The Synthetic Routes of Tizanidine hydrochloride

Tizanidine hydrochloride is a muscle relaxant drug that is commonly used to treat spasticity and other muscle-related conditions.
It is synthesized through several synthetic routes, each with its own advantages and disadvantages.
In this article, we will discuss three of the most common synthetic routes for Tizanidine hydrochloride.

Route 1: Synthesis via Benzylidene Malonate

This route involves the synthesis of benzylidene malonate, which is then converted into Tizanidine hydrochloride.
The synthesis of benzylidene malonate involves the reaction of malonic acid diethyl ester with benzaldehyde in the presence of a base such as sodium hydroxide.
This reaction results in the formation of a mixture of two isomers, which are then separated usingchromatography.
The desired isomer is then treated with hydrogen chloride to form benzylidene malonate hydrochloride.

Advantages of this route include:

• The synthesis of benzylidene malonate is relatively straightforward and can be easily scaled up for commercial production.
  
• The use of a mild base such as sodium hydroxide reduces the risk of explosion or fire that can occur with more reactive bases.
  
• The separation of the two isomers using chromatography is relatively straightforward and can also be easily scaled up.
  

Disadvantages of this route include:

• The use of hydrogen chloride gas, which is highly toxic and corrosive, requires careful handling and storage.
  
• The final product, benzylidene malonate hydrochloride, is a solid that must be further processed to form the desired hydrate form of Tizanidine hydrochloride.
  

Route 2: Synthesis via Chloromethylation

This route involves the synthesis of Tizanidine hydrochloride via chloromethylation, which involves the reaction of trimethyl phosphate with chloroform in the presence of a base such as pyridine.
This reaction results in the formation of a mixture of products, which are then separated using chromatography.
The desired product, Tizanidine hydrochloride, is then hydrolyzed using hydrochloric acid to form the desired hydrate form.

Advantages of this route include:

• The synthesis of Tizanidine hydrochloride via chloromethylation can be performed in a single step, making it a relatively simple and efficient route.
  
• The use of a mild base such as pyridine reduces the risk of explosion or fire that can occur with more reactive bases.
  
• The final product, Tizanidine hydrochloride, is a solid that does not require further processing to form the desired hydrate form.
  

Disadvantages of this route include:

• The use of chloroform, a highly toxic and volatile solvent, requires careful handling and storage.
  
• The separation of the desired product from the mixture of products using chromatography can be challenging and may require additional processing steps.
  

Route 3: Synthesis via N-Formylation

This route involves the synthesis of Tizanidine hydrochloride via N-formylation, which involves the reaction of N-formyl piperidine with malonic acid diethyl ester in the presence of a base such as sodium hydroxide.
This reaction results in the formation of a mixture of products, which are then separated using chromatography.
The desired product, Tizanidine hydrochloride, is then treated with hydrogen chloride to form the desired hydrate form.

Advantages of this route include:

• The synthesis of Tizanidine hydrochloride via N-formylation can also be performed in a single step, making it a relatively simple and efficient route.
  
• The use of a mild