Reductive cyclization Reissert indole synthesis

The classic Reissert indole synthesis, involving the reductive cyclization of o-ni-trophenylpyruvic acid, has been used for synthesis of 2-ethoxycarbonyl-4-alkoxymethylindo-les.92 The modified Reissert reaction, involving the reductive cyclization of an o-nitrophenyl acetoaldehyde, has been adapted to solid-phase synthesis.93... 

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

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

In 1897, Reissert reported the synthesis of a variety of substituted indoles from o-nitrotoluene derivatives. Condensation of o-nitrotoluene (5) with diethyl oxalate (2) in the presense of sodium ethoxide afforded ethyl o-nitrophenylpyruvate (6). After hydrolysis of the ester, the free acid, o-nitrophenylpyruvic acid (7), was reduced with zinc in acetic acid to the intermediate, o-aminophenylpyruvic acid (8), which underwent cyclization with loss of water under the conditions of reduction to furnish the indole-2-carboxylic acid (9). When the indole-2-carboxylic acid (9) was heated above its melting point, carbon dioxide was evolved with concomitant formation of the indole (10). 

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