4.1. General Remarks. All solvents and starting materials were purchased from Merck and Sigma-Aldrich used without any additional purification. Analytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254 Al-plates. 1H NMR and 13C NMR spectra were recorded on a Bruker Avance DRX-500 machine using DMSO-d6 as solvent and TMS as an internal standard at room temperature (DMSO-d6 1H NMR: δ (ppm) =2.50 ppm; 13C NMR: δ (ppm) =39.9 ppm; CDCl3 1HNMR: δ (ppm) = 7.26 and 13C-NMR: δ (ppm) = 77.00 ppm). Chemical shifts were reported in ppm scale. FT-IR spectra of samples were obtained on ABB Bomem MB100 spectrometer with potassium bromide (KBr) pellets. Melting points were determined using an Electrothermal 9100 apparatus and are uncorrected. Elemental analysis was done by LECO Truspec.
4.2. Experimental procedure for the synthesis of compounds 3 (3a-3w), 4 (4a-4d), and 5 (5a-5g).
To a solution of isatin derivatives (1a-1w, 0.3mmol) in alcoholic solvents (2.0 mL), phosphonium ylide (2, 0.3 mmol) was added and stirred at room temperature for 30 min to afford the corresponding isatin chalcone. Upon completion of the reaction, the reaction color changes from orange to red. In the next step, carbon disulfide (0.3 mmol) and primary (1°) amines (0.3 mmol) were added to the reaction mixture and stirred for more 1.5 h to form products 3a-3w (the general procedure used for synthesizing the products 3a-3w was also employed for compounds 4a-4d,except using secondary (2°) amines in place of primary (1°) amines). Upon completion of the reaction, the reaction color changes from red to pale yellow. In this stage, if we added KOH (15 mg, 0.8 equiv.) to the reaction mixture, products 3 or 4 easily converted to dispirocyclopentane- bisoxindoles (5a-5g) after 30-90 min of stirring (first, the reaction color changes from pale yellow to red, and then from red to white). After completion of the reaction, the organic products were simply filtered off and the precipitate was washed with EtOH. The pure products were dried in air and directly characterized by 1H NMR, 13C NMR, elemental and FT-IR analysis. In addition, the structure of compound 3c was confirmed by X-ray crystallographic analysis.
1-allyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3a)
white solid; yield (96 mg, 81 %); m.p. 178-180 °C; 1H NMR (500 MHz, CDCl3) δ 3.09 (3H, s), 4.35 (1H, d.d., J= 5.0 Hz), 4.44 (1H, d, J= 5.0 Hz), 4.46 (1H, d, J= 5.0 Hz), 4.53 (1H, d.d, J= 5.0 Hz), 5.33 (2H, quintet, J= 15.0 Hz), 5.87 (1H, m), 6.93 (1H, d, J= 10.0 Hz), 7.08 (2H, t, J= 5.0 Hz), 7.31 -7.59 (6H, m), 8.15 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.7, 43.2, 46.9, 56.8, 100.2, 110.2, 118.6, 123.7, 123.8, 124.8, 125.4, 129.2, 129.3, 129.4, 130.2, 141.8, 143.5, 176.5, 191.4 ppm; IR (KBr) ν= 3300-3080, 1675, 1640, 1609 cm-1; Anal.
Calcd. for C21H20N2O2S2: C, 63.61; H, 5.08; N, 7.06; Found: C, 63.45; H, 5.16; N, 6.75 %.
1-benzyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3b)
white solid; yield (112 mg, 84 %); m.p. 160-162 °C; 1H NMR (500 MHz, CDCl3) δ 3.12 (3H, s), 4.46 (1H, d, J= 5.0 Hz), 4.52 (1H, d, J= 5.0 Hz), 4.79 (1H, d, J= 10.0 Hz), 5.23 (1H, d, J= 10.0 Hz), 6.81 (1H, d, J= 10.0 Hz), 7.05 (2H, t, J= 5.0 Hz), 7.23 -7.62 (11H, m), 8.19 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.7, 44.8, 47.0, 56.9, 100.2, 110.4, 123.7, 123.8, 124.7, 125.4, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 141.8, 143.5, 176.9, 191.4 ppm; IR (KBr) ν= 3300-3161, 1675, 1614 cm-1; Anal. Calcd. for C25H22N2O2S2: C, 67.24; H, 4.97; N, 6.27; Found: C, 67.01; H, 5.11; N, 6.08 %.
3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3c)
white solid; yield (102 mg, 86 %); m.p. 172-174 °C; 1H NMR (500 MHz, CDCl3) δ 1.04 (3H, t, J= 10.0 Hz), 1.78 (2H, m), 3.09 (3H, s), 3.69 (1H, m), 3.86 (1H, m), 4.42 (1H, d, J= 5.0 Hz), 4.43 (1H, d, J= 5.0 Hz), 6.96 (1H, d, J= 10.0 Hz), 7.08 (2H, t, J= 5.0 Hz), 7.34 -7.60 (6H, m), 8.27 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 11.6, 20.8, 32.7, 42.6, 46.8, 56.8, 100.2, 109.6, 123.6, 123.8, 124.7, 124.8, 125.6, 129.2, 129.4, 141.9, 143.9, 176.7, 191.4 ppm; IR (KBr) ν= 3300-3050, 1670, 1609 cm-1; Anal. Calcd. for C21H22N2O2S2: C, 63.29; H, 5.56; N, 7.03; Found: C, 62.97; H, 5.68; N, 6.87 %
5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3d)
white solid; yield (100 mg, 77 %); m.p. 150-152 °C; 1H NMR (500 MHz, CDCl3) δ 1.03 (3H, t, J= 5.0 Hz), 1.76 (2H, m), 3.08 (3H, s), 3.66 (1H, m), 3.84 (1H, m), 4.37 (1H, d, J= 5.0 Hz), 4.42 (1H, d, J= 5.0 Hz), 6.88 (1H, d, J= 10.0 Hz), 7.08 (1H, s), 7.33 -7.57 (6H, m), 8.06 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 11.5, 20.8, 32.7, 42.8, 46.9, 56.6, 100.1, 100.2, 110.5, 124.3, 124.7, 127.2, 129.3, 129.4, 129.5, 141.6, 142.5, 176.2, 191.1 ppm; IR (KBr) ν = 3300-3056, 1675, 1609 cm-1; Anal. Calcd. for C21H21ClN2O2S2: C, 58.25; H, 4.89; N, 6.47; Found: C, 58.01; H, 5.04; N, 6.21 %
1-allyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3e)
white solid; yield (107 mg, 83 %); m.p. 154-156 °C; 1H NMR (500 MHz, CDCl3) δ 3.08 (3H, s), 4.32 (1H, d.d, J= 5.0 Hz), 4.39 (1H, d, J= 5.0 Hz), 4.47 (1H, d, J= 5.0 Hz), 4.54 (1H, d.d, J= 5.0 Hz), 5.33 (2H, quintet, J= 15.0 Hz), 5.84 (1H, m), 6.86 (1H, d, J= 10.0 Hz), 7.09 (1H, s), 7.31 -7.58 (6H, m), 7.95 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.8, 43.3, 46.9, 56.6, 100.2, 111.2, 118.9, 124.3, 124.7, 127.1, 129.3, 129.4, 129.9, 141.5, 156.7, 176.5, 191.0 ppm; IR (KBr) ν= 3300-3086, 1672, 1643, 1612 cm-1; Anal. Calcd. for C21H19ClN2O2S2: C, 58.53; H, 4.44; N, 6.50; Found: C, 58.22; H, 4.51; N, 6.35 %.
1-benzyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3f)
white solid; yield (114 mg, 79 %); m.p. 128-130 °C; 1H NMR (500 MHz, CDCl3) δ 3.12 (3H, s), 4.41 (1H, d, J= 5.0 Hz), 4.54 (1H, d, J= 5.0 Hz), 4.75 (1H, d, J= 10.0 Hz), 5.23 (1H, d, J= 10.0 Hz), 6.73 (1H, d, J= 10.0 Hz), 7.03 (1H, s), 7.21 -7.60(11H, m), 7.99 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.8, 44.9, 47.1, 56.7, 100.2, 111.3, 124.2, 124.7, 127.1, 127.6, 128.3, 129.2, 129.3, 129.4, 129.5, 129.5, 134.0, 141.5, 142.0, 176.5, 191.0 ppm; IR (KBr) ν= 3350-3100, 1678, 1615 cm-1; Anal. Calcd. for C25H21ClN2O2S2: C, 62.42; H, 4.40; N, 5.82; Found: C, 62.15; H, 4.53; N, 5.65%.
3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3g)
white solid; yield (101 mg, 91 %); m.p. 170-172 °C; 1H NMR (500 MHz, CDCl3) δ 3.09 (3H, s), 3.33 (3H, s), 4.43 (1H, d, J= 5.0 Hz), 4.45 (1H, d, J= 5.0 Hz), 6.94 (1H, d, J= 10.0 Hz), 7.09 (2H, t, J= 5.0 Hz), 7.36 -7.59 (6H, m), 8.26 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 27.0, 32.8, 46.9, 56.7, 100.2, 109.3, 123.6, 123.9, 124.7, 125.3, 129.2, 129.3, 129.5, 142.0, 144.3, 176.6, 191.5 ppm; IR (KBr) ν= 3400-3150, 1676, 1604 cm-1; Anal. Calcd. for C19H18N2O2S2: C, 61.60; H, 4.90; N, 7.56; Found: C, 61.35; H, 4.96; N, 7.41 %
3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3h)
white solid; yield (93 mg, 87 %); m.p. 164-166 °C; 1H NMR (500 MHz, CDCl3) δ 3.09 (3H, s), 4.44 (1H, d, J= 5.0 Hz), 4.46 (1H, d, J= 5.0 Hz), 6.98 (1H, d, J= 10.0 Hz), 7.07 (2H, t, J= 5.0 Hz), 7.32 -7.59 (6H, m), 7.88 (1H, s), 8.10 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.8, 47.3, 56.7, 100.2, 109.6, 123.8, 124.0, 124.7, 125.9, 129.3, 129.4, 129.5, 141.2, 141.7, 178.4, 191.7 ppm; IR (KBr) ν= 3350, 3300-3150, 1673, 1610 cm-1; Anal. Calcd. for C18H16N2O2S2: C, 60.65; H, 4.52; N, 7.86; Found: C, 60.53; H, 4.60; N, 7.75 %
3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-isopropylindolin-2-one (3i)
white solid; yield (110 mg, 92%); m.p. 180-182 °C; 1H NMR (500 MHz, CDCl3) δ 1.56 (6H, d, J= 5.0 Hz), 3.09 (3H, s), 4.36 (1H, d, J= 5.0 Hz), 4.38 (1H, d, J= 5.0 Hz), 4.63 (1H, septet, J= 5.0 Hz), 7.06 (2H, t, J= 5.0 Hz), 7.10 (1H, d, , J= 10.0 Hz), 7.32 -7.58 (6H, m), 8.32 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 19.3, 19.6, 32.7, 45.4, 46.7, 57.4, 100.2, 110.8, 123.3, 123.9, 124.8, 125.9, 129.3, 129.3, 141.8, 143.2, 176.5, 191.5 ppm; Anal. Calcd. for C21H22N2O2S2: C, 63.29; H, 5.56; N, 7.03; Found: C, 63.13; H, 5.64; N, 6.85 %
Ethyl-2-(3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3j)
white solid; yield (126 mg, 95%); m.p. 142-144 °C; 1H NMR (500 MHz, CDCl3) δ 1.31 (3H, t, J= 5.0 Hz), 3.08 (3H, s), 4.28 (2H, q, J= 5.0 Hz), 4.42 (1H, d, J= 15.0 Hz), 4.47 (1H, d, J= 5.0 Hz), 4.53 (1H, d, J= 5.0 Hz), 4.68 (1H, d, J= 15.0 Hz), 6.83 (1H, d, J= 10.0 Hz), 7.12 (2H, t, J= 5.0 Hz), 7.30 -7.61 (6H, m), 7.88 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 14.3, 32.8, 42.1, 46.8, 56.6, 62.3, 100.2, 109.3, 123.9, 124.2, 124.8, 125.1, 129.3, 129.3, 129.5, 141.8, 143.0, 166.8, 176.9, 191.6 ppm; Anal. Calcd. for C22H22N2O4S2: C, 59.71; H, 5.01; N, 6.33; Found: C, 59.63; H, 5.11; N, 6.21 %
3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3k)
white solid; yield (119 mg, 80%); m.p. 176-178 °C; 1H NMR (500 MHz, CDCl3) δ 3.11 (3H, s), 4.52 (1H, d, J= 5.0 Hz), 4.61 (1H, d, J= 5.0 Hz), 5.44 (1H, d, J= 10.0 Hz), 5.57 (1H, d, J= 10.0 Hz), 6.74(1H, d, J= 10.0 Hz), 7.05-7.21 (3H,m), 7.44-7.69 (9H, m), 7.84 (1H, d, J= 10.0 Hz), 7.94 (1H, d, J= 10.0 Hz), 8.11 (1H, d, J= 10.0 Hz) 8.22 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 32.8, 42.7, 47.2, 56.9, 100.3, 110.6, 122.6, 123.7, 124.0, 124.7, 124.8, 125.5, 126.0, 126.1, 126.9, 128.6, 129.1, 129.2, 129.3, 129.4, 129.5, 130.9, 133.9, 141.8, 143.8, 177.1, 191.3 ppm; Anal. Calcd. for C29H24N2O2S2: C, 70.13; H, 4.87; N, 5.64; Found: C, 69.97; H, 5.04; N, 5.49%
1-benzyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3l)
white solid; yield (114 mg, 83 %); m.p. 152-154 °C; 1H NMR (500 MHz, CDCl3) δ 1.29 (3H, t, J= 5.0 Hz), 3.35 (1H, q, J= 10.0 Hz), 3.94 (1H, q, J= 5.0 Hz), 4.42 (1H, d, J= 5.0 Hz), 4.52 (1H, d, J= 5.0 Hz), 4.79 (1H, d, J= 15.0 Hz), 5.25 (1H, d, J= 15.0 Hz), 6.82 (1H, d, J= 10.0 Hz), 7.06 (2H, t, J= 5.0 Hz), 7.18 -7.65 (11H, m), 8.26 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 13.4, 42.3, 44.7, 47.1, 57.0, 100.9, 110.3, 123.7, 123.8, 124.8, 125.5, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 142.6, 143.6, 177.0, 190.8 ppm; Anal. Calcd. for C26H24N2O2S2: C, 67.80; H, 5.25; N, 6.08; Found: C, 67.61; H, 5.37; N, 5.93 %.
1-allyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3m)
white solid; yield (93 mg, 76 %); m.p. 136-138 °C; 1H NMR (500 MHz, CDCl3) δ 1.26 (3H, t, J= 10.0 Hz), 3.32 (1H, q, J= 10.0 Hz), 3.90 (1H, q, J= 10.0 Hz), 4.37 (1H, d.d, J= 5.0 Hz), 4.41 (1H, d, J= 5.0 Hz), 4.46 (1H, d.d, J= 5.0 Hz), 4.51 (1H, d, J= 5.0 Hz), 5.33 (2H, quintet, J= 15.0 Hz), 5.85 (1H, m), 6.92 (1H, d, J= 10.0 Hz), 7.09 (2H, t, J= 5.0 Hz), 7.34 -7.62 (6H, m), 8.20 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 13.4, 42.3, 43.1, 47.0, 56.9, 100.9, 110.1, 118.5, 123.7, 123.8, 124.8, 125.4, 129.1, 129.3, 129.4, 130.2, 142.6, 157.5, 176.5, 190.8 ppm; Anal. Calcd. for C22H22N2O2S2: C, 64.36; H, 5.40; N, 6.82; Found: C, 64.27; H, 5.51; N, 6.68 %.
3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3n)
white solid; yield (91 mg, 74 %); m.p. 140-142 °C; 1H NMR (500 MHz, CDCl3) δ 1.04 (3H, t, J= 10.0 Hz), 1.26 (3H, t, J= 10.0 Hz), 1.79 (2H, m), 3.32 (1H, m), 3.72 (1H, m), 3.89 (2H, m), 4.39 (1H, d, J= 5.0 Hz), 4.41 (1H, d, J= 5.0 Hz), 6.95 (1H, d, J= 10.0 Hz), 7.07 (2H, t, J= 5.0 Hz), 7.26 -7.62 (6H, m), 8.34 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 11.6, 13.4, 20.8, 40.2, 42.6, 47.0, 56.9, 100.9, 109.6, 123.6, 123.8, 124.8, 125.6, 129.1, 129.2, 129.4, 142.7, 144.0, 176.7, 190.9 ppm; Anal. Calcd. for C22H24N2O2S2: C, 64.15; H, 5.86; N, 6.79; Found: C, 63.81; H, 5.92; N, 6.58 %
5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3o)
white solid; yield (114 mg, 85 %); m.p. 134-136 °C; 1H NMR (500 MHz, CDCl3) δ 1.03 (3H, t, J= 10.0 Hz), 1.25 (3H, t, J= 10.0 Hz), 1.78 (2H, m), 3.30 (1H, t, J= 5.0 Hz), 3.68 (1H, t, J= 5.0 Hz), 3.88 (2H, m), 4.32 (1H, , d, J= 5.0 Hz), 4.42 (1H, d, J= 5.0 Hz), 6.88 (1H, d, J= 10.0 Hz), 7.07 (1H, s), 7.32 -7.60 (6H, m), 8.12 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 11.5, 13.3, 20.8, 42.3, 42.7, 47.0, 56.7, 100.9, 110.5, 121.4, 124.3, 124.7, 129.2, 129.4, 142.4, 156.2, 176.3, 190.5 ppm; Anal. Calcd. for C22H23ClN2O2S2: C, 59.11; H, 5.19; N, 6.27; Found: C, 58.93; H, 5.24; N, 6.12 %
ethyl-2-(3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3p)
white solid; yield (103 mg, 75 %); m.p. 138-140 °C; 1H NMR (500 MHz, CDCl3) δ 1.26 (3H, t, J= 5.0 Hz), 1.32 (3H, t, J= 5.0 Hz), 3.30 (1H, q, J= 5.0 Hz), 3.91 (1H, q, J= 5.0 Hz), 4.28 (2H, q, J= 5.0 Hz), 4.40 (1H, d, J= 15.0 Hz), 4.44 (1H, d, J= 5.0 Hz), 4.53 (1H, d, J= 5.0 Hz), 4.73 (1H, d, J= 15.0 Hz), 6.83 (1H, d, J= 10.0 Hz), 7.10 (2H, t, J= 5.0 Hz), 7.33 -7.61 (6H, m), 7.91 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 13.4, 14.3, 42.1, 42.3, 47.0, 56.6, 62.3, 100.9, 109.3, 123.9, 124.1, 124.8, 125.1, 129.2, 129.3, 129.5, 142.6, 143.1, 166.9, 176.9, 191.0 ppm; Anal. Calcd. for C23H24N2O4S2: C, 60.51; H, 5.30; N, 6.14; Found: C, 60.38; H, 5.42; N, 5.97 %
1-benzyl-5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3q)
white solid; yield (121 mg, 82 %); m.p. 198-200 °C; 1H NMR (500 MHz, CDCl3) δ 1.57 (3H, t, J= 5.0 Hz), 3.53 (2H, q, J= 10.0 Hz), 3.94 (1H, d, J= 5.0 Hz), 4.16 (1H, d, J= 5.0 Hz), 4.99 (2H, s), 6.66 (1H, d, J= 10.0 Hz), 7.14 (1H, d, J= 5.0 Hz), 7.27 -7.63 (10H, m), 8.02 (1H,s) 8.04 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 39.9, 41.3, 44.2, 110.0, 125.0, 127.3, 127.8, 127.9, 128.0, 128.3, 128.3, 128.8, 129.0, 130.8, 133.7, 135.5, 142.1, 177.4, 196.5 ppm; Anal. Calcd. for C26H23ClN2O2S2: C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.76; N, 5.41 %
3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3r)
white solid; yield (106 mg, 92 %); m.p. 140-142 °C; 1H NMR (500 MHz, CDCl3) δ 1.27 (3H, t, J= 5.0 Hz), 3.30 (1H, m), 3.34 (3H, s), 3.90 (1H, m), 4.42 (1H, d, J= 5.0 Hz), 4.43 (1H, d, J= 5.0 Hz), 6.94 (1H, d, J= 10.0 Hz), 7.09 (2H, m), 7.38 -7.62 (6H, m), 8.30 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 13.4, 27.0, 42.3, 47.1, 56.7, 101.0, 109.3, 123.6, 123.8, 124.8, 125.3, 129.1, 129.3, 129.5, 142.8, 144.3, 176.7, 190.9 ppm; Anal. Calcd. for C20H20N2O2S2: C, 62.47; H, 5.24; N, 7.29; Found: C, 62.21; H, 5.33; N, 7.10 %
3-(-3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3s)
white solid; yield (125 mg, 88 %); m.p. 130-132 °C; 1H NMR (500 MHz, CDCl3) δ 1.07 (3H, t, J= 10.0 Hz), 1.81 (2H, m), 3.70 (1H, t, J= 10.0 Hz), 3.87(1H, t, J= 10.0 Hz), 4.36 (1H, d, J= 5.0 Hz), 4.48 (1H, d, J= 5.0 Hz), 4.52 (1H, d, J= 10.0 Hz), 5.12 (1H, d, J= 10.0 Hz), 6.95 (1H, d, J= 10.0 Hz), 7.07 (2H, t, J= 5.0 Hz), 7.20 -7.59 (11H, m), 8.25 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 11.7, 20.9, 42.6, 46.7, 50.2, 57.0, 101.0, 109.6, 123.6, 123.8, 125.0, 125.5, 127.0, 128.0, 128.4, 129.0, 129.2, 129.5, 136.7, 142.6, 143.9, 176.5, 193.0 ppm; Anal. Calcd. for C27H26N2O2S2: C, 68.33; H, 5.52; N, 5.90; Found: C, 68.10; H, 5.61; N, 5.76 %.
3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3t)
white solid; yield (122 mg, 91 %); m.p. 140-142 °C; 1H NMR (500 MHz, CDCl3) δ 3.34 (3H, s), 4.38 (1H, d, , J= 5.0 Hz), 4.48 (1H, d, J= 10.0 Hz), 4.51 (1H, d, J= 5.0 Hz), 5.14 (1H, d, J= 10.0 Hz), 6.93 (1H, d, J= 10.0 Hz), 7.09 (2H, t, J= 5.0 Hz), 7.21-7.59 (11H, m), 8.17 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 27.1, 46.7, 50.3, 56.8, 101.1, 109.3, 123.7, 123.8, 125.0, 127.0, 128.0, 128.3, 129.0, 129.2, 129.6, 132.0, 136.6, 142.7, 144.3, 176.5, 193.1 ppm; Anal. Calcd. for C25H22N2O2S2: C, 67.24; H, 4.97; N, 6.27; Found: C, 66.98; H, 5.11; N, 6.03 %.
1-allyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3u)
white solid; yield (123 mg, 87 %); m.p. 132-134°C; 1H NMR (500 MHz, CDCl3) δ 4.41 (2H, d, J= 5.0 Hz), 4.48 (1H, d.d, J= 5.0 Hz), 4.50 (1H, d, J= 5.0 Hz), 4.52 (1H, d.d, J= 5.0 Hz), 5.14 (1H, d, J= 10.0 Hz), 5.35 (2H, quintet, J= 10.0 Hz), 5.90 (1H, m), 6.93 (1H, d, J= 5.0 Hz), 7.08 (2H, t, J= 5.0 Hz), 7.20 -7.60 (11H, m), 8.09 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 43.1, 46.7, 50.2, 57.0, 101.0, 110.2, 118.6, 123.7, 125.0, 125.3, 127.0, 128.0 , 128.4, 129.0, 129.2, 129.4, 130.4, 136.6, 142.5, 143.5, 176.3, 193.0 ppm; Anal. Calcd. for C27H24N2O2S2: C, 68.62; H, 5.12; N, 5.93; Found: C, 68.43; H, 5.26; N, 5.78 %.
1-benzyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3v)
white solid; yield (124 mg, 79 %); m.p. 154-156 °C; 1H NMR (500 MHz, CDCl3) δ 4.46 (1H, d, J= 5.0 Hz), 4.49 (1H, d, J= 5.0 Hz), 4.51 (1H, d, J= 5.0 Hz), 4.80 (1H, d, J= 10.0 Hz), 5.20 (2H, d, J= 10.0 Hz), 6.82 (1H, d, J= 10.0 Hz), 7.05 (2H, t, J= 5.0 Hz), 7.19 -7.62 (16H, m), 8.10 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 44.7, 46.8, 50.3, 57.0, 101.1, 110.2, 123.7, 123.8, 124.9, 125.4, 127.0, 127.6, 128.0, 128.1, 128.5, 129.0, 129.2, 129.2, 129.4, 134.7, 136.7, 142.6, 143.5, 176.7, 193.0 ppm; Anal. Calcd. for C31H26N2O2S2: C, 71.24; H, 5.01; N, 5.36; Found: C, 71.02; H, 5.12; N, 5.10 %.
3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3w)
white solid; yield (132 mg, 77%); m.p. 140-142 °C; 1H NMR (500 MHz, CDCl3) δ 4.49 (1H, d, J= 5.0 Hz), 4.52 (1H, d, J= 5.0 Hz), 4.56 (1H, d, J= 10.0 Hz), 5.19 (1H, d, J= 10.0 Hz), 5.43 (1H, d, J= 10.0 Hz), 5.58 (1H, d, J= 10.0 Hz), 6.75(1H, d, J= 10.0 Hz), 7.05-7.69 (17H, m), 7.86 (1H, d, J= 10.0 Hz), 7.95 (1H, d, J= 10.0 Hz), 8.14 (1H, d, J= 10.0 Hz) 8.16 (1H, s) ppm; 13C NMR (176 MHz, CDCl3) δ 42.8, 47.0, 50.3, 56.9, 100.0, 101.1, 110.6, 122.7, 123.7, 123.9, 124.9, 125.0, 125.9, 126.2, 127.0, 127.0, 128.0, 128.3, 128.7, 129.1, 129.2, 129.3, 129.3, 129.5, 130.9, 133.9, 136.6, 142.6, 143.8, 176.9, 192.9 pm; Anal. Calcd. for C35H28N2O2S2: C, 73.40; H, 4.93; N, 4.89; Found: C, 73.27; H, 5.09; N, 4.71 %
1-(1-allyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4a)
white solid; yield (102 mg, 83 %); m.p. 114-116 °C; 1H NMR (500 MHz, CDCl3) δ 3.38 (3H, s), 3.62 (3H, s), 3.92 (1H, d, J= 5.0 Hz), 4.47 (2H, d.d, J= 5.0 Hz), 5.35 (2H, d.d, J= 5.0 Hz), 5.97 (1H, quintet, J= 5.0 Hz), 6.84 (2H, d, J= 5.0 Hz), 7.01 (1H, d, J= 5.0 Hz), 7.25 (1H, d, J= 5.0 Hz), 7.43 -7.58 (4H, m), 8.02 (2H, d , J= 10.0 Hz) ppm; 13C NMR (176 MHz, CDCl3) δ 35.2, 42.5, 46.2, 57.5, 109.2, 117.8, 122.9, 126.6, 127.8, 128.5, 128.7, 128.9, 131.2, 131.7, 132.6, 133.9, 136.4, 137.7, 176.1, 191.3, 194.1 ppm; Anal. Calcd. for C22H22N2O2S2: C, 64.36; H, 5.40; N, 6.82; Found: C, 64.24; H, 5.48; N, 6.67 %.
1-(1-benzyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4b)
white solid; yield (102 mg, 74 %); m.p. 140-142 °C; 1H NMR (500 MHz, CDCl3) δ 3.38 (3H, s), 3.63 (3H, s), 4.01 (1H, d, J= 5.0 Hz), 5.05 (2H, d, J= 10.0 Hz), 6.71 (1H, d, J= 5.0 Hz), 6.88 (1H, d, J= 5.0 Hz), 6.98 (1H, t, J= 5.0 Hz), 7.16 (1H, t, J= 5.0 Hz), 7.34 -7.59 (9H, m), 8.05 (2H, d , J= 10.0 Hz) ppm; 13C NMR (176 MHz, CDCl3) δ 41.7, 44.1, 46.3, 46.5, 57.5, 94.4, 109.1, 122.4, 123.9, 126.5, 127.5, 127.6, 128.5, 128.7, 129.0, 133.6, 134.9, 136.2, 143.6, 176.3, 194.2, 194.2 ppm; Anal. Calcd. for C26H24N2O2S2: C, 67.80; H, 5.25; N, 6.08; Found: C, 67.57; H, 5.37; N, 5.92%.
1-(1-allyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4c)
white solid; yield (108 mg, 81 %); m.p. 110-112 °C; 1H NMR (500 MHz, CDCl3) δ 3.39 (3H, s), 3.64 (3H, s), 3.90 (1H, d, J= 5.0 Hz), 4.45 (2H, d.d, J= 5.0 Hz), 5.34 (2H, d.d, J= 5.0 Hz), 5.95 (1H, quintet, J= 5.0 Hz), 6.79 (2H, d, J= 5.0 Hz), 7.20 (1H,d, J= 5.0 Hz), 7.45 -7.60 (4H, m), 7.97 (2H, d , J= 10.0 Hz) ppm; 13C NMR (176 MHz, CDCl3) δ 41.6, 42.6, 46.2, 46.6, 57.5, 100.0, 109.9, 117.8, 124.2, 127.9, 128.4, 128.9, 129.3, 131.3, 132.2, 133.8, 134.7, 164.6, 184.5, 193.9 ppm; Anal. Calcd. for C22H21ClN2O2S2: C, 59.38; H, 4.76; N, 6.30; Found: C, 59.22; H, 4.84; N, 6.21 %.
1-(1-benzyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4d)
white solid; yield (119 mg, 80 %); m.p. 132-134 °C; 1H NMR (500 MHz, CDCl3) δ 3.39 (3H, s), 3.99 (3H, s), 3.99 (1H, d, J= 5.0 Hz), 5.03 (2H, d, J= 10.0 Hz), 6.61 (1H, d, J= 5.0 Hz), 6.85 (1H, d, J= 5.0 Hz), 7.12(1H, d, J= 5.0 Hz), 7.35 -7.60 (9H, m), 8.01 (2H, d , J= 10.0 Hz) ppm; 13C NMR (176 MHz, CDCl3) δ 41.7, 44.2, 46.4, 46.7, 57.5, 110.0, 124.3, 127.5, 127.7, 128.4, 128.8, 128.8, 129.0, 133.8, 134.6, 135.8, 142.2, 176.0, 193.9, 194.0 ppm; Anal. Calcd. for C26H23ClN2O2S2: C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.81; N, 5.49 %.
1,1''-diallyl-2'-benzoyl-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5a)
white solid; yield (79 mg, 86 %); m.p. 258-260 °C; 1H NMR (500 MHz, DMSO-d6) δ 2.95 (3H, s), 3.93 (2H, d.d, J= 15.0 Hz), 4.21 (1H, d, J= 15.0 Hz), 4.53 (2H, d.d, J= 15.0 Hz), 4.80 (1H, d, J= 15.0 Hz), 5.14 (1H, quintet, J= 10.0 Hz), 5.21 (2H, t, J= 15.0 Hz), 5.27 (1H, s), 5.77 (1H, quintet, J= 10.0 Hz), 5.96 (1H, s), 6.57 (1H, d, J= 5.0 Hz ), 6.63 (1H, d, J= 5.0 Hz ), 6.68 (1H, s), 6.98 -7.23 (13H, m), 7.374 (1H, t, J= 5.0 Hz ), 7.86 (1H, d, J= 5.0 Hz), 8.06 (1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 41.9, 43.1, 58.3, 60.0, 60.7, 61.6, 84.5, 89.3, 100.0, 108.8, 109.4, 116.9, 118.4, 122.0, 123.9, 125.0, 125.9, 126.2, 126.6, 127.3, 127.6, 127.9, 129.1, 130.6, 131.6, 131.9, 133.3, 136.8, 137.6, 142.5, 143.8, 176.3, 179.3, 196.6 ppm; Anal. Calcd. for C39H34N2O5: C, 76.70; H, 5.61; N, 4.59; Found: C, 76.51; H, 5.76; N, 4.34 %;
2'-benzoyl-4'-hydroxy-1,1''-dimethyl-5'-(octyloxy)-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5b)
white solid; yield (88 mg, 89 %); m.p. 222-224 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.79-1.19 (15H, m), 2.79 (3H,s), 2.85 (1H, t, J = 10.0 Hz), 3.08 (3H,s), 3.17 (1H, t, J = 10.0 Hz), 5.22 (1H, s), 5.99 (1H, s), 6.56 (1H, d, J = 5.0 Hz), 6.75 (2H, t, J = 5.0 Hz), 6.97 -7.49 (14H, m), 7.82 (1H, d, J = 5.0 Hz), 8.09 (1H, d, J = 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 14.4, 22.5, 25.8, 26.2, 27.1, 28.9, 29.0, 29.6, 31.6, 58.5, 61.6, 64.6, 84.6, 87.5, 108.0, 108.8, 112.7, 122.0, 123.8, 125.7, 126.1, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 131.6, 133.2, 136.8, 137.5, 143.3, 144.5, 176.6, 179.7, 196.6 ppm; Anal. Calcd. for C42H44N2O5: C, 76.80; H, 6.75; N, 4.27; Found: C, 76.64; H, 6.83; N, 4.08 %.
1,1''-diallyl-2'-benzoyl-4'-hydroxy-4'-phenyl-5'-propoxydispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5c)
white solid; yield (76 mg, 79 %); m.p. 166-168 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.49 (3H, t, J= 10.0 Hz), 1.10 (2H, m), 2.88 (1H, q, J= 10.0 Hz), 3.13 (1H, q , J= 10.0 Hz), 3.97 (2H, d.d, J= 15.0 Hz ), 4.21 (1H, d, J= 15.0 Hz), 4.51 (2H, d.d, J= 15.0 Hz), 5.81 (1H, d, J= 15.0 Hz), 5.16 (1H, quintet, J= 10.0 Hz), 5.22 (1H, t, J= 15.0 Hz), 5.28 (1H, t, J= 10.0 Hz), 5.75 (1H, quintet, J= 10.0 Hz), 6.04 (1H, s), 6.59 (1H, d, J= 5.0 Hz ), 6.64 (1H, d, J= 5.0 Hz ), 6.71 (1H, s), 6.98 -7.24 (13H, m), 7.37 (1H, t, J= 5.0 Hz ), 7.86 (1H, d, J= 5.0 Hz), 8.04 (1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 10.7, 22.9, 41.9, 43.2, 58.4, 61.6, 64.5, 73.8, 84.5, 87.9, 100.0, 101.0, 108.8, 109.3, 116.9, 119.0, 122.0, 123.8, 125.9, 126.2, 126.7, 127.3, 127.5, 127.8, 128.7, 129.1, 130.5, 131.5, 131.9, 133.2, 136.8, 137.6, 142.6, 143.7, 176.3, 179.4, 196.6 ppm; Anal. Calcd. for C41H38N2O5: C, 77.09; H, 6.00; N, 4.39; Found: C, 76.89; H, 6.14; N, 4.21 %
4'-hydroxy-2'-methyl-4'-phenyl-5'-propoxy-1,1''-dipropyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5d)
white solid; yield (72 mg, 75 %); m.p. 210-212 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.49 (3H, t, J= 10.0 Hz), 0.55 (3H, t, J = 10.0 Hz), 0.93 (3H, t, J= 10.0 Hz), 1.00 (2H, m), 1.11 (2H, m), 1.47-1.66 (2H, m), 2.86-3.15 (2H, m ), 3.20-3.38 ( 2H, m), 3.50-3.77 (2H, m), 5.23 (1H, s), 6.03 (1H, s), 6.66 (1H, d, J = 10.0 Hz), 6.76 (1H, s), 6.79 (2H, d, J= 10.0 Hz), 6.96 (2H, d, J= 5.0 Hz), 7.02-7.19 (9H, m), 7.25 (1H, t, J= 10.0 Hz), 7.36 (1H, t, J= 10.0 Hz), 7.84 (1H, d, J= 5.0 Hz), 8.04 (1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 10.7, 11.6, 11.9, 20.4, 21.0, 23.0, 41.3, 42.5, 58.4, 61.5, 64.2, 73.8, 84.6, 87.9, 100.0, 108.2, 109.0, 121.7, 123.6, 125.9, 126.1, 126.6, 127.2, 127.4, 128.6, 129.1, 130.7, 133.1, 136.9, 137.7, 143.1, 144.4, 176.4, 179.6, 196.6 ppm; Anal. Calcd. for C41H42N2O5: C, 76.61; H, 6.59; N, 4.36; Found: C, 76.43; H, 5.71; N, 4.19
2'-benzoyl-1,1''-di(but-2-en-1-yl)-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5e)
white solid; yield (79 mg, 83 %); m.p. 206-208 °C; 1H NMR (500 MHz, DMSO-d6) δ 1.41 (3H, d, J= 10.0 Hz ), 1.65 (3H, d, J= 10.0 Hz), 2.93 (3H, t, J= 10.0 Hz), 3.80 (1H, d, J= 10.0 Hz), 3.98 (1H, d, J= 10.0 Hz), 4.19 (1H, d, J= 10.0 Hz), 4.41 (1H, d, J= 10.0 Hz), 4.46 (1H, m), 5.93 (1H, m), 5.26 (1H, s), 5.38 (1H, m), 5.72 (1H, m), 5.94 (1H, s), 6.54-6.67 (3H, m), 6.92 -7.24 (13H, m), 7.36 (1H, t, J= 5.0 Hz ), 7.84 (1H, d, J= 5.0 Hz), 8.04 (1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 13.4, 18.0, 36.6, 37.7, 41.0, 42.3, 58.2, 59.8, 61.4, 64.2, 84.5, 89.3, 108.7, 109.4, 121.9, 123.8, 124.2, 124.6, 125.9, 126.1, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.5, 143.9, 176.1, 179.1, 196.5 ppm; Anal. Calcd. for C41H38N2O5: C, 77.09; H, 6.00; N, 4.39; Found: C, 76.88; H, 6.08; N, 4.19 %
2'-benzoyl-1,1''-di(but-2-en-1-yl)-5'-ethoxy-4'-hydroxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dionedione (5f)
white solid; yield (79 mg, 81 %); m.p. 162-164 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.72 (3H, t, J= 5.0 Hz ), 1.41 (3H, d, J= 10.0 Hz ), 1.64 (3H, d, J= 10.0 Hz), 2.95 (1H, q, J= 10.0 Hz), 3.23 (1H, q, J= 5.0 Hz), 3.80 (1H, d, J= 10.0 Hz), 3.95 (1H, d, J= 10.0 Hz), 4.19 (1H, d, J= 10.0 Hz), 4.42 (1H, d, J= 10.0 Hz), 4.4.67 (1H, m), 4.93 (1H, m), 5.26 (1H, s), 5.39 (1H, m), 5.73 (1H, m), 6.03 (1H, s), 6.56-6.69 (3H, m), 6.94 -7.24 (13H, m), 7.36 (1H, t, J= 5.0 Hz ), 7.84 (1H, d, J= 5.0 Hz), 8.02 (1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 13.5, 15.6, 18.0, 36.6, 37.6, 41.0, 42.2, 58.4, 61.4, 64.2, 67.6, 84.6, 87.8, 108.7, 109.3, 121.9, 123.7, 124.3, 124.6, 125.9, 126.1, 126.5, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.6, 143.9, 176.1, 179.2, 196.6 ppm; Anal. Calcd. for C42H40N2O5: C, 77.28; H, 6.18; N, 4.29; Found: C, 77.05; H, 6.32; N, 4.10% .
2'-benzoyl-5'-ethoxy-4'-hydroxy-4'-phenyl-1,1''-dimethyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5g)
white solid; yield (70 mg, 85%); m.p. 266-268 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.69 (3H, t, J= 10.0 Hz), 2.79 (3H, s), 2.96 (1H, q, J= 10.0 Hz), 3.11 (3H, s), 3.19 (1H, q, J= 10.0 Hz ), 5.23 (1H, s), 6.02 (1H, s), 6.58 (1H, d, J = 10.0 Hz), 6.75 (2H, d, J = 10.0 Hz), 6.90 -7.13 (10H, m), 7.18 (2H, t, J= 10.0 Hz), 7.26 (1H, t J= 10.0 Hz), 7.35 (1H, t, J= 10.0 Hz), 7.83 (1H, d, J= 5.0 Hz), 8.08(1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 15.7, 26.2, 27.1, 58.6, 61.6, 64.6, 67.4, 84.6, 87.4, 108.0, 108.8, 121.9, 123.8, 125.7, 126.0, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 133.1, 136.8, 137.5, 143.3, 144.6, 176.6, 179.7, 196.6 ppm.