Synthesis
Synthesis of 1,5-Dichloroanthracene 3 [26, 6]
1,5-Dichloroanthraquinone 4 (10.0 g, 36.1 mmol) and Zinc dust (50.0 g, 765 mmol) were suspended in 200 mL of aqueous 28% NH3 with stirring for 3 h at 100 0C. After cooling to r.t., the reaction mixture was separated by filtration and the filtrate was eluted and extracted several times with CH2Cl2. The CH2Cl2 organic phases were collected, dried over MgSO4, filtered and concentrated under vacuum. To the residual crude, 500 mL isopropanol and 50 mL aqueous HC1 (12 M) were added. After refluxing the reaction mixture for 3 h, the mixture was cooled, concentrated in vacuo and then partitioned between CH2Cl2 and aqueous 5% NaHC03. The CH2Cl2 organic phase was collected, dried with MgSO4, filtered and concentrated to give crude 1,5-dichloroanthracene 3. This crude was crystallized using a CH2Cl2-Petroleum ether mixture. The product 1,5-dichloroanthracene 3 was dried in the air for 24 h (7.5 g, 30.49 mmol) as yellow-orange needles in a 84.45 % yield; mp 187–188 0C; IR (KBr): υ = 681, 720, 736, 778, 849, 873, 903, 958, 996, 1145, 1162, 1212, 1300, 1449, 1530, 1618 cm− 1; 1H NMR (CDCl3, 400 MHz): δ = 7.40–7.61 (m, 4 H, ArH), 8.00 (dd; j = 2.92 Hz, 2 H, ArH), 8.42 (s, 1 H, ArH), 8.84 (s, 1 H, ArH) ppm. 13C NMR (CDCl3, 100 MHz): δ = 124.37, 125.42, 125.58, 126.29, 128.24, 131.7, 132.8 ppm.
Synthesis of 1,5-dichloro-9,10-dihydro-9,10-ethanoanthracene-12-carbaldehyde 2 at -15 0C
Into a previously − 15 0C cooled solution of 1,8-dichlorolanthracene 3 (500 mg, 2 mmol) in 70 mL CH2Cl2, acrolein (0.65 mL, 9.3 mmol) was added. Then, BF3·OEt2 (0.5 mL, 4.05 mmol) was drop wisely added and the mixture was allowed to stir at -15 0C for 1 hour then at room temperature for 4 hours. The reaction was then quenched with sat. NaCl and extracted with CH2Cl2. The organic layers were collected, dried with Na2SO4, filtered and concentrated. The crude product was preliminary purified by column chromatography on silica gel using dichloromethane -petroleum ether (1:1) to afford aldehyde 3 (450 mg, 1.49 mmol) as three isomeric adducts in a 74 % yield; IR (KBr): υ = 576, 706, 775, 1169, 1264, 1458, 1570, 1723, 2961, 3024, 3047 cm− 1. A mixture of isomeric adducts (300 mg, 1 mmol) was separated by column chromatography on silica gel (1:1-Hexane: toluene) to give the initially eluted two isomers of 2 (2a) (160 mg, 0.53 mmol) as yellow viscous with the following characteristics; 1H NMR (CDCl3, 400 MHz): δ = 1.93–2.04 (m, 2H, H-C11), 2.14–2.22(m, 2H, H-C11), 2.8–2.89 (m, 2H, H-C12), 4.93 (pent, J = 2.74 Hz, 2H H-C10), 5.26 (dd, J = 7.2, 2.45 Hz, 2H, H-C9), 7.1–7.47 (m, 12H, H-Ar), 9.52 (d, J = 0.8, 1H, H-CHO), 9.56 (d, J = 0.8, 1H-CHO) ppm. 13C NMR (CDCl3, 100 MHz): δ = 27.29, 27.32, 40.37, 41.50, 41.59, 49.87, 51.07, 122.45, 122.48, 122.56, 123.54, 123.77, 126.78, 127.11, 127.17, 127.24, 127.28, 127.50, 127.78, 129.35, 123.38, 129.57, 130.23, 136.58, 138.98, 140.61, 140.79, 140.94, 143.25, 145.08, 145.37, 200.91, 201.17 ppm. and a pure isomer of 2 (2b) (140 mg, 0.46 mmol) as white solid with the following characteristics; 1H NMR (CDCl3, 400 MHz): δ = 1.99–2.06 (m, 1H, H-C11), 2.11–2.18 (m, 1H, H-C11), 2.77–2.84 (m, 1H, H-C12), 4.44 (t, J = 0.8 Hz, 1H, H-C10), 4.72 (d, J = 0.8 Hz, 1H, H-C9), 7.21–7.45 (m, 6H, H-Ar), 9.45 (d, J = 0.8, 1H, H-CHO) ppm. 13C NMR (CDCl3, 100 MHz): δ = 28.76, 43.69, 45.20, 51.22, 123.45, 123.51, 123.64, 124.53, 125.96, 125.99, 126.28, 126.55, 139.37, 142.12, 143.79, 144.06, 202.73 ppm.
Synthesis of 1,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-12-yl)-N-methylmethanamine 1 [27]
To a 5o mL two-neck round-bottom flask connected to a condenser capped with a H2 balloon and a rubber septum, a 100 mg Pd-C catalyst was added. The flask was evacuated and backfilled with H2 two times. Then a solution of aldehyde 2 (50 mg, 0.165 mmol) in methanol (3 mL) and (0.25 mL, 2 M) of methylamine solution in methanol were added into flask by syringe through septum. After 1.5 h of the reaction time, the reaction mixture was filtered and washed with CH2Cl2, then removed the solvent to afford the amine 1 with the following characteristics: IR (KBr): υ = 706, 740, 1266, 1422, 2987, 3055 cm− 1, 1H NMR (CDCl3, 500 MHz): δ = 1.25–1.28 (m, 1H, H-C11), 1.95–2.11 (m, 1H, H-C11), 2.25–2.29 (m, 2H, H-C12, H-C1/, CH2), 2.32 (s, 3H, H-CH3), 2.43–2.47 (m, 1H, H-C1/, CH2), 4.29 (t, J = 2.12, 1H, H-C10), 4.47 (d, J = 1.64, 1H, H-C9), 7.07–7.17 (m, 3H, Ar-H), 7.19–7.46 (m, 3H, Ar-H) ppm; DEPT 90: 35.80 (↑CH), 43.73 (CH), 46.05 (↑CH); DEPT 135: 33.02 (↓CH2), 33.39 (↑CH3), 35.80 (↑CH), 43.73 (↑CH), 46.05 (↑CH), 54.31 (↓CH2) ppm; MS (ES) m/z (%) = 318 (100) [M+], 284 (70), 250 (18), 184 (40), 117 (62), 85 (40); HRMS (ES) Calcd for C18H18 NCl2 [M+] 318.0816, Found 318.0815.
Synthesis of Z/E-Ethyl 3-(1,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-12- yl)propenoate 5
Into a 50-mL round-bottomed flask containing aldehyde 2 (755 mg, 2.5 mmol) pre-dissolved in a 15 mL dichloromethane, a two equivalent Wittig reagent (Carbethoxymethylene)triphenylphosphorane (174 mg, 5 mmol) was added. The reaction mixture was stirred overnight at room temperature, then solvent was removed to purify via silica gel column chromatography using the eluent system (Ethyl acetate/Petroleum ether, 1:20) affording unsaturated ester 5 as Z/E isomer (700 mg, 1.9 mmol, 76 %) in ratio of 1: 3.5 respectively as yellow oil with the following characteristics; IR (KBr): υ = 650, 735, 909, 1036, 1097, 1170, 1240, 1271, 1305, 1369, 1461, 1650, 1709, 2254, 2875, 2971, 3537 cm− 1; 1H NMR (CDCl3, 400 MHz): δ = 1.15–1.35 (m, 6H, H-CH3 (Z/E)), 1.45–1.52 (m, 1H, H-11), 2.07–2.12 (m, 1H, H-11), 2.73–2.80 (m, 1H, H-12), 4.12–4.18 (q, J = 25, 2H, ), 4.22 (d, J = 5, 1H, H-9), 4.26 (q, J = 25, 2H, ), 4.34 (t, J = 3, 1H, H-10), 4.35 (t, J = 2, 1H, H-10), 5.78 (d, J = 25 Hz, 1H, ), 6.45 (dd, J = 15, 5, 1H, ), 7.1–7.19 (m, 6H, Ar-H), 7.25–7.35 (m, 6H, Ar-H) ppm. For only (E) HSQC and 13C NMR (CDCl3, 100 MHz): δ = 14, 33.9 (CH3), 43 (CH2, C11), 40.09 (C12), 43 (C10), 48 (C9), 59.8 (-O-CH2-), 120.7, 122.9, 123.2, 123.5, 125.03, 125.06, 125.08, 125.1, 134, 139.5, 143.4, 143.6, 143.9, 152, 167 ppm; HRMS (ES) Calcd for C21H18 O2Cl2Na [M+] 395.0582, Found 395.0576.
Synthesis of Ethyl 3-(1,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-12- yl)propanoate 6
Two-necked round-bottom flask containing Pd/C (70 mg, 10%) was wetted with ethanol. After evacuation and charging flask with hydrogen (H2, balloon) two times, a solution of unsaturated ester 5 (820 mg, 2.2 mmol) in 15 ml ethanol was added. The mixture was stirred overnight at room temperature under H2, then filtered through celite with CH2Cl2. The solvent was removed in vacuo to give the saturated ester 6 (350 mg, 0.93 mmol, 42 %) as yellow oil with the following characteristics; 1H NMR (CDCl3, 400 MHz): δ = 1.15–1.2 (m, 1H, H-C11), 1.21–1.30 (m, 4H; 1H-C/1, 3H, H-CH3), 1.47–1.56 (m, 1H, H-C/1), 1.87–1.95 (m, 1H, H-C12), 2-2.12 (m, 1H, H-C11), 2.33 (t, J = 12, 2H, H-C/2), 4.08 (q, J = 10 Hz, 2H, -O-CH2-), 4.15 (d, J = 0.4 Hz, 1H, H- C9), 4.26 (t, J = 2 Hz, 1H, H-C10), 7.1–7.20 (m, 3H, Ar-H), 7.25–7.35 (m, 3H, Ar-H) ppm; HSQC (CDCl3, 100 MHz): δ = 14, 30.05 (CH3), 30.05 (CH2, C/2), 31.15 (CH2, C/1), 34 (CH2, C11), 38 (C10), 49 (C9), 60 (CH2, -O-CH2-) ppm; HRMS (ES) Calcd for C21H20 O2Cl2Na [M+] 397.0738, Found 397.0735.