How is acetophenone phenylhydrazone catalyzed into 2-phenylindole?

1 Answer
Ernest Z.
Oct 6, 2016

Here's my proposal for the mechanism for the Fischer indole synthesis of 2-phenylindole.

Explanation:

Note: For convenience, I am using #"HCl"# as the acid and #"Cl"^"-"# as the conjugate base, but you should use the acid and base that were used in your synthesis.

Step 1. Protonation of the phenylhydrazone

Protonation

Step 2. Tautomerization to an enamine

Tautomerization

Step 3. Cyclic [3,3]-sigmatropic rearrangement

This forms a diimine and results in the loss of aromaticity.

Sigmatropic rearrangement

Step 4. Re-aromatization

Re-aromatization

Step 5. Protonation of the imine

Protonation

Step 6. Cyclization

Cyclization

Step 7. Deprotonation of the ammonium ion

Deprotonation

Step 8. Protonation of the primary amine

Protonation

Step 9. Elimination of ammonia

This forms a stable, aromatic indole.

Elimination of NH₃

And that is my proposed mechanism for the formation of 2-phenylindole.

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