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Friedlaender Synthesis
Yafa M’arouf Ezzat Zaqzouq
Dr. Fu’ad Mahmod
Table of Contents
Objectives
Background
Reaction and Mechanism
Application and recent literature
Conclusion
References
Objectives
*To understand Friedlaender synthesis.
*To show the equation & the mechanism of the
reaction.
*To gain some knowledge about the applications &
recent literatures related to the reaction.
Background
The Friedländer synthesis is the chemical reaction of
2-aminobenzaldehydes with ketones to form quinoline
derivatives. It is named after German chemist Paul
Friedländer (1857-1923). The simple and straightforward
method for the synthesis of polysubstituted quinolines
was reported by Friedländer in 1882. Friedländer
reactions are generally carried out either by refluxing an
aqueous or alcoholic solution of reactants in the
presence of base or by heating a mixture of the
reactants at high temperatures ranging from 150-220°C
in the absence of catalyst.(1)
Reaction and Mechanism
Friedlaender Synthesis
The starting materials for this quinoline synthesis are o-amino aryl
aldehydes or ketones and a ketone possessing an α-methylene
group. After an initial amino-ketone condensation, the intermediate
undergoes base- or acid-catalyzed cyclocondensation to produce
a quinoline derivative. (2)
Mechanism of the Friedlaender Synthesis
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. (2)
Application and recent literature
*Rapid and efficient synthesis of poly-substituted quinolines assisted by
p-toluene sulphonic acid under solvent-free conditions: (4)
*Molecular iodine: a highly efficient catalyst in the synthesis of quinolines
via Friedländer annulation: (4)
*Transition-Metal-Free Indirect Friedländer Synthesis of Quinolines
From Alcohols: (4)
*Ionic Liquid-Promoted Regiospecific Friedlander Annulation: (4)
Conclusion
The Friedländer synthesis is the chemical reaction
of 2-aminobenzaldehydes with ketones to form
quinoline derivatives.
This reaction has been catalyzed by trifluoroacetic
acid, toluenesulfonic acid, iodine, and Lewis
acids.
References
1.http://chem-info.blogspot.com/2011/04/friedlaenderquinoline-synthesis.html
2.http://www.organic-chemistry.org/namedreactions/
friedlaender-synthesis.shtm
3.http://www.lookchem.com/Chempedia/BasicChemical/Chemical-Reaction/8340.html
4.http://en.wikipedia.org/wiki/Friedl%C3%A4nder_
synthesis