11/15/11 - Leimgruber-Batcho Indole Synthesis

This annulation reaction produces the molecule Indole, which is much similar to the previous reaction Quinoline in that it is a nitrogen contaning heterocyclic molecule.  This molecule retains its importance in the pharmaceutical industry where many drugs contains this molecule and derivatives of this molecule.  It is originally contained within coal-tar, where the first synethsis was completed by heating aniline and ethylene glycol in the presence of a catalyst.  But in 1976, Leimgruber and Batcho came along to propose this very efficient synthesis of this molecule starting with o-nitrotoluenes.  In the first step the o-nitrotoluene is converted into an enamine, and then this enamine goes through a reductive cyclisation to form the Indole.


Ref:
Batcho, A. D.; Leimgruber, W. Org. Synth. 1985, 63, 214–220.