Background and overview of preparation and application of 2-chlorophenylboronic acid
2-Chlorophenylboronic acid is a monohalogenated phenylboronic acid. Monohalogenated phenylboronic acid is an important pharmaceutical and organic light-emitting diode (OLED) intermediate. As an important intermediate containing both halogen and boric acid groups, It is widely used in Suzuki coupling and Sonogashira coupling.
Preparation and application of 2-chlorophenylboronic acid
A preparation method of 2-chlorophenylboronic acid:
Step 1. Add 83.32g (0.9mol) n-butyl chloride to 360mL ether to obtain a n-butyl chloride solution; place 12g (0.5mol) magnesium chips into a 500ml three-necked bottle, add 40mL ether, and take an ice bath 0°C, under nitrogen protection conditions, add the above n-butyl chloride solution dropwise with stirring, control the dropping speed so that the temperature does not exceed 10°C, start timing from the dropwise addition of the n-butyl chloride solution, and react for 3 hours to obtain an ether solution of n-butyl magnesium chloride. ;
Step 2: Take 17.45 (0.08 mol) 1-butyl-2,3-dimethylimidazole acetate, add 1.84 g (0.025 mol) lithium carbonate under stirring conditions, stir and mix evenly to obtain a catalyst; weigh Take 13.77g of the above catalyst, add it to the diethyl ether solution of n-butylmagnesium chloride in step 1, mix evenly, cool to 15°C, and add dropwise 2-chloroiodobenzene solution (66.24g (0.28mol) 2 under nitrogen protection and stirring conditions) – A mixed solution of chloroiodobenzene and 200mL ether), control the dropping speed so that the temperature does not exceed 20°C, start timing from the dropwise addition of 2-chloroiodobenzene solution, and react for 3 hours to obtain 2-chlorophenylmagnesium chloride solution;
Step 3: Dissolve 402.8g (1.75mol) of tributyl borate in 420 mL of diethyl ether to obtain a solution of tributyl dibromopyridine borate; under nitrogen protection, add dropwise the 2-chlorophenyl compound prepared in step 2 to it. Magnesium chloride solution, control the dropping speed so that the temperature does not exceed 20°C, start timing from the dropwise addition of 2-chlorophenylmagnesium chloride solution, react for 1.5h, control the temperature at 5°C, dropwise add an acetic acid solution with a mass concentration of 45wt%, start with the dropwise addition of acetic acid Start timing the solution, hydrolyze for 35 minutes, extract the water phase twice with 100 mL ethyl acetate, wash the extract twice with 200 mL saturated brine, remove the solvent under reduced pressure, add 50 mL petroleum ether and 50 mL ethyl acetate for recrystallization, and filter with suction. After drying, 37.77g of pure white powdery 2-chlorophenylboronic acid was obtained.
Based on the molar amount of 2-chloroiodobenzene, the total yield of the three steps is 86.2%, the HPLC content is 99.79%, the content of 2-iodobenzene boric acid is less than 0.001%, and the content of o-diphenylboronic acid is 0.002% .
Preparation and application of 2-chlorophenylboronic acid
CN201910805203.0 provides a method for preparing the functional complex RGO-IONP-PEG, including: (1) dissolving C18PMH and NH2-PEG-OCH3 in a dichloromethane solution; adding metal iron salts and EDC, and heating in microwave Catalyze the reaction under radiation; add 2-(thiophene-2-methyl)phenylboronic acid and catalyze the reaction with microwave radiation; transfer to a constant temperature water bath of 50-65°C, stir, and blow dry to obtain the crude product solid powder; dialyze to obtain C18-PMH- PEG complex; (2) Mix the RGO-IONP nanocomposite and C18-PMH-PEG complex, stir for 3 to 5 minutes, and ultrasonicate; add 2-chlorophenylboronic acid, catalyze the reaction with microwave radiation, centrifuge, and wash to obtain The compound of the invention greatly shortens the overall process time of pyridylthiourea and improves the yield of C18-PMH-PEG compound and RGO-IONP-PEG nano functional compound.
References
[1] [Chinese invention] CN202010688238.3 Preparation method of monohalogenated phenylboronic acid
[2] CN201910805203.0 Preparation method of functional complex RGO-IONP-PEG
