Hydrochloric Acid → 5-Iodo-1H-indazole

Participants

Reaction Conditions

Reaction Steps

A solution of 5-aminoindazole (5.0 g, 38 mmol) and ice (32 g) in water (16 mL) was further cooled with an ice bath. To this slurry was added concentrated hydrochloric acid (16 mL), followed immediately by sodium nitrite (2.9 g, 41 mmol in 11 mL water). After stirring for 10 min at 0° C., potassium iodide (7.5 g, 45 mmol) was added and the solution was slowly warmed to 40° C. until gas evolution slowed. The reaction mixture was stirred in a 50° C. oil bath for 30 min further, then cooled to room temperature and 3M aqueous sodium hydroxide solution (40 mL) was added, followed by 50% aqueous sodium bicarbonate solution (40 mL). The solution was vacuum filtered and a brown solid was collected, taken up in 100 mL tetrahydrofuran and stirred with 100 mL of dry silica. To this slurry was added hexanes (66 mL), and the mixture was filtered through celite/fritted glass using 40% tetrahydrofuran/hexanes to rinse the silica. Trituration from ethyl acetate gave 1.6 g (18%) of 5-iodo-1H-indazole. 1H NMR (400 MHz, CDCl3): 10.55 (broad s, 1H), 8.14 (m, 1H), 8.02 (d, 1H), 7.61 (dd, 1H), 7.31 (m, 1H); MS (EI) for C7H5N2I: 245 (MH+).

Provenance & Evidence