Combes quinoline ring closur

Pyridine ring closure on Combes synthesis of quinolines 92KGS1011. 

The formation of quinolines and benzoquinolines by the condensation of primary aryl amines with P-diketones followed by an acid catalyzed ring closure of the Schiff base intermediate is known as the Combes quinoline synthesis. The closely related reaction of primary aryl amines with p-ketoesters followed by the cyclization of the Schiff base intermediate is called the Conrad-Limpach reaction and it gives 4-hydroxyquinolines as products. ... 

Yamashkin, S. A., Yudin, L. G., Kost, A. N. Pyridine ring closure in synthesis of quinolines according to Combes (review). Khim. Geterotsikl. Soedin. 1992,1011-1024. 

Combes quinoline synthesis. Formation of quinolines by condensation of (i-di ketones with primary arylamines followed by acid-catalyzed ring closure of the intermediate Schiff base. 

This reaction was first reported by Combes in 1888. It is the synthesis of quinolines by the condensation of primary aromatic amines with acetoacetone or other -diketones followed by cyclization in the presence of sulfuric acid. This method provides a rapid access to the 2,4-substituted quinoline skeleton but, it suffers from low regioselectivity, such as in the case of meto-substituted anilines with two different ortho positions for ring closure. It was found that polyphosphoric acid is a better catalyst than sulfuric acid for the cyclization," and the factors that affect this reaction have been reviewed by Roberts and Turner. ... 

---