Reissert indole synthesis


The Reissert indole synthesis is a series of chemical reactions designed to synthesize indole or substituted-indoles from ortho-nitrotoluene 1 and diethyl oxalate 2.
Potassium ethoxide has been shown to give better results than sodium ethoxide.

Reaction mechanism

The first step of the synthesis is the condensation of o-nitrotoluene 1 with a diethyl oxalate 2 to give ethyl o-nitrophenylpyruvate 3. The reductive cyclization of 3 with zinc in acetic acid gives indole-2-carboxylic acid 4. If desired, 4 can be decarboxylated with heat to give indole 5.

Variations

Butin modification

In an intramolecular version of the Reissert reaction, a furan ring-opening provides the carbonyl necessary for cyclization to form an indole. A ketone side chain is present in the final product, allowing further modifications.