Friedländer synthesis

This reaction has been catalyzed by trifluoroacetic acid, toluenesulfonic acid, iodine, and Lewis acids.

Several reviews have been published.

Mechanism

Two viable reaction mechanisms exist for this reaction. In the first mechanism 2-amino substituted carbonyl compound 1 and carbonyl compound 2 react in a rate-limiting step to aldol adduct 3. This intermediate loses water in an elimination reaction to unsaturated carbonyl compound 4 and then loses water again in imine formation to quinoline 7. In the second mechanism the first step is Schiff base formation to 5 followed by Aldol reaction to 6 and elimination to 7.

The Pfitzinger reaction and the Niementowski quinoline synthesis are variations of the Friedländer reaction.