Iodine → 4-Chloro-2-iodo-6-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

4-Chloro-2-methylbenzoic acid (1.7 g, 10 mmol), palladium(II) acetate (112 mg, 0.5 mmol), iodobenzene diacetate (6.44 g, 20 mmol) and elemental iodine (5.08 g, 20 mmol) were dissolved in N,N-dimethylformamide (50 mL) and stirred overnight at 100° C. The reaction mixture was cooled to room temperature, diluted with methyl-tert-butylether and 2M hydrochloric acid and washed with 10% aqueous solution of sodium metabisulphite. Organic phase was extracted with 2M sodium hydroxide and the resulting basic aqueous phase was acidified with concentrated aqueoushydrochloric acid and re-extracted with methyl-tert-butylether. The solvent was removed under reduced pressure affording 4-chloro-2-iodo-6-methylbenzoic acid (2.8 g, 94% yield) without further purification. So obtained iodinated benzoic acid (2.8 g, 9.4 mmol) was dissolved in N,N-dimethylformamide (25 mL) and methyliodide (1.25 mL, 20 mmol) and potassium carbonate (2.8 g, 20 mmol) were added. The reaction mixture was stirred overnight at room temperature, diluted with methyl-tert-butylether and washed with water, 1M sodium hydroxide, water and brine. Solvent was removed under reduced pressure and the crude was purified by flash chromatography (n-hexane/diethyl ether 100:2) to give title compound (2.2 g, 75% yield).

Provenance & Evidence