Pyridinecarbaldehyde oximes

In 1965, Breslow and Chipman discovered that zinc or nickel ion complexes of (E)-2-pyridinecarbaldehyde oxime (5) are remarkably active catalyst for the hydrolysis of 8-acetoxyquinoline 5-sulfonate l2). Some years later, Sigman and Jorgensen showed that the zinc ion complex of N-(2-hydroxyethyl)ethylenediamine (3) is very active in the transesterification from p-nitrophenyl picolinate (7)13). In the latter case, noteworthy is a change of the reaction mode at the aminolysis in the absence of zinc ion to the alcoholysis in the presence of zinc ion. Thus, the zinc ion in the complex greatly enhances the nucleophilic activity of the hydroxy group of 3. In search for more powerful complexes for the release of p-nitrophenol from 7, we examined the activities of the metal ion complexes of ligand 2-72 14,15). 

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 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 Because of its instability, 2-pyridinecarboxaldehyde has been replaced by more efficient derivatives.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. 

The most advantageous 2-pyridinecarbaldehyde derivative proved to be the acetal (example 3, Table 9) although, unlike the oxime, it was not commercially available. The acetal also usually afforded crystalline intermediate salts (181 Z = 0(CH2)20), but in addition made possible for the first time high temperature cyclization in PPA, permitting cyclization to rings deactivated by a nitro (example 25) or sulfo group (example 24). 

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