N5O4S2: C, 49.39; H, 2.68; N, 16.94, Found: C, 49.71; H, 2.97; N, 16.60.
5-(4-methoxybenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (9). Yield: 72%. M.p. 284–286 °C. IR (KBr): 3097 (NH), 1696 (C = O), 1563, 1351 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.14 (bs, 1H, NH); 7.93 (bs, 1H, furan); 7.83 (s, 1H, = CH); 7.64 (bs, 2H, aromatic); 7.56 (bs, 1H, furan); 7.15 (bs, 2H, aromatic); 3.84 (s, 3H, OCH3). MS (m/z, %): 429 (M+, 6), 212 (81), 164 (100), 149 (52), 138 (34), 121 (29), 110 (19), 97 (32), 82 (61), 69 (54), 57 (71). Anal. Calcd. For C17H11N5O5S2: C, 47.55; H, 2.58; N, 16.31, Found: C, 47.89; H, 2.27; N, 16.43.
5-(4-(methylthio)benzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (10). Yield: 70%. M.p. 305–307 °C. IR (KBr): 3080 (NH), 1710 (C = O), 1560, 1352 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.03 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.75 (bs, 1H, = CH); 7.57 (bs, 3H, aromatic, furan); 7.43 (bs, 2H, aromatic); 2.5 (s, 3H, CH3). MS (m/z, %): 445 (M+,18), 368 (14), 180 (100), 165 (42), 121 (19), 97 (25), 83 (31), 69 (43), 57 (63). Anal. Calcd. For C17H11N5O4S3: C, 45.83; H, 2.49; N, 15.72, Found: C, 46.11; H, 2.20; N, 15.37.
5-(2-bromobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (11). Yield: 78%. M.p. 293–295 °C. IR (KBr): 3120 (NH), 1716 (C = O), 1561, 1352 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.20 (bs, 1H, NH); 7.90 (bs, 1H, furan); 7.82–7.44 (m, 6H, = CH, furan, aromatic). MS (m/z, %): 478 (M+ + 2, 23), 476 (M+, 22), 214 (100), 212 (99), 97 (42), 69 (54), 57 (76). Anal. Calcd. For C16H8BrN5O4S2: C, 40.18; H, 16.71; N, 14.64, Found: C, 40.52; H, 16.36; N, 14.28.
5-(3-bromobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (12). Yield: 78%. M.p. 293–295 °C. IR (KBr): 3072 (NH), 1720 (C = O), 1571,1354 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.22 (bs, 1H, NH); 7.90 (bs, 1H, furan); 7.87–7.55 (m, 6H, = CH, furan, aromatic). MS (m/z, %): 478 (M+ + 2, 28), 476 (M+, 27), 214 (100), 212 (99), 97 (51), 82 (39), 57 (74). Anal. Calcd. For Anal. Calcd. For C16H8BrN5O4S2: C, 40.18; H, 16.71; N, 14.64, Found: C, 39.97; H, 16.93; N, 14.29.
5-(4-bromobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (13). Yield: 91%. M.p. 336–338 °C. IR (KBr): 3095 (NH), 1716 (C = O), 1569, 1352 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.17 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.76 (bs, 3H, = CH, aromatic); 7.58 (bs, 3H, furan, aromatic). MS (m/z, %): 478 (M+ + 2, 40), 476 (M+, 39), 214 (100), 212 (99), 133 (30), 89 (38). Anal. Calcd. For Anal. Calcd. For C16H8BrN5O4S2: C, 40.18; H, 16.71; N, 14.64, Found: C, 39.91; H, 16.99; N, 14.83.
5-(2-chlorobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (14). Yield: 68%. M.p. 304–306 °C. IR (KBr): 3092 (NH), 1719 (C = O), 1579, 1362 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.21 (bs, 1H, NH); 7.94–7.52 (m, 7H, = CH, furan, aromatic). MS (m/z, %): 435 (M+ + 2, 4), 433 (M+, 12), 170 (33), 168 (100), 69 (35), 57 (44). Anal. Calcd. For C16H8ClN5O4S2: C, 44.30; H, 1.86; N, 16.14, Found: C, 44.39; H, 2.01; N, 16.02.
5-(3-chlorobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (15). Yield: 75%. M.p. 288–290 °C. IR (KBr): 3092 (NH), 1718 (C = O), 1518, 1356 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.20 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.79–7.58 (m, 6H, = CH, furan, aromatic). MS (m/z, %): 435 (M+ + 2, 5), 433 (M+, 15), 170 (33), 168 (100), 139 (44), 111 (22), 85 (20), 69 (38), 57 (48). Anal. Calcd. For C16H8ClN5O4S2: C, 44.30; H, 1.86; N, 16.14, Found: C, 44.59; H, 1.69; N, 16.10.
5-(4-chlorobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (16). Yield: 90%. M.p. 284–286 °C. IR (KBr): 3115 (NH), 1711 (C = O), 1564, 1351 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.17 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.79 (s, 1H, = CH); 7.66–7.58 (m, 5H, furan, aromatic). MS (m/z, %): 435 (M+ + 2,6), 433 (M + ,2), 170 (33), 168 (100), 139 (47), 111 (21), 85 (25), 69 (24), 57 (35). Anal. Calcd. For C16H8ClN5O4S2: C, 44.30; H, 1.86; N, 16.14, Found: C, 44.48; H, 1.76; N, 16.02.
5-(2,6-dichlorobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (17). Yield: 86%. M.p. 237–239 °C. IR (KBr): 3128 (NH), 1710 (C = O), 1581, 1348 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.20 (bs, 1H, NH); 7.89 (bs, 1H, furan); 7.98–7.56 (m, 5H, = CH, furan, aromatic). MS (m/z, %): 471 (M+ + 4, 10), 469 (M+ + 2, 7), 467 (M+, 1), 432 (90), 206 (100), 204 (66), 202 (11), 167 (21), 123 (19), 82 (28), 69 (10),53 (10). Anal. Calcd. For C16H7Cl2N5O4S2: C, 41.04; H, 1.51; N, 14.96, Found: C, 41.14; H, 1.74; N, 14.33.
5-(4-fluorobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (18). Yield: 75%. M.p. 269–271 °C. IR (KBr): 3137 (NH), 1715 (C = O), 1575, 1349 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.18 (bs, 1H, NH); 7.92 (bs, 1H, furan); 7.25 (s, 1H, = CH); 7.75 (bs, 2H, aromatic); 7.61 (bs, 1H, furan); 7.45 (bs, 2H, aromatic). MS (m/z, %): 417 (M+,18), 152 (100), 85 (13), 71 (12), 57 (20). Anal. Calcd. For C16H8FN5O4S2: C, 46.04; H, 1.93; N, 16.78, Found: C, 46.33; H, 1.80; N, 16.92.
5-(3-Hydroxybenzylidene)-2-[5-(5-nitro-furan-2-yl)-[1,3,4]thiadiazol-2-ylimino]-thiazolidin-4-one (19). Yield: 75%. M.p. 319–320 °C. IR (KBr): 3202 (OH), 3098 (NH), 1718 (C = O), 1562, 1350 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.14 (bs, 1H, NH); 10.01 (bs, 1H, OH); 7.91 (bs, 1H, furan); 7.72 (bs, 1H, = CH); 7.59 (bs, 1H, furan); 7.36(bs, 1H, aromatic); 7.11 (bs, 1H, aromatic); 7.06 (s, 1H, aromatic); 6.91 (bs, 1H, aromatic). MS (m/z, %): 415 (M+,5), 311 (100), 238 (84), 173 (47), 150 (22), 121 (58), 82 (80). Anal. Calcd. For C16H9N5O5S2: C, 46.26; H, 2.18; N, 16.86, Found: C, 45.99; H, 2.08; N, 17.05.
5-(4-Hydroxybenzylidene)-2-[5-(5-nitro-furan-2-yl)-[1,3,4]thiadiazol-2-ylimino]-thiazolidin-4-one (20). Yield: 94%. M.p. 258–260 °C. IR (KBr): 3133 (OH), 3116 (NH), 1717 (C = O), 1569, 1351 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.02 (bs, 1H, NH); 10.41 (bs, 1H, OH); 7.73 (bs, 1H, furan); 7.72 (bs, 1H, = CH); 7.58 (bs, 2H, aromatic); 7.55 (bs, 1H, furan); 6.97 (bs, 2H, aromatic). MS (m/z, %): 415 (M+,3), 311 (100), 238 (88), 212 (14), 173 (29), 150 (24), 121 (54), 110 (21), 99 (25), 82 (86), 60 (83). Anal. Calcd. For C16H9N5O5S2: C, 46.26; H, 2.18; N, 16.86, Found: C, 46.39; H, 2.29; N, 16.69.
5-(2-nitrobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (21). Yield: 56%. M.p. 302–304 °C. IR (KBr): 3131 (NH), 1738 (C = O), 1580, 1342 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.21 (bs, 1H, NH); 8.22 (bs, 1H, aromatic); 8.06 (bs, 1H, aromatic); 7.95 (bs, 1H, furan); 7.89–7.76 (m, 3H, aromatic, = CH); 7.57 (bs, 1H, furan). MS (m/z, %): 444 (M+,22), 179 (63), 97(55), 69(75), 57(100). Anal. Calcd. For C16H8N6O6S2: C, 43.24; H, 1.81; N, 18.91, Found: C, 43.48; H, 1.70; N, 18.69.
5-(3-nitrobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (22). Yield: 70%. M.p. 285–287 °C. IR (KBr): 3262 (NH), 1743 (C = O), 1572, 1354 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.23 (bs, 1H, NH); 8.52 (s, 1H, aromatic); 8.31 (bs, 1H, aromatic); 8.08 (bs, 1H, aromatic); 7.97–7.91 (m, 3H, furan, aromatic, = CH); 7.61 (bs, 1H, furan). MS (m/z, %): 444 (M+,28), 179 (66), 97 (51), 86 (43), 69 (72), 57 (100). Anal. Calcd. For C16H8N6O6S2: C, 43.24; H, 1.81; N, 18.91, Found: C, 43.13; H, 1.23; N, 18.80.
5-(4-nitrobenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (23). Yield: 88%. M.p. 344–346 °C. IR (KBr): 3215 (NH), 1727 (C = O), 1562, 1352 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.2 (bs, 1H, NH); 8.37 (bs, 2H, aromatic); 7.89 (bs, 4H, aromatic, furan, = CH); 7.59 (bs, 1H, furan). MS (m/z, %): 444 (M+, 20), 268 (16), 211 (17), 179 (58), 163 (10), 149 (28), 133 (21), 111 (24), 97 (43), 84 (68), 69 (70), 57 (100). Anal. Calcd. For C16H8N6O6S2: C, 43.24; H, 1.81; N, 18.91, Found: C, 42.91; H, 1.68; N, 19.09.
5-(4-(dimethylamino)benzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (24). Yield: 81%. M.p. 349–351 °C. IR (KBr): 3135 (NH), 1703 (C = O), 1573, 1303 (NO2). 1H-NMR (400 MHz, DMSO-d6): 12.84 (bs, 1H, NH); 7.88 (bs, 1H, furan); 7.63 (bs, 1H, = CH); 7.53 (bs, 1H, furan); 7.46 (bs, 2H, aromatic), 6.83 (bs, 2H, aromatic), 3.01 (bs, 6H, CH3). MS (m/z, %): 442 (M+, 12), 262 (11), 177 (100), 163 (22), 97 (19),83 (21), 69 (29), 57 (48). Anal. Calcd. For C18H14N6O4S2: C, 48.86; H, 3.19; N, 18.99, Found: C, 48.57; H, 3.02; N, 19.11.
5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (25). Yield: 62%. M.p. 217–219 °C. IR (KBr): 3613 (OH, non-bonded), 3789 (OH, bonded), 3130 (NH), 1698, 1668 (C = O), 1575, 1348 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.02 (bs, 1H, NH), 9.81, 8.03 (bs, 1H, OH, Z/Eisomers), 7.92 (bs, 1H, Furan), 7.87 (s, 1H, = CH, Z-isomer), 7.79 (s, 1H, furan), 7.67 (s, 1H, aromatic), 7.64 (s, 1H, = CH, E-isomers), 7.48 (s, 1H, aromatic), 1.44, 1.41 (s, 18H, CH3, Z/E-isomers). MS (m/z, %): 442 (M+, 12), 262 (11), 177 (100), 163 (22), 97 (19),83 (21), 69 (29), 57 (48). Anal. Calcd. For C24H25N5O5S2: C, 54.64; H, 4.78; N, 13.27, Found: C, 54.31; H, 4.65; N, 13.06.
2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)-5-((pyridin-3-yl)methylene)thiazolidin-4-one (26). Yield: 97%. M.p. 299–301 °C. IR (KBr): 3116 (NH), 1719 (C = O), 1569, 1349 (NO2). 1H-NMR (400 MHz, DMSO-d6) 12.96 (bs, 1H, NH); 8.91 (bs, 1H, pyridine); 8.67 (bs, 1H, pyridine); 8.07 (bs, 1H, pyridine); 7.90 (s, 1H, furan); 7.85 (bs, 1H, pyridine); 7.65 (s, 1H, = CH); 7.57 (bs, 1H, furan). MS (m/z, %): 400 (M+,40), 368 (13), 135 (100), 97 (14), 82 (22), 69 (24), 57 (29). Anal. Calcd. For C15H8N6O4S2: C, 45.00; H, 2.01; N, 20.99, Found: C, 45.28; H, 2.18; N, 21.16.
5-((1H-indol-2-yl)methylene)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one (27). Yield: 78%. M.p. 359–361 °C. IR (KBr): 3112 (NH), 1694 (C = O), 1572, 1351 (NO2). 1H-NMR (400 MHz, DMSO-d6): 12.95 (bs, 1H, NH); 12.22 (bs, 1H, NH); 8.07 (bs, 1H, furan); 7.89–7.22 (m, 7H, aromatic, furan, = CH). MS (m/z, %): 438 (M+,59), 212 (54), 173 (100), 97 (39), 82 (48), 69 (24), 57 (78). Anal. Calcd. For C18H10N6O4S2: C, 49.31; H, 2.30; N, 19.17, Found: C, 49.62; H, 2.56; N, 19.02.
2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)-5-((furan-2-yl)methylene)thiazolidin-4-one (28). Yield: 96%. M.p. 324–326 °C. IR (KBr): 3130 (NH), 1704 (C = O), 1565, 1358 (NO2). 1H-NMR (400 MHz, DMSO-d6): 12.98 (bs, 1H, NH); 8.16 (bs, 1H, furan); 7.91 (bs, 1H, nitrofuran); 7.65 (bs, 1H, = CH); 7.59 (bs, 1H, furan); 7.17 (bs, 1H, nitrofuran); 6.78 (bs, 1H, furan). MS (m/z, %): 389 (M+,34), 212 (49), 124 (100), 97 (36), 83 (31), 69 (71), 57 (84). Anal. Calcd. For C14H7N5O5S2: C, 43.19; H, 1.81; N, 17.99, Found: C, 42.97; H, 1.95; N, 17.08.
5-(5-Nitro-furan-2-ylmethylene)-2-[5-(5-nitro-furan-2-yl)-[1,3,4]thiadiazol-2-ylimino]-thiazolidin-4-one (29). Yield: 93%. M.p. 259–261 °C. IR (KBr): 3140 (NH), 1714 (C = O), 1580, 1347 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.25 (bs, 1H, NH); 7.93 (bs, 1H, furan); 7.83 (bs, 1H, furan); 7.69–7.64 (m, 2H, = CH, furan); 7.37 (bs, 1H, furan). MS (m/z, %): 434 (M+, 52), 388 (68), 238 (21), 169 (100), 139 (19), 111 (29), 95 (78), 82 (24), 69 (14). Anal. Calcd. For C14H6N6O7S2: C, 38.71; H, 1.39; N, 19.35, Found: C, 38.36; H, 1.20; N, 19.52.
2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)-5-((thiophen-2-yl)methylene)thiazolidin-4-one (30). Yield: 85%. M.p. 314–316 °C. IR (KBr): 3102 (NH), 1727 (C = O), 1545, 1351 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.06 (bs, 1H, NH); 8.05 (bs, 2H, furan, thiophen); 7.89 (bs, 1H, thiophen); 7.71 (s, 1H, = CH); 7.57 (bs, 1H, furan); 7.29 (bs, 1H, thiophen). MS (m/z, %): 405 (M+, 34), 140 (100), 96 (25), 82 (13), 69 (10). Anal. Calcd. For Found: C14H7N5O4S3: C, 41.48; H, 1.74; N, 17.27, Found: C, 41.66; H, 1.52; N, 17.10.
2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)-5-((5-nitrothiophen-2-yl)methylene)thiazolidin-4-one (31). Yield: 79%. M.p. 301–303 °C. IR (KBr): 3132 (NH), 1720 (C = O), 1530, 1359 (NO2). 1H-NMR (400 MHz, DMSO-d6): 13.14 (bs, 1H, NH); 8.22 (bs, 1H, thiophen); 8.08 (bs, 1H, thiophen); 7.90 (bs, 1H, furan); 7.71 (s, 1H, = CH); 7.60 (bs, 1H, furan). MS (m/z, %): 450 (M+, 3), 368 (33), 313 (29), 264 (18), 236 (34), 185 (19), 109 (27), 97 (55), 83 (60), 69 (69), 57 (100). Anal. Calcd. For C14H6N6O6S3: C, 37.33; H, 1.34; N, 18.66, Found: C, 37.62; H, 1.19; N, 18.39.