Enolizable methylene groups, reaction compounds

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. 

Considering the electrophilic nature of the reaction mechanism, suitable coupling components for the synthesis of azo pigments should carry a nucleophilic center on the aromatic ring system (naphthols) or should be enolizable compounds with reactive methylene functions. Naphthols enter the reaction as naphtholates compounds with reactive methylene groups participate as enolates. 

The following types of compounds undergo coupling reactions with diazo compounds (a) Phenols, (b) Enolizable keto compounds of an aliphatic character, having a reactive methylene group which may be part of an open chain or a ring system, either homocyclic or heterocyclic. This group of compounds may be represented by the formula ... 

The ideal approach for the preparation of conjugated carbonyl compounds having an exo-methylene group would be via a mixed aldol condensation of an enolizable carbonyl substrate with formaldehyde as the electrophilic partner. However, formaldehyde is a very powerful electrophile and tends to react more than once with enols and enolates. This shortcoming can be circumvented by converting the formaldehyde to an iminium ion (Mannich reagent) by reaction with a secondary amine, usually dimethy-lamine, and a catalytic amount of HCl. 

Titanium tetrachloride and a tertiary amine are a useful catalyst for Knoevenagel condensation [149] as shown in Eq. (45) [150]. Because the reaction can be performed under mild conditions, acid-sensitive functional groups survive the reaction conditions and the optically active center at the enolizable position did not racemize (Eq. 45). More examples of the titanium-catalyzed Knoevenagel condensation are shown in Table 5. Alkylation of an (unsaturated) (iV,0)-acetal with active methylene compounds was performed analogously in the presence of TiCU and NEts (Eq. 46) [154]. Depending on the structure of the active methylene compounds, carbon-carbon bond... 

Peterson Alkenylation. The Peterson alkenylation reaction continues to be the major use of trimethylsilylmethyllithium (1) and converts a carbonyl group to a methylene (eq 1). Some enan-tioselectivity has been seen for the addition of 1 to benzaldehyde in the presence of chiral ligands. The ketone substrates can contain functional groups that are con5)atible with the basic conditions. The use of cerium(III) chloride to promote nucleophilic addition of 1 to an enolizable carbonyl compound has continued to prove advantageous. ... 

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