1-BROMO-4-IODO-2-(TRIFLUOROMETHYL)BENZENE

393-36-2

364-11-4

The general procedure for the synthesis of 2-bromo-5-iodobenzotrifluoride from 5-amino-2-bromobenzotrifluoride was as follows: first, 4-bromo-3-(trifluoromethyl)aniline (500 mg, 2.08 mmol) was dissolved in a mixture of preheated concentrated sulfuric acid (37% w/w, 0.51 mL, 4.6 eq.) and water (2.3 mL, concentration = 3.4 M). Under vigorous stirring, the reaction mixture was cooled to -10 °C (using an ice-salt bath), at which point the aniline bisulfate precipitated as a slurry. Subsequently, an aqueous solution of sodium nitrite (NaNO2, 158 mg, 1.1 eq.) was added slowly and dropwise (1.06 mL, concentration = 2.15 M). After continued stirring at -8 °C for 40 min, an aqueous solution of potassium iodide (KI, 495 mg, 1.43 equiv) (0.4 mL, concentration = 8 M) and copper powder (4 mg) were added. The reaction mixture was gradually warmed to room temperature (ice bath removed) and stirred for 30 minutes. Next, the reaction was heated to reflux (102 °C) and kept for 1 hour. Upon completion of the reaction, it was cooled to room temperature, diluted with water and the aqueous layer was extracted with dichloromethane (DCM, 3 x 20 mL). The combined organic phases were washed sequentially with saturated sodium thiosulfate (Na2S2O3, 20 mL) and brine (20 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: hexane) to afford the target compound 2-bromo-5-iodobenzotrifluoride in 93% yield (679 mg) as an orange solid. The structure of the product was confirmed by 1H NMR and 13C NMR.