1. 2-Bromobenzaldehyde (50 g, 270 mmol), aminoglyoxal dimethyl acetal (28.4 g, 270 mmol) and toluene (400 mL) were mixed under argon protection and heated to reflux. The dehydration reaction was carried out for 2.0 hours using a Dean-Stark apparatus. After dehydration was completed, reflux was continued for 1.0 hour.
2. Upon completion of the reaction, toluene was removed by evaporation under reduced pressure, the residue was dissolved in dichloromethane (600 mL), and the solution was cooled to 0°C. The reaction was then purged by evaporation under reduced pressure.
3. Aluminum chloride (118.9 g, 891.7 mmol) was slowly added to the cooled solution under argon protection, and the reaction mixture was then stirred at 45°C for 2.0 hours.
4. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the mixture was cooled to room temperature and slowly poured into ice water.
5. The dichloromethane layer was separated by alkalizing the mixture with 10% sodium hydroxide solution. The aqueous layer was re-extracted with dichloromethane (2 x 100mL).
6. The methylene chloride layer was combined, washed with brine and dried over anhydrous sodium sulfate.
7. The dichloromethane was removed by evaporation and the residue was purified by column chromatography on silica gel (100-200 mesh) to afford 8-bromoisoquinoline as an off-white solid (28 g, 49.8% yield) using a 5-8% ethyl acetate solution in hexane as the mobile phase.
MS (ESI) m/z: 208 [M(79Br)+1], 210 [M(81Br)+1]; 1H NMR (400 MHz, DMSO-d6): δ 7.17 (t, J=7.8 Hz, 1H); 7.91 (d, J=6.0 Hz, 1H); 8.02 (d, J=8.4 Hz, 1H); 8.05 (d, J= 8.8 Hz, 1H); 8.65 (d, J=5.2 Hz, 1H); 9.48 (s, 1H).
