Pyrazine carboxylic acid

Methyl pyrazine-2-carboxylic acid is refluxed with thionyl chloride in anhydrous benzene for approximately 12 hours. Benzene and thionyl chloride excess is removed by distillation. Then some anhydrous dioxane is added and this acid chloride solution is allowed to drop into p-(/3-aminoethyl)-benzenesulfonamide suspension in dioxane and anhydrous pyridine. The resulting mixture is then refluxed for 3 hours. Dioxane is removed by distillation and then the residue is washed with water and acetic acid. The raw acylated sulfonamide is then filtered and crystallized from 95% ethanol, thus obtaining a product of MP 200 to 203 C. 

Fluorobenzene to fluorodihydrocatechol and fluorocatechol Conversion of 2,5-dimethyl pyrazine to 5-metyl pyrazine-2-carboxylic acid, conversion of 5-ethyl-2-methyl pyridine to... 

It has been known that alternating LB films consisting of two different amphiphiles have noncentrosymmetric structures, and therefore, are expected to provide piezoelectric, pyroelectric and nonlinear optical properties. Therefore, we prepared alternating LB films consisting of 5-(p-dodecyloxyphenyl)pyrazine-2-carboxylic acid (DOPC)... 

A systematic study to identify solid oxide catalysts for the oxidation of methane to methanol resulted in the development of a Ga203—M0O3 mixed metal oxide catalyst showing an increased methanol yield compared with the homogeneous gas-phase reaction.1080,1081 Fe-ZSM-5 after proper activation (pretreatment under vacuum at 800-900°C and activation with N20 at 250°C) shows high activity in the formation of methanol at 20°C.1082 Density functional theory studies were conducted for the reaction pathway of the methane to methanol conversion by first-row transition-metal monoxide cations (MO+).1083 These are key to the mechanistic aspects in methane hydroxylation, and CuO+ was found to be a likely excellent mediator for the reaction. A mixture of vanadate ions and pyrazine-2-carboxylic acid efficiently catalyzes the oxidation of methane with 02 and H202 to give methyl hydroperoxide and, as consecutive products, methanol and formaldehyde.1084 1085... 

Hydrogen peroxide can be replaced by molecular oxygen in vanadium-catalyzed hydroxylations of arenes, as first reported by Mukaiyama (Eq. 3) [24]. Improved versions were later described by Battistel (VCl3/ascorbate) [25] and Shul pin ((n-Bu)4NV03/pyrazine-2-carboxylic acid/ascorbic acid) [26], It is noteworthy that a molecular oxygen/sacrificial reductant (crotonaldehyde, zinc, or ascorbate) combination was used (cf. Udenfriend s reagent above) and that the mechanism is most likely to involve hydroxyl radicals. 

The pyrazinecarboxylic acids have properties similar to the pyridinecarboxylic acids and aromatic carboxylic acids in general. The pKa of pyrazine-2-carboxylic acid is 2.92 it is thus considerably stronger than pyridine-2-carboxylic acid (pff0 5.52), and comparable in acidic strength to pyridazine-3-carboxylic acid (pKa 3.0). The pKa values of pyrazine-2,3-dicarboxylic acid are 0.9 and 3.57.231 Pyrazinecarboxylic acids form colored salts with Fe11 ions and they are readily esterified and decarboxylated. 

The amides of pyrazine-2-carboxylic acids and -2,3-dicarboxylic acids undergo the Hofmann reaction. In the case of the conversion of pyrazinamide to aminopyrazine (Scheme 20), the intermediate sodium carbamate can be isolated.219 Pyrazinamides react with phosphoryl chloride to give the corresponding cyanopyra-... 

Thin-layer chromatography indicates that prolonged reaction of pyrazine 1,4-dioxide with acetic anhydride gives the mono-iV-oxide, together with other unidentified products.406 Pyrazine mono-A-oxide is also formed on reaction of pyrazine-2-carboxylic acid 4-oxide with acetic anhydride.408... 

Quantification. Gas Chromatography-Mass Spectrometry. In serum or urine pyrazinamide, pyrazine-2-carboxylic acid and 5-hydroxypyrazine-2-carboxylic acid, sensitivity 10 ng/ml for pyrazinamide—J. Koboz et al., J. Chromat., 1978,147, 337-347. 

Disposition in the Body. Well absorbed after oral administration. Metabolised by hydrolysis to pyrazine-2-carboxylic acid and subsequent hydroxylation to 5-hydroxypyrazine-2-carboxylic acid. In 24 hours, about 30 to 40% of a dose is excreted in the urine as pyrazine-2-carboxylic acid and less than 4% as unchanged drug the 5-hydroxy metabolite is also excreted in the urine. 

After an oral dose of 3 g to one subject, a peak serum concentration of 134 pg/ml was attained in 1 hour the serum concentration of pyrazine-2-carboxylic acid was 20 to 30 pg/ml after the first hour and the concentration of 5-hydroxypyrazine-2-carboxylic acid ranged between 3 and 8 M-g/ml over a period of 12 hours (J. Roboz et al., ibid.). 

The pronounced electron-withdrawing nature of the 1,2,5-thia-diazole ring is evidenced by the fact that its carboxylic acid derivatives are highly acidic. The titration curve of the dicarboxylic acid exhibits two breaks with and Kai, equal to 1.59 and 4.14, respectively. The monocarboxylic acid is also strongly acidic and has a piTa of 2.47, comparable to that of ornitrobenzoic acid 2.18) and pyrazine-2-carboxylic acid (pifa 2.80). In general the piTa values for the thiadiazole carboxylic acids are in fair agreement with the pica s of the corresponding p3U azine acids (see Table II). 

MTO/H2O2 also catalyzes the insertion of oxygen into a variety of activated and nonactivated C-H bonds. Alcohols or ketones are formed as shown in eq. (9). In the case of tertiary substrates alcohols are obtained as products. Suitable substrates proved that the reaction is stereospecific with retention of the configuration [2, 3]. The reaction can be accelerated by the addition of pyrazine-2-carboxylic acid, which also increases the total yield [3]. 

Oxalic acid x 2/Bipyridine x 2/ Phenanthroline x 2/Picolinic acid, Bipyridine/Picolinic acid x 2/ Picolinic acid, Phenanthroline/ Pyrazine-2-carboxylic acid x 2 2,2 21 147-151... 

Hydroxypyrazine-2-carboxylic acid (Fig. 19-35) is a versatile building block in the synthesis of new antituberculous agents, e.g. 5-chloro-pyrazine-2-carboxylic acid esters. The regioselective hydroxylation of pyrazine-2-carboxylic acid is catalyzed by a hydroxylase (E2, E. C. 1.5.1.13). This second enzyme is also in the applied suspended whole cells from Agrobacterium sp. The biomass is separated by ultrafiltration (cutoff 10 kDa) after the biotransformation. 5-Hydroxypyrazine-2-carboxylic acid is precipitated from the permeate by acidification with sulfuric acid to pH 2.5. 

In contrast to the biotransformation, the chemical synthesis of 5-substituted pyrazine-2-carboxylic acid leads to a mixture of 5- and 6-substituted pyrazine-carboxylic acids and requires multiple steps. 

The thermal decarboxylation of several 3,4-dihydro-3-oxopyrido[2.3-b]pyrazine-2-carboxylic acids 8 is known.18 23... 

Dihydro-3-oxopyrido[2,3-A>]pyrazine-2-carboxylic acid (8a 1.9 g, 10 mmol) was heated under N2 at 250 C until effervescence ceased (2-3 min), and the residue was sublimed at 230 cC/2 Torr. Crystallization of the sublimate (0.76 g) from boiling H,0 (30 mL) gave pale-yellow needles yield 0.56 g (38%) mp 239 240 C. 

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