Pyridinium salts Ortoleva-King reaction

Both 2-methyl- and 4-methyl-quinolizinium salts undergo the Ortoleva-King reaction (Scheme 37) to produce the expected pyridinium salts and these with p-dialkylamino-nitrosobenzenes were found to give nitrones (46) (65JPR(27)306). 

Ortoleva-King reaction refers to the direct reaction of an active methyl or methylene compound 1 with iodine and pyridine to generate the corresponding pyridinium iodide 2 along with an equivalent of pyridine hydroiodide salt 3. 

After a simple filtration or sometimes without isolating the pyridinium salt product, the Ortoleva-King reaction may be followed by further chemical transformation, giving rise to a variety of synthetically useful compounds. 

The Ortoleva-King reaction also found application in the following sequence where a methyl or methylene compound such as 2-methylthiazole 16 was converted to the corresponding aldehyde 197 The preparation of pyridinium salt 17 via Ortoleva-King reaction of 16 was followed by nitrone formation to give 18, whose hydrolysis led to desired aldehyde 19. This mild sequence is especially suitable for the preparation of sensitive aldehydes, which might be difficult to obtain using other synthetic approaches. 

The required pyridinium salts can be obtained by the King-Ortoleva reaction (see p 273), as is shown by the synthesis of benzothiazole-2-carbaldehyde 237. In the Krohnke reaction, the heterocycle pyridine ensures the targeted conversion CH3 -> CH=0 of methyl groups in arenes or heteroarenes [78]. 

Giovanni Ortoleva was the first to recognize the possibility of preparing pyridinium salts by heating cinnamic acid, iodine and pyridine in 1899, and the titled reaction was later reported by L. Carroll King in 1944." This elegant method offers direct access to synthetically useful pyridinium iodide salts. Even today, its potential remains underdeveloped. 

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