Isoquinoline (1; 12.9 g, 0.1 mol, 1.0 equiv) was slowly added to concentrated H2SO4 (100 mL) pre-cooled to 0 °C under mechanical stirring. Under vigorous stirring, TCCA (12.8 g, 55 mmol, 1.65 eq.) was added in 4 batches while the reaction temperature was controlled not to exceed 10 °C. The reaction was carried out at 10 °C for a period of 2 hours. After the reaction mixture was stirred continuously at 10 °C for 24 h, the reaction progress was monitored by GC-MS. Subsequently, the reaction mixture was poured into crushed ice (~200 g) and the precipitate was collected by filtration. The pH of the filtrate was adjusted to 2 with concentrated ammonia solution, cooled sufficiently and filtered again. The filtrate was extracted with toluene (6 x 75 mL) to remove the by-product 5,8-dichloroisoquinoline (16). The aqueous phase was further alkalized with concentrated ammonia to pH 6, at which point the precipitate precipitated was filtered, washed with water and dried at room temperature. The final product was purified by recrystallization from methylcyclohexane in 15% yield. 5-Chloroisoquinoline was obtained as 7.60 g (45% yield), melting point 70-72 °C. IR (ATR): 1580, 1489, 1371, 1267, 1204, 1140, 1065, 984, 822, 750, 687, 628, 536 cm1. 1H NMR (400 MHz, CDCl3): δ= 9.27 (s, 1H), 8.64 (1H). 1H), 8.64 (d, J = 6.0 Hz, 1H), 8.02 (d, J = 6.0 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H).13C NMR (100 MHz, CDCl3): δ= 152.4, 143.9, 133.9, 133.5, 133.5 cm1. 1H NMR (400 MHz, CDCl3): δ= 152.4, 143.9, 143.9, 133.5 cm 143.9, 133.7, 131.0, 130.3, 129.4, 127.3, 126.7, 116.9.
