Friedländer Annulation in the Synthesis of Azaheterocyclic Compounds

Abstract

Publisher Summary Since 1882, when Friedlander reported the synthesis of quinolines from the condensation of o-aminoaryl carbonyl compounds and enolizable methylene groups, this method has become more and more popular in azaheterocyclic synthesis. This versatile method is used for the preparation of a large number of nitrogen-containing heterocyclic compounds, such as quinoline derivatives, pyridines, camptothecins, acridines, tacrine analogs, phenanthrolines, naphthyridines, anthyridines, and anthrazoline derivatives. This chapter discusses the application of Friedlander type methods in all these broad ranges of heterocyclic syntheses, highlighting old and recent research that has been carried out in this field. The simplest azaheterocycles that can be synthesized via the Friedlander mechanism are the quinolines. Classical Friedlander reactions are generally carried out by refluxing either an aqueous or an alcoholic solution of reactants in the presence of a base. Alternatively, the reaction is performed by heating a mixture of the reactants at temperatures ranging from 150 to 220C in the absence of a catalyst. Typical catalysts for the Friedlander reaction include bases, such as piperidine, sodium ethoxide, sodium tert-butoxide, KOH, NaOH, and MeONa.