Synthesis of novel 2-methyl-4-carboxyquinolines, the new by-products of the Doebner reaction

Abstract

The Doebner reaction is the chemical reaction of an aniline with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids. Although Doebner reaction is a simple procedure for synthesis of 4-carboxyquinolines, which the product precipitates from the reaction mixtures with high purity, its yield is not high due to the formation of different reaction by-products. In the present study we found a new by-product (2-methylquinoline-4-carboxilic acid derivative), in Doebner reaction. We synthesized new 2-methylquinoline-4-carboxilic acid derivatives simply by stirring pyruvic acid and aromatic amine in ethanol with high purity. Generally, we found that aniline derivatives possessing electron donating groups are needed for the synthesis of 2-methylquinoline-4-carboxilic acid derivatives in ethanol. ¹H-NMR data of products revealed that this reaction is regioseletive and ring closure occurs on the position with less steric hindrance. The order of mixing of the reactants plays a key role in determining the type of products in the Doebner reaction.

Graphical Abstract

Keywords:

• Doebner reaction
• 2-methylquinoline-4-carboxilic acid
• pyruvic acid
• quinoline
• synthesis

Disclosure statement

The authors declare that there is no conflict of interests.

Additional information

Funding

The authors are grateful to Research Deputy of Mashhad University of Medical Sciences for financial support of this study as part of thesis of Negar Omidkhah.