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Process method for synthesizing 4-mercaptophenylboronic acid

A technology of mercaptophenylboronic acid and a process method, which is applied in the field of synthesizing 4-mercaptophenylboronic acid, can solve problems such as poor atom economy, low total yield, and poor safety, and achieve simplified operation, increased reaction yield, and shortened reaction steps Effect

Pending Publication Date: 2022-02-18
大连双硼医药化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The method undergoes three steps of reaction, the steps are long, the total yield is not high, and the total yield is 62.3%. It is protected by tert-butyldimethylchlorosilane, and finally removed. The atom economy is poor
The second step reaction needs to use highly active n-butyl lithium for ultra-low temperature reaction, which has poor safety and high energy consumption

Method used

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  • Process method for synthesizing 4-mercaptophenylboronic acid
  • Process method for synthesizing 4-mercaptophenylboronic acid
  • Process method for synthesizing 4-mercaptophenylboronic acid

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Step A: Add 83.9g (1eq) of p-bromothiophenol, 0.8g (0.007eq) of iodine and 420g of isopropanol into the reaction flask, control the temperature at 50±5°C, and add 27.7g (0.55eq) of 30% hydrogen peroxide dropwise , the dropwise addition was completed, and the reaction was stirred at 50° C. for 1 hour, and a sample was taken by HPLC to confirm the completion of the reaction.

[0027] Post-processing: add 0.5g sodium bisulfite to quench the reaction, after starch potassium iodide test paper detects that there is no peroxide, distill isopropanol under reduced pressure, extract the water layer twice with 150g dichloromethane, combine the organic layer, and add the organic layer Dry over anhydrous sodium sulfate, filter anhydrous sodium sulfate, and evaporate the filtrate to dryness under reduced pressure to obtain 84.3 g of solid product 4,4'-dibromodiphenyl disulfide, with an HPLC purity of 99.2%, and a quantitative yield.

[0028] Step B: Under the protection of nitrogen, ...

Embodiment 2

[0031] Step A: Add 83.9g (1eq) of p-bromothiophenol, 1.1g (0.01eq) of iodine and 420g of ethanol into the reaction flask, control the temperature at 50±5°C, add 33.2g (0.55eq) of 25% hydrogen peroxide dropwise, drop After the addition was complete, the reaction was stirred at 55° C. for 1 hour, and a sample was taken by HPLC to confirm the completion of the reaction.

[0032] Post-treatment: add 1g of sodium bisulfite to quench the reaction, after starch potassium iodide test paper detects that there is no peroxide, distill ethanol under reduced pressure, extract the water layer twice with 150g of ethyl acetate, combine the organic layers, and add anhydrous sulfuric acid to the organic layer Dry over sodium, filter anhydrous sodium sulfate, and evaporate the filtrate to dryness under reduced pressure to obtain 83.5 g of solid product 4,4'-dibromodiphenyl disulfide, with a HPLC purity of 99.4% and a quantitative yield.

[0033] Step B: under the protection of nitrogen, 12.8g (2...

Embodiment 3

[0036] Step A: Add 83.9g (1eq) of p-bromothiophenol, 0.8g (0.007eq) of iodine and 420g of isopropanol into the reaction flask, control the temperature at 50±5°C, and add 25.7g (0.51eq) of 30% hydrogen peroxide dropwise , the dropwise addition was completed, and the reaction was stirred at 55° C. for 1 hour, and a sample was taken by HPLC to confirm the completion of the reaction.

[0037] Post-treatment: add 0.5g sodium bisulfite to quench the reaction, after starch potassium iodide test paper detects that there is no peroxide, distill isopropanol under reduced pressure, extract the water layer twice with 150g toluene, combine the organic layer, add anhydrous Dry over sodium sulfate, filter anhydrous sodium sulfate, and evaporate the filtrate to dryness under reduced pressure to obtain 82.6 g of solid product 4,4'-dibromodiphenyl disulfide, with an HPLC purity of 99.5% and a yield of 99%.

[0038]Step B: Under the protection of nitrogen, 11.6g (2.2eq) of magnesium metal was ad...

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Abstract

The invention discloses a process method for synthesizing 4-mercaptophenylboronic acid, and belongs to the technical field of medical intermediates. The method comprises the following steps: taking p-bromothiophenol as a raw material, oxidizing the p-bromothiophenol with hydrogen peroxide to generate 4, 4 '-dibromodiphenyl disulfide; and then carrying out Grignard or n-butyllithium / boronation, carrying out one-pot reduction reaction in a sodium borohydride / alcohol solvent, quenching and acidifying to obtain the 4-mercaptophenylboronic acid. The method has the advantages of originality, short steps, high yield, mild conditions and simplicity in operation. The problems of long steps, low yield, ultralow temperature and difficulty in product purification of other literature methods are avoided. The method has potential technical advantages and is suitable for industrial large-scale production.

Description

technical field [0001] The invention relates to a process for synthesizing 4-mercaptophenylboronic acid, which belongs to the field of synthesis of pharmaceutical intermediates. Background technique [0002] 4-Mercaptophenylboronic acid is a mercapto-containing organoboronic acid compound, and this type of biomolecules has begun to be used in the field of boron neutron capture therapy (BNCT). At the same time, organoboronic acid compounds are widely used in the Suzuki reaction to construct various C-C single bonds. [0003] In recent years, the synthesis of 4-mercaptophenylboronic acid has received more and more attention. The synthesis of 4-mercaptophenylboronic acid mainly contains the following two methods: [0004] Method 1. Leng Yanguo et al. reported a method for preparing 4-mercaptophenylboronic acid in CN104788483A. The 4-mercaptophenylboronic acid protected by methyl or tert-butyl is used as a raw material, and the 4-mercaptophenylboronic acid is prepared through...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 孙福元郑鹏
Owner 大连双硼医药化工有限公司
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