Vinylpyridines picolines

An industrially important example is the condensation of a- (2) or y-picoline (4) with aqueous formaldehyde to form the corresponding ethanolpyridines, 2-ethanolpyridine [104-74-2] (22) and 4-ethanolpyridine [5344-27-4] respectively, followed by dehydration of the alcohols to give 2- (23) or 4-vinylpyridine. 

The relative production volumes of pyridine compounds can be ranked in the following order pyridine (1) > P-picoline (3) > a-picoline (2)> niacin (27) or niacinamide (26)> 2-vinylpyridine (23)> piperidine (18). U.S. and Japanese production was consumed internally as well as being exported, mainly to Europe. European production is mosdy consumed internally. Growth in production of total pyridine bases is expected to be small through the year 2000. 

The primary use of a-picoline (2) is as a precursor of 2-vinylpyridine (23). It is also used in a variety of agrochemicals and pharmaceuticals, such as nitrapyrin [1929-82-4] (60) to prevent loss of ammonia from fertilizers picloram [1918-02-1] (61), a herbicide and amproHum [121 -25-5] (62), a coccidiostat. 

The main use of y-picoline (4) is in the production of the antituberculosis agent, isonia2id (31). Compound (4) is also used to make 4-vinylpyridine, and subsequendy polymers. 

The total consumption of 2-methylpyridine (a-picoline) in 1980 has been estimated at 12,000 tons [81CI(L)23]. Half is produced for the U.S. market, whereas the demand in both Western Europe and Japan lies between 2000 and 2500 tons per annum. A significant outlet for 2-methylpyridine is in the production of 2-chloro-6-(trichloromethyl)pyri-dine, which is used as a nitrification inhibitor in agricultural chemistry and in the manufacture of the defoliant 4-amino-2,5,6-trichloropicolinic acid. The major commercial outlet for 2-methylpyridine is, however, its use as a starting material for the production of 2-vinylpyridine [Eq.(7)]. 

Problem 20.51 From pyridine (PyH), 2-picoline (2-PyMe), and any reagent without the pyridine ring prepare (a) 2-acetylpyridine, (5) 2-vinylpyridine, (c) 2-cyclopropylpyridine, (d) 2-PyCH2CH2CH,COOH, (e) 2-PyC(Me)=CHCH, (/) 2-pyridinecarboxaldehyde. Any synthesized compound can be used in ensuing steps. 

The stilbazoles have been synthesized using three different routes, and these are now described briefly (Figs. 2 and 3). The first attempts involved reacting 4-alkoxybenzaldehyde with 4-picoline in acetic anhydride, which led to extremely poor yields of the stilbazoles after a week s work (2). This route was subsequently superseded by a Heck coupling method in which 4-vinylpyridine was reacted with 4-alkoxyiodobenzene in the presence of a palladium catalyst (2). The reaction worked very... 

CPB2044). However, much more interesting are two further technical syntheses of the important nucleophilic catalyst DMAP (228) and related 4-aminopyridines. Treatment of 4-cyanopyridine (274), produced on a technical scale by ammonoxidation of y-picoline, with 2-vinylpyridine (275) in the presence of hydrochloric acid gives the crystalline quaternary salt 276. This salt is readily aminated by an aqueous solution of dimethyla-mine at room temperature with liberation of cyanide. The resulting aminated quaternary salt is finally cleaved by 40% NaOH to DMAP (228) and 2-vinylpyridine (275), which is recycled after separation of228 and 275 by distillation (79USP4I58093). 

The vinylpyridine ampholyte VPC used in the experiments is an oxymethylated copolymer of 2-methyl-3 vinylpyridine and divinylbenzene with picolinic acid as the functional groups. 

Amine adducts of Re3Clg are isolated only for weak bases (pyrazine, 2,6-dimethyl-pyrazine, 3-chloropyridine). Even Re3Cl9(py)3 undergoes spontaneous reduction to Re(II) products, but [ReCl2L] stoichiometries dominate when Re3Cl9 reacts with L = py, isoquinoline, fS- and y-picoline, 2-methylquinoline, and benzimidazole. For a-picoline, 2,6-lutidine, 2-vinylpyridine, and quinoline, the [ReCl2,3Lo.67]n stoichiometry... 

The monomers generally were obtained in high yield with none of the problems of multiple substitution evident in the preparation of phenolic Mannich monomers (2). The reaction of acetone with excess diallylamine and formaldehyde could be made to yield a disubstituted product, but this was difficult to isolate in a highly purified form. Monomers such as VII could be obtained from a-picoline by a Mannich reaction but the yields were much lower than those obtained with the 2-vinylpyridine/ diallylamine reaction. 

In a true biphasic system (i.e. with no PTC agent) with toluene as the organic phase, nitrobenzene and nitrotoluene were reduced with high efficiency with CO + H20 catalyzed by RhCl3.3H20, [Rh CO ] or [ RhCl(l,5-hexadiene) 2] (12 mol aniline/mol Rh.h, at room temperature and 1 bar CO) [364], Other nitroarenes reacted similarly, however, no or only negligible reaction took place with nitroaliphatics. Nitrobenzene is the standard substrate in such reactions, its reduction to aniline was also catalyzed by c/s-[Rh(CO)2(2-picoline)2]PF6 [365] and analogous cis-[Rh(CO)2(amine)2]PF6 complexes immobilized on poly(4-vinylpyridine) [366],... 

Pyridine bases namely 2 4-picolines are important commodity chemicals which are used in pharmaceuticals, rubber eind agricultural industries. 2-picoline is consumed for several different pesticides, and is used in the production of 2-vinylpyridine, which is a component of styrene-butadiene-vinylpyridine terpolymer latexes. The major outlet for 4-picoline is for the manufacture of 4-vinylpyridine and INH an anti-tubercular drug. The stringent specifications laid down for these products in pharmaceutical and agricultural applications can not be met from natural sources namely from coal carbonisation byproducts. Synthetic pyridine is the only answer to this problem. 

Pyridine derivatives are precursors of many chemical products of medicinal, agricultural, and industrial importance. Pyridine itself is used not only as a solvent, but also as a starting material for pharmaceuticals, herbicides, insecticides, and fungicides. a-Picoline is a precursor for 2-vinylpyridine which is used in the production of an adhesive for textile tire cord. The major use of y-picoline is in the production of isonicotinic hydrazide, an antituberculosis agent. / -Picoline and 2-methyl-5-ethylpyridine are important intermediates in the production of two members of the vitamin B family, nicotinamide, and nicotinic acid (also known as vitamin B3). All this shows there is a substantial need for the production of picolines. The following text describes a novel route to a-picoline which might in the future lead to new processes. 

The largest use of a-picoline (2) is for production of 2-vinylpyridine (11) which, with butadiene and styrene, is converted into a terpolymer latex. This latex provides a coating that stiffens fabrics (e. g. nylon, polyester, rayon) that are incorporated into biased-ply car tires. The 2-vinylpyridinc assists in binding the rubber to the fabric carcass. a-Picoline is also used as a precursor to nitrapyrin (12), which prevents nitrogen loss from soil, and the herbicide picloram (13). 

When nicotine was vaporized by flask distillation into a stream of helium passing through a horizontal unpacked silica tube above 600°, equivalent amounts of myosmine and 3-vinylpyridine were produced, as well as small amounts of pyridine, 3-picoline, 3-ethylpyridine, metanicotine, benzonitrile, 3-cyanopyridine, naphthalene, 3-(buta-l,3-dienyl)pyridine, quinoline, nicotine, isoquinoline, nornicotyrine, 1,7-diazaindene, and two unknown compounds. Nornicotine, nicotyrine, iV-methylmyosmine, nicotinamide, and nicotinic acid were not detected 115). 

Nicotine pyrolyzed in a stream of nitrogen at 500°-800° produced as major products myosmine, 3-vinylpyridine, and 3-cyanopyridine, along with nornicotine, pyridine, 3-picoline, 3-ethylpyridine, pyrrole, quinoline, isoquinoline, and 3,2 -dipyridyl 116). 

Alpha-picoline (2-picoline 2-methylpryridine) is used for the production of 2-vinylpyridine, which, when copolymerized with butadiene and styrene, produces a product that can be used as a latex adhesive which is used in the manufacture of car tires. Other uses are in the preparation of 2-beta-methoxyethyl-pyridine (known as promintic, an anthelmintic for cattle) and in the synthesis of a 2-picoline quaternary compound (amprolium), which is used against coccidiosis in young poultry. Beta-picoline (3-picoline 3-methylpryridine) can be oxidized to nicotinic acid, which, with the amide form (nicotinamide), belongs to the vitamin B complex both products are widely used to fortify human and animal diets. Gama-picoline (4-picoline 4-methylpyridine) is an intermediate in the manufecture of isonicotinic acid hydra-zide (isoniazide), which is a tuberculostatic drug. 2,6-Lutidine (2,6-dimethylpyridine) can be converted to dipicolinic add, which is used as a stabilizer for hydrogen peroxide and peracetic acid. 

The methyl group of a-picoline reacts, by virtue of its C-H acidity, with formaldehyde to form 2-pyridyl ethanol, which gives 2-vinylpyridine in the presence of bases. Vinylpyridine serves as a co-monomer in the production of modified styrene-butadiene rubber and special polyacrylic fibers to improve dye absorption. 

In addition, y-picoline is used in small amounts to produce 4-vinylpyridine. 

During preparation of polyelectrolytes from poly(4-vinyl-pyridine) (P-4-VP) and alkyl halides, some puzzling phenomena were observed by Coleman and Fuoss. These authors found quaternization of pyridine, 4-picoline and 4-isopropylpyridine with n-butyl bromide in tetramethylene sulfone followed normal second-order kinetics. Similar results were reported by Hinshelwood and coworkersfor the reaction of pyridine and alkyl halides. However, on quaternization of poly(4-vinylpyridine) under the same conditions, they observed... 

Vinylpyridine is synthesized from a-picoline as follows in Figure 5.25. 

The reactions between picolines and vinylpyridines in presence of sodium require further comment. Recent work s summarized below (the starting alkylpyridines were used in excess), requires the revision of earlier results ... 

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