Synthesis process of amantadine


Physical and chemical properties
Amantadine is also known as tricyclodecanamine. Slightly soluble in water, soluble in chloroform, melting point 180-192 °C (sealed). White crystalline powder, odorless and tasteless. Stable to light and air, soluble in 2.5 times water, soluble in 5 times ethanol, 18 times chloroform, insoluble in benzene and ether.
    
Use
In addition to the prevention and early treatment of Asian influenza A-11, it can also be combined with antibiotics to treat sepsis and viral pneumonia, and has fever-reducing effect. It also has an anti-tremor paralysis effect.
    
Amantadine production status
China's amantadine was first developed and marketed by Northeast Pharmaceutical General Factory in 1971. At present, the main domestic manufacturers are Northeast Pharmaceutical General Factory, Zhejiang Kangyu Pharmaceutical, Zhejiang Dier Chemical, etc., of which Zhejiang Kangyu Pharmaceutical has an annual output of 300 tons, with a market share of about 45%.
    
Synthesis method
  
Synthesis method - synthesis of amantadine from bromoadamantane
  
The second synthesis method - amantadine synthesis by reducing nitro with zinc powder
  
A synthesis method - hydrazine hydrate reduction nitro method to synthesize amantadine
  
Method: The method of synthesizing amantadine from bromoadamantane is still the main process for the industrial production of amantadine, which can be seen in the industrial production line, at present, it has irreplaceable advantages. Therefore, on this basis, if the production process can be improved as much as possible, the amount of bromine can be reduced or other bromine-containing substances that can replace bromine can be found for halogenation reaction, so as to reduce environmental pollution as much as possible, if at the same time can provide better reaction selectivity and yield, it will produce better profits and promote the rapid development of amantadine production. As described in the above experiment, in the existing process, the full and uniform contact between adamantane and bromine as much as possible will facilitate the reaction with high selectivity and high yield, and if the boiling point of the solvent is too low in the reaction, the reaction will not be able to proceed. However, the yield of this reaction is not too high, and it is quite different from the other two methods.
  
The second method: the reduction of 1-nitroadamantane by zinc powder reduction method is relatively simple, the reaction speed is faster, and the yield is high, but the metal sludge produced will cause serious pollution.
  
The third method: hydrazine hydrate reduction method hydrazine hydrate is a carcinogen, which also has toxic and pollution problems.
  
By improving the second method, the amorphous alloy catalyst is used for hydroreduction reaction, which realizes multiple applications, reduces production costs, and the used waste catalyst can be recycled into other nickel compounds to achieve green environmental protection and pollution-free production, which is used by domestic manufacturers.

 

 

Related news


Reni nickel catalyst science knowledge(1)

Physical and chemical properties: Reni nickel catalyst before activation is silver-gray amorphous powder (nickel-aluminum alloy powder), with a moderate degree of flammability, partial activation in the presence of water and the production of hydrogen easy agglomeration, long-term exposure to air is easy to weather. Nickel-aluminum alloy powder is activated into gray-black particles, accompanied by active hydrogen, extremely unstable, oxidative combustion in the air, must be immersed in water or ethanol for preservation. It was first used by American engineer Murray Rainey as a catalyst in the hydrogenation of vegetable oils. The preparation process is to treat nickel-aluminum alloy with concentrated sodium hydroxide solution, in this process, most of the aluminum will react with sodium hydroxide and dissolve, leaving a lot of micropores of different sizes. In this way, the surface of Raininickel is a fine gray powder, but from a microscopic point of view, each tiny particle in the powder is a three-dimensional porous structure, this porous structure greatly increases its surface area, and the large surface area brings high catalytic activity, which makes Raininickel widely used as a heterogeneous catalyst in organic synthesis and industrial hydrogenation reactions. Since "Rainey" is a registered trademark of Grace Chemicals, strictly speaking, only products manufactured by the company's Davidson Chemical Division can be called "Lanny Nickel". The term "metal backbone catalyst" or "sponge-metal catalyst" is used to refer to catalysts with a microporous structure and physical and chemical properties similar to Raney nickel.