Friedländer synthesis

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

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

References

1. Organic Syntheses, Coll. Vol. 3, p.　56 (1955); Vol. 28, p.　11 (1948). (Article)
2. Friedländer, P. (1882). "Ueber o-Amidobenzaldehyd". Chemische Berichte . 15 (2): 2572–2575. doi:10.1002/cber.188201502219.
3. Friedländer, P.; Gohring, C. F. (1883). "Ueber eine Darstellungsmethode im Pyridinkern substituirter Chinolinderivate". Ber. 16 (2): 1833–1839. doi:10.1002/cber.18830160265.
4. Shaabani, A.; Soleimani, E.; Badri, Z. (2007). "Triflouroacetic Acid as an Efficient Catalyst for the Synthesis of Quinoline". Synthetic Communications. 37 (4): 629–635. doi:10.1080/00397910601055230. S2CID   98625429.
5. 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. PMID   16358003.
6. 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. PMID   16358006.
7. 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.
8. Manske, R. H. (1942). "The Chemistry of Quinolines". Chem. Rev. 30: 113–144. doi:10.1021/cr60095a006.
9. Bergstrom, F. W. (1944). "Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline". Chem. Rev. 35 (2): 77–277. doi:10.1021/cr60111a001.
10. Cheng, C.-C.; Yan, S.-J. (2004). "The Friedländer Synthesis of Quinolines". Organic Reactions. doi:10.1002/0471264180.or028.02. ISBN   0471264180.
11. 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. PMID   19361199.