2-HYDROXY-4-IODO-BENZALDEHYDE

50-00-0

533-58-4

38170-02-4

Step 1: Preparation of 2-hydroxy-4-iodobenzaldehyde Magnesium chloride (MgCl2, 19.5 g, 204 mmol) was added batchwise to a frozen solution of commercially available 2-iodophenol (30 g, 136 mmol) in acetonitrile (ACN) while keeping the reaction temperature below 10 °C. Paraformaldehyde (28.6 g, 954 mmol) and triethylamine (TEA, 76 mL, 545 mmol) were subsequently added and the reaction was exothermic to 15 °C. The reaction mixture was heated to 72 °C and maintained for 2 hours. Upon completion of the reaction, it was cooled to room temperature, poured into saturated aqueous ammonium chloride solution (500 mL) and extracted with ethyl acetate (2 x 150 mL). The organic phases were combined and washed sequentially with aqueous sodium bicarbonate (NaHCO3) (2 × 150 mL), aqueous 1N hydrochloric acid (HCl) (2 × 150 mL) and brine (2 × 150 mL). The organic layer was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by fast column chromatography (silica gel, 5% ethyl acetate/hexane). The target fractions were collected, combined and the solvent was removed under reduced pressure to give 2-hydroxy-4-iodobenzaldehyde (27 g, 79% yield) as a yellow solid. The salicylaldehyde derivative was of suitable purity and could be used directly in the subsequent reaction.