Eco-Friendly Synthesis of Iodinated Aromatic Build...

◆Approaches to the synthesis of iodinated molecules include diazotization–iodination reaction and electrophilic iodination using iodine or iodide in combination with an oxidant.

◆Using molecular iodine and hydrogen peroxide in aqueous medium is one of the most useful protocols, which addresses the growing concern over environmental pollution and sustainable development.

◆Water as a reaction solvent was employed in the iodination of N-methylpyrazole 20 with iodine in the presence of hydrogen peroxide (0.6 equiv).

◆The 4-iodo-Nmethylpyrazole product 5 was conveniently isolated directly by filtration from the reaction mixture in 91% yield (16.2 kg).

Procedure

A 100-L RBF with a water bath was charged with N-methylpyrazole (7.0 kg, 85.3 mol) and water (30 L), followed by iodine (11.0 kg, 43.5 mol). After a 10 min age, 4-iodo-N-methylpyrazole (15 g) was charged as seed. 30% H2O2 (5.2 L, 51.2 mol) was charged over 30 min, the temperature increasing from 18 to 32°C. After 42 h of stirring, the slurry was cooled to 10°C. Ten percent NaHSO3(aq) (20 L) was slowly charged as quench, keeping the internal temperature below 20°C. The resulting light-tan slurry was stirred at room temperature for 3 hand isolated by filtration. The wet cake was washed with water (5×20 L). The wet cake was dried in the vacuum oven (30−35°C,∼200 mm vac, N2 sweep) for 3d (The product was shown to sublime when left to dry on a funnel under vacuum and nitrogen).