Pyridine source

MeCN, acetonitrile DMF, dimethylformamide Me2SO, dimethyl sulfoxide py, pyridine. Source Ref. 1. 

Nonanoic acid vinyl pyridine source a-Picoline vinyl resin modifier Dioctyl maleate vinylidene chloride mfg. 

UV spectrum of pyridine. (Source Silverstein RM, Bassier GC, Morrill TC, Spectroscopic Identification of Organic Compounds, John Wiley and Sons, New York 1974.)... 

PDLA = poly(DJj-lactide). PLLA = poly(L-lactide). PVP = poly(vinyl pyridine). Source Ad ted from Shenoy et aL 2005b. 

Pyridine Substrate Peroxide (Source) Aniline+ NOOR A a B 2-Amino- thiazole NOOR ... 

P-Picoline may serve as an important source of nicotinic acid [59-67-6] for dietary supplements. A variety of substituted pyridines may be prepared from acrolein (75—83). 

Many valuable chemicals can be recovered from the volatile fractions produced in coke ovens. Eor many years coal tar was the primary source for chemicals such as naphthalene [91-20-3] anthracene [120-12-7] and other aromatic and heterocycHc hydrocarbons. The routes to production of important coal-tar derivatives are shown in Eigure 1. Much of the production of these chemicals, especially tar bases such as the pyridines and picolines, is based on synthesis from petroleum feedstocks. Nevertheless, a number of important materials continue to be derived from coal tar. 

There are no natural sources of pyridine compounds that are either a single pyridine isomer or just one compound. For instance, coal tar contains a mixture of bases, mosdy aLkylpyridines, in low concentrations. Few commercial synthetic methods produce a single pyridine compound, either most produce a mixture of aLkylpyridines, usually with some pyridine (1). Those that produce mono- or disubstituted pyridines as principal components also usually make a mixture of isomeric compounds along with the desired material. 

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. 

Raw Material and Energy Aspects to Pyridine Manufacture. The majority of pyridine and pyridine derivatives are based on raw materials like aldehydes or ketones. These are petroleum-derived starting materials and their manufacture entails cracking and distillation of alkanes and alkenes, and oxidation of alkanes, alkenes, or alcohols. Ammonia is usually the source of the nitrogen atom in pyridine compounds. Gas-phase synthesis of pyridines requires high temperatures (350—550°C) and is therefore somewhat energy intensive. 

Pyridine carboxamide [98-92-0] (nicotinamide) (1) and 3-pyridine carboxylic acid [59-67-6] (nicotinic acid) (2) have a rich history and their early significance stems not from their importance as a vitamin but rather as products derived from the oxidation of nicotine. In 1867, Huber prepared nicotinic acid from the potassium dichromate oxidation of nicotine. Many years later, Engler prepared nicotinamide. Workers at the turn of the twentieth century isolated nicotinic acid from several natural sources. In 1894, Su2uki isolated nicotinic acid from rice bran, and in 1912 Funk isolated the same substance from yeast (1). 

About 50—80% of the trigonelline is decomposed during roasting. Trigonelline is a probable source for niacin [59-67-6] but also a source of some of the aromatic nitrogen compounds such as pyridines, pyrroles, and bicycHc compounds found in coffee aroma (16). Certain acids, such as acetic, formic. 

Sources of Raw Materials. Coal tar results from the pyrolysis of coal (qv) and is obtained chiefly as a by-product in the manufacture of coke for the steel industry (see Coal, carbonization). Products recovered from the fractional distillation of coal tar have been the traditional organic raw material for the dye industry. Among the most important are ben2ene (qv), toluene (qv), xylene naphthalene (qv), anthracene, acenaphthene, pyrene, pyridine (qv), carba2ole, phenol (qv), and cresol (see also Alkylphenols Anthraquinone Xylenes and ethylbenzenes). 

The other main source of various pyridopyridazines from pyridines are the [4 + 2] cycloaddition reactions, already mentioned (Section 2.15.8.3), between vinylpyridines and azodicarboxylic esters (79T2027, 79KGS639) or triazolidinediones e.g. 78KGS651). 2-Vinyl-pyridines gave reduced pyrido[3,2-c]pyridazines (370), 4-vinylpyridines gave [3,4-c] analogues, whilst 2-methyl-5-vinylpyridine furnishes a mixture of the [2,3-c] and [4,3-c] compounds. Yields are low, however, and these remain curiosities for practical synthetic purposes. 

The electronic environment of an a-substituent on pyridine (319) approaches that of a substituent on the corresponding imino compound (320) and is intermediate between those of substituents on benzene and substituents attached to carbonyl groups (321, 322) (cf. discussion in Chapter 2.02). Substituents attached to certain positions in azole rings show similar properties to those of a- and y-substituents on pyridine. However, the azoles also possess one heteroatom which behaves as an electron source and which tends to oppose the effect of other heteroatom(s). 

Heating or irradiating alkenes in the presence of sulfur gives relatively low yields of thiiranes. For example, a mixture of sulfur and norbornadiene in pyridine-DMF-NHa at 110 °C gave a 19% yield of the monoepisulfide of norbornadiene as compared with a 78% yield by the method of Scheme 120 (79JCS(Pi)228). Often 1,2,3-trithiolanes are formed instead of thiiranes. The sesquiterpene episulfides in the essential oil of hops were prepared conveniently by irradiation of the terpene and sulfur in cyclohexane (Scheme 135) (80JCS(Pl)3li). Phenyl, methyl or allyl isothiocyanate may be used as a source of sulfur atoms instead of elemental sulfur. 

Pyridine hydrobromide perbromide (Pyr HBr Br2) has been employed as a convenient, easily weighed source of bromine for small scale-reactions. The chlorine analog has also been used in this connection. 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

Figure 4-12. Stopped-flow study of the pyridine-catalyzed hydrolysis of acetic anhydride, showing the formation and decay of the acetylpyridinium ion intermediate. Initial concentrations were 0.087 M pyridine, 2.1 x im M acetic anhydride the pH was 5.5 ionic strength, 1.0 M temperature, 25 C. Five hundred data points tabsorbance at 280 nm) were measured in I s. The smooth curve is a ht to Eq. (3-27). Source Data of D. Khossravi and S.-F. Hsu, University of Wisconsin.

Riboflavin was first isolated from whey in 1879 by Blyth, and the structure was determined by Kuhn and coworkers in 1933. For the structure determination, this group isolated 30 mg of pure riboflavin from the whites of about 10,000 eggs. The discovery of the actions of riboflavin in biological systems arose from the work of Otto Warburg in Germany and Hugo Theorell in Sweden, both of whom identified yellow substances bound to a yeast enzyme involved in the oxidation of pyridine nucleotides. Theorell showed that riboflavin 5 -phosphate was the source of the yellow color in this old yellow enzyme. By 1938, Warburg had identified FAD, the second common form of riboflavin, as the coenzyme in D-amino acid oxidase, another yellow protein. Riboflavin deficiencies are not at all common. Humans require only about 2 mg per day, and the vitamin is prevalent in many foods. This vitamin... 

Modifications of this method, such as the use of the more stable diazonium trifluoroacetates and the decomposition of benzenedia-zonium zincichloride with zinc dust, have been used as sources of aryl radicals, although not in the arylation of heterocyclic compounds. Pyridine, quinoline, and thiophene can be phenylated by treatment with benzenediazonium chloride and aluminum trichloride. ... 

The quantitative phenylation of pyridine has been studied by two groups of workers. Dannley and Gregg showed that 2-, 3-, and 4-phenylpyridine are formed in relative amounts 58 28 14 in the phenylation of pyridine with dibenzoyl peroxide, as estimated by infrared spectrophotometry. Hey and his co-workers obtained the ratios shown in Table I for the phenylation of pyridine using four different sources of phenyl radicals. ... 

The reactivity of pyridine relative to that of benzene has been measured using the competitive technique developed by Ingold and his schoool for corresponding studies of electrophilic aromatic substitution. The validity of the method applied to free-radical reactions has been discussed. Three sources of the phenyl radical have been used the results obtained are set out in Table II. 

Pyridine has been phenylated with the following free-radical sources benzenediazonium chloride with aluminum trichloride the Gomberg reaction " phenylhydrazine and metal oxides A -nitroso-acetanilide dibenzoyl peroxide phenylazotriphenylmethane di-phenyliodonium hydroxide and electrolysis of benzoic acid. ° Although 2-phenylpyridine usually accounts for over 50% of the total phenylated product, each of the three phenyl derivatives can be obtained from the reaction by fractional recrystallization of the... 

Of the four possible 5-deoxy-pent-4-enofuranoses, the D-erythro-isomer was of interest as a potential source of derivatives of L-lyxofuranose. For this purpose, a vinyl ether having the D-en/ hro-configuration has been prepared from derivatives of D-ribose. Condensation of D-ribose with acetone in the presence of methanol, cupric sulfate and sulfuric acid at 30°C., as described by Levene and Stiller(30) afforded a sirupy product consisting mainly of methyl 2,3-O-isopropylidene-D-ribofuranose (40). Treatment of a pyridine solution of the sirup with tosyl chloride... 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

The rapid synthesis of heteroaromatic Hantzsch pyridines can be achieved by aromatization of the corresponding 1,4-DHP derivative under microwave-assisted conditions [51]. However, the domino synthesis of these derivatives has been reported in a domestic microwave oven [58,59] using bentonite clay and ammoniiun nitrate, the latter serving as both the source of ammonia and the oxidant, hi spite of some contradictory findings [51,58,59], this approach has been employed in the automated high-throughput parallel synthesis of pyridine libraries in a 96-well plate [59]. In each well, a mixture of an aldehyde, ethyl acetoacetate and a second 1,3-dicarbonyl compound was irradiated for 5 min in the presence of bentonite/ammonium nitrate. For some reactions, depending upon the specific 1,3-dicarbonyl compound used. 

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