Indoles 95Alternative routes to arylhydrazines for Fischer cyclisations are useful, for example aryl halides can be substrates
using transition metal-catalysed N-arylation. N-Boc-hydrazine aminates various aryl iodides forming N-aryl-N-Boc-
hydrazines for use directly in the Fischer sequence (the Boc is lost during the reaction).
Benzophenone hydrazone can be similarly used to produce arylhydrazones of benzophenone from aryl halides, and
these can be utilised directly, acid-catalysed exchange with the desired ketone in situ being followed by the Fischer
sequence.
Synthesis of indoles from ortho-nitrotoluenes(1,2- and 2,3-bonds made)
The hydrogens of the methyl group of ortho-nitrotoluenes are acidifi ed because the anion produced is stabilised by
resonance interaction with the nitro group. The Leimgruber–Batcho synthesis takes advantage of this acidity.
An ortho-nitrotoluene is simply heated with dimethylformamide dimethyl acetal (DMFDMA) giving an isolable enam-
ine, reduction of which, in acidic conditions, then leads to the indole. The fi nal stages in the sequence are closely similar
to the fi nal steps in the Fischer sequence.