Condensation of β-dicarbonyl compounds with halogenopyridinecarboxylic acids. A convenient synthesis of some naphthyridine derivatives

Abstract

Condensation reactions of o-halogenopyridinecarboxylic acids with carbanions in the presence of copper or copper salts have been investigated. For example, 2-bromopyridine-3-carboxylic acid reacted with acetylacetone and with ethyl acetoacetate to give 2-acetonylpyridine-3-carboxylic acid and ethyl 3-carboxy-2-pyridylacetate respectively. This bromo-acid condensed similarly with β-diketones and β-keto-esters, and with diethyl malonate, an acyl group being eliminated by ethanolysis in each case. 2-Substituted 1,3-dicarbonyl compounds did not react. Examples of such condensations have been obtained with three of the four possible o-halogeno-acid isomers of the pyridine series. 4-halogenopyridine-3-carboxylic acid being the exception. These products are useful intermediates in the synthesis of naphthyridine derivatives. Thus 2-acetonylpyridine-3-carboxylic acid condensed with ammonia to form 7-methyl-1,6-naphthyridin-5(6H)-one and with amines, hydroxylamine, and hydrazine to give corresponding 6-substituted compounds, but reaction with methylhydrazine yielded 2,5-dihydro-2,4-dimethylpyrido[3,2-d][1,2]diazepin-1-one.