Pyridinecarbaldehyde synthesis

The first synthesis of the benzo[6]quinolizinium ion (Scheme 98, Table 9, example 1) was by hydrobromic acid-catalyzed cyclization of the quaternary salt formed between 2-pyridinecarbaldehyde and benzyl bromide. Aromatic cyclodehydration has continued to the present as almost the only method used for the preparation of the acridizinium ion, its derivatives and benzo analogs. Because of its instability, 2-pyridinecarboxaldehyde has been replaced by more efficient derivatives. The first of these was the oxime (example 2) which not only gave a better overall yield, but also made possible the isolation of a crystalline intermediate (181 Z = NOH). The disadvantages are that it is not suitable for high temperature cyclizations involving polyphosphoric acid, and some products (182) (e.g. example 10, Table 10) may tend to form double salts with hydroxylamine hydrobromide. 

Multicomponent one-pot reactions continue to be the focus of heterocyclic synthesis when multi-bonds are formed. Malononitrile condenses with 3-pyridinecarbaldehyde and a ketone to form a substituted bipyridine (Equation 179) <1995JCM146>. In another condensation, with aniline being the ultimate source of the tetrahydroquinoline nitrogen atom, iodine is used as a catalyst in a reaction that was optimized for yield and diastereoselectivity (Equation 180) <2005SL2357>. 

Several such oxides have been made by primary synthesis for example, 3-phenylethynyl-4-pyridinecarbaldehyde oxime (47) gave 3-phenyl-2,6-naphthyridine 2-oxide (48) (K2C03, EtOH, reflux 80%).641... 

The Komblum oxidation can be combined with halogenadon to provide a very convenient synthesis of 2 and 4-pyridinecarbaldehydes from the corresponding picolines (equation 4). ... 

Following the synthesis of substituted indole A-oxides via a TiC -mediated MBH reaction of a-oxo cyclic ketene-S ,iS -acetal with 2-nitrobenzaldehydes, Dong and Liu and their co-workers further developed a novel method to rapidly synthesize indolizines from MBH adducts 509, which in turn were prepared from the reaction of a-EWG ketene S ,A-acetals with 2-pyridinecarbaldehyde... 

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