3-Methyl-5-ethylpyridine, oxidation

Although an inherently more efficient process, the direct chemical oxidation of 3-methylpyridine does not have the same commercial significance as the oxidation of 2-methyl-5-ethylpyridine. Liquid-phase oxidation procedures are typically used (5). A Japanese patent describes a procedure that uses no solvent and avoids the use of acetic acid (6). In this procedure, 3-methylpyridine is combined with cobalt acetate, manganese acetate and aqueous hydrobromic acid in an autoclave. The mixture is pressurized to 101.3 kPa (100 atm) with air and allowed to react at 210°C. At a 32% conversion of the picoline, 19% of the acid was obtained. Electrochemical methods have also been described (7). 

Nicotinic acid Nicotinic acid, pyridine-3-carboxylic acid (20.2.9) is synthesized industrially by heating a paraldehyde trimer of acetaldehyde, under pressure with ammonia, which leads to the formation of 2-methyl-5-ethylpyridine, followed by oxidation with nitric acid which gives the desired product [22-25]. 

For production of niacinamide in the past, methylethylpyridine was oxidized with nitric acid to yield niacin, and P-picoline was treated with air and ammonia to produce the nitrile that was then hydrolyzed to niacinamide. A more modern process can produce both niacin and niacinamide from a single feedstock, either P-picoline or 2-methyl-5-ethylpyridine by oxidative ammonolysis, a combination of oxidation and animation. 

Source Food sources meat, fish, milk, whole grains, yeast. Commercial sources synthetic niacin is made by oxidation of nicotine, quinoline, or 2-methyl-5-ethylpyridine (from ammonia and formaldehyde or acetaldehyde). 

METHYL-5-ETHYLPYRIDINE (104-90-5) Combustible liquid (flash point 155°F/68°C also listed at 165°F/73°C). Violent reaction with strong oxidizers. May form heat-sensitive explosive materials with digold ketenide. Incompatible with alcohols, aldehydes, alkylene oxides, cresols, caprolactam solution, epichlorohydrin, organic anhydrides, glycols, maleic anhydride, phenols. Attacks copper and its alloys. 

The sodium derivatives of 2- and 4-picoline and of their 1-oxides react with alkyl nitrites to give good yields of the pyridine aldoximes247a, 6i3 but the 3-isomers fail or give traces of products. The oxides are more reactive than the parent bases. 4-Ethylpyridine performed satisfactorily in the reaction, 2,6-lutidine gave a good yield of the monoxime, and 2,4-lutidine reacted at the 4-methyl group247a. 

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