Preparation background and overview of 2-methoxyphenylboronic acid
2-Methoxyphenylboronic acid is an arylboronic acid. Arylboronic acid can be used as a safe and environmentally friendly new arylation reagent and is widely used in various fine chemicals containing aryl structures such as medicine, pesticides, and advanced materials. Product research and production. The reaction of arylboronic acids and halogenated compounds plays a decisive role in today’s drug synthesis. This type of reaction was first proposed by the Japanese scientist Suzuki’s team and won the Nobel Prize in Chemistry in 2010.
Preparation of 2-methoxyphenylboronic acid
Preparation report of 2-methoxyphenylboronic acid 1.
Under nitrogen protection, add magnesium (2.9 g, 1.2 times), tetrahydrofuran (20 ml) and dibromoethane (1.9 g) to a 250 ml three-necked flask with a dropping funnel; then add it to the dropping funnel 2-Methoxybromobenzene (17.1 g, 0.1 mol), trimethyl borate (36.8 g, 3.5 times) and tetrahydrofuran (50 ml) were added as solvents. Heat to 40°C to activate the magnesium powder, then slowly add the mixture in the dropping funnel dropwise, control the speed until the reaction temperature does not exceed 60°C, stir the reaction until the magnesium basically disappears, and then heat and reflux for 6 hours. Stop heating, cool the cold mica to room temperature, and hydrolyze it with 5% dilute hydrochloric acid until pH<2. The THF solvent is recovered by distillation. As the solvent decreases, the product precipitates; it is cooled, filtered, and recrystallized in methanol/water to obtain 2-methoxyphenylboronic acid.
Preparation report 2 of 2-methoxyphenylboronic acid,
(1) Preparation of Grignard reagent 2-methoxyphenylmagnesium bromide:
Take a dry 250ml four-neck bottle, two condenser tubes, a 100ml constant pressure funnel and a thermometer. Under the protection of N2, add 3.0g magnesium chips and 100ml of freshly steamed THF into a four-neck bottle, and raise the temperature until the dimethyl sulfoxide slightly boils. Under the protection of N2, transfer 14.56g of 2-bromomethoxybenzene diluted with 50ml of THF from which water has been removed to a constant pressure funnel, and slowly add it dropwise to the THF solution containing magnesium chips. Complete the dropwise addition in about 2 hours. Maintain this temperature and stir for 5 hours. After obtaining the Grignard reagent, proceed directly to the next step.
(2) Preparation of 2-methoxyphenylboronic acid:
Take a dry 500ml four-neck bottle, a 250ml constant pressure funnel, a thermometer, a mechanical stirring device and a low temperature device. Under the protection of N2, add 25 ml of THF and 30.0 g of tributyl borate into a four-necked bottle, cool the temperature to -10°C, and slowly pass the Grignard reagent prepared above through a constant pressure funnel. Add dropwise to the reaction kettle and complete the addition within about 2 hours. Maintain this temperature and stir for 12h. Add 10% sulfuric acid dropwise until the pH of the mixed solution is about 3-4. At this time, there is a certain amount of precipitation in the kettle. Filter, distill the liquid phase under reduced pressure, and recover the solvent. The solid phase is also washed with ethyl acetate 30ml × 3 times. The organic phase was distilled under reduced pressure to recover all the ethyl acetate, and then continued distillation under reduced pressure to obtain a large amount of light yellow solid, which was washed with cold water and dried to obtain a crude product with a yield of 89%.
References
[1] [Chinese invention] CN201810715935.6 Preparation method of arylboronic acid
[2] [Chinese invention] CN201410324727.5 Preparation method of arylboronic acid
