Friedlander quinoline ring synthesis

Shamma s synthesis (Scheme 29) leaves the formation of the quinoline ring to a late stage, building up a tricyclic pyridone-ketone (121) which is then subjected to a Friedlander quinoline ring synthesis. 

Friedlander quinoline ring synthesis, modified 19, 856 Fries rearrangement (s. a. 

Two-stage Friedlander quinoline ring synthesis s. 15, 667 Azomethinium salts... 

An alternative approach to the tetracyclic systan forms the heterocyclic ring by nucleophilic addition of an amine to a carbonyl group. Application of the Friedlander quinoline synthesis to various methoxy-1-tetralones yields the methoxy-5,6-dihydrobenz-[c]acridines, which are dehydrogenated to the aromatic compound by distillation from palladium-charcoal (M. Croisy-Delcey et al. J. med. Chem., 1983, 26, 303). 

The approach to camptothecin by Danishefsky et alP revolves arpund an interesting synthesis of pyridones via nucleophilic addition to 1,3-dicarbethoxy allene. The C ring of camptothecin has been established by a Dieckmann closure followed by attachment of the quinoline ring using the Friedlander synthesis. Construction of ring E gives desoxycamptothecin, which readily undergoes oxidation to camptothecin. 

Since various substituents are tolerated, the Friedlander reaction is of preparative value for the synthesis of a large variety of quinoline derivatives. The benzene ring may bear for example alkyl, alkoxy, nitro or halogen substituents. Substituents R, R and R" also are variable. The reaction can be carried out with various carbonyl compounds, that contain an enolizable a-methylene group. The reactivity of that group is an important factor for a successful reaction. 

One of the more common ways to synthesize quinolines is through the Friedlander synthesis as a result, there have been a number of variations and improvements published for this reaction. Chelucci et al. presented a version of the Friedlander synthesis where the condensation and azaannulation reactions were carried out in a one-pot process. Additionally, they were able to synthesize quinoline analogs that were regiospecifically functionalized on both the pyridine and benzo-fused rings (Scheme 24) <05TL767, 05TL3493>. 

Beier and Pastyrikova (13MI411) reported that reductive ring opening of SFs-substituted benzisoxazoles 78a, 79a using iron in aqueous AcOH resulted in excellent yields of ori/ o-aminobenzophenones 100, 101, which can be used as precursors for the synthesis of other SFs-substituted heterocycles such as quinazoHnes (see Section 2.8), as weU as for the synthesis of SFs-substituted quinolines. Thus 6-SFs-quinoline 102 was prepared in high yield by the Friedlander annulation reaction of 101 with excess ethyl acetoacetate in the presence of catalytic cerium (IV) ammonium nitrate (CAN). Similarly, aminoketone 100 was condensed in good yield with cyclohexanone to provide 7-SFs-quinoline 103 (Scheme 25). 

Friedlander Reaction Friedlander condensation is one of the most used and cited reactions in organic synthesis and it is the method of choice for the synthesis of a large variety of nitrogen heterocyclic ring systems such as quinolines, naphthyridines, phenanthrolines, quindolines, or acridones [142]. 

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