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CN-122010825-A - Preparation method of 2, 5-dibromo-3-methylpyridine

CN122010825ACN 122010825 ACN122010825 ACN 122010825ACN-122010825-A

Abstract

The invention discloses a preparation method of 2, 5-dibromo-3-methylpyridine, which comprises the steps of firstly synthesizing an intermediate product by using 2-amino-3-methylpyridine and bromine, then enabling the intermediate product to directly carry out diazotization reaction after secondary bromine adding in hydrobromic acid solution, obtaining a crude product by adjusting pH value by sodium hydroxide solution, and finally obtaining a high-purity 2, 5-dibromo-3-methylpyridine product by recrystallization. According to the invention, the intermediate product is synthesized firstly, and then the diazotization route without heavy metal ion catalysis is carried out by the intermediate product, so that the problems of complex process and high difficulty in treating the produced wastewater containing heavy metal ions in the traditional synthesis process are fundamentally solved, and the continuous use of the recovered solvent is realized. The method has the advantages of simple route, high efficiency, high product purity, no generation of wastewater containing heavy metal ions, economy and environmental protection, and suitability for industrial production. Has great significance for the technical improvement of the product.

Inventors

  • WEI JUNBO
  • ZHANG CHENGXIN
  • ZHONG SHIQIANG
  • LI SHANQING
  • ZHAO HAIBO

Assignees

  • 山东省海洋化工科学研究院

Dates

Publication Date
20260512
Application Date
20260203

Claims (8)

  1. 1. A preparation method of 2, 5-dibromo-3-methylpyridine is characterized by comprising the following steps: (1) Mixing 2-amino-3-methylpyridine with an organic solvent, then dropwise adding bromine at a temperature of between-5 and 10 ℃, continuously carrying out full reaction at the temperature of between-5 and 10 ℃ after the dropwise adding, carrying out solid-liquid separation after the reaction is finished, washing the separated solid with the organic solvent, and obtaining an intermediate product after washing; (2) Mixing the intermediate product with hydrobromic acid, then dropwise adding bromine at the temperature of-5-10 ℃, continuously carrying out full reaction at the temperature of-5-10 ℃ after the dropwise adding is finished, dropwise adding sodium nitrite aqueous solution at the temperature of-5-10 ℃ after the reaction is finished, continuously carrying out full reaction at the temperature of-5-10 ℃, regulating the pH value of the system to 8-9 by using sodium hydroxide aqueous solution after the reaction is finished, and obtaining a crude product of 2, 5-dibromo-3-methylpyridine through phase separation; (3) Mixing the 2, 5-dibromo-3-methylpyridine crude product with an organic solvent, heating to reflux, cooling after full reflux for recrystallization, carrying out solid-liquid separation after the recrystallization is finished, and drying the obtained solid to obtain the 2, 5-dibromo-3-methylpyridine.
  2. 2. The method for producing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein the molar ratio of 2-amino-3-methylpyridine to bromine in the step (1) is 1:1.0-1.2.
  3. 3. The method for producing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (1), the time for dropping bromine is 0.25 to 0.5 hour, and the time for sufficient reaction after dropping is 1 to 2 hours.
  4. 4. The method for preparing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (1), the organic solvent is dichloromethane or chloroform.
  5. 5. The method for preparing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (2), the molar ratio of the intermediate product to hydrogen bromide is 1:1.0-1.5, the molar ratio of the intermediate product to bromine is 1:1.3-1.5, and the molar ratio of the intermediate product to sodium nitrite is 1:1.5-1.8.
  6. 6. The method for preparing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (2), the dropping time of bromine is 0.25-0.5 hours, the sufficient reaction time after the dropping of bromine is 1.0-2.0 hours, the dropping time of sodium nitrite aqueous solution is 0.5-1.0 hours, and the sufficient reaction time after the dropping of sodium nitrite aqueous solution is 1.0-2.0 hours.
  7. 7. The method for preparing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (2), the mass concentration of hydrobromic acid is 45% -48%, the mass concentration of sodium nitrite aqueous solution is 30% -35%, and the mass concentration of sodium hydroxide aqueous solution is 15-30%.
  8. 8. The method for preparing 2, 5-dibromo-3-methylpyridine according to claim 1, wherein in the step (3), the organic solvent is methanol or ethanol.

Description

Preparation method of 2, 5-dibromo-3-methylpyridine Technical Field The invention relates to a preparation method of 2, 5-dibromo-3-methylpyridine. Background 2, 5-Dibromo-3-methylpyridine is an organic compound having a unique chemical structure, and the product has excellent physical and chemical properties such as high melting point, low boiling point, good stability, etc., making it excellent in various industrial processes. In the field of medicine, 2, 5-dibromo-3-methylpyridine can be used as a key intermediate for synthesizing various medicines, can be used for preparing compounds with antibacterial, anti-inflammatory or anti-tumor activities, can obtain medicine molecules with specific pharmacological actions by modifying and reforming the structures of the compounds, and has important significance for improving the quality and curative effect of the medicines. In the field of pesticides, the product can be used as a high-efficiency and low-toxicity pesticide intermediate, is favorable for promoting the development of green agriculture, can be used for deriving a compound with high-efficiency insecticidal, bactericidal or herbicidal activity, and provides support for developing environment-friendly and low-toxicity efficient pesticide varieties. The method has application in the aspect of organic photoelectric material synthesis, can be used for preparing organic materials with special optical and electrical properties, is used for manufacturing photoelectric devices such as Organic Light Emitting Diodes (OLED), organic solar cells and the like, and is beneficial to improving the performance and efficiency of the devices and the like. The existing preparation methods of the 2, 5-dibromo-3-methylpyridine mainly comprise a direct bromination method, a pyridine derivative conversion method, a palladium catalytic coupling method and the like. The main stream is pyridine derivative converting process, which synthesizes 2-amino-3-methyl pyridine, acetic anhydride, liquid bromine and sodium hydroxide into intermediate product 2-amino-3-methyl-5-bromopyridine, and diazotizing reaction under the catalysis of cuprous bromide to obtain 2, 5-dibromo-3-methylpyridine. The process is longer, and the waste water containing heavy metals is produced by using acetic anhydride and cuprous bromide as catalysts. Disclosure of Invention The invention aims to solve the problems of long process route, high wastewater treatment difficulty, low product yield and the like in the prior art. Providing a process route for obtaining the 2, 5-dibromo-3-methylpyridine by adding bromine in one step and then adopting diazotization reaction without heavy metal ion catalysis, and recycling the solvent. The method has the advantages of simple route, high efficiency, high product purity, no generation of wastewater containing heavy metal ions, economy and environmental protection, and suitability for industrial production. In order to achieve the above purpose, the preparation method of the 2, 5-dibromo-3-methylpyridine provided by the invention comprises the following steps: (1) Mixing 2-amino-3-methylpyridine with an organic solvent, then dropwise adding bromine at a temperature of between-5 and 10 ℃, continuously carrying out full reaction at the temperature of between-5 and 10 ℃ after the dropwise adding, carrying out solid-liquid separation after the reaction is finished, washing the separated solid with the organic solvent, and obtaining an intermediate product after washing; (2) Mixing the intermediate product with hydrobromic acid, then dropwise adding bromine at the temperature of-5-10 ℃, continuously carrying out full reaction at the temperature of-5-10 ℃ after the dropwise adding is finished, dropwise adding sodium nitrite aqueous solution at the temperature of-5-10 ℃ after the reaction is finished, continuously carrying out full reaction at the temperature of-5-10 ℃, regulating the pH value of the system to 8-9 by using sodium hydroxide aqueous solution after the reaction is finished, and obtaining a crude product of 2, 5-dibromo-3-methylpyridine through phase separation; (3) Mixing the 2, 5-dibromo-3-methylpyridine crude product with methanol or ethanol, heating to reflux, cooling after full reflux, recrystallizing, carrying out solid-liquid separation after the recrystallization is finished, and drying the obtained solid to obtain the 2, 5-dibromo-3-methylpyridine. In the step (1), the molar ratio of the 2-amino-3-methylpyridine to the bromine is 1:1.0-1.2. In the step (1), the dropwise adding time of bromine is 0.25-0.5 hour, and the time of full reaction after the dropwise adding is 1-2 hours. In the step (1), the organic solvent is dichloromethane or chloroform, the amount of the dichloromethane or the chloroform is limited to be capable of completely dissolving the 2-amino-3-methylpyridine, of course, the better the fluidity of the system is, the better the reaction effect is, the cost and the reaction effect are compre