Cyanopyridines from pyridine 1-oxides

This general method has been used to prepare 2- and 4-cyanopyridine from pyridine-1-oxide in 32% and 49% yields, respectively 2-cyano-4,6-dimethylpyridine (73%) from 4,6-dimethylpyridine-l-oxide 2-cyanoquinoline (93%) from quinoline-1-oxide and 1-cyanoisoquinoline (95%) from isoquinoline-2-oxide. ... 

A number of routes are available for the synthesis of 2,2 -bipyridines where one of the pyridine rings is built up from simpler entities. For example, condensation of 2-(aminomethyl)pyridine (31) with acetaldehyde or acetylene over a silicon-alumina catalyst at 450°C gives 2,2 -bipyridine, ° whereas 2-cyanopyridine reacts with acetylene at 120°C in the presence of a cobalt catalyst to afford 2,2 -bipyridine in 95% yield.2-Acetylpyridine with acrolein and ammonia gives 2,2 -bipyridine in the presence of dehydrating and dehydrogenating catalysts, and related condensations afford substituted 2,2 -bipyridines. ° In a similar vein, condensation of benzaldehyde with 2 mol of 2-acetylpyridine in the presence of ammonia at 250°C affords 2,6-di(2-pyridyl)-4-phenylpyridine, ° and related syntheses of substituted 2,2 6, 2"-terpyridines have been described. Likewise, formaldehyde with two moles of ethyl picolinoylacetate and ammonia, followed by oxidation of the product and hydrolysis and decarboxylation, affords a good... 

Nicotinic acid and nicotinamide, members of the vitamin B group and used as additives for flour and bread enrichment, and as animal feed additive among other applications, are made to the extent of 24 million pounds (nearly 11 million kilograms) per year throughout the world. Nicotinic acid (pyridine-3-caiboxylic acid), also called niacin, has many uses. See also Niacin. Nicotinic acid is made by the oxidation of 3-picolme or 2-mcthyl-5-cthylpyridine (the isocinchomcnc acid produced is partially deearboxylated). Alternatively, quinoline (the intermediate quinolinic acid) is partially deearboxylated with sulfuric add in the presence of selenium dioxide at about 300° C or with nitric acid, or by electrochemical oxidation. Nicotinic acid also can be made from 3-picoline by catalytic ammoxidation to 3-cyanopyridine, followed by hydrolysis. 

Cobalt(II) salts are effective catalysts for the oxidation of 1,2-glycols with molecular oxygen in aprotic polar solvents such as pyridine, 4-cyanopyridine, benzonitrile, DMF, anisole, chlorobenzene and sulfolane. Water, primary alcohols, fatty acids and nitrobenzene are not suitable as solvents. Aldehydic products are further oxidized under the reaction conditions. Thus, the oxidative fission of rram-cyclo-hexane-l,2-diol gives a mixture of aldehydes and acids. However, the method is of value in the preparation of carboxylic acids from vicinal diols on an industrial scale for example, decane-1,2-diol is cleaved by oxygen, catalyzed by cobalt(II) laurate, to produce nonanoic acid in 70% yield. ... 

An aerobic oxidation of tertiary amines catalyzed by Cobalt Schiff-base complexes afforded N-oxides in high yields [120]. The reaction was run at room temperature with 0.5 mol% of the cobalt catalyst 35 (Eq. (8.28)). The presence of molecular sieves (5 enhanced the rate of the reaction. With this procedure, various pyridines were oxidized to their corresponding N-oxides in yields ranging from 50 to 85%. Electron-deficient pyridines such as 4-cyanopyridine gave a slow reaction with only 50% yield. 

The retro-Hofmann consideration is based on the availability of pyridine-3-carboxamide on a large scale. Actually, this compound, known as nicotinamide or vitamin B3, is produced in multi-ton quantities from 3-methylpyridine [20, 21]. For this building block, the catalytic industrial process is based on the one-pot cyclization of acrolein, ammonia and propanal in the presence of oxides of Sb(II), Ti(IV) or V(V) as catalysts. 3-Methylpyridine is submitted to amoxidation, the combined action of oxygen and ammonia to obtain 3-cyanopyridine (Scheme 8.9) [22]. 

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