Iodine → 5-Iodobenzene-1,3-diol

Participants

Reaction Steps

Preparation of substituted iodobenzene 39, conversion of 38 to the corresponding thiol, and formation of diphenylsulfide 40: 3,5-Dihydroxyiodobenzene was prepared from 3,5-dimethoxyaniline (Aldrich) by diazotization and iodine introduction followed by demethylation of the methoxy groups all under standard conditions. This material (3.78 g 16.0 mmol) was dissolved in CH2Cl2 (30 mL). Triethylamine (11.15 mL, 80 mmol), acetic anhydride (4.55 mL, 48 mmol) and DMAP (390 mg, 3.2 mmol) were added and the reaction stirred for 16 h. The reaction was evaporated to dryness, and passed through a plug of silica gel eluting with 4:1 hexane:ethyl acetate to afford the desired product. This material (12.8 mmol) was dissolved in a mix of ethanol (32 mL) and benzene (16 mL). Potassium hydroxide (0.72 g, 12.8 mmol) was dissolved in 8 mL ethanol and added over 30 min. After 30 min the reaction was diluted with ether and washed with 0.5N H2SO4, sat NaHCO3, sat NaCl, dried over Na2SO4, and evaporated. The product was recrystallized from toluene to afford 86% yield of the monoacetate which was dissolved in CH2Cl2 (50 mL) and triethylamine (3.45 mL, 24.8 mmol), DMAP (0.3 g, 2.5 mmol) and benzoyl chloride (1.8 mL, 15.5 mmol) was added. The reaction was complete in 10 min then diluted with CH2Cl2 and washed with sat NH4Cl, sat NaHCO3, and sat NaCl. The solution was dried (Na2SO4) and evaporated. Purification was accomplished via silica chromatography 19:1 hexane:ethyl acetate to afford 4.4 g (95% yield) of desired product 39.

Provenance & Evidence