Oxidation methylpyridine

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

Compound (27) may also be obtained dkecdy by oxidation of P-picoline (3) or by exhaustive oxidation of 5-ethyl-2-methylpyridine (7), followed by decarboxylation of the initially formed pyridine-2,5-dicarboxyhc acid [100-26-5] (28) (eq. 8) (30). 

In an alternative approach, 2-methylglutaronitrile (8) is hydrogenated and cyclized to give high yields of 3-methylpyridine. The feedstock for this process is produced as a by-product of the production of adiponitrile. Oxidative cyclization of 2-methylglutaronitrile to nicotinonitrile (9) has been described (4). 

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). 

Picoline-V-oxide (4-methylpyridine-l-oxide) [1003-67-4] M 109.1, m 182-184 , 185-186 , 186-188 , pK 1.29. Recryst from EtOH-EtOAc, Mc2C0-Et20 or C6H6. [Bullitt and Maynard 7 Am Chem Soc 76 1370 1954 Boekelheide and Linn J Am Chem Soc 76 1286 1954]. 

Cyclohexeiie oxide and metallated 2-methylpyridine reacted to afford a produet which gave the NMR results 37. Identify the relative configuration of the product and assign the resonances. 

Methylpyridine-l-oxide (3-picoline-l-oxide) may be prepared by a method similar to that employed for pyridine-1-oxide. To a mixture of 600-610 ml. of glacial acetic acid and... 

Methylpyridine-l-oxide has been prepared by the oxidation of 3-methylpyridine with hydrogen peroxide in glacial acetic acid, with 40% peracetic acid and sodium acetate, and with per benzoic acid in benzene. ... 

Methyl-4-nitropyridine-l-oxide has been prepared by the nitration of 3-methylpyridine-l-oxide hydrochloride with a mixture of concentrated sulfuric acid and potassium nitrate. The I)reparation of this compound has been mentioned briefly by Talikowa, but no experimental details have been given. 

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 —... 

Meroquinenine, CgHjjOaN (meroquinene), formed by the oxidation of all four alkaloids and of cinchoninone or quininone and by the hydrolysis of quinenine or cinchenine (p. 489), crystallises from methyl alcohol in needles, m.p. 223-4° (dee.), [ajp -f- 27-5° (H2O). It gives a nitrosoamine, m.p. 67°, and a monoacetyl derivative, m.p. 110°, and can be esterified the ethyl ester hydrochloride has m.p. 165°. When oxidised by chromic acid it yields formic and cincboloiponic acids. On reduction with zinc dust and hydriodic acid, it adds on two atoms of hydrogen forming cincholoipon, CgH jOaN, and when heated with hydrochloric acid at 250-60° gives 3-ethyl-4-methylpyridine ()3-collidine). 

Pellagra is a disease caused by a deficiency of niacin (C6H5NO2) in the diet. Niacin can be synthesized in the laboratory by the side-chain oxidation of 3-methylpyridine with chromic acid or potassium permanganate. Suggest a reasonable structure for niacin. 

Fig. 23. Liquid-liquid phase behavior in the system 2-methylpyridine-deuterium oxide [from Schneider (SI)].

Whereas 2-methylpyridine-N-oxide 881a reacts rather slowly with TCS 14/ NaCN/NEt3 in DMF at 100-110°C, sterically hindered 2-methoxycarbonyl- 881b, 2-isopropyl- 881c, or 2-tert-butylpyridine-N-oxide 881d have not yet been reacted in the presence of NEts or DBU in DMF with the much less bulky but apparently as yet unknown dimethylsilyl cyanide Me2HSiCN 883 (which can probably be gener-... 

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