Hydrogen Bromide → 5-Bromo-1-chloroisoquinoline

Participants

Reaction Conditions

Reaction Steps

To a 500 mL round-bottomed flask containing 1-chloroisoquinolin-5-amine (Step 2, 5.8 g, 32.5 mmol) in H2O (33 mL) and 40% HBr (14 mL) chilled to −50 C in an ice bath, was added a freshly prepared solution of (Sodium nitrate (2.47 g, 35.7 mmol) in 8 mL of H2O) drop-wise over 15 minutes. After the addition, the mixture was kept at 2° C., while stirred an additional 20 minutes. Then urea (0.192 g, 3.2 mmol) was added in order to decompose excess nitrate in the reaction mixture. After an additional 5 minutes of stirring the diazonium salt mixture was transferred into a dropping funnel. The diazonium salt was added drop-wise into a heated (70° C.) solution of Copper (1) Bromide (4.66 g, 32.5 mmol) in 40% HBr (30 mL)). After the addition, the mixture was heated to 80° C. for 1.5 hours. Then the mixture was allowed to cool to ambient temperature. The solid, which had formed in the reaction mixture, was collected by filtration. Then recrystallized from hot EtOAc and Hexanes, after drying, gave a brown crystalline solid, which was titled product (4.576 g; 18.9 mmol). MS (ESI pos. ion) m/z: 243 (M+H). Calc'd Exact Mass for C9H5BrCl: 242.5

Provenance & Evidence