3- Hydroxypyridine reaction with carbon dioxide

Pyridin-2-one undergoes the Kolbe reaction with carbon dioxide under pressure to give a good yield of the 5-carboxylic acid (60%). Pyridin-4-one also reacts readily to give 3-mono- or 3,5-di-carboxylic acids. The nature of the products derived from a Kolbe reaction with 3-hydroxypyridine is very susceptible to the reaction conditions. This is illustrated by the difference in behaviour of the sodium and potassium salts (equation 56). When the sodium salt is heated rapidly to 280 °C with carbon dioxide at atmospheric pressure the 2-carboxylic acid (8%) is the only product. Under the same conditions the potassium salt gives a mixture of 2- (3%) and 6- (24%) carboxylic acids (75RCR823). 

Hydroxypyridine undergoes the Kolbe reaction (with carbon dioxide to give the carboxylic acid) the Na salt reacts mainly at the 2-, and the K salt at the 6-position. Uracil undergoes the Reimer-Tiemann reaction with sodium hydroxide/chloroform to give 5-formyluracil. 

The titanium-mediated photocatalytic oxidation of a pyridine solution was conducted by Low et al. (1991). They proposed that the reaction of OH radicals with pyridine was initiated by the addition of a OH radical forming the 3-hydro-3-hydroxypyridine radical followed by rapid addition of oxygen forming 2,3-dihydro-2-peroxy-3-hydroxypyridine radical. This was followed by the opening of the ring to give At-(formylimino)-2-butenal which decomposes to a dialdehyde and formamide. The dialdehyde is oxidized by OH radicals yielding carbon dioxide and water. Formamide is unstable in water and decomposes to ammonia and formic acid. Final products also included ammonium, carbonate, and nitrate ions. 

Electron-attracting substituents should assist this reaction. However, with acetic anhydride in acetonitrile, 2-picolinic acid 1-oxide gives mainly pyridine 1-oxide and carbon dioxide, whilst the same reaction carried out under ultra-violet irradiation proceeds similarly but with the formation of a little more 2-hydroxypyridine. The methyl esters of the pyridine-carboxylic acid 1-oxides behave normally, but there is no evidence that the methoxycarbonyl group promotes the reaction, and 2-cyanopyridine 1-oxide does not react with acetic anhydride . The results of a kinetic study of the rearrangement of pyridine 1-oxide in acetic anhydride exclude the intramolecular rearrangement of the free cation (113) and also a free radical process. There remain the two possibilities of nucleophilic substitution by reaction between... 

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