[Synthesis]
To a solvent mixture of ether (80 mL) and tetrahydrofuran (80 mL), n-butyllithium (19.3 mL, 2.5 M hexane solution, 48 mmol) was slowly added dropwise at -78 °C. Subsequently, a solution of 5-bromoisoquinoline (5.0 g, 24 mmol) in tetrahydrofuran (10 mL) was added dropwise. The reaction mixture was stirred at -78 °C and under argon protection for 30 min. Referring to the method of Pearson et al. in Journal of Heterocyclic Chemistry, Vol. 6, No. 2, pp. 243-245 (1969), a tetrahydrofuran (10 mL) solution of N,N-dimethylformamide (3.30 g, 45 mmol) was rapidly added to the lithium isoquinolinium solution after it was cooled to -78°C. The mixture was continued to be stirred at -78 °C for 15 minutes. Subsequently, ethanol (20 mL) and saturated ammonium chloride solution were added. The resulting suspension was slowly warmed to room temperature. The organic and ether extracted layers were combined and dried with anhydrous sodium sulfate. Purification by silica gel column chromatography (SiO2-H, hexane solution of 50% ethyl acetate) and ethanol recrystallization afforded isoquinoline-5-carbaldehyde (2.4 g, 15 mmol, 64% yield) as a light yellow solid with a melting point of 114-116 °C.1H NMR (DMSO-d6) δ 10.40 (s, 1H), 9.44 (s, 1H), 8.85 (d 1H, J = 6.0 Hz), 8.69 (d, 1H, J = 6.0 Hz), 8.45 (m, 2H), 7.90 (t, 1H, J = 7.2 Hz); 13C NMR (DMSO-d6) δ 194.23, 153.5, 146.2, 140.2, 135.2, 132.6, 130.2, 128.6, 127.5, 117.2. Calculated elemental values (C10H7NO-0.05H2O): C, 75.99; H, 4.53; N, 8.86. Measured values: C, 75.98; H, 4.66; N, 8.68. |