The Synthetic Routes of Barnidipine

Barnidipine is a pharmaceutical compound that is used to treat hypertension and angina pectoris.
It belongs to a class of drugs known as calcium channel blockers, which work by relaxing the smooth muscle in the walls of blood vessels, causing them to widen and allowing blood to flow more easily.
The compound has a complex chemical structure, which makes its synthesis challenging and interesting.
This article will discuss the synthetic routes of Barnidipine.

One of the most common methods of synthesizing Barnidipine is through the 4-nitrophenylhydrazone route.
This involves the reaction of 4-nitrophenol with hydrazine hydrate in the presence of a base such as sodium hydroxide.
The resulting 4-nitrophenylhydrazone is then treated with a carboxylic acid, such as cyclohexanecarboxylic acid, to form the desired compound.

Another route to Barnidipine involves the use of the Williamson ether synthesis.
This process begins by treating a phenol with an aqueous solution of potassium hydroxide, followed by the addition of a halogen such as chlorine or bromine.
The resulting Williamson ether is then treated with chloroform and an aqueous solution of sodium hydroxide to form the hydrazone.
Finally, the hydrazone is treated with a carboxylic acid to form the final compound.

Another route to Barnidipine is the reaction of 4-nitrophenylhydrazine with (RS)-1-[(2S)-2-(dihydroxyphenyl)acetyl]pyrrolidine-2,5-dione in the presence of a Lewis acid catalyst such as aluminum chloride.
This reaction leads to the formation of the desired compound through a series of intermediate steps.

Barnidipine can also be synthesized through the application of Buccholz reaction.
In this process, a phenol is treated with chloroform and an aqueous solution of sodium hydroxide to form the corresponding Williamson ether.
The Williamson ether is then treated with a source of hydrogen chloride, such as hydrochloric acid, in the presence of a Lewis acid catalyst such as aluminum chloride to form the desired compound.

In summary, there are several synthetic routes to Barnidipine, each with its own set of advantages and challenges.
The choice of synthetic route depends on the availability of starting materials and the desired yield and purity of the final product.
The Williamson ether synthesis and the Buccholz reaction are two of the most commonly used methods for the synthesis of Barnidipine.