Practical Multigram Synthesis of 3,3,3',3'-Tetramethyl-1,1'-spirobisindane-5,5'-diamino-6,6'-diol

Experimental Section

Spirobisindane derivatives 2,11 3a, and 4a9 were prepared according to the procedures reported in the literatures.

6,6'-Dibenzyloxy-3,3,3',3'-tetramethyl-1,1'-spirobisin-dane (3b). A mixture of spirobisindanediol 2 (9.24 g, 30 mmol), benzyl chloride (11.3 g, 90 mmol) and K2CO3 (12.4 g, 90 mmol) in CH3CN (120 mL) was stirred at reflux temperature for 8 h. The reaction mixture was poured into water, extracted with CH2Cl2 (3 × 100 mL), and dried over MgSO4. The solvent was evaporated under reduced pre-ssure. The resulting solid was filtered with petroleum ether to produce pure 3b (10.5 g, 72%) as a white solid. mp 184-185 °C; IR (KBr) 1601, 1484, 1358, 1014 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.33 (s, 6H, two CH3), 1.37 (s, 6H, two CH3), 2.25 (d, J = 12.9 Hz, 2H, CH2), 2.35 (d, J = 13.2 Hz, 2H, CH2), 4.92 (s, 4H, CH2Ph), 6.43 (d, J = 2.3 Hz, 2H, aromatic), 6.87 (dd, J = 8.2 and 2.3 Hz, 2H, aromatic), 7.08 (d, J = 8.5 Hz, 2H, aromatic), 7.27-7.39 (m, 10H, two Ph); 13C NMR (75 MHz, CDCl3) δ 30.5, 31.8, 42.9, 57.8, 59.6, 70.1, 110.2, 114.0, 122.4, 127.6, 127.8, 128.4, 137.1, 144.9, 151.9, 158.5. Anal. Calcd for C35H36O2: C, 86.03; H, 7.43. Found: C, 85.85; H, 7.29.

6,6'-Dibenzyloxy-3,3,3',3'-tetramethyl-5,5'-dinitro-1,1'-spirobisindane (4b). To a chilled mixture (0 °C) of glacial acetic acid (130 mL), 60% HNO3 (24.8 mL, 360 mmol), and 97% H2SO4 (16.0 mL, 300 mmol), dibenzyloxyspirobi-sindane 3b (14.6 g, 30 mmol) were slowly added. The reaction mixture was stirred for 5 min at 0 °C and then at room temperature for 5 h. The reaction mixture was poured into ice water and the precipate was filtered off. The crude product was dissolved in CH2Cl2, dried over MgSO4, and evaporated under reduced pressure. The resulting solid was filtered with Et2O to produce pure 4b (13.0 g, 75%) as a slightly yellowish solid. mp 175-178 °C; IR (KBr) 1616, 1580, 1521, 1347, 1289 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.35 (s, 6H, two CH3), 1.40 (s, 6H, two CH3), 2.17 (d, J = 13.2 Hz, 2H, CH2), 2.38 (d, J = 13.5 Hz, 2H, CH2), 4.98 (two d, J = 12.3 Hz, 4H, CH2Ph), 6.31 (s, 2H, aromatic), 7.21-7.34 (m, 10H, two Ph), 7.66 (s, 2H, aromatic); 13C NMR (75 MHz, CDCl3) δ 30.1, 31.4, 43.4, 58.4, 58.8, 71.0, 110.4, 119.5, 126.9, 128.1, 128.6, 135.4, 140.1, 144.5, 151.8, 155.5. Anal. Calcd for C35H34N2O6: C, 72.65; H, 5.92; N, 4.84. Found: C, 72.53; H, 5.81; N, 4.98.

3,3,3',3'-Tetramethyl-1,1'-spirobisindane-5,5'-dinitro-6,6'-diol (5). To a chilled (0-5 °C) solution of 4a (8.52 g, 20 mmol) in CH2Cl2 was added BBr3 (5.8 mL, 60 mmol) dropwise manner. The reaction mixture was stirred at same temperature for 1 h. The mixture was poured into cold saturated aq. NaHCO3 solution (500 mL), and extracted with CH2Cl2 (200 mL × 3). The combined organic layers were dried (MgSO4) and the solvent was evaporated under re-duced pressure. The resulting solid was filtered with Et2O-petroleum ether to produce pure 5 (6.77 g, 85%) as a yellow solid. mp 238-241 °C;8 1H NMR (300 MHz, CDCl3) δ 1.37 (s, 6H, two CH3), 1.44 (s, 6H, two CH3), 2.28 (d, J = 13.2 Hz, 2H, CH2), 2.42 (d, J = 13.2 Hz, 2H, CH2), 6.54 (s, 2H, aromatic), 7.92 (s, 2H, aromatic), 10.61 (s, 2H, OH); 13C NMR (75 MHz, CDCl3) δ 30.1, 31.6, 43.4, 58.2, 58.7, 114.8, 118.7, 133.6, 145.1, 155.3, 160.5.

3,3,3',3'-Tetramethyl-1,1'-spirobisindane-5,5'-diamino-6,6'-diol (6). To a stirred suspension of 4b (11.6 g, 20 mmol) and 10% Pd-C (638 mg, 0.6 mmol) in refluxing ethanol (300 mL) was added NH2NH2·H2O (19.4 mL, 400 mmol) drop-wise manner. After stirring at reflux temperature for 8 h, the reaction mixture was filtered with celite and washed with EtOH (20 mL). The organic phase was poured into water and the precipitate was filtered off and dried to give pure 6 (4.73 g, 70%) as a white solid. mp 262-265 °C; IR (KBr) 3492, 3376, 3285, 1616, 1506, 1322 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 1.20 (s, 6H, two CH3), 1.25 (s, 6H, two CH3), 1.97 (d, J = 12.6 Hz, 2H, CH2), 2.14 (d, J = 12.6 Hz, 2H, CH2), 4.31 (s, 4H, NH2), 6.04 (s, 2H, aromatic), 6.37 (s, 2H, aromatic), 8.65 (s, 2H, OH); 13C NMR (75 MHz, DMSO-d6) δ 30.7, 31.7, 42.3, 56.2, 59.7, 107.0, 109.1, 135.5, 138.7, 142.2, 143.8.