Synthesis
The general procedure for the synthesis of 5-chloro-2-methylphenylboronic acid from trimethyl borate and 4-chloro-2-iodotoluene was carried out as follows: firstly, magnesium shavings (0.346 g, 14.25 mmol) were activated by heating in an oven at 120°C for 16 hours. Anhydrous tetrahydrofuran (50 ml) and a small amount of iodine crystals were added to the activated magnesium crumbs using pre-oven dried glassware. Subsequently, 4-chloro-2-iodotoluene was added via syringe and the reaction system was ensured to be in an oxygen-free environment. The reaction mixture was heated and refluxed for 5.5 hours under a continuous flow of argon gas. Upon completion of the reaction, the system was cooled to -78°C (using a dry ice-acetone bath) and a solution of anhydrous tetrahydrofuran (10 ml) of trimethyl borate (2.47 g, 23.76 mmol) was slowly added dropwise. After the dropwise addition, the reaction system was allowed to warm up slowly to room temperature and stirring was continued for 16 hours. At the end of the reaction, the reaction was quenched by careful addition of 1 M hydrochloric acid (20 ml), followed by extraction of the reaction mixture with ether (3 x 50 ml). The organic phases were combined, washed with water (3 x 50 ml), dried with magnesium sulfate and concentrated under reduced pressure. Finally, the residue was washed with hexane to afford the target product 5-chloro-2-methylphenylboronic acid (0.537 g, 26% yield) as a white powder.
