Sulfuric Acid → 3-Cyclopropyl-5-iodoisothiazole

Participants

Reaction Conditions

Reaction Steps

To a water (1.4 mL) and ice (5.0 cc) suspension was added 3-cyclopropylisothiazol-5-amine (500 mg, 3.57 mmol) followed by concentrated sulfuric acid (1.4 mL). A solution of sodium nitrite (258 mg, 3.74 mmol) in water (5.0 mL) was added dropwise at 0° C., and the mixture was stirred at 0° C. for 1 hour. Next, a solution of potassium iodide (622 mg, 3.74 mmol) in water (3.5 mL) was added dropwise at 0° C., and the mixture was heated at 80° C. for 1 hour. Ethyl acetate at 0° C. was added and the mixture was neutralized with potassium carbonate. The organic layer was separated, dried over magnesium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography (Flash 60 column) eluting with hexane/EtOAc (19:1) to give the title compound as green oil (356.5 mg, 40%). 1H NMR (500 MHz, CDCl3) δ ppm 0.92-0.98 (m, 2H), 0.98-1.04 (m, 2H), 2.13-2.20 (m, 1H), 7.06 (s, 1H).

Provenance & Evidence