General procedure for the synthesis of 2,4,6-tribromo-1,3,5-trimethylbenzene from 1,3,5-trimethylbenzene: 1-methoxy-3,5-dimethylbenzene (100 mg, 0.73 mmol), N-bromosuccinimide (NBS, 260 mg, 1.46 mmol), and a stainless steel ball (5 mm in diameter) were placed in a 10 mL stainless steel grinding jar. The ball milling reaction was carried out and the reaction process was monitored by thin layer chromatography (TLC) and proton nuclear magnetic resonance (1H NMR). Upon completion of the reaction, the reaction mixture was transferred to 30 mL of ethyl acetate and cooled at 0 °C. The product in the filtrate and the precipitated spent succinimide were separated by filtration through filter paper. The filtrate was concentrated under vacuum to give 250 mg (85% yield) of 2,4,6-tribromo-1,3,5-trimethylbenzene as a colorless powder. To test the efficiency of the large-scale reaction, a monobromination reaction was also carried out with 1.3 g of 1-methoxy-3,5-dimethylbenzene for 1 h. The product was isolated in 87% yield. During the reaction, the grinding equipment was suspended and a small amount of sample was removed from the reaction tank for TLC and 1H NMR analysis, after which the reaction was continued, and the time of this operation was not included in the total reaction time.
