Synthesis of 4-Substituted Pyridines and their Homologs

Abstract

Hydrolysis of 2-substituted 4-cyanopyridine with hydrochloric acid, hydrobromic acid, or sodium hydroxide affords the corresponding 2-substituted isonicotinic acid in 60-80% yield. Substituents tested were methyl, chloro, bromo, hydroxyl, and 2, 6-dimethyl groups. Heating of these acids with ethanolic sulfuric acid or methanolic hydrochloric acid, application of thionyl chloride to form the acid chloride, and treatment with ethanol gives the ester. 4-Cyanopyridines and their N-oxides were derived to the corresponding thioisonicotinamides or their N-oxides in 65-85% yields by introduction of hydrogen sulfide in a solution or suspension of the substituted pyridines in pyridine, in the presence of triethylamine.