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Preparation method of boric acid derivatives

A technology of o-hydroxyphenylboronic acid and alkoxyphenylboronic acid, which is applied in the field of organic synthesis, can solve problems such as low total yield, hindered separation, and long reaction route, so as to reduce the generation of by-products, reduce post-treatment pressure, and improve Yield and Purity Effects

Pending Publication Date: 2020-11-17
商河知济新材料技术中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] (1) Use phenylboronic acid as a raw material to obtain hydroxyphenylboronic acid through nitration reaction, catalytic hydrogenation reaction, diazotization reaction, and then hydrolysis. The disadvantage of this method is that the reaction route is long, the economic cost is high, and the selectivity of the reaction is relatively high. Difference
[0005] (2) Use o-halogenated phenol as raw material, react with n-butyllithium at low temperature, then react with boric acid ester, and finally obtain hydroxyphenylboronic acid product through hydrolysis. This method uses o-bromophenol as raw material, and the cost is higher, and Need to add a large amount of n-butyllithium reaction, which is not conducive to large-scale production
The disadvantage of this method is: because the protection of the hydroxyl group is not carried out, BuLi is needed twice as much as the substance, and the cost is high. In addition, the ether solution of BuLi is used, and this solution is unstable and needs to be prepared immediately, which is not safe. inconvenient
The dilithium salt of bromophenol has low solubility in hexane (the reactant is suspended at the end of this step), which hinders the exchange with borate in the next step. It is also difficult to separate and refine. At least three recrystallizations are required, resulting in The yield dropped a lot, and the yield of p-hydroxyphenylboronic acid was only 14%
[0008] (5) Using bromophenol as a raw material, after its phenolic hydroxyl group is protected with a silicon ether protecting group, it is made into a Grignard reagent, and then reacted with a borate ester and hydrolyzed to obtain a hydroxyphenylboronic acid product. The total yield of this method is still the same. Very low, only 30%, and bromophenol is also used as raw material, and the production cost is relatively high
[0010] (7) Using m-hydroxyaryl bromide (or m-hydroxyaryl iodide) and biboronic acid pinacol ester as raw materials, under the action of a palladium catalyst, m-hydroxyphenylboronic acid pinacol ester is obtained through coupling reaction, and then hydrolyzed to obtain m-Hydroxyphenylboronic acid, the disadvantage of this method is that the catalyst is expensive

Method used

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preparation example Construction

[0028] The invention provides a method for preparing hydroxyphenylboronic acid, which is characterized by comprising the following steps: dissolving alkoxyphenylboronic acid and acid chloride compound in a first organic Solvent, then add aluminum chloride, and then start heating. During the reaction process, the temperature is raised by 10°C every 15 minutes until the temperature rises to 30-100°C, and then the constant temperature reaction is carried out for 1-2h to obtain the intermediate compound, and the pH of the system is adjusted by adding alkali. 9-11, continue to use acid to adjust the pH of the aqueous layer to 3-4, extract with the second organic solvent, collect the organic layer, concentrate, and recrystallize with the third organic solvent to obtain hydroxyphenylboronic acid.

[0029] According to the preparation method of a hydroxyphenylboronic acid described in the present invention, preferably, the hydroxyphenylboronic acid is selected from o-hydroxyphenylboron...

Embodiment 1

[0039] Use a vacuum pump to evacuate the reactor to -0.1Mpa, lower the temperature of the reactor to 0°C, add 1.52kg (10mol) of p-methoxyphenylboronic acid, 1kg (12.7mol) of acetyl chloride, and 12L of toluene into the reactor, and mix Stir until uniform, then add 1 mol of aluminum chloride, during the reaction process, increase the temperature by 10°C every 15 minutes until the temperature rises to 50°C, and then react at a constant temperature for 1h (the methyl chloride gas generated during the reaction is removed to the recovery system by vacuum) , to obtain the intermediate compound, add sodium carbonate solution to adjust the pH value of the system to 9, obtain the aqueous layer, continue to use hydrochloric acid to adjust the pH value of the aqueous layer to 3, extract with ethyl acetate, collect the organic layer, concentrate, and recrystallize with heptane , 1.25 kg of p-hydroxyphenylboronic acid was obtained with a yield of 90.6% and a purity of 98.8%.

Embodiment 2

[0041]Use a vacuum pump to evacuate the reactor to -0.1Mpa, lower the temperature of the reactor to 10°C, add 1.66kg (10mol) of p-ethoxyphenylboronic acid, 1.57kg (20mol) of acetyl chloride, and 15L of toluene into the reactor, and mix Stir until uniform, then add 2mol aluminum chloride, increase the temperature by 10°C every 15 minutes during the reaction, until the temperature rises to 80°C, and then react at a constant temperature for 2h (the monochloroethane gas generated during the reaction is removed by vacuum to the recovery system ), to obtain the intermediate compound, add potassium carbonate solution to adjust the pH of the system to be 9, obtain the water layer, continue to use sulfuric acid to adjust the pH of the water layer to be 3, extract with ethyl acetate, collect the organic layer, concentrate, and reconstitute with heptane Crystallize to obtain 1.29 kg of p-hydroxyphenylboronic acid with a yield of 93.5% and a purity of 99.1%.

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Abstract

The invention provides a preparation method of o-hydroxyphenylboronic acid. The method is characterized by comprising the following steps: dissolving o-alkoxy phenylboronic acid and an acyl chloride compound in a first organic solvent under the vacuum condition of -0.1 MPa and at a temperature of 0-10 DEG C, adding aluminum chloride, starting heating, heating by 10 DEG C every 15 minutes in the reaction process until the temperature is raised to 30-100 DEG C, carrying out a heat preservation reaction for 1-2 h to obtain an intermediate compound, adding alkali to adjust the pH value of the system to 9-11, continuously adjusting the pH value of the water layer to 3-4 by using acid, extracting by using a second organic solvent, collecting the organic layer, concentrating, and recrystallizingby using a third organic solvent to obtain o-hydroxyphenylboronic acid. According to the method, the reaction temperature is relatively mild, the reaction time can be obviously shortened, the dosage of the catalyst is reduced, and the yield and the purity are relatively high.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a method for synthesizing boric acid derivatives, more specifically to a method for synthesizing hydroxyphenylboronic acid. Background technique [0002] The Suzuki reaction is used in synthetic chemistry to construct various types of sp 2 One of the important methods of the type C-C single bond, organoboronic acid as one of the main raw materials of this reaction has always maintained a relatively strong market demand. Hydroxyboronic acid is also widely used in daily chemical and pharmaceutical synthesis because it can conveniently introduce phenol structural units into molecules through Suzuki coupling reaction. [0003] The preparation method of hydroxyphenylboronic acid reported in the prior art mainly contains following several kinds: [0004] (1) Use phenylboronic acid as a raw material to obtain hydroxyphenylboronic acid through nitration reaction, catalytic hydrogenatio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 卢正祥
Owner 商河知济新材料技术中心