The general procedure for the synthesis of 3,5-dimethyl-4-iodophenol from 3,5-dimethylphenol was as follows: 395 mL of 36% hydrochloric acid was slowly added to a 1 L methanol solution containing 59.1 g (484 mmol) of 3,5-dimethylphenol, which was cooled intermittently to maintain the reaction temperature between 20°C and 30°C. The reaction was then carried out over a period of 5 min by dropwise addition of 54.3 g (327 mmol) of potassium iodide and 33.5 g (157 mmol) of potassium iodate to 500 mL of water. Subsequently, a solution prepared from 54.3 g (327 mmol) of potassium iodide and 33.5 g (157 mmol) of potassium iodate dissolved in 500 mL of water was added dropwise to the reaction system over a period of 5 min. It was observed that the solution gradually turned red and became turbid, followed by the formation of a tan precipitate. The reaction mixture was stirred continuously for 20 h at room temperature before being cooled in an ice bath, the precipitate was collected by filtration and washed with a pre-cooled 2:1 (v:v) water/methanol mixture. The resulting brown solid was purified by several recrystallizations from hot methanol and water, resulting in 36.4 g (15% yield) of white acicular crystals with a melting point of 131-132°C, which were identified as 3,5-dimethyl-4-iodophenol. The structure of the compound was confirmed by 1H NMR (δ, CDCl3) 8.03 (br s, 1H), 6.52 (s, 2H), and 2.35 (s, 6H) as well as by mass spectra (m/e) 248 (M+, 100%), 121, 91, and 77.
