O-nitrophenylpyruvic acid

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). 

Ethyl o-nitrophenylpyruvate and o-nitrophenylpyruvic acid 14-21 have been prepared by condensation of o-nitrotoluene with diethyl oxalate in the presence of potassium ethoxide,4 14 sodium ethoxide,16-20 or sodium methoxide.21 Sodium ethoxide is less reactive, however, and cannot be substituted successfully for potassium ethoxide in the present procedure, as it gives a very poor yield and poor quality of precipitated sodium salt. With sodium ethoxide the reaction does not appear to go to completion even under the conditions of refluxing ethanol usually employed,16-21 which are considerably more severe than the room temperature conditions employed with potassium ethoxide in the present procedure. o-Nitrophenylpyruvic add has also been prepared by hydrochloric acid hydrolysis of o-nitro-a-acetamino-dnnamic azlactone.4... 

Nitrophenyl)-2-hydroxyiminopropanoic acid (o-Nitrophenylpyruvic acid oxime)... 

Stoll and colleagues prepared 4-, 5-, and 6-hydroxy-tryptamines from the corresponding hydroxyindoles, which were synthesized via a Reissert protocol [10], Plieninger s group used this method to access 4- and 6-bromoindoles [11], and Bergmann and Pelchowicz realized both 5- and 6-fluoroindoles from the respective o-nitrophenylpyruvic acids [12], In addition to these... 

This chapter has focused solely on the classic Reissert reductive cychzation of o-nitrophenylpyruvic acids (and pyruvates) to indoles. The myriad other reductive cycliza-tions of nitro carbonyl compounds to give indoles are relegated to subsequent chapters. 

The potassium salt of ethyl o-nitrophenylpyruvate is prepared essentially according to the method of Wislicenus and Thoma.14 However, the isolation of ethyl o-nitrophenylpyruvate has been eliminated by liberating the ester from its potassium salt in the acetic acid used as solvent for the hydrogenation. Catalytic... 

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