Friedlander quinoline ring

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... 

Polyquinolines (PQ) are obtained by the Friedlander reaction of a bis-o-aminoaromatic aldehyde (or ketone) with an aromatic hisketomethylene reactant [Concilio et al., 2001 Stille, 1981]. The quinoline ring is formed hy a combination of an aldol condensation and imine formation (Eq. 2-221). Polymerization is carried out at 135°C in m-cresol with poly (phosphoric acid) as the catalyst. The reaction also proceeds under base catalysis, but there... 

The reaction is often used to effect ring closure.154 The Friedlander quinoline synthesis155 is an example ... 

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 use of the Friedlander approach to the quinoline ring system is well documented, and new examples are reported each year. In this example, the reaction occurs without the need for an external catalyst, appears to catalyze... 

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. 

Indolizino-quinoline 250, the ring system present in camphotecine and mappicine, has been prepared using classical Friedlander reaction under microwave irradiation conditions [160]. The reaction was successfully carried out in AcOH as the solvent and gave good results even with unstable o-amino benzaldehydes 248 (Scheme 92). 

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>. 

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