Pyridine 2-carboxylic acid, from 2-methylpyridine

The nature of the base, CmHijN, varies. When produced from pure Mupinine, m.p. 68-9°, it furnishes on oxidation only 3-methylpyridine-2-carboxylic acid (XV) and pyridine-2 3-dicarboxylic acid. If, however, lupinine, m.p. 63-3°, is used, the resulting pyridine base on oxidation furnishes in addition 2-n-butylpyridine-6-carboxylic acid (XVI) and 6-methylpyridine-2-carboxylic acid (XVII). The conclusion is drawn that lupinine, m.p. 63-3°, is a mixture of 1-lupinine (XI) with aZlolupinine (XII), each of these components furnishing its own lupinane (XIII and XIV), and that these two lupinanes contribute to the final degradation product, the tertiary pyridine base, CioHuN, the two isomerides 2-w-Ijutyl-3-inethylpyridine (XVIII) and 2-w-butyl-6-raethylpyridine (XIX) respectively. These interrelationships are shown by the following scheme —... 

Significantly improved yields of pyridine-3-carboxylic acids are obtained by oxidising 2,5- and 5,6-dihalo-3-methylpyridines with tetrabutylammonium permanganate rather than with potassium permanganate.Pyridyl oxazolines derived from pyridine-3- and - -carboxylic acids on treatment with a lithiating reagent (methyllithium or lithium 2,2,6,6-tetramethylpiperidide) followed by an electrophile, provide - and 3- substituted pyridines in good yield. 7 Photolysis of pyridine-2,3-dicarboxylic acid... 

Nicotinic acid (pyridine-3-carboxylic acid), mp 236°C, was first obtained by oxidation of the alkaloid nicotine by KMn04. It is produced commercially from 5-ethyl-2-methylpyridine (see p 291). Nicotinic acid and its amide belong to the B group of vitamins (vitamin B5). The daily requirement of an adult is ca. 20 mg. Deficiency of nicotinic acid causes pellagra, a skin disease. 

An interesting variant on this scheme to form alkylpyridinecarboxylic acids by nitric acid oxidation has been described by Czech workers starting with 2,4- or 2,6-lutidine these bases are condensed with formaldehyde to yield unsymmetrical j3-(hydroxyethyl)methylpyridines. Nitric acid oxidation now occurs preferentially at the hydroxylated side chain yielding the corresponding methylpicolinic acids. Thus, 2,4-lutidine (X-60) is converted to a separable mixture of 4-(/3-hydroxyethyl)-2-methylpyridine (X-61), 4-[tris(hydroxy-methyl)methyl]-2-methylpyridine (X-62), and 2-( -hydtoxymethyl)4-methyl-pyridine (X-63). Nitric acid oxidation yields 2-methylpyridine-4-carboxylic acid (X-64) from X-61 and X-62, and 4-methylpyridine-2-carboxylic acid (X-65) from X-63. A similar reaction sequence carried out with 2,6-lutidine (X-66) affords ultimately 6-methylpyridine-2-carboxylic acid (X-67). 

Electrolytic reduction of pyridine-2- and -4-carboxylic acids can be used to give methylpyridines 52 and zinc and acetic acid produce either the methylpyridines or the hydroxymethylpyridines. However, from nicotinic acid the second method produces piperidine, and electrochemical reduction of these acids can be conducted to give piperidine-carboxylic acids, tetrahydropyridine-carboxylic acids and tetrahydro-methylpyridinesi ". ... 

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