3-picoline manufacture

Important commercial alkylpyridine compounds are a-picoline (2), Ppicoline (3), y-picoline (4), 2,6-lutidine (5), 3,5-lutidine (6), 5-ethyl-2-methylpyridine (7), and 2,4,6-coUidine (8). In general, the alkylpyridines serve as precursors of many other substituted pyridines used in commerce. These further substituted pyridine compounds derived from alkylpyridines are in turn often used as intermediates in the manufacture of commercially usehil final products. 

Cyanopyridines are usually manufactured from the corresponding picoline by catalytic, vapor-phase ammoxidation (eq. 7) in a fixed- or fluid-bed reactor (28). 3-Cyanopyridine (25) is the most important nitrile, as it undergoes partial or complete hydrolysis under basic conditions to give niacinamide... 

Commercial Manufacture of Pyridine. There are two vapor-phase processes used in the industry for the synthesis of pyridines. The first process (eq. 21) uti1i2es formaldehyde and acetaldehyde as a co-feed with ammonia, and the principal products are pyridine (1) and 3-picoline (3). The second process produces only alkylated pyridines as products. 

Uses Intermediate in the manufacture of many chemicals (e.g., glycerine, 1,3,6-hexanediol, P-chloropropionaldehyde, 1,2,3,6-tetrahydrobenzaldehyde, P-picoline, nicotinic acid), pharmaceuticals, polyurethane, polyester resins, liquid fuel, slimicide herbicide anti-microbial agent control of aquatic weeds in irrigation canals and ditches warning agent in gases. 

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)]. 

Lead difluoride is used in low melting glasses in glass coatings to reflect infrared rays in phosphors for television-tuhe screens for nickel plating on glass and as a catalyst for the manufacture of picoline. 

Synthetic Methods of Manufacture. Due to rising demand, production of the pyridine bases by large-scale synthesis passed the volume of tar bases extracted from coal tar in the 1960s. By the early 1970s. capacity in the United States for the synthetic manufacture of pyridine, the picolines, and 2-methyl-5-ethylpyridine (MEP) was in the tens of millions of pounds. All of these products can be made by condensation reactions of aldehydes and ammonia, MEP is no lunger made in the United Stales,... 

Ding et al. [88] used anion-exchange chromatog-raphy-ICP-MS to determine different forms of chromium in chromium picolinate products which are used as dietary supplements and appear to assist in weight loss. A Dionex AS7 anion-exchange column was used to separate Cr(III)-EDTA chelate and Cr(VI) in the supplements. Only 1% total chromium recoveries were obtained and this was attributed to retention of the chromium species on-column. The use of RP-HPLC proved to be more effective and complete chromium recoveries were obtained, based on the amounts stated on the manufacturer s product labels. 

Alternatively, 3-picoline is produced by vapor phase cyclization of 2-methyl-pentane-1,5-diamine (Fig. 2.25) over, for example, H-ZSM-5 followed by palladium-catalyzed dehydrogenation [78]. This diamine is a by-product of the manufacture of hexamethylenediamine, the raw material for nylon 6,6, and these two reactions are key steps in the Lonza process for nicotinamide production (see Chapter 1) [79]. 

Organic eluents are not very common in these applications. The respective manufacturer recommends the use of pyridinecarboxylic acids such as picolinic acid or isonicot-inic acid only for operating separator columns such as ION-200 and Vydac IC 405. 

Pyridine bases such as 3-picoline and MEP are predominantly manufactured by the Chichibabin reaction, where a mixture of aldehydes or ketones is reacted with ammonia. Thus, formaldehyde, acetaldehyde and ammonia react in the gas phase to produce a mixture of pyridine and 3-picoline. By choosing the appropriate aldehyde or ketone, catalyst and phase (liquid or gas phase), the composition of the mixture can be varied at will, depending on the desired end-product. In the gas phase, silica alumina catalysts are often used, while in the liquid phase acid catalysts based on phosphoric or acetic acid are employed. In the 1990s, Reilly patented MET and BEA-based zeolite catalyst compositions for ammonia-aldehyde conversions to pyridine, picolines and alkyl pyridines. 

Picoline is obtained, typically in a 1 2 ratio along with the main product pyridine, by the gas-phase reaction of acetaldehyde, formaldehyde and ammonia. The lack of selectivity of this reaction to either pyridine or picoline has hitherto meant that the economy of the major product (pyridine) has determined the price and availability of picoline. Consequently, producers of pyridine have been able to control the quantity and prices of picoline on the market. This has led to the search for alternative feedstock and manufacturing processes for picoline. 

This relatively simple compound 231 requires the 4-C1 picolinic acid chloride 227 easily made in high yield by the S0C12 reaction described earlier. This has the advantage of simultaneously turning the acid into the acid chloride. Formation of the amide 228 and then the diaryl ether is followed by coupling with an isocyanate 230 to make the unsymmetrical urea 231. This large scale synthesis is planned for manufacture.33... 

VP is currently manufactured by condensation of 2-picoline with aqueous formaldehyde to... 

Pyridines and picolines are manufactured on a fairly large scale (together over 50.000 t/a) whereas 3,5- and 2,6-dimethylpyridines (lutidines) are made on a 10 - 100 t/a scale. 

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. 

Introduction of heteroatoms, e. g. N, S, or O, into hydrocarbon molecules adds substantial value, and new routes for such reactions are of continuous interest to the chemical industry. The two main classes of aromatic N-containing hydrocarbons are the arylamines and the aromatic N-heterocyclic compounds. The aryl-amines, which are required industrially, are manufactured by nitration of aromatics to nitroaromatics, followed by hydrogenation to arylamines [1,2]. Because of the lower demand for aromatic heterocycles than for arylamines, coal tar is still an important source of pyridine and methylpyridines (picolines). Increasing demand for aromatic heterocyclic compounds has led to processes in which aldehydes and ketones are condensed with NH3 to furnish pyridine and alkylated pyridines [3,4]. 

Acide iso-nicotinique AI3-19239 4-Carboxypyridine 1,4-Dihydroisonicotinic acid EINECS 200-228-2 y-Picolinic acid y-Pyridinecarboxyiic acid INA Isonicotinic acid NSC 1483 4-Picolinic acid 4-Pyridinecarboxylic acid p-Pyridinecarboxylic acid. Chemical intermediate in the manufacture of its hydrazide. isoniazid, an antituberculosis drug. Colorless crystals mp 319 soluble in H2O (0.52 g/100 ml), less soluble in organic solvents. Raschig GmbH Reilly Ind. 

The manufacture of pyridine from acetaldehyde is nearly as large as the production of acetate esters. Pyridines and related picolines are made from the vapor phase reaction of acetaldehyde with ammonia. The major use for... 

Formation of 2-Chloromethylpyridines. A combination of tosyl chloride and NEt3 can be used to convert substituted 2-picoline-lV-oxides to the corresponding 2-chloromethylpyri-dines. This reaction has been exploited for the synthesis of a variety of 2-[2-(pyridylmethyl)-thio]-l//-benzimidazoles, key intermediates in the manufacturing of H+/K+-ATPase inhibitors, in a one-pot procedure (eq 56). 

Alpho-picoline is a liquid which is very soluble in water, forming a constant-boiling mixture with it. It is olso soluble In ethyl alcohol ond ethyl ether. It may be used in the manufacture of olkoloids, phormaceuticals, ontioxidants, and rubber accelerotors. 

Beta-picoline is similar to the olpho compound. It is soluble in water with which it forms o constant-boiling mixture it is also soluble in ethyl olcohol and ethyl ether. Suggested uses for it are in the manufacture of alkaloids, pharmaceuticals and rubber occeleratars. It is also o starting moterial for the production of nicotinic acid and nicotinic acid amide. 

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. 

Background of the Invention. Although the key intermediate required to produce fluazifop butyl, ch1orf1uazuron and fluazinam is 2,5-CTF (8), some other (chloro-)tfm-pyridines occur as byproducts in the manufacturing process (simultaneous vapor-phase chlorination and fluorination of 3-picoline) developed by ISK, as shown in Figure 3. 2,3-CTF and 2,6,3-DCTF can be reduced to TF, which can then be re-fed to the reaction. However, since direct separation and effective application of the byproducts is undoubtedly preferable with respect to cost performance, we sought an appropriate agrochemical mother-skeleton to which such 3-tfm-pyridine intermediates can be introduced. 

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