CoachThe Fischer indole synthesis heats the phenylhydrazone of an aldehyde or ketone with an acid catalyst: the hydrazone tautomerises to an ene-hydrazine, which undergoes a [3,3] sigmatropic rearrangement; cyclisation and loss of ammonia give the indole.
![The Fischer indole synthesis from acetone phenylhydrazone. Acid turns the hydrazone into its ene-hydrazine tautomer; the [3,3] rearrangement breaks the N–N bond and makes a C–C bond between the ring carbon ortho to nitrogen and the terminal CH2; the new amine attacks the imine, and loss of ammonia gives 2-methylindole.](/images/onecourse/chapters/chemistry-4/b3-heterocycles/fig-a129fbc767b0.svg)
![The Fischer indole synthesis from acetone phenylhydrazone. Acid turns the hydrazone into its ene-hydrazine tautomer; the [3,3] rearrangement breaks the N–N bond and makes a C–C bond between the ring carbon ortho to nitrogen and the terminal CH2; the new amine attacks the imine, and loss of ammonia gives 2-methylindole.](/images/onecourse/chapters/chemistry-4/b3-heterocycles/fig-04406a6cf107.svg)