Synthesis
The general procedure for the synthesis of 5-bromo-6-(bromomethyl)benzo[d][1,3]dioxole from piperonal was as follows: bromine (3.36 g, 21 mmol) was added slowly and dropwise to a solution of piperonal (3.0 g, 20 mmol) in chloroform (15 mL). The reaction mixture was heated to 60 °C and the reaction was stirred at this temperature for 12 hours. Upon completion of the reaction, the mixture was cooled to room temperature and diluted with the addition of dichloromethane (60 mL). Subsequently, the organic phase was washed sequentially with saturated aqueous sodium bicarbonate (2 x 20 mL) and brine (20 mL), and the organic layer was dried with anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give the crude product 5-bromo-6-(bromomethyl)benzo[d][1,3]dioxole (5.88 g, 100% yield), which solidified on standing. A portion of the crude product (2.44 g, 8.33 mmol) was taken and dissolved in tetrahydrofuran and the solution was cooled to -78 °C. Under nitrogen protection, lithium aluminum hydride (348 mg, 9.16 mmol) was added in batches and the reaction was stirred at -78 °C for 3 hours. Subsequently, lithium aluminum hydride (80 mg, 2.03 mmol) was added and stirring was continued for 1 hour. Upon completion of the reaction, ethyl acetate was carefully added to quench the excess lithium aluminum hydride, followed by methanol (20 mL). The insoluble salt was removed by filtration and the filtrate was concentrated under reduced pressure to afford the target product 5-bromo-6-(bromomethyl)benzo[d][1,3]dioxole (1.76 g, 99% yield), which could be used in the subsequent reaction without further purification. The product was characterized by 1H-NMR (CDCl3): δ 7.01 (s, 1H), 6.73 (s, 1H), 5.95 (s, 2H), 2.32 (s, 3H).
