Friedländer synthesis

The Friedländer synthesis is a chemical reaction of 2-aminobenzaldehydes^[1] with ketones to form quinoline derivatives.^[2][3] It is named after German chemist Paul Friedländer (1857–1923).

The Friedländer synthesis

Friedländer synthesis
Named after	Paul Friedländer
Reaction type	Ring forming reaction
Identifiers
Organic Chemistry Portal	friedlaender-synthesis

This reaction has been catalyzed by trifluoroacetic acid,^[4] toluenesulfonic acid,^[5] iodine,^[6] and Lewis acids.^[7]

Several reviews have been published.^[8][9][10]

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.^[11]

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

See also

• Doebner-Miller reaction
• Povarov reaction
• Skraup reaction