Fischer indole synthesis

Schematic of the Fischer indole synthesis. Reagents: phenyl hydrazine with ortho hydrogen, aldehyde, ketone, acid catalyst. Product: indole.

The Fischer indole synthesis is an organic reaction used to convert a phenyl hydrazine and an aldehyde or ketone to an indole using an acid catalyst. The mechanism begins with formation of a phenylhydrazone through the acid catalyzed reaction of the hydrazine with the carbonyl. The phenylhydrazone then rearranges to the enamine and gets protonated on the phenyl nitrogen. An "ene reaction" (3,3-sigmatropic rearrangement) ensues, resulting in a diimine and loss of aromaticity. Additional key steps include rearomatization, formation of a cyclic aminal, and the expulsion of ammonia to give the indole product.[1][2]

Mechanism

Mechanism of the Fischer indole synthesis.

References:

1.
Fischer, E.; Jourdan, F. Ber. Dtsch. Chem. Ges. 1883, 16, 2241–2245.
2.
Fischer, E.; Hess, O. Ber. Dtsch. Chem. Ges. 1884, 17, 559–568.