[Synthesis]
General procedure for the synthesis of 1-acetylisoquinoline from 1-cyanoisoquinoline: An ether solution of methylmagnesium bromide (8.1 mL, 24.3 mmol) was dissolved in 16 mL of tetrahydrofuran under nitrogen protection in a pre-oven-dried 100 mL two-necked round-bottomed flask. The reaction system was cooled to 0 °C and 1-isoquinolinecarbonitrile (3.0 g, 19.5 mmol) was added after dilution with 8 mL of ether. The reaction mixture was heated to reflux for 1 h. Subsequently, the reaction was cooled to 0 °C and quenched with 20 mL of 6 M hydrochloric acid. The reaction solution was warmed to 50 °C and maintained for 2 h. After cooling, it was poured into 75 mL of 2 N sodium hydroxide solution. The mixture was extracted with ethyl acetate (3 x 80 mL), the organic phases were combined and dried over potassium carbonate. The dried organic phase was concentrated under vacuum to give the crude product as an amber colored oil. The crude product was purified by silica gel column chromatography (150 g, 230-400 mesh) with 10% acetone/hexane as eluent and 22 mL of fractions were collected. The fractions 16-26 were combined and concentrated to give 2.1 g of 1-acetylisoquinoline (62% yield). The product was analyzed by NMR hydrogen spectrum (CDCl3, TMS): δ 2.87 (s, 3H), 7.64-7.73 (m, 2H), 7.80 (d, J = 5.5 Hz, 1H), 7.83-7.88 (m, 1H), 8.58 (d, J = 5.5 Hz, 1H), 8.94-8.98 (m, 1H) ppm; NMR carbon spectrum ( CDCl3): δ 28.6, 124.6, 125.7, 126.9, 127.0, 129.1, 130.3, 137.0, 141.0, 152.8, 202.7 ppm confirmed. Thin layer chromatography (silica gel-60, F-254): Rf = 0.45 (acetone/hexane, 20%). IR spectrum (νmax, liquid film): 3054, 1694, 1582, 1358, 1239, 1133, 940, 833, 750 cm-1. Mass spectrum: [M/Z] (relative intensity): 171 (63). Elemental analysis: Calculated values (C11H9NO): C, 77.17; H, 5.30; N, 8.18. Measured values: C, 77.09; H, 5.33; N, 8.10. |