3.1.2. General Procedure for Synthesis of the Target Bis-indoles (7a–f and 9a–h), and 11
To a hot stirred solution of key intermediate 1H-indole-2-carbohydrazide 5 (0.18 gm, 1 mmoL) in absolute ethyl alcohol (7 mL) and glacial acetic acid (catalytic amount), the appropriate N-unsubstituted 1H-indole-2,3-dione 6a–f, N-substituted 1H-indole-2,3-dione 8a–h, or 1-tetralone 10 (1 mmoL) was added. The resulting mixture was refluxed for 2 hours, and then the formed solid was filtered off while hot, washed with cold isopropyl alcohol, dried and recrystallized from DMF to afford target bis-indoles (7a–f and 9a–h), and 11, respectively.
N′-(5-Fluoro-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (7a)
Red powder, m.p. 281–283 °C; (yield 70%), IR: 3327, 3270 (NH) and 1694 (C=O); 1H NMR δ ppm: 4.19 (brs, 2H, CH2-C=O), 6.85–6.88 (m, 1H, Ar-H), 6.95 (m, 1H, Ar-H), 7.05 (t, 1H, Ar-H, J = 7.5 Hz), 7.19 (t, 1H, Ar-H, J = 7.5 Hz), 7.32 (m, 2H, Ar-H), 7.58 (d, 1H, Ar-H, J = 7.5 Hz), 8.14 (s, 1H, Ar-H), 10.82 (s, 1H, NH of isatin, D2O exchangeable), 10.96 (s, 1H, NH of hydrazide, D2O exchangeable), 11.23 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 28.26 (CH2-C=O), 107.26, 107.89, 111.33, 111.42, 113.06, 113.26, 115.58, 115.65, 18.52, 118.63, 121.07, 124.56, 127.28, 136.02, 138.54, 139.95, 156.56, 158.44, 162.57 (C=O of isatin), 164.81 (C=O of hydrazide); MS m/z [%]: 356.15 [M+, 100], 157.03 [11.35], 130.12 [25.10]; Anal. Calcd. for C18H13FN4O2: C, 64.28; H, 3.90; N, 16.66; found C, 63.93; H, 3.94; N, 16.73.
N′-(5-Chloro-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (7b)
Orange powder, m.p. 292–294 °C; (yield 74%), IR: 3450, 3338 (NH) and 1694 (C=O); 1H NMR δ ppm: 4.11 (brs, 2H, CH2-C=O), 6.87 (d, 1H, Ar-H, J = 8.5 Hz), 6.96-6.99 (m, 1H, Ar-H), 7.05 (t, 1H, Ar-H, J = 7.5 Hz), 7.31-7.35 (m, 2H, Ar-H), 7.38 (d, 1H, Ar-H, J = 8.0 Hz), 7.57 (d, 1H, Ar-H, J = 8.0 Hz), 8.33 (s, 1H, Ar-H), 10.92 (s, 1H, NH of isatin, D2O exchangeable), 11.20 (s, 1H, NH of hydrazide, D2O exchangeable), 11.33 (s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C18H13ClN4O2: C, 61.28; H, 3.71; N, 15.88; found C, 60.95; H, 3.66; N, 15.97.
N′-(5-Bromo-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (7c)
Orange powder, m.p. > 300 °C; (yield 85%), IR: 3365, 3219, 3182 (NH) and 1726, 1692 (C=O); 1H NMR δ ppm: 4.11 (brs, 2H, CH2-C=O), 6.83 (d, 1H, Ar-H, J = 8.5 Hz), 6.96–6.99 (m, 1H, Ar-H), 7.04 (t, 1H, Ar-H, J = 7.5 Hz), 7.31-7.35 (m, 2H, Ar-H), 7.51 (d, 1H, Ar-H, J = 8.0 Hz), 7.57 (d, 1H, Ar-H, J = 8.0 Hz), 8.43 (s, 1H, Ar-H), 10.93 (s, 1H, NH of isatin, D2O exchangeable), 10.96 (s, 1H, NH of hydrazide, D2O exchangeable), 11.33 (s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C18H13BrN4O2: C, 54.43; H, 3.30; N, 14.10; found C, 54.85; H, 3.28; N, 14.02.
2-(1H-Indol-3-yl)-N′-(5-methyl-2-oxoindolin-3-ylidene)acetohydrazide (7d)
Red powder, m.p. > 300 °C; (yield 78%), IR: 3363, 3309, 3191 (NH) and 1691 (C=O); 1H NMR δ ppm: 2.24, 2.50 (2s, 3H, CH3), 3.87, 4.18 (2s, 2H, CH2-C=O), 6.76-6.81 (m, 1H, Ar-H), 6.97 (t, 1H, Ar-H, J = 7.5 Hz), 7.07-7.14 (m, 2H, Ar-H), 7.30–7.59 (m, 4H, Ar-H), 10.95 (s, 1H, NH of isatin, D2O exchangeable), 11.08, 11.12 (2s, 1H, NH of hydrazide, D2O exchangeable), 12.51, 12.96 (2s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 18.57, 20.53, 18.14, 32.32, 106.38, 107.03, 110.83, 111.42, 111.52, 118.45, 118.67, 119.87, 120.92, 121.04, 121.29, 124.32, 124.81, 126.99, 127.27, 131.61, 131.79, 140.02, 162.55, 168.32, 173.32; MS m/z [%]: 332.11 [M+, 80.08], 157.24 [40.03], 130.19 [100]; Anal. Calcd. for C19H16N4O2: C, 68.66; H, 4.85; N, 16.86; found C, 68.83; H, 4.80; N, 16.97.
2-(1H-Indol-3-yl)-N′-(5-nitro-2-oxoindolin-3-ylidene)acetohydrazide (7e)
Yellow powder, m.p. 289–291 °C; (yield 80%), IR: 3399, 3147 (NH) and 1728, 1686 (C=O); 1H NMR δ ppm: 4.13 (brs, 2H, CH2-C=O), 6.95-7.00 (m, 1H, Ar-H), 7.04–7.08 (m, 2H, Ar-H), 7.33–7.35 (m, 2H, Ar-H), 7.58 (d, 1H, Ar-H, J = 8.0 Hz), 8.19-8.28 (m, 1H, Ar-H), 9.04 (s, 1H, Ar-H), 10.96 (s, 1H, NH of isatin, D2O exchangeable), 11.50 (s, 1H, NH of hydrazide, D2O exchangeable), 11.81 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 18.57 (CH2-C=O), 111.31, 111.40, 111.49, 115.08, 115.62, 118.51, 118.63, 120.70, 121.03, 121.48, 127.21, 136.00, 136.12, 141.99, 142.75, 147.42, 149.13, 162.76 (C=O of isatin), 165.04 (C=O of hydrazide); Anal. Calcd. for C18H13N5O4: C, 59.50; H, 3.61; N, 19.28; found C, 59.67; H, 3.57; N, 9.34.
N′-(5,7-Dimethyl-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (7f)
Brown powder, m.p. 294–296 °C; (yield 73%), IR: 3432, 3267, 3180 (NH) and 1725, 1692 (C=O); 1H NMR δ ppm: 2.13 (s, 3H, CH3 of isatin), 2.20 (s, 3H, CH3 of isatin), 4.14 (brs, 2H, CH2-C=O), 6.96–6.99 (m, 2H, Ar-H), 7.07 (brs, 1H, Ar-H), 7.35 (br s, 2H, Ar-H), 7.58 (d, 1H, Ar-H, J = 8.0 Hz), 7.84 (s, 1H, Ar-H), 10.71 (s, 1H, NH of isatin, D2O exchangeable), 10.98 (s, 1H, NH of hydrazide, D2O exchangeable), 11.06 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 15.80, 15.99, 20.34, 107.21, 111.40, 111.48, 115.01, 118.32, 118.59, 119.59, 121.05, 121.27, 124.67, 127.28, 130.55, 131.55, 134.05, 136.05, 139.85, 162.20; Anal. Calcd. for C20H18N4O2: C, 69.35; H, 5.24; N, 16.17; found C, 69.46; H, 5.20; N, 16.11.
N′-(1-Allyl-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9a)
Orange powder, m.p. 218–220 °C; (yield 75%), IR: 3354, 3238 (NH) and 1704 (C=O); 1H NMR δ ppm: 4.12 (brs, 2H, CH2-C=O), 4.36 (s, 2H, N-CH2), 5.13-5.16 (m, 2H, CH2=CH-), 5.82-5.87 (m, 1H, N-CH2-CH), 6.96-7.09 (m, 4H, Ar-H), 7.34 (s, 2H, Ar-H), 7.39 (t, 1H, Ar-H, J = 8.0 Hz), 7.58 (d, 1H, Ar-H, J = 8.0 Hz), 8.16 (s, 1H, Ar-H), 10.99 (s, 1H, NH of hydrazide, D2O exchangeable), 11.02 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 29.84 (CH2-C=O), 41.48 (N-CH2), 107.22, 109.84, 111.45, 114.73, 116.93, 118.64, 121.15, 122.18, 124.62, 125.60, 131.80, 132.27, 136.06, 143.75, 163.09; MS m/z [%]: 358.23 [M+, 41.07], 157.15 [34.19], 130.26 [100]; Anal. Calcd. for C21H18N4O2: C, 70.38; H, 5.06; N, 15.63; found C, 70.21; H, 5.13; N, 15.75.
2-(1H-Indol-3-yl)-N′-(2-oxo-1-propylindolin-3-ylidene)acetohydrazide (9b)
Orange powder m.p. 207–208 °C; (yield 77%), IR: 3317, 3282 (NH) and 1705 (C=O); 1H NMR δ ppm: 0.85 (brs, 3H, CH2-CH3), 1.59 (brs, 2H, CH2-CH3), 3.68 (t, 2H, N-CH2), 3.89, 4.20 (2s, 2H, CH2-C=O), 6.96 (t, 1H, Ar-H, J = 7.5 Hz), 7.07–7.19 (m, 2H, Ar-H), 7.30–7.43 (m, 4H, Ar-H), 7.58 (d, 1H, Ar-H, J = 7.5 Hz), 7.69 (s, 1H, Ar-H), 10.95, 11.09 (2s, 1H, NH of hydrazide, D2O exchangeable), 12.44, 12.91 (2s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C21H20N4O2: C, 69.98; H, 5.59; N, 15.55; found C, 70.12; H, 5.62; N, 15.43.
N′-(1-(sec-Butyl)-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9c)
Orange powder, m.p. 199–201 °C; (yield 68%), IR: 3451, 3294 (NH) and 1707 (C=O); 1H NMR δ ppm: 0.87 (d, 6H, -CH(CH3)2, J = 2.5 Hz), 2.03 (brs, 1H, -CH(CH3)2), 3.52 (d, 2H, N-CH2-CH(CH3)2, J = 2.5 Hz), 4.13 (brs, 2H, CH2-C=O), 6.97–7.07 (m, 3H, Ar-H), 7.12 (d, 1H, Ar-H, J = 8.5 Hz), 7.34 (brs, 2H, Ar-H), 7.39 (t, 1H, Ar-H, J = 8.5 Hz), 7.59 (d, 1H, Ar-H, J = 7.5 Hz), 8.14 (brs, 1H, Ar-H), 10.98 (s, 1H, NH of hydrazide, D2O exchangeable), 11.18 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 19.91 (-CH(CH3)2), 26.62 (-CH(CH3)2), 46.58 (N-CH2), 107.23, 109.74, 111.44, 114.60, 118.66, 121.12, 122.01, 124.61, 125.58, 127.24, 132.31, 132.45, 136.06, 144.38, 163.55; MS m/z [%]: 374.23 [M+, 100], 157.10 [18.76], 130.38 [59.05]; Anal. Calcd. for C22H22N4O2: C, 70.57; H, 5.92; N, 14.96; found C, 70.69; H, 5.87; N, 15.02.
N′-(1-Benzyl-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9d)
Red powder, m.p. 223–225 °C; (yield 76%), IR: 3308, 3245 (NH) and 1706 (C=O); 1H NMR δ ppm: 4.15 (brs, 2H, CH2-C=O), 4.96 (s, 2H, benzylic protons), 6.98 (d, 3H, Ar-H, J = 7.5 Hz), 7.06 (t, 1H, Ar-H, J = 7.5 Hz), 7.25-7.35 (m, 8H, Ar-H), 7.60 (d, 1H, Ar-H, J = 8.5 Hz), 8.17 (brs, 1H, Ar-H), 10.99 (s, 1H, NH of hydrazide, D2O exchangeable), 11.23 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 42.64, 107.22, 109.86, 111.45, 114.82, 118.66, 121.14, 122.32, 124.64, 125.68, 127.23, 127.51, 128.72, 132.23, 136.08, 136.18, 143.60, 163.54; MS m/z [%]: 408.25 [M+, 32.23], 157.11 [100], 130.05 [48.95]; Anal. Calcd. for C25H20N4O2: C, 73.51; H, 4.94; N, 13.72; found C, 73.63; H, 4.91; N, 13.63.
N′-(1-(4-Fluorobenzyl)-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9e)
Red powder, m.p. 227–229 °C; (yield 72%), IR: 3353, 3115 (NH) and 1723 (C=O); 1H NMR δ ppm: 4.15 (brs, 2H, CH2-C=O), 4.94 (s, 2H, benzylic protons), 6.95–7.02 (m, 3H, Ar-H), 7.06 (t, 1H, Ar-H, J = 8.0 Hz), 7.13 (t, 2H, Ar-H, J = 8.0 Hz), 7.34–7.37 (m, 5H, Ar-H), 7.59 (d, 1H, Ar-H, J = 7.5 Hz), 8.16 (brs, 1H, Ar-H), 10.99 (s, 1H, NH of hydrazide, D2O exchangeable), 11.23 (s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C25H19FN4O2 (344.38): C, 70.41; H, 4.49; N, 13.14; found C, 70.73; H, 4.46; N, 13.11.
N′-(1-(4-Cyanobenzyl)-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9f)
Yellow powder, m.p. 233–234 °C; (yield 80%), IR: 3290, 3247 (NH), 2230 (C≡N) and 1704 (C=O); 1H NMR δ ppm: 4.14 (brs, 2H, CH2-C=O), 4.95 (s, 2H, benzylic protons), 6.99 (d, 2H, Ar-H, J = 7.5 Hz), 7.06 (t, 2H, Ar-H, J = 7.5 Hz), 7.34 (t, 3H, Ar-H, J = 7.5 Hz), 7.52 (t, 1H, Ar-H, J = 7.5 Hz), 7.60 (d, 1H, Ar-H, J = 7.5 Hz), 7.64 (d, 1H, Ar-H, J = 7.5 Hz), 7.73 (d, 1H, Ar-H, J = 7.5 Hz), 7.85 (s, 1H, Ar-H), 8.14 (brs, 1H, Ar-H), 11.00 (s, 1H, NH of hydrazide, D2O exchangeable), 11.24 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 42.01 (CH2), 107.21, 109.68, 111.46, 111.62, 115.02, 118.63, 122.46, 123.28, 124.64, 129.90, 129.98, 130.91, 131.40, 132.10, 137.96, 142.32, 143.32, 160.79 (C=O of isatin), 163.67 (C=O of hydrazide); Anal. Calcd. for C26H19N5O2: C, 72.04; H, 4.42; N, 16.16; found C, 71.82; H, 4.48; N, 16.28.
N′-(1-Benzyl-5-bromo-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9g)
Orange powder, m.p. 210–211 °C; (yield 82%), IR: 3367, 3282 (NH) and 1739, 1669 (C=O); 1H NMR δ ppm: 4.14 (brs, 2H, CH2-C=O), 4.96 (s, 2H, benzylic protons), 6.93 (d, 1H, Ar-H, J = 8.0 Hz), 6.96 (t, 1H, Ar-H, J = 7.5 Hz), 7.05 (t, 1H, Ar-H, J = 7.5 Hz), 7.25–7.36 (m, 7H, Ar-H), 7.53 (d, 1H, Ar-H, J = 8.0 Hz), 7.59 (d, 1H, Ar-H, J = 8.0 Hz), 8.47 (brs, 1H, Ar-H), 10.97 (s, 1H, NH of hydrazide, D2O exchangeable), 11.48 (s, 1H, NH of indol, D2O exchangeable); 13C NMR δ ppm: 42.71 (CH2), 107.21, 111.44, 111.62, 114.35, 116.46, 118.53, 118.63, 121.06, 124.54, 127.19, 127.55, 128.03, 1289.74, 134.24, 135.89, 136.01, 142.65, 163.26; Anal. Calcd. for C25H19BrN4O2: C, 61.61; H, 3.93; N, 11.50; found C, 61.79; H, 3.88; N, 11.57.
N′-(5-Bromo-1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-2-(1H-indol-3-yl)acetohydrazide (9h)
Brown powder, m.p. 183–185 °C; (yield 80%), IR: 3423, 3343 (NH) and 1730 (C=O); 1H NMR δ ppm: 4.13 (s, 2H, CH2-C=O), 4.95 (s, 2H, benzylic protons), 6.97 (d, 2H, Ar-H, J = 8.5 Hz), 7.05 (t, 1H, Ar-H, J = 8.0 Hz), 7.13 (t, 2H, Ar-H, J = 8.5 Hz), 7.33–7.37 (m, 4H, Ar-H), 7.55 (d, 1H, Ar-H, J = 8.0 Hz), 7.58 (d, 1H, Ar-H, J = 7.5 Hz), 8.45 (s, 1H, Ar-H), 10.97 (s, 1H, NH of hydrazide, D2O exchangeable), 11.49 (s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C25H18BrFN4O2: C, 59.42; H, 3.59; N, 11.09; found C, 59.58; H, 3.55; N, 11.16.
N′-(3,4-Dihydronaphthalen-1(2H)-ylidene)-2-(1H-indol-3-yl)acetohydrazide (11)
White crystals, m.p. 244–245 °C; (yield 84%), IR: 3315, 3246 (NH) and 1692 (C=O); 1H NMR δ ppm: 1.81 (d, 2H, CH2, J = 6.0 Hz), 2.61 (m, 2H, CH2), 2.74 (d, 2H, CH2, J = 5.6 Hz), 3.78, 4.13 (2s, 2H, CH2-C=O), 6.95–7.09 (m, 2H, Ar-H), 7.19–7.27 (m, 4H, Ar-H), 7.34 (t, 1H, Ar-H, J = 7.6 Hz), 7.57, 7.62 (2d, 1H, Ar-H, J = 8.0, 8.0 Hz), 8.00, 8.10 (2d, 1H, Ar-H, J = 7.2, 7.6 Hz), 10.41, 10.43 (s, 1H, NH of hydrazide, D2O exchangeable), 10.86, 10.90 (s, 1H, NH of indol, D2O exchangeable); Anal. Calcd. for C20H19N3O: C, 75.69; H, 6.03; N, 13.24; found C, 75.86; H, 5.99; N, 13.32.