The Synthetic Routes of 1-BENZYL-5,6-DIHYDROPYRIDIN-2(1H)-ONE

The synthesis of 1-benzyl-5,6-dihydropyridin-2(1H)-one, also known as Aubéronine, is a complex organic chemical reaction that involves several steps and can be achieved through both natural and synthetic routes.
In this article, we will focus on the synthetic routes of 1-benzyl-5,6-dihydropyridin-2(1H)-one, which have been developed and refined over the years in the chemical industry.

Natural route

1-Benzyl-5,6-dihydropyridin-2(1H)-one is naturally occurring in certain plants, and it can be extracted and isolated from these plants through various chemical methods.
However, this route is not practical for industrial-scale production of the compound due to the limited yield and the availability of the plants.

Synthetic routes

There are several synthetic routes for the production of 1-benzyl-5,6-dihydropyridin-2(1H)-one, each with its advantages and disadvantages.
Some of the most commonly used synthetic routes include:

1. Grignard reaction followed by Hofmann elimination

This route involves the preparation of a Grignard reagent from benzaldehyde and magnesium metal, followed by the application of the Grignard reagent to a suitable substrate, such as acetylene or vinyl bromide, to form a vicinal diol.
The Hofmann elimination reaction is then carried out to form 1-benzyl-5,6-dihydropyridin-2(1H)-one.

2. Allerton condition reaction

This route involves the reaction of benzyl chloride with an aqueous solution of sodium hydroxide, followed by treatment with a Lewis acid catalyst, such as aluminum chloride, to form the corresponding benzyl alcohol.
The benzyl alcohol is then reduced to form 1-benzyl-5,6-dihydropyridin-2(1H)-one using a reducing agent such as lithium aluminum hydride.

3. Reductive nitration of benzyl chloride

In this route, benzyl chloride is treated with sodium nitrate in the presence of a solvent such as acetic acid.
The reaction involves several stages, including the formation of benzyl nitrate, which is then reduced to form the corresponding benzyl alcohol.
The benzyl alcohol is then treated with a reducing agent, such as lithium aluminum hydride, to form 1-benzyl-5,6-dihydropyridin-2(1H)-one.

4. Reductive alkylation of toluene with benzaldehyde

This route involves the reaction of toluene with benzaldehyde in the presence of a reducing agent, such as hydrogen or lithium aluminum hydride, to form a vicinal diol.
The diol is then treated with a suitable reagent, such as acetylene or vinyl bromide, to form 1-benzyl-5,6-dihydropyridin-2(1H)-one.

Advantages and disadvantages of synthetic routes

Each of the synthetic routes for the production of 1-benzyl-5,6-dihydropyridin-2(1H)-one has its own advantages and disadvantages.
The Grignard reaction followed by Hofmann elimination and the Allerton condition reaction are two of the most commonly used synthetic routes.
The Grignard reaction followed by Hofmann elimination is a well-established method for the synthesis of 1-benzyl-5,6-dihydro