The general procedure for the synthesis of 2-bromo-6-methylphenol from o-cresol is as follows:
Example 36 Synthesis of 2-bromo-6-methylphenol
To a dichloromethane (500 mL) solution of o-cresol (20.0 g, 0.19 mol) and diisopropylamine (2.63 mL, 18.5 mmol), a dichloromethane (500 mL) solution of N-bromosuccinimide (NBS, 32.9 g, 0.19 mol) was slowly added dropwise, and the dropwise process lasted for 7 hours. After completion of the titration, the reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the reaction mixture was acidified to pH=1 with concentrated hydrochloric acid and subsequently diluted by adding sulfuric acid and water (400 mL). The organic layer was separated, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent to give 34.6 g of crude product in 97% yield. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 2.30 (s, 3H), 5.54 (s, 2H), 6.71 (t, J=7.6 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H).
