Ethionamide: Ethionamide, 2-(ethyl)isonicotinthioamide (34.1.18), a derivative of isoni-cotinic acid, is synthesized by the following scheme. Diethyl oxalate is condensated with methylethylketone in the presence of sodium ethoxide to form the ethyl ester of propi-onylpyruvic acid (34.1.12). Condensation of this with cyanoacetamide results in heterocy-clization, to form 3-cyano-4-carboethoxy-6-ethyl-2-pyridone (34.1.13), which is hydrolyzed with hydrochloric acid to give 4-carboxy-6-ethyl-2-pyridone (34.1.14). Reacting this with a mixture of phosphorous oxychloride and pentachloride gives 6-ethyl-2-chloroisonicotinic acid chloride, which is subsequently treated with ethyl alcohol to obtain the ethyl ester of 6-ethyl-2-chloroisonicotinic acid (34.1.15). Reducing this with hydrogen over a palladium catalyst removes the chlorine atom at position 2 of the pyridine ring, giving the ethyl ester of 6-ethylisonicotinic acid (34.1.15). Interacting this with ammonia, followed by dehydration of the resulting amide of 6-ethylisonicotinic acid using phosphorous pentoxide gives the nitrile of 6-ethylisonicotinic acid (34.1.17). Finally, reacting this with hydrogen sulfide gives ethionamide [29-32].
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