General procedure for the preparation of N-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-aryl-5-benzoylamino-1,3-diphenyl-2-pyrazoline-5-carbohydrazides (6a,b).
Each of compounds 5a,b (1 mmol) was added to a solution of compound 2 (1 mmol) in toluene (10 mL). The reaction mixture was then heated under reflux for 11/2 hour, concentrated, and diluted with petroleum ether (bp. 40-60 °C). After decantation, the residue obtained was boiled in ethanol (5 mL), filtered, and cooled. The formed precipitate was collected by filtration and recrystallized from ethanol giving colorless crystals of 6a,b.
N-(5,6-Diphenyl-1,2,4-triazin-3-yl)-5-benzoylamino-1,3,4-triphenyl-2-pyrazoline-5-carbohydrazide (6a). Using the general procedure, 5a gave 6a (73%); mp. 218-219°C; IR (cm-1): 3405, 3277 (NH str.), 3063, 3038 (aromatic CH str.), 2922, 2866, 2855 (pyrazolinyl aliphatic CH str.), 1709 (hydrazide C=O str.), 1685 (amide C=O str.), 1627 (C=N str.), 1601 (aromatic C=C str.), 1505, 1480 (NH bend.), 1365, 1312, 1283, 1251 (C-N str.), 762, 697 (aromatic CH bend.); 1H-NMR (DMSO-d6) δ 11.31, 10.31 [2s, 2H (exch.), hydrazide NHNH], 7.72 [s, 1H (exch.), amide NH], 7.57-6.82 (m, 30H, ArH's), 5.64 (s, 1H, pyrazolinyl CH); 13C-NMR (DMSO-d6) δ 171.5, 164.8 (C=O), 157, 152, 146.5, 142.5 (C=N), 136.2, 134.6, 132.2, 131.5 (aromatic C), 130.5, 129.5, 129.4, 128.7, 128.6, 128.5, 128.2, 127.6, 127.3, 127.2, 127.0. 126.2 (aromatic CH), 81.6 (pyrazolinyl C), 63.5 (pyrazolinyl CH); Anal. for C44H34N8O2 Calcd.: C, 74.77; H, 4.85; N, 15.85. Found: C, 74.60; H, 5.00, N, 15.70.
N-(5,6-Diphenyl-1,2,4-triazin-3-yl)-5-benzoylamino-1,3-diphenyl-4-(2-methoxyphenyl)-2-pyrazoline-5-carbohydrazide (6b). Using the general procedure, 5b gave 6b (41%); mp. 210-212°C; IR (cm-1): 3396, 3267 (NH str.), 3059, 3028 (aromatic CH str.), 2964, 2932, 2883, 2833 (OCH3 and pyrazolinyl aliphatic CH str.), 3059, 3028, 2997 (aromatic CH str.), 1709 (hydrazide C=O str.), 1682 (amide C=O str.), 1597(aromatic C=C str.), 1495, 1473, 1445 (NH bend.), 1358, 1331, 1290, 1252 (C-N str.), 1067, 1028 (C-O str. of OCH3), 762, 692 (aromatic CH bend.); 1H-NMR (DMSO-d6) δ 11.23, 10.28 [2 brs, 2H (exch.), hydrazide NHNH], 7.97 [s, 1H (exch.), amide NH] 7.61-6.50 (m, 29H, ArH's), 5.87 (s, 1H, pyrazolinyl CH), 3.60 (s, 3H, OCH3); 13C-NMR (DMSO-d6) δ 171.64, 164.30, (C=O), 157.28, 146.84, 142.78, 136.41 (C=N), 135.95, 134.76, 132.74, 132.49, 132.45, 132.41, 131.46 (aromatic C), 130.54, 129.70. 129.31, 129.20, 128.74, 128.64, 128.40, 128.29, 126.86, 126.08, 125.89, 121.68, 120.33, 115.15, 115.09, 114.99 (aromatic CH), 110.04 (pyrazolinyl C), 80.55 (pyrazolinyl CH), 55.04 (OCH3); Anal. for C45H36N8O3 Calcd.: C, 73.35; H, 4.92; N, 15.21. Found: C, 73.50; H, 5.00; N, 15.40.
General procedure for the preparation of 4-aryl-5-benzoylamino-1,3-diphenyl-2-pyrazoline-5-carbohydrazides (8a,b). To a suspension of each of compounds 5a,b (1 mmol) in methanol (20 mL) was added 80% hydrazine hydrate (0.5 mL). While the reaction mixture of compound 8a was shaken for ten minutes at room temperature, that of compound 8b was heated under reflux for one hour. The reaction mixtures of each compound were then left overnight at room temperature. The colorless precipitate formed was collected by filtration and recrystallized from methanol to give colorless crystals of 8a,b.
5-Benzoylamino-1,3,4-triphenyl-2-pyrazoline-5-carbohydrazide (8a). Using the general procedure, 5a gave 8a (73%); mp. 214-215°C; IR (cm-1): 3400, 3325 (NH, NH2 str.), 3065, 3034 (aromatic CH str.), 2930 (pyrazolinyl CH str.), 1669 (C=O str.), 1625 (C=N str.), 1601 (aromatic C=C str.), 1503, 1480 (NH bend.), 1374, 1321, 1280, 1243 (C-N str.), 750, 696 (aromatic CH bend.); 1H-NMR (DMSO-d6) δ 10.05 [s, 1H (exch.), hydrazide NH], 8.07 [s, 1H (exch.), amide NH], 7.60-6.86 (m, 20H, ArH's), 5.32 (s, 1H, pyrazolinyl CH), 4.54[s, 2H (exch.), NH2]; MS m/z 475 (M+, 1.3%); Anal. for C29H25N5O2 Calcd.: C, 73.24; H, 5.30; N, 14.73. Found: C, 73.20; H, 5.25; N, 14.60.
5-Benzoylamino-1,3-diphenyl-4-(2-methoxyphenyl)-2-pyrazoline-5-carbohydrazide (8b). Using the general procedure, 5b gave 8b (74%); mp. 230°C; IR (cm-1): 3384, 3334,3284 (NH, NH2 str.), 3061, 3025 (aromatic CH str.), 2954, 2942, 2901, 2835 (OCH3 and pyrazolinyl aliphatic CH str.), 1684 (hydrazide C=O str.), 1672 (amide C=O str.), 1636 (C=N str.), 1604 (aromatic C=C str.), 1497, 1475 (NH bend.), 1375, 1294, 1250 (C-N str.), 1167, 1028 (C-O str. of OCH3), 750, 692 (aromatic CH bend.); 1H-NMR (DMSO-d6) δ 10.25 [s, 1H (exch.), hydrazide NH], 8.18 [s, 1H (exch.), amide NH], 7.56-6.49 (m, 19H, ArH's), 5.59 (s, 1H, pyrazolinyl CH), 4.61[s, 2H (exch.), NH2], 3.82 (s, 3H, OCH3); MS m/z 505 (M+, 0.4%); Anal. for C30H27N5O3 Calcd.: C, 71.27; H, 5.38; N, 13.85. Found: C, 71.30; H, 5.50; N, 14.00.
N-Arylidene-4-aryl-1,3-diphenylpyrazole-5-carbohydrazides (9a-g).
General Procedure A: To a solution of each of compounds
8a,b (1 mmol) in either acetic acid (12 mL) or n-butanol (20 mL) was added the appropriate aryl aldehyde (1 mmol) and the reaction mixture was then heated under reflux for a time as shown as in
Table 1. The crystalline colorless precipitates of compounds
9a-d,f were collected by filtration, washed with methanol, and recrystallized from the appropriate solvent. Pure
9e,g were obtained from their reaction mixtures via dilution with water, collection of the formed precipitate by filtration, and recrystallization from the appropriate solvent.
Table 1.
9 | Reaction Solvent | Reflux Time | Recrystallization Solvent |
---|
a | n-Butanol | 3 hours | EtOH |
b | Acetic acid | 20 minutes | n-Butanol |
c | Acetic acid | 11/2 hour | Acetic acid |
d | Acetic acid | 11/2 hour | Acetic acid |
e | Acetic acid | 2 hours | Ethanol |
f | Acetic acid | 11/4 hour | Ethanol |
g | Acetic acid | 2 hours | Ethanol |
General Procedure B: To compound 8a (1 mmol) was added 4-methylbenzaldehyde (1 mmol) and 3 drops of piperidene. The reaction mixture was then heated (oil bath) at 120 °C till complete dissolution which was followed by an immediate resolidification. The reaction mixture was allowed to cool to room temperature, diluted with methanol, and the formed colorless crystalline product was collected by filtration and recrystallized from ethanol giving colorless crystals of 9c, identical with the product 9c obtained from general procedure A (mp. and mixed mp. as well as analytical and spectral data).
N-Benzylidene-1,3,4-triphenylpyrazole-5-carbohydrazide (9a). Using general procedure A, 8a gave 9a (34%); mp. 229-230°C; IR (cm-1): 3584-3291 (OH str. of hydrazole tautomer), 3213 (NH str.), 3066, 3028 (aromatic CH str.), 1674 (hydrazide C=O str.) 1655 (C=N str.), 1597 (aromatic C=C str.), 1556, 1500 (NH bend.), 1365, 1313, 1275, 1246 (C-N str.), 760, 692 (aromatic CH bend.); 1H-NMR (CDCl3) δ 10.03, 8.43 [ 2brs,1H (exch.), hydrazide (53.7%) - hydrazole (46.3%) tautomeric proton], 7.73-7.07 (m, 21H, ArH's, N=CH); Ms m/z 442 (M+, 13.7%); Anal. for C29H22N4O Calcd.: C, 78.71; H, 5.01; N, 12.66. Found: C, 78.80; H, 5.20; N, 12.80.
N-(2-Hydroxybenzylidene)-1,3,4-triphenylpyrazole-5-carbohydrazide (9b). Using general procedure A, 8a gave 9b (88%); mp.283-285°C; IR (cm-1): 3200-2500 (OH str.), 3178 (NH str.), 3055, 3007 (aromatic CH str.), 1722 (hydrazide C=O str.), 1651(C=N str.), 1601 (aromatic C=C str.), 1545, 1499 (NH bend.), 1367, 1331, 1313, 1292, 1277, 1250, 1186, 1184, 1149 [C-N, C-O (phenolic) str.], 758, 692 (aromatic CH bend.); 1H-NMR (DMSO-d6) δ 12.36 [s, 1H (exch.), 2-(OH)-C6H4] 10.70, 9.96 [2s, 1H (exch.), hydrazide (63.3%) - hydrazole (36.7%) tautomeric proton], 8.30 (s, 1H, N=CH), 7.72-6.73 (m, 19H, ArH's); Anal. for C29H22N4O2 Calcd.: C, 75.97; H, 4.83; N, 12.22. Found: C, 76.00; H, 4.76; N, 12.00.
N-(4-Methylbenzylidene)-1,3,4-triphenylpyrazole-5-carbohydrazide (9c). Using the general procedures A and/or B, 8a gave 9c (67%) and / or (70%), respectively; mp. 222-223°C; IR (cm-1): 3342-2400 (OH str. of hydrazole tautomer), 3197 (NH str.), 3052, 3000 (aromatic CH str.), 2947, 2919 (CH str. of CH3), 1672 (hydrazide C=O str.) 1653 (C=N str.), 1603 (aromatic C=C str.), 1564, 1500 (NH bend.), 1372, 1335, 1322, 1311, 1292, 1279, 1256, 1211-1027 [C-O (of hydrazole tautomer), C-N str.], 765,757, 702, 684 (aromatic CH bend.); 1H-NMR (CDCl3) δ 10.45, 8.50 [2s, 1H (exch.), hydrazide (61.0%) - hydrazole (39.0%) tautomeric proton], 7.65-7.08 (m, 20H, ArH's, N=CH), 2.33 (s, 3H, CH3); MS m/z 456 (M+, 12.0%); Anal. for C30H24N4O Calcd.: C, 78.92; H, 5.30; N, 12.27. Found: C, 78.90; H, 5.40; N, 12.40.
N-(4-Methoxybenzylidene)-1,3,4-triphenylpyrazole-5-carbohydrazide (9d). Using general procedure A, 8a gave 9d (83%); mp. 245-247°C; IR (cm-1): 3713-2555 (OH str.of hydrazole tautomer), 3194 (NH str.), 3055, 3006 (aromatic CH str.), 2967, 2927, 2838 (CH str. of OCH3), 1673 (hydrazide C=O str.), 1651 (C=N str.), 1604 (aromatic C=C str.), 1565, 1506 (NH bend.), 1369, 1306, 1251, 1172-1028 [C-O, C-N str.), 762,701 (aromatic CH bend.); 1H-NMR (CDCl3) δ 9.93, 8.40 [2s, 1H (exch.), hydrazide (52.2%) - hydrazole (47.8%) tautomeric proton], 7.69-6.83 (m, 20H, ArH's, N=CH), 3.84 (s, 3H, OCH3); Anal. for C30H24N4O2 Calcd.: C, 76.25; H, 5.12; N, 11.86. Found: C, 76.40; H, 5.08; N, 12.00.
N-Benzylidene-1,3-diphenyl-4-(2-methoxyphenyl)-pyrazole-5-carbohydrazide (9e). Using general procedure A, 8b gave 9e (80%); mp. 175-176°C; IR (cm-1): 3200-2500 (OH str. of hydrazole tautomer), 3196 (NH str.), 3067 (aromatic CH str.), 2987, 2930, 2856 (CH str. of OCH3), 1670 (hydrazide C=O str.) 1651 (C=N str.), 1612, 1595 (aromatic C=C str.), 1556, 1499 (NH bend.), 1364, 1273,1242-1074 (C-O, C-N str.), 760, 700, 692 (aromatic CH bend.); 1H-NMR (CDCl3) δ 9.83, 9.43 [2s, 1H (exch.), hydrazide (27.8%) - hydrazole (72.2%) tautomeric proton], 7.72-6.95 (m, 20H, ArH's, N=CH), 3.85 (s, 3H, OCH3); Anal. for C30H24N4O2 Calcd.: C, 76.25; H, 5.12; N, 11.86. Found: C, 76.40; H, 5.10; N, 11.60.
N-(2-Hydroxybenzylidene)-1,3-diphenyl-4-(2-methoxyphenyl)-pyrazole-5-carbohydrazide (9f). Using general procedure A, 8b gave 9f (81%); mp. 207-208°C; 1H-NMR (CDCl3): δ 10.69 [s, 1H (exch.), OH], 9.37 [s, 1H (exch.), NH], 7.89 (s, 1H, N=CH), 7.67-6.84 (m, 18H, ArH's), 3.84 (s, 3H, OCH3); Anal. for C30H24N4O3 Calcd.: C, 73.75; H, 4.95; N, 11.47. Found: C, 73.80; H, 5.00; N, 11.62.
N-(4-Methoxybenzylidene)-1,3-diphenyl-4-(2-methoxyphenyl)-pyrazole-5-carbohydrazide (9g). Using general procedure A, 8b gave 9g (85%); mp. 178-180°C; IR (cm-1): 3645-3266 (OH str. of hydrazole tautomer), 3175 (NH str.), 3068, 3005 (aromatic CH str.), 2962, 2933, 2902, 2837(CH str. of OCH3), 1685 (hydrazide C=O str.) 1650 (C=N str.), 1603 (aromatic C=C str.), 1547, 1509 (NH bend.), 1366, 1307,1254 , 1170-1026 (C-O, C-N str.) 758, 694 (aromatic CH bend.); 1H-NMR (CDCl3): δ 9.74, 9.34 [2s,1H (exch.), hydrazide (25.0%) - hydrazole (75.0%) tautomeric proton], 7.72-6.86 (m, 19H, ArH's, N=CH), 3.83(s, 6H, OCH3); Anal. for C31H26N4O3 Calcd.: C, 74.08; H, 5.21; N, 11.15. Found: C, 74.12; H, 5.10; N, 11.60.
N-Acetyl-1,3,4-triphenylpyrazole-5-carbohydrazide (10). To compound 8a (1 mmol) was added acetic acid (15 mL) and the reaction mixture was heated under reflux for 11/4 hour. After cooling, the reaction mixture was poured onto water and the formed precipitate was collected by filtration and recrystallized from ethanol as colorless crystals of 10 (83%); mp. 237-238°C; IR (cm-1): 3194 (NH str.), 3055, 3009 (aromatic CH str.), 2968, 2914, 2839 (CH str. of CH3), 1672 (C=O str.), 1651 (C=N str.), 1605 (aromatic C=C str.), 1564, 1512, 1500 (NH bend.), 1371, 1306, 1279, 1250 (C-N str.), 772, 768, 704, 690 (aromatic CH bend.); 1H-NMR (DMSO-d6): δ 10.76, 9.98 [2s, 2H (exch.), hydrazide NHNH], 7.97-7.26 (m, 15H, ArH's), 1.85 (s, 3H, CH3CO); Anal. for C24H20N4O2 Calcd.: C, 72.71; H, 5.08; N, 14.13. Found: C, 72.80; H, 5.10; N, 14.50.
2-(1,3,4-Triphenylpyrazol-5-yl)-5-phenyl-1,3,4-oxadiazole (11). A mixture of compound 8a (1 mmol), benzoic acid (1 mmol), and phosphororus oxychloride (1 mmol) was heated under reflux for 11/2 hour. After cooling to room temperature, the reaction mixture was poured onto crushed ice, stirred, decanted and diluted with water. The residue obtained after a second decantation was boiled with methanol. The solidified residue obtained on cooling was collected by filtration and recrystallized from N,N-dimethylformamide as colorless crystals of 11 (23%); mp.185°C; 1H-NMR (DMSO-d6): δ 7.69-7.34 (m, ArH's); MS m/z 440 (M+, 49.9); Anal. for C29H20N4O Calcd.: C, 79.07; H, 4.57; N, 12.72. Found: C, 79.10; H, 4.62; N, 12.69.
General procedure for the preparation of 2-(4-Aryl-5-benzoylamino-1,3-diphenyl-2-pyrazolin-5-yl)-1,3,4-oxadiazole-5(4H)-thiones (12a,b). To a solution containing 95% ethanol (5 mL) and potassium hydroxide (1 mmol, dissolved in the least amount of water), were added compounds 8a,b (1 mmol) followed by carbon disulfide (1.5 mmol). The reaction mixture was heated under reflux for 3 hours till all the evolution of hydrogen sulfide ceased. After decantation, the supernatant solution was evaporated, diluted with water (while a milky solution was obtained), and acidified with hydrochloric acid containing ice. The reaction mixture was allowed to stand at room temperature for 15 minutes, filtered, and the solid obtained was washed well with water and dried at room temperature. The crude products were then recrystallized from ethanol as colorless crystals of 12a,b.
2-(5-Benzoylamino-1,3,4-triphenyl-2-pyrazolin-5-yl)-1,3,4-oxadiazole-5(4H)-thione (12a). Using the general procedure, 8a gave 12a (81%); mp. 236-237°C; IR (cm-1): 3421, 3157 (NH str.), 3063, 3030 (aromatic CH str.), 2945, 2926, 2852 (pyrazolinyl CH str.), 1683 (amide C=O str.), 1600 (aromatic C=C str.), 1507, 1489, 1469 (NH bend.), 1331, 1286, 1255 (C-N str.), 1199, 1153,1019 (=C-O-C= str.), 1064 (C=S str.), 761, 649 (aromatic CH bend.); 1H-NMR (DMSO-d6): δ 14.60 [brs, 1H (exch.), oxadiazolyl NH], 9.85 [s, 1H (exch.), amide NH], 7.83-7.10 (m, 20H, ArH's), 5.90 (s, 1H, pyrazolinyl CH); Anal. for C30H23N5O2S Calcd.: C, 69.61; H, 4.48; N, 13.53; S,6.19. Found: C, 69.50; H, 4.50; N, 13.59; S, 6.15.
2-[5-Benzoylamino-1,3,-diphenyl-4-(2-methoxyphenyl)-2-pyrazolin-5-yl]-1,3,4-oxadiazole-5(4H)-thione (12b). Using the general procedure, 8b gave 12b (81%); mp. 140°C; IR ((cm-1): 3375, 3139 (NH str.), 3067 (aromatic CH str.), 2938, 2836 (OCH3 and pyrazolinyl aliphatic CH str.), 1682 (amide C=O str.), 1602 (aromatic C=C str.), 1498, 1470, 1446 (NH bend.), 1343, 1328, 1293, 1253 (C-N str.), 1190, 1149, 1106, 1027 (=C-O-C= str., C-O str. of OCH3), 1069 (C=S str.), 759, 699 (aromatic CH bend.); 1H-NMR (DMSO-d6): δ 14.52 [brs, 1H (exch.), oxadiazolyl NH], 9.69 [s, 1H (exch.), amide NH], 7.78-6.78 (m,19H, ArH's), 6.32 (s, 1H, pyrazolinyl CH), 3.85 (s, 3H, OCH3); Anal. for C31H25N5O3S Calcd.: C, 67.99; H, 4.60; N, 12.79; S,5.85. Found: C, 68.12 H, 4.62; N, 12.69; S,5.82.
N-(N-Phenylthiocarbamoyl)-5-benzoylamino-1,3-diphenyl-4-(2-methoxyphenyl)-2-pyrazoline-5-carbo-hydrazide (13). To a suspension of 8b (1 mmol) in absolute ethanol (25 mL) was added phenyl isothiocyanate (1.01 mmol), and the mixture was heated under reflux for 21/2 hours (all materials went into solution after 45 minutes of heating under reflux). The reaction mixture was concentrated, allowed to cool, and upon scratching, the product precipitated as colorless crystals. The crude product was collected by filtration and recrystallized from ethanol as colorless crystals of 13 (75%) mp.145-146°C; IR (cm-1): 3371, 3327, 3150, 3110 (NH str.), 3059,3029 (aromatic CH str.), 2964, 2923, 2880, 2842 (OCH3 and pyrazolinyl aliphatic CH str.), 1718 (hydrazide C=O str.), 1678 (amide C=O str.), 1651, 1625 (C=N str.), 1599 (aromatic C=C str.), 1543,1497, 1473, 1442 (NH bend.), 1380, 1357, 1320, 1291, 1252 (C-N str.), 1210-1025 (C-O str.), 1070 (C=S str.), 758, 692 (aromatic CH bend.); 1H-NMR (DMSO-d6): δ 10.79, 9.92, 9.34, 9.15 [3s, 1brs, 4H (exch.), 4NH], 7.80-6.55 (m, 24H, ArH's), 6.23 (s, 1H, pyrazolinyl CH), 3.76 (s, 3H, OCH3); Anal. for C37H32N6O3S Calcd.: C, 69.35; H, 5.03; N, 13.11; S, 5.04. Found: C, 69.1, H, 5.30; N, 13.00; S, 5.10