Synthesis
1-Chloro-3-nitro-2-trifluoromethylbenzene (221.27 g, 0.981 mol) was used as a raw material in a 5 L multi-necked flask equipped with a mechanical stirrer, thermocouple casing, condenser, nitrogen inlet line, and a dropping funnel with ethanol (denatured with 5% methanol and isopropanol, 3.46 L), water (0.87 L), zinc powder (384.71 g, 5.885 mol) and anhydrous calcium chloride (108.88 g, 0.981 mol). The mixture was heated to reflux and reacted overnight. The progress of the reaction was monitored by GC to confirm the complete disappearance of the feedstock (tR = 3.52 min) and the formation of the product (tR = 3.25 min). After completion of the reaction, the mixture was cooled to 30 °C and filtered through a diatomaceous earth pad (200 g). The solid was washed with ethanol (2 × 500 mL), the filtrate was combined and concentrated. Ethyl acetate (0.5 L) was added to the residue and the organic layer was separated and washed sequentially with water (2 × 500 mL) and brine. The aqueous layer was then back-extracted with ethyl acetate (2 × 0.5 L). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and the volatiles were evaporated to give 175.31 g (91% yield) of 3-chloro-2-trifluoromethylaniline (80.9% GC purity). The structure of the product was confirmed by 1H NMR and 19F NMR analyses, and 10-20% impurities and 0.5 equivalents of ethyl acetate were detected. The purity of the product met the requirements of the next reaction and no further purification was required.GC analysis conditions: DB5 column (30 m × 0.32 mm ID, 0.25 μm film thickness), temperature program 75-300 ℃, ramp rate 15 ℃/min, injector temperature 275 ℃, detector temperature 350 ℃. Mass spectrometry analysis (APCI): m/z 196.1 (M+1, calculated value 195.0).
