Benzo quinolizinium salts, preparation

As part of a study of the properties of the easily prepared salts (154 Scheme 89) (61JOC4944), it was discovered that their exposure to hydrogen peroxide in acetic acid followed by warming led to ring contraction and loss of sulfur, with formation of benzo[a]quinolizinium salts. Present evidence (62JOC4475, 66JOC978) indicates that the extrusion of sulfur occurs after the salt has been oxidized to the sulfoxide level. Despite the modest yields (Table 5), this ring contraction has preparative potential as well as theoretical interest. The variety of arenethiols (150) and 2-bromopyridines (151) available makes a variety of substituted 2-phenylthiopyridines (152) accessible as intermediates. 

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 Because of its instability, 2-pyridinecarboxaldehyde has been replaced by more efficient derivatives.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 benzo[bond formation takes place, followed by loss of hydrogen. In view of the publication of an improved method for making styrylpyridinium salts (160) (69JMC1079) the photochemical method appears to offer an advantageous route to the parent compound (2). 

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