78% |
Stage #1: methanol With sodium Inert atmosphere;
Stage #2: 3,6-dibromoquinoline With copper(l) iodide In N,N-dimethyl-formamide for 6h; Inert atmosphere; Reflux; |
4.6. Synthesis of 3,6-dimethoxyquinoline (18)
Freshly cut sodium (0.7 g, 30 mmol) was added to dry methanol(25 mL) under nitrogen gas atmosphere. When dissolution wascomplete, the warm solution was diluted with dry dimethylformamidby addition of vacuum dried cuprous iodide (1.0 g,0.51 mmol). After dissolution, 3,6-dibromoquinoline (16) (450 mg,1.05 mmol) into dry DMF (30 mL) was added. The reaction mixturewas stirred magnetically under a nitrogen gas atmosphere at reflux(ca 150 C) for 6 h. The reaction's progress was monitored by TLCuntil the starting material was all consumed. After cooling to rt,H2O (25 mL) and CHCl3 (50 mL) were added to the reaction mixture.The organic layers were separated, washed with H2O (2 20 mL),and dried over Na2SO4. The solvent was removed and the crudeproduct was passed through a short silica gel (3 g) column elutingwith AcOEt/hexane (1:3, 100 mL). After filtration and purification,the resultant productwas 3,6-dimethoxyquinoline (18). Pale yellowpowder solid (156 mg, 78% yield): mp 84e86 C: 1H NMR(400 MHz, CDCl3) d 8.54 (d, J24 2.4 Hz, 1H, H2), 7.95 (d, J87 9.2 Hz,1H, H8), 7.32 (d, J42 2.4 Hz, 1H, H4), 7.22 (dd, J78 9.2 Hz,J75 2.8 Hz, 1H, H7), 7.03 (d, J57 2.4 Hz, 1H, H5), 3.96 (s, 3H, OCH3),3.94 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) d 158.4 (q), 153.7 (q),141.7, 139.4 (q), 130.6, 130.1 (q), 119.0, 111.8, 104.8, 55.5 (OCH3), 55.4(OCH3). All data were identical to that reported in the literature.23 |