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Preparation method of 2, 5-dibromopyridine

A technology of dibromopyridine and hydroxypyridine, which is applied in the field of preparation of 2,5-dibromopyridine, can solve the problems of easy decomposition and explosion, high activity, and large amount of waste water, and achieve reduced waste water production, high regioselectivity, and easy The effect of the operation

Active Publication Date: 2021-04-20
甘肃瀚聚药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The advantage is that the yield per step is about 85%, but the disadvantage is that the diazonium salt is unstable, has high activity, and is easy to decompose and explode under the impact of heat, which is not conducive to safety and environmental protection. There is a lot of waste water in the post-treatment process, which is not conducive to industrial development.
[0007] However, in the above synthetic route, the diazonium salt generated by the diazotization reaction is unstable, and it is prone to decomposition and explosion under the action of light and heat, and there are problems such as industrial production safety. Therefore, some 2,5- In-depth research on the synthesis process of dibromopyridine to provide a better, safe and stable reaction route, in line with industrial production, to meet the growing market demand

Method used

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  • Preparation method of 2, 5-dibromopyridine
  • Preparation method of 2, 5-dibromopyridine
  • Preparation method of 2, 5-dibromopyridine

Examples

Experimental program
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Effect test

Embodiment 1

[0022]

[0023] Put 50g (0.526mol) of 2-hydroxypyridine and 250mL of acetonitrile into the reaction bottle, control the temperature at -10-0°C and add 93.6g (0.526mol) of NBS in batches, after the addition, raise the temperature to 15-25°C to react 1 Hour. Sample HPLC was used to detect the completion of the reaction of the raw materials, and the ratio of the product 2-hydroxy-5-bromopyridine to the isomer 2-hydroxy-3-bromopyridine was 94:6. Concentrate the reaction solution under reduced pressure at 45°C, raise the temperature of the remaining materials to 50°C, dissolve the materials, measure the pH=6.0-7.0, add 750mL of water to control the temperature at 45-50°C, and slowly cool down to 20-25°C, the materials precipitate and Stir at temperature for 3 hours and filter. The filter cake was rinsed with water and petroleum ether, and dried to obtain 82.6 g of 2-hydroxy-5-bromopyridine, with a yield of 90.3%, HPLC: 95.6%. 1 HNMR (400MHz, CDCl 3 ):11.73(s,1H),7.70(d,1H),7....

Embodiment 2

[0025]

[0026] Put 50g (0.526mol) of 2-hydroxypyridine and 200mL of 1,2-dichloroethane into the reaction flask, and add 90g (0.315mol) of dibromohydantoin in batches under control of the temperature at -10-0°C. After the addition is complete, Raise the temperature to 20-25°C and react for 1.5 hours. Sample HPLC was used to detect the completion of the reaction of the raw materials, and the ratio of the product 2-hydroxy-5-bromopyridine to the isomer 2-hydroxy-3-bromopyridine was 93:7. Add sodium bisulfite aqueous solution to quench, separate layers, extract the aqueous phase with 1,2-dichloroethane, combine the organic phases, wash with water to pH = 6.0-7.0, dry the organic phase with anhydrous sodium sulfate to obtain 2- Hydroxy-5-bromopyridine in 1,2-dichloroethane solution 435g, HPLC: 92.6%, yield 92.0%; to be brominated in the next step.

Embodiment 3

[0028]

[0029] Under nitrogen protection, drop 50g (0.287mol) 2-hydroxyl-5-bromopyridine, 7.3g (0.014mol) tris (pentafluorophenyl) borane and 200mL acetonitrile into the reaction flask, drop 93.2g ( 0.344mol) phosphorus tribromide, slowly warming up to reflux reaction for 5 hours after the dropwise addition. Detect that the reaction of the raw materials is complete, concentrate under reduced pressure at 55°C until no liquid flows, pour the remaining liquid into 200mL of ice water, add saturated sodium carbonate solution to adjust the pH=8.0-9.0, extract with dichloromethane, concentrate the solvent under reduced pressure, add 35mL of iso Propanol was replaced, the temperature was raised to 50°C, 100 mL of water was added, the temperature was slowly lowered to precipitate a solid, filtered, and the filter cake was dried to obtain 56.3 g of 2,5-dibromopyridine, with a yield of 82.7%, HPLC: 99.7%. 1 HNMR (400MHz, CDCl 3 ): 8.81(d,1H), 8.35(d,1H), 8.13(d,1H).

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Abstract

The invention discloses a preparation method of 2, 5-dibromopyridine, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: reacting 2-hydroxypyridine serving as a raw material with a bromination reagent to obtain 2-hydroxy-5-bromopyridine; and then reacting with a bromination reagent under the action of a Lewis acid catalyst to obtain 2, 5-dibromopyridine. The method is completed in two steps, an isomer obtained in the first step of reaction does not need to be purified, and a product with the purity of 99.5% or above can be obtained through recrystallization once in the last step.

Description

technical field [0001] The invention relates to a preparation method of 2,5-dibromopyridine, which belongs to the technical field of pharmaceutical synthesis. Background technique [0002] Pyridine derivatives are widely used in the synthesis of pesticides, medicines and natural products, such as antibiotics, anti-tumor, anti-ulcer and antihypertensive drugs. The pyridine ring and the benzene ring are bioisosteres, and the pyridine ring has higher biological activity and less toxic side effects. Pyridine derivatives are universal potential building blocks for nitrogen-containing bioactive molecules. Alkaloids mostly contain saturated six-membered nitrogen heterocyclic structures, so pyridine derivatives can be used to cleverly construct alkaloid skeleton units, which is of great significance for the synthesis of nitrogen-containing heterocyclic alkaloids. [0003] 2,5-Dibromopyridine, English name: 2,5-Dibromopyridine, CAS 624-28-2, as a pyridine skeleton intermediate, its...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/61C07D213/64
Inventor 查正兴马飞鸿杜景峰谭再佩
Owner 甘肃瀚聚药业有限公司
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