3.1. General
IR spectra were recorded on a Perkin-Elmer 883 spectrophotometer and peaks are expressed as ν (cm-1). NMR spectra were recorded on a JEOL ECP 400 (400 MHz) instrument in CDCl3 and chemical shifts are expressed as δ ppm, and coupling constants (J) are given in Hertz. MS spectra and HRMS were performed at the Department of Organic Chemistry of the University of Hannover-Germany using EI at 70 eV.
9-Allylanthracene (4). A solution of anthrone 3 (5.01 g, 25.8 mmol) in anhydrous THF (100 mL) was slowly added to allylmagnesium bromide (33 mL, 33 mol, 1 M solution, Aldrich). The mixture was stirred for 8 h at room temperature. The reaction mixture was subsequently acidified with 10% HCl, the organic layer was separated, and the aqueous layer was extracted with ether (2 × 50 mL). The combined organic layer was washed with water, dried over Na2SO4 and the solvent was evaporated. To the crude product was added 25 mL benzene, 6 g P4O10 and stirred for 6 h at room temperature. The P4O10 was filtered off and the benzene was removed under vacuum. The crude product was purified by flash column chromatography (hexane-dichloromethene 1:1) to give 4 (4.6 g, 82%) as a yellow solid, m.p. 46 ºC; IR (KBr): ν = 3047, 2945, 1620, 1444, 729 cm-1; 1H-NMR δ 4.37 (d; J = 5.48 Hz, 2H, H-1'), 4.97 (dd; J =10.24, 1.48 Hz, 1H, H-3'), 5.06 (dd; J= 16.84,1.48 Hz, 1H, H-3'), 6.21–6.28 (m; 1H, H-2'), 7.28–7.60 (m; 9H, aromatic -H); 13C-NMR δ 32.00, 116.00, 124.89, 125.36, 126.25, 128.20, 130.06, 131.56, 131.71, 134.05, 136.50. MS (EI) m/z (%) = 218 (100) [M+], 203 (54), 191 (27), 176 (5), 165 (7); HRMS (EI) Calcd. for C17H14 [M+] 218.1096, Found 218.1097.
12-Bromo-9-(prop-2-en-1-yl)-9,10-dihydro-9,10-ethanoanthracen-12-carbaldehyde (5). A mixture of 9-allylanthracene (4, 2.1 g, 9.65 mmol) and α-bromoacroline (2.61 g, 19.3 mmol) in benzene (10 mL) was heated under reflux 24 h and allowed to cool to room temperature. The reaction mixture was concentrated and the crude product was purified by flash column chromatography on silica gel (petroleum ether-ethyl acetate 30:1) to give 5 (2.33 g, 68.6%) as a white solid, m.p. 145 ºC; IR (KBr): ν = 3070, 2970, 1716, 1631, 435, 914, 748 cm-1; 1H-NMR δ 2.2 (dd; J = 14, 2.9 Hz, 1H, H-11), 3.01 (dd; J = 14, 2.9 Hz, 1H, H-11), 3.43–3.49 (m, 1H, H-1'), 3.81–3.86 (m, 1H, H-1'), 4.33 (t; J = 2.9 Hz, 1H, H-10), 5.27–5.31 (m, 1H, H-3'), 5.44–5.49 (m, 1H, H-3'), 5.95–6.05 (m; 1H, H-2'), 7.12–7.53 (m; 8H, aromatic-H), 9.35 (s; H-C=O); 13C-NMR δ 31.47, 42.13, 43.83, 52.85, 75.45, 117.89, 123.66, 125.57, 126.05, 126.95, 136.67, 139.19, 143.12, 191.04; MS (EI) m/z (%) = 352 (23), 354 (24) [M+], 274 (35), 273 (84), 272 (100), 219 (67), 218 (100), 215 (62), 204 (27), 203 (70), 202 (66), 191 (49), 178 (21), 165 (32); HRMS (EI) Calcd. for C20H17BrO, C20H17BrO [M+] 352.0465, Found 352.0463.
11-Hydroxy-9-(prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracen-12-one (6). To a solution of the Diels-Alder adduct 5 (2 g, 5.69 mmol) in THF (20 mL) was added 1M aqueous NaOH (21 mL). The mixture was stirred at room temperature for 4 h, extracted with ether twice, washed with water, dried with MgSO4 and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (petroleum ether-ethyl acetate 5:1) to give 6 (1 g, 60.5%) as a white solid, m.p. 152 ºC; IR (KBr): ν = 3512, 3464, 3022, 2920, 1701, 1448, 1350, 1124, 731 cm-1; 1H-NMR δ 2.79 (dd; J = 15.5, 1.5 Hz, 1H, H-11), 3.15(dd; J = 15.5, 6.6 Hz, 1H, H-11), 3.37–3.45 (m; 1H, H-2'), 3.82–3.88 (m; 1H, H-2'), 4.03 (d; J = 3.5 Hz, 1H, H-O), 4.11(d; J = 3.5 Hz, 1H, H-10), 4.32 (dd; J = 6,1.5 Hz, 1H, H-9), 5.14–5.17 (m; 1H, H- H-3'), 5.35–5.39 (m; 1H, H-3'), 5.58–5.67 (m; 1H, H-2'); 13C-NMR δ 32.55, 43.50, 50.24, 50.32, 84.23, 119.25, 126.09, 126.49, 126.75, 127.57, 134.96, 140.25, 143.88, 208.22; MS (EI) m/z (%) = 290 (48) [M+], 218 (100), 217 (71), 215 (53), 203 (67.77), 202 (60), 191 (57), 178 (34), 152 (11); HRMS (EI) Calcd. for C20H18O2 [M+] 290.1305, Found 290.1307.
9-(Prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracen-12-one (7). To a solution of SmI2 (2.1 g, 5.2 mmol) in THF (2 mL) was added solution of compound 6 (0.75 g, 2.6 mmol) in THF (6 mL). The mixture was stirred at room temperature for 4 h, hexane was added , the mixture was filtered concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (petroleum ether-ethyl acetate 5:1) to give 7 (0.4 g, 56%) as a white solid, m.p. 128 ºC. IR (KBr): ν = 3070, 2912, 1683, 1475, 1448, 717cm-1; 1H-NMR δ 2.61 (s; 2H, H-13), 2.75 (d; J = 3.68 Hz, 2H, H-11), 3. 25 (d; J = 5.84 Hz, 2H, H-1'), 4.27 (t; J = 3.68 Hz, 1H, H-10), 5.15 (dd; J = 10.28, 1.84 Hz, 1H, H-3'), 5.30 (dd; J = 17.6, 1.84 Hz, 1H, H-3'), 5.69 (m; 1H, H-2'), 7.20–7.23 (m; 8H, aromatic-H); 13C-NMR δ 37.62, 43.56, 43.62, 50.26, 59.42, 118.25 134.60, 124.98, 126.31, 126.91, 127.11, 134.60, 140.11, 142.01, 208.88; MS (EI) m/z (%) = 274 (100) [M+], 275 (23), 231 (28), 217 (41), 216 (19), 215 (38), 203 (20), 202 (27), 191 (43), 189 (24); HRMS (EI) Calcd. for C20H18O [M+] 274.1359, Found 274.1358.
9-(Prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracene (8). A mixture of ketone 7 (0.88 g, 3.21 mmol), KOH (0.72 g, 12.83 mmol), hydrazine hydrate (2.285 g, 45.7 mmol) and triethyleneglycol (4 mL) was stirred at 150 ºC for 5 h. Then the water was removed by a Dean-Stark separator, and the reaction mixture was heated for a further 5 h to 200–210 ºC. After cooling to room temperature, the reaction mixture was treated with dil. HCl (until pH = 2 was reached). The aqueous layer was extracted with toluene, and the combined organic phases were washed with brine, dried with MgSO4 and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (petroleum ether-ethyl acetate 5:1) to give 8 (0.63 g, 57%) as a yellow oil. IR (CDCl3): ν = 3068, 3016, 2958, 2926, 1473, 1452, 752 cm-1; 1H-NMR δ 1.25–1.29 (m; 2H, H-12), 1.31 (t; J = 6.6 Hz, 2H, H-13), 1.63 (t; J = 5.88, 2H, H-11), 3.19 (t; J = 2.58 Hz, 2H, H-1'), 3.99 (t; J = 3.68 Hz, 1H, H-10), 5.17 (m; 1H, H-3'), 5.27 (m; Hz, 1H, H-3'), 5.79 (m; 1H, H-2'), 7.22–7.29 (m; 8H, aromatic-H); 13C-NMR δ 23.53, 29.86, 39.22, 39.39, 45.71, 46.70, 117.42, 124.45, 126.08, 126.32, 126.37, 136.70, 143.25, 143.94; MS (EI) m/z (%) = 260 (61) [M+], 232 (19), 231 (42), 220 (27), 219 (85), 218 (55), 217 (53), 204 (18), 203 (53), 202 (60), 192 (29), 191 (100), 189 (61), 178 (44), 176 (15),165 (36), 152 (16); HRMS (EI) Calcd. for C20H20 [M+] 260.1563, Found 260.1565.
2-(9,10-Dihydro)-9,10-propanoanthracen-9-yl)ethanal (9). The tetracyclic alkene 8 (0.3 g, 1.15 mmol) was dissolved in CH2Cl2 (ca. 9 mL) and ozonolyzed at -78 ºC. After the reaction was complete (blue color), Me2S (6 equiv.) was added, and the reaction mixture was stirred for a further 4 h while it warmed to room temperature, and the volatile components were removed under vacuum. The crude product was purified by flash column chromatography on silica gel (petroleum ether-ethyl acetate 15:1) to give 9 (0.18 g, 60%) as a white solid, m.p. 94 ºC; IR (CDCl3): ν = 3064, 3018, 2931, 2856, 1728, 1477, 1452, 754 cm-1; 1H-NMR δ 1.22–1.26 (m; 2H, H-12), 1.67 (t; J = 4.4 Hz, 2H, H-13), 1.72–1.72 (m; 2H, H-11), 2.81 (dd; J = 16.88, 3.68 Hz, 1H, H-1'), 2.94 (dd; J = 16.88, 2.96 Hz, 1H, H-1'), 3.99 (t; J = 3.68 Hz, 1H, H-10), 6.96–7.23 (m; 8H, aromatic-H), 10.14 (s; H-C=O); 13C-NMR δ 22.10, 29.15, 37.84, 45.94, 46.53, 57.94, 126.08, 126.22, 126.37, 126.51, 142.59, 143.35, 202.48; MS (EI) m/z (%) = 262 (38) [M+], 234(37), 233(56), 220(44), 219(80), 218(67), 205(42), 204(26), 203(31), 202(32), 192(55), 191(100), 189(53), 178(44.85), 176(17), 165(33), 152(25); HRMS (EI) Calcd. for C19H18O [M+] 262.1359, Found 262.1358.
2-(9,10-dihydro-9,10-propanoanthracen-9-yl)-N-methylethanamine (2). Titanium(IV) isopropoxide (0.1 mL, 0,25 mmol) was added to a commercially available solution of methylamine in methanol (2M, 7.5 mL) followed by the addition of the aldehyde 9 (0.22 mL, 0.22 mmol). The reaction mixture was stirred at ambient temperature for 4 h, after which sodium borohydride (7.7 mg, 0.19 mmol) was added and the resulting mixture was further stirred for another period of 4 h. The reaction was then quenched by the addition of water (0.1 mL), the resulting inorganic precipitate was filtered and washed with diethyl ether (2 mL). The organic layer was separated and the aqueous part was further extracted with diethyl ether (2 × 4 mL). The combined ether extracts were dried over K2CO3. Removal of the solvent under vacuum gave bishomobenzoctamine 2 in high purity (0.04 g, 57%) as a white viscous liquid. IR (CDCl3): ν = 3448, 3338, 2962, 2926, 2852, 1598, 1475, 1450, 1261, 1093, 1020, 800 cm-1; 1H-NMR δ 1.09 (t; J = 6.6 Hz, 2H, H-13), 1.19–1.62 (m, 6H, H1', H11, H-12), 2.24 (s; 3H, CH3), 2.51–2.28 (m; 2H, H-2'), 2.32 (s; 1H, NH), 3.97 (t; J = 4.4 Hz, 1H, H-10), 7.19–7.40 (m; 8H, aromatic-H); MS (EI) m/z (%) = 277 (33) [M+], 262 (33), 234 (16), 233 (26), 220(22), 219 (84), 218 (23), 205 (16), 203 (19), 202 (20), 192 (25), 191 (100), 189 (29), 178 (19); HRMS (EI) Calcd. for C20H23N [M+] 277.1829, Found 277.1830.