Bases Pyridine

Historical. Pyridines were first isolated by destructive distillation of animal bones in the mid-nineteenth century (2). A more plentifiil source was found in coal tar, the condensate from coking ovens, which served the steel industry. Coal tar contains roughly 0.01% pyridine bases by weight. Although present in minute quantities, any basic organics can be easily extracted as an acid-soluble fraction in water and separated from the acid-insoluble tar. The acidic, aqueous phase can then be neutrali2ed with base to Hberate the pyridines, and distilled into separate compounds. Only a small percentage of worldwide production of pyridine bases can be accounted for by isolation from coal tar. Almost all pyridine bases are made by synthesis. 

Commercial Manufacture of Specific Pyridine Bases. Condensation of paraldehyde with ammonia at 230°C and autogenous pressure (eq. 22) is used to manufacture 5-ethyl-2-methylpyridine (7). This is one of the few Hquid-phase processes used in the industry to make relatively simple aLkylpyridines, and one of the few processes known to make a single alkylpyridine product selectively. 

Worldwide production of pyridine bases in the late 1980s was estimated at thousands of tons a year. Production was concentrated mainly in the United States, Western Europe, and Japan. Production statistics are not complete for any of the principal producing areas and trade statistics are also incomplete. 

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. 

Pjridine Bases. Formerly, pyridine bases were recovered from coal-tar light oils (18), but in more recent years synthetic pyridine and methylpyridine have mostiy replaced the coal-tar products. 

Materials of these types have T s of some 290-300°C and some grades are claimed to be stable to about 400°C. Whilst resistant to hydrocarbons, halogenated hydrocarbons, ethers and acids the polymers are soluble in such materials as dimethylformamide, N-methylpyrrolidone and pyridine. Bases can cause stress cracking. These non-crystalline polymers are tough at temperatures as low as -46°C whilst at 260°C they have the strength shown by PTFE at room temperature. The polymers also exhibit excellent electrical insulation properties. 

The raw material has to be washed to remove impurities. Diluted sodium hydroxide allows the removal of phenols and benzonitrile, and diluted sulphuric acid reacts with pyridine bases. The resulting material is distilled to concentrate the unsaturated compounds (raw feedstock for coumarone-indene resin production), and separate and recover interesting non-polymerizable compounds (naphthalene, benzene, toluene, xylenes). Once the unsaturated compounds are distilled, they are treated with small amounts of sulphuric acid to improve their colour activated carbons or clays can be also used. The resulting material is subjected to polymerization. It is important to avoid long storage time of the feedstock because oxidation processes can easily occur, affecting the polymerization reaction and the colour of the coumarone-indene resins. 

Aromatic hydrocarbon resins. The polymerization procedure and variables in the reactions of the aromatic hydrocarbon resins are similar to those for the coumarone-indene resins. However, the Cg feedstreams used in the polymerization of the aromatic hydrocarbon resins do not contain significant amounts of phenols or pyridine bases, so they are submitted directly to fractional distillation. Distillation produced more byproducts than light coal-tar oils. The aromatic hydrocarbon resins obtained have softening points between liquid and 125°C and Gardner colour of 6 to 11. By changing distillation conditions, aromatic hydrocarbon resins with softening points between 65 and 170°C and Gardner colour of 5 to 10 can also be obtained. 

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 —... 

Oxidations usually proceed in the dark at or below room temperature in a variety of solvents ranging from aqueous bicarbonate to anhydrous benzene-pyridine. Base is quite commonly used to consume the hydrogen halide produced in the reaction, as this prevents the formation of high concentrations of bromine (or chlorine) by a secondary process. The reaction time varies from a few minutes to 24 hours or more depending on the nature of the reagent and the substrate. Thus one finds that NBS or NBA when used in aqueous acetone or dioxane are very mild, selective reagents. The rate of these oxidations is noticeably enhanced when Fbutyl alcohol is used as a solvent. In general, saturated, primary alcohols are inert and methanol is often used as a solvent. 

Pyridine base eliminations of a-bromo ketones cannot be recommended for general use because of the side reactions already discussed. The semi-carbazone-pyruvic acid method should be employed if strict absence of isomerization is required in the dehydrobromination of 2- or 4-bromo-3-ke-tones. This procedure is not applicable for the preparation of -3-ketones,... 

Ester eliminations are normally one of two types, base catalyzed or pyrolytic. The usual choice for base catalyzed j5-elimination is a sulfonate ester, generally the tosylate or mesylate. The traditional conditions for elimination are treatment with refluxing collidine or other pyridine base, and rearrangement may occur. Alternative conditions include treatment with variously prepared aluminas, amide-metal halide-carbonate combinations, and recently, the use of DMSO either alone or in the presence of potassium -butoxide. 

Contains Nitrogen.—First test the original solid ni liquid by heating in a hard-glass tube with soda-lime (p. 2), and notice if the smell is that of ammonia (ammonia salt, amide or cyanide), an amine (amine or amino-acid) or a pyridine base (alkaloid). 

Pyridine bases are well known as ligands in complexes of transition metals, and it might well be anticipated that the equilibrium constants for the formation of such complexes, which are likely to be closely related to the base strength, would follow the Hammett equation. Surprisingly, only very few quantitative studies of such equilibria seem to have been reported, and these only for very short series of compounds. Thus, Murmann and Basolo have reported the formation constants, in aqueous solution at 25°, of the silver(I) complexes... 

Chapman and co-workershave shown that, in the reactions of nitro-2-chloropyridines with piperidine, aryl amines, or pyridine bases, a 5-nitro group activates more than a 3-nitro group (cf. Table VII, p. 276). 

The rate of reaction of a series of nucleophiles with a single substrate is related to the basicity when the nucleophilic atom is the same and the nucleophiles are closely related in chemical type. Thus, although the rates parallel the basicities of anilines (Tables VII and VIII) as a class and of pyridine bases (Tables VII and VIII) as a class, the less basic anilines are much more reactive. This difference in reactivity is based on a lower energy of activation as is the reactivity sequence piperidine > ammonia > aniline. Further relationships among the nucleophiles found in this work are morpholine vs. piperidine (Table III) methoxide vs. 4-nitrophenoxide (Table II) and alkoxides vs. piperidine (Tables II, III, and VIII). Hydrogen bonding in the transition state and acid catalysis increase the rates of reaction of anilines. Reaction rates of the pyridine bases are decreased by steric hindrance between their alpha hydrogens and the substituents or... 

Reductive amination with pyridine bases 99UK61. 

Complexing extraction of pyridine bases from coal coking products with organic solvents 97KGS3. 

The solvent system N2O4/DMF has been employed for the preparation of inorganic esters, e.g., phosphates and sulfates [221] as well as organic esters. The latter products were obtained by reacting the polymer with acyl chlorides, or acid anhydrides in the presence of a pyridine base. The nitrite ester formed has been successfully trans-esterified by the reaction with RCOCl... 

Pyridine is added to neutralize small amounts of hydrogen iodide, which is often present in iodotrimethylsilane as a result of hydrolysis by contact with moisture. The amount of by-products, including cyclohexyl iodide, is reduced by the presence of pyridine. Hindered pyridine bases such as 2,6-di-terf-butyl-4-methylpyridine" have also been used for this purpose by the submitters. The pyridine bases do not appear to react with iodotrimethylsilane. 

Data, such as those in the tabulation for a group of related pyridine bases, provided convincing evidence (10). 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

EtNH2 + pt2NH + Et3N +CH3CN + pyridinic bases 10% 14% 39% (4.56)... 

Mixtures of EtjNH and EtjN and pyridinic bases can be obtained from the reaction of acetylene and EtNHj under similar conditions [235]. EthyUdeneimine was proposed as an intermediate in the formation of ethylamines and acetonitrile. 

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