1) Preparation of 1-chloro-2-iodo-4-nitrobenzene (Compounds 1-3)
2-Chloro-5-nitroaniline (40 g, 232.0 mmol) was dissolved in a mixed solution of concentrated sulfuric acid (32 mL) and water (320 mL) using mechanical stirring. The reaction solution was cooled to -5 °C and a solution of sodium nitrite (18.2 g, 0.26 mol) in water (69 mL) was added slowly and dropwise. The reaction mixture was stirred under ice bath conditions for 0.5 h. Subsequently, a solution of potassium iodide (69.3 g, 0.41 mol) in water (277 mL) was added slowly, controlling the reaction temperature to be below 5 °C. Stirring was continued for 3 hours. After completion of the reaction, it was extracted with ethyl acetate at 0 °C. The organic phases were combined, washed with saturated sodium thiosulfate (Na2S2O3) solution, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The residue was recrystallized by isopropanol/hexane (300 mL/100 mL) mixed solvent to give compounds 1-3 (38 g, 58% yield) as light tan crystalline solids.
1H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 8.8 Hz, 1H), 8.16 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 8.70 (d, J = 2.8 Hz, 1H).
