Example 1: Synthesis of 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethanone
1,4-Dichlorobenzene (20 g, 136 mmol) was dissolved in anhydrous tetrahydrofuran (200 mL) and cooled to -78°C. With stirring, n-butyllithium (150 mmol, dissolved in 60 mL of hexane) was added slowly. The reaction mixture was stirred at -78°C for 1 hr. Subsequently, methyl trifluoroacetate (18 mL, 179 mmol) was added dropwise over 30 min. The reaction mixture was slowly warmed to 0°C and stirring was continued for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of pre-cooled saturated aqueous ammonium chloride solution (100 mL). The organic and aqueous phases were separated. The organic phase was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (200 mL). The aqueous phase was extracted once with ethyl acetate (200 mL). The organic phases were combined and washed with saturated saline (200 mL). The organic phase was separated, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with ethyl acetate/hexane (1/10, v/v) as eluent to give 1-(2,5-dichlorophenyl)-2,2,2-trifluoroacetophenone as an orange oil (28.5 g, 86% yield).
1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 7.56-7.50 (m, 2H).
