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 compound4 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]
^Shaabani, A.; Soleimani, E.; Badri, Z. (2007). "Triflouroacetic Acid as an Efficient Catalyst for the Synthesis of Quinoline". Synthetic Communications. 37 (4): 629–635.
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10.1080/00397910601055230.
S2CID98625429.
^Jia, C.-S.; Zhang, Z.; Tu, S.-J.; Wang, G.-W. (2006). "Rapid and efficient synthesis of poly-substituted quinolines assisted by p-toluene sulphonic acid under solvent-free conditions: Comparative study of microwave irradiation versus conventional heating". Org. Biomol. Chem.4 (1): 104–110.
doi:
10.1039/b513721g.
PMID16358003.
^Wu, J.; Xia, H.-G.; Gao, K. (2006). "Molecular iodine: A highly efficient catalyst in the synthesis of quinolines via Friedländer annulation". Org. Biomol. Chem.4 (1): 126–129.
doi:
10.1039/b514635f.
PMID16358006.
^Varala, R.; Enugala, R.; Adapa, S. R. (2006). "Efficient and Rapid Friedlander Synthesis of Functionalized Quinolines Catalyzed by Neodymium(III) Nitrate Hexahydrate". Synthesis. 2006 (22): 3825–3830.
doi:
10.1055/s-2006-950296.
^Jose Marco-Contelles; Elena Perez-Mayoral; Abdelouahid Samadi; Marıa do Carmo Carreiras; Elena Soriano (2009). "Recent Advances in the Friedlander Reaction". Chemical Reviews. 109 (6): 2652–71.
doi:
10.1021/cr800482c.
PMID19361199.