Indoles, synthesis, Reissert

The classic Reissert indole synthesis, involving the reducdve cyclization of o-ni-trophenylpymvic acid, has been used for synthesis of 2-ethoxycarbonyl-4-alkoxymethylindo-les The modified Reissert reacdon, involving the reducdve cyclizadon of an o-rdtrophenyl acetoaldehyde, has been adapted to solid-phase synthesis... 

The Reissert indole synthesis involves base-catalyzed condensation of an o-nitrotoluene derivative with an ethyl oxalate, which is followed by reductive cy-clization to an indole-2-carboxylic acid derivative. 

Amino groups in compounds of type (23, Z=NH) are frequently derived from nitro groups. In the Reissert indole synthesis, o-nitrotoluene undergoes Claisen condensation with oxalic ester to yield the pyruvic ester (24). When this is reduced with Zn-AcOH the corresponding amino derivative spontaneously cyclizes to the 2-ethoxycarbonylindole (25) (63OS(43)40). 

Weinreb s synthesis4 has two OMe groups where the ortho-quinone will be and puts in the pyrrole last. The idea was to use a Reissert indole synthesis where reduction of the nitro group in 42 would lead to condensation with the ketone. 

The mechanism of the formation of 4-nitroindole parallels the Reissert indole synthesis and is discussed in references 2 and 3. 

Reissert indole synthesis. Condensation of an o-nitrotoluene with oxalic ester, reduction to the amine, and cyclization to the indole. 

Indoles are obtained by specific cyclizations (Fischer synthesis, Reissert synthesis, Batcho-Leimgruber synthesis, Nenitzescu synthesis), as are carbazoles from biphenylene or diphenyl-amines and pyrrolidines (Hofmann-Loffler reaction). 

That s the Fischer indole synthesis. The Reissert synthesis in some respects is more straightforward. The first step is a distant relative of a Claisen condensation, but a (nitro-group stabilized) benzylic anion takes the place of an enolate anion to add to the carbonyl group of the ester as shown ... 

This reaction is related to the Reissert Indole Synthesis. 

This reaction is closely related to the Reissert Indole Synthesis, which consists of a decarboxylation in the final step. ... 

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