Friedlaender Synthesis

The starting materials for this quinoline synthesis are o-aminoaryl 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.

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Mechanism of the Friedlaender Synthesis

Recent Literature

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
C.-S. Jia, Z. Zhang, S.-J. Tu, G.-W. Wang, Org. Biomol. Chem., 2006, 4, 104-110.

Molecular iodine: a highly efficient catalyst in the synthesis of quinolines via Friedländer annulation
J. Wu, H.-G. Xia, K. Gao, Org. Biomol. Chem., 2006, 4, 126-129.

Environmentally Friendly Nafion-Mediated Friedländer Quinoline Synthesis under Microwave Irradiation: Application to One-Pot Synthesis of Substituted Quinolinyl Chalcones
C.-K. Chan, C.-Y. Lai, C.-C. Wang, Synthesis, 2020, 52, 1779-1794.

Transition-Metal-Free Indirect Friedländer Synthesis of Quinolines from Alcohols
R. Martínez, D. J. Ramón, M. Yus, J. Org. Chem., 2008, 73, 9778-9780.

Visible-Light-Mediated Oxidative Cyclization of 2-Aminobenzyl Alcohols and Secondary Alcohols Enabled by an Organic Photocatalyst
J.-x. Xu, N.-l. Pan, J.-x. Chen, J.-w. Zhao, J. Org. Chem., 2021, 86, 10747-10754.

Silver Phosphotungstate: A Novel and Recyclable Heteropoly Acid for Friedländer Quinoline Synthesis
J. S. Yadav, B. V. S. Reddy, P. Sreedhar, R. S. Rao, K. Nagaiah, Synthesis, 2004, 2381-2385.

Efficient and Rapid Friedlander Synthesis of Functionalized Quinolines Catalyzed by Neodymium(III) Nitrate Hexahydrate
R. Varala, R. Enugala, S. R. Adapa, Synthesis, 2006, 3825-3830.

Ionic Liquid-Promoted Regiospecific Friedlander Annulation: Novel Synthesis of Quinolines and Fused Polycyclic Quinolines
S. S. Palimkar, S. A. Siddiqui, T. Daniel, R. J. Lahoti, K. V. Srinivasan, J. Org. Chem., 2003, 68, 9371-9378.

Synthesis of Quinolines via Friedländer Reaction in Water and under Catalyst-Free Conditions
Q. Shen, L. Wang, J. Yu, M. Liu, J. Qiu, L. Fang, F. Guo, J. Tang, Synthesis, 2012, 44, 389-392.

One-Pot Friedländer Quinoline Synthesis: Scope and Limitations
A.-H. Li, D. J. Beard, H. Coate, A. Honda, M. Kadablbajoo, A. Kleinberg, R. Laufer, K. M. Mulvihill, A. Nigro, P. Rastogi, M. W. Siu, A. G. Steinig, T. Wang, D. Werner, A. P. Crew, M. J. Mulvihill, Synthesis, 2010, 1629-1632.

Highly Regioselective Friedländer Annulations with Unmodified Ketones Employing Novel Amine Catalysts: Syntheses of 2-Substituted Quinolines, 1,8-Naphthyridines, and Related Heterocycles
P. G. Dormer, K. K. Eng, R. N. Farr, G. H. Humphrey, J. C. McWilliams, P. J. Reider, J. W. Sager, R. P. Volante, J. Org. Chem., 2003, 68, 467-477.

Solvent-Free Enantioselective Friedländer Condensation with Wet 1,1′-Binaphthalene-2,2′-diamine-Derived Prolinamides as Organocatalysts
A. Bañón-Caballero, G. Guillena, C. Nájera, J. Org. Chem., 2013, 78, 5349-5356.