What Is The Mechanism Of 2-Phenylindole From Fisher Indole Synthesis?


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The Fischer Indole Synthesis reaction was originally discovered by Hermann Emil Fischer, after whom the reaction was named. This reaction produce heterocycle indole (an aromatic) from the reaction of a ketone or an aldehyde with phenylhydrazine. The reaction must be performed under specific acidic conditions.

This reaction is now commonly used to make drugs of the triptan class, specifically anti migraine drugs.

The main step of this reaction involves rearranging the [3,3] sigmatropic, which results in the sigma bond being broken between two existing nitrogen atoms.

The broken sigma bon will then link two rings together with a Carbon - Carbon bond.

In order to ensure that the reaction is successful, the scientist must be very particular about their choice of acid catalyst. The following Brønsted acids have been marked as successful for this reaction:

• Hydrochloric acid (HCl).
• Sulfuric acid (H2SO4).
• P-Toluenesulfonic acid.
• Polyphosphoric acid.

The follow Lewis acids have been listed as useful, but not as powerful as the Brønsted acids listed above:

• Iron chloride.
• Boron trifluoride.
• Aluminium chloride.
• Zinc chloride.

The initial reaction that takes place between the phenylhydrazine and the ketone or aldehyde will form a phenylhydrazone. This will then isomerize will a respective enamine, sometimes called an ene-hydrazine.

Protonation will then occur. During this stage, a cyclic [3,3] sigmatropic rearrangement takes place will produces an imine.

The imine that has been produced will form an aminal, or a cyclic aminoacetal.

Under the product, the acid catalyst (one chosen from the two lists above) will get rid of the ammonia (NH3).

This results in a favorable aromatic indole when the reaction is complete.

The following link will direct you to an organic chemistry website which will show each of the steps of Fischer Indole Synthesis reaction that have been outlined above: http://www.organic-chemistry.org/namedreactions/fischer-indole-synthesis.shtm.

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