Batcho-Leimgruber indole synthesis

What is Batcho-Leimgruber indole synthesis?

The Batcho-Leimgruber indole synthesis, also known as the Leimgruber-Batcho reaction, was first reported by Batcho and Leimgruber in 1971. It is a two-step process for indole synthesis that is mild and general.

Batcho-Leimgruber indole synthesis - Leimgruber-Batcho reaction
Batcho-Leimgruber indole synthesis

The first step involves the condensation between substituted o-nitrotoluene and N,N-dimethylformamide dimethyl acetal to produce an o-nitrophenylacetaldehyde enamine, while the second step involves reductive cyclization to produce the indole. Reducing reagents such as Fe(II), hydrogen, dithionite, and hydrazine hydrate-Raney Nickel can be used to reduce the nitro group, but the combination of hydrazine hydrate-Raney Nickel generally gives a better yield than other reducing reagents reported.

This reaction is particularly useful for synthesizing indoles with substituents at the benzene ring rather than at the heterocyclic pyrrole ring.

The application of this reaction is not limited to synthesizing indoles with substituents in the benzene ring, rather than the pyrrole moiety. Moreover, this method has also been modified for the synthesis of amides and esters through solid-support synthesis.