Hydrogen Peroxide → 6-Methoxyquinoline-2-carbonitrile

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Reaction Steps

Compounds of formula II can be manufactured starting from commercially available 6-methoxy-quinoline (1) that can converted to the N-oxide 2 by reaction with hydrogen peroxide and a solvent like acetic acid under refluxing conditions. The 6-methoxy-quinoline-1-oxide is reacted with silver cyanide and benzoyl chloride to obtain the 6-methoxy-quinoline-2-carbonitrile 3 via a modification of the Reisset'sche reaction (Ber., 38, 1610 (1905). Hydrolysis of the cyano group can be affected by employing an acidic or basic medium. We find it convenient to use a base like sodium hydroxide and after acidic treatment of the mixture we obtained the corresponding 6-methoxy-quinoline-2-carboxylic acid 4. Removal of the methyl group with an acid like hydrobromic acid 48% in water gives 6-hydroxy-quinoline-2-carboxylic acid (5). The acid can be esterified with an alcohol like ethanol and an acid like sulfuric acid to yield the 6-hydroxy-quinoline-2-carboxylic acid ester II, for example 6-hydroxy-quinoline-2-carboxylic acid ethyl ester (IIa).

Provenance & Evidence