Background and overview of preparation and application of 2-hydroxyphenylboronic acid
2-Hydroxyphenylboronic acid is an important molecular fragment for the preparation of new drugs for the treatment of diabetes. It is also an important intermediate for organic synthesis of medicines and pesticides. It is widely used in Suzuki cross-coupling reactions and is the precursor for the preparation of 2-hydroxybiphenyl compounds. Key intermediates. Suzuki-Miyaura coupling reaction (SMC) is an important reaction to construct various C-C single bonds, and its main raw material is organic boronic acid compounds. Among them, 2-hydroxyphenylboronic acid is an important compound among organic boric acid compounds and has important application value in the fields of organic synthesis and pharmaceutical chemical industry.
Preparation and application of 2-hydroxyphenylboronic acid
Preparation and application report of 2-hydroxyphenylboronic acid 1.
Dissolve 5g phenol in 25mLTHF, add p-toluenesulfonic acid according to 4.2×10-3mol/L and cool it to 5℃, then add 5.4g 3,4-dihydropyran dropwise to it and mix it with The molar ratio of phenol is 1.2:1. After naturally raising the temperature to 20°C, the reaction was maintained for 5.5 hours to obtain a mixed solution containing the phenol intermediate;
After replacing the above mixed solution containing the phenol intermediate with N2 three times, add the above mixed solution containing the phenol intermediate at a temperature of -70°C at a dropping speed of 0.01g/min. n-butyllithium, and the molar ratio of n-butyllithium to phenol is 1.35:1. After the dripping is completed, incubate the reaction for 15 minutes, naturally rise to 20°C, and react with the incubation for 1 hour to obtain the pre-reaction solution;
Add triisopropyl borate to the above-mentioned pre-reaction solution of -aminophenylboronic acid pinacol ester at a temperature of 70°C at a dropping speed of 0.1g/min, and the triisopropyl borate and phenol intermediates The molar ratio is 1:1. After the dripping is completed, incubate the reaction for 1 hour to obtain the solution to be hydrolyzed;
Add 2mol/L hydrochloric acid to the above solution to be hydrolyzed until pH=2, stir for 1 hour, separate the liquids, extract the aqueous phase three times with ethyl acetate, combine the organic phases, and dry with 20g anhydrous magnesium sulfate for 20 minutes. Filter the drying agent and concentrate to obtain the crude product of 2-hydroxyphenylboronic acid;
After distilling the above crude product under reduced pressure, adding n-hexane for pulping, filtering to obtain a filter cake, washing the filter cake with n-hexane, and drying at 30°C for 4 hours to obtain 2-hydroxyphenylboronic acid.
Preparation and application report of 2-hydroxyphenylboronic acid 2.
A 10-liter glass reactor is equipped with mechanical stirring, a thermometer, and a constant pressure dropping funnel. Add 940g of raw materials phenol and 940g of dihydropyran under nitrogen protection. Add 94g of catalyst pyridine p-toluenesulfonate under stirring and react. For 8 hours, distill under reduced pressure at 60°C to remove the low boiling matter in the system; then add 3000g tetrahydrofuran and 1.2 equivalents of triisopropyl borate to the phenol into the reaction flask, cool to -80°C, and add dropwise the solution to the phenol. 1.5 equivalents of n-butyllithium, continue to react at -80°C for 8 hours after dropping, slowly heat the reaction solution to -30°C, add 2000g of water to the system, adjust the pH value to 1 with hydrochloric acid, and react at 30°C for 2 hours , distill under reduced pressure at 60°C, remove the solvent in the system, add 3000g of water, reflux for 2 hours, cool to 5°C, filter with suction to obtain a white wet product, dry it at 80°C to obtain the product, the molar yield (in terms of phenol total) 73%.
Preparation and application report 3 of 2-hydroxyphenylboronic acid
Use a vacuum pump to evacuate the reaction kettle to -0.1Mpa, lower the temperature of the reaction kettle to 10°C, and add 1.52kg (10mol) o-methoxyphenylboronic acid, 1.57kg (20mol) acetyl chloride, and 12L into the reaction kettle. Toluene, mix and stir until uniform, then add 2 mol of aluminum chloride, increase the temperature by 10°C every 15 minutes during the reaction, until the temperature rises to 100°C, and then react at a constant temperature for 1.5 hours (the methyl chloride gas generated during the reaction is removed by vacuum to the recovery system) to obtain the intermediate compound, add sodium carbonate solution to adjust the pH value of the system to 10, and obtain an aqueous layer. Continue to use hydrochloric acid to adjust the aqueous layer to a pH of 4, extract with ethyl acetate, collect the organic layer, concentrate, and use Recrystallize from n-hexane to obtain 1.27kg of 2-hydroxyphenylboronic acid, with a yield of 92% and a purity of 99.3%.
Preparation and application of 2-hydroxyphenylboronic acid
CN201510063264.6 discloses a method for preparing 2′-bromo-2-hydroxybiphenyl compounds. This method uses brominated aromatic hydrocarbons and 2-hydroxyphenylboronic acid as raw materials, Pd(PPh3)4 as the catalyst, and K2CO3 is a base, toluene/ethanol/water is used as the solvent, the reaction temperature is 85-90 degrees Celsius, and the reaction is carried out for 8 hours under a nitrogen protection system to synthesize the target compound. This synthesis method is simple, has a high yield, and has mild conditions. , has good application prospects.
References
[1][China invention, China invention authorization] Preparation method of CN201410145635.02-hydroxyphenylboronic acid
[2][China invention, China invention authorization] CN201410063438.4 A method for preparing 2-hydroxyphenylboronic acid
[3] [Chinese invention] CN202010977853.6 Preparation method of boric acid derivatives
[4]CN201510063264.6 A method for preparing 2′-bromo-2-hydroxybiphenyl compounds
