Hydrogenation pyridinecarboxylic acids

Hydrogenation of 3-pyridinecarboxylic acids is apt to be accompanied by extensive decarboxylation (2S), but this unwanted reaction can be prevented by carrying out the reaction in the presence of one equivalent of base (33,79). Ruthenium (33), rhodium (29), platinum oxide (2S,59), and palladium (30) have all proved effective catalysts for reduction of pyridinecarboxylic acids to the saturated acid. 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

The bis(picolinate)iron(II) complex [Fe (PA)2 PAH = picolinic acid, 2-pyridinecarboxylic acid] in combination with hydrogen peroxide (HOOH) is an effective Fenton reagent for organic substrates, and has reactivities and product profiles that are closely similar to those for traditional aqueous Fenton reagents. This system reacts with hydrocarbon substrates (c-CeHu) via an intermediate that results from the nucleophihc addition by HOOH to the electrophilic Fe (PA)2 center (equation 78). ... 

The hydrogenation of 2- and 4-pyridinecarboxylic acids proceeded best in water over a platinum catalyst at room temperature and 3-4 atmospheres of hydrogen. Nicotinic acid (3-pyridinecarboxylic acid) was, however, decarboxylated under these conditions. 25 This compound, as well as the pyridine alkanoic acids (except 2-pyridine acetic acid which is easily decarboxylated), was hydrogenated at room temperature and 3-4 atmospheres of hydrogen over a rhodium catalyst in water to which had been added a slight excess of ammonium hydroxide. Product isolation merely involved the removal... 

Freifelder found that pyridinecarboxylic acids can be hydrogenated smoothly over Rh-AljOa in ammonia solution. A particularly significant example is the hydrogenation of nicotinic acid to nipecotic acid, since this had not previously been accomplished without decarboxylation. 

Picolinoxylidide is prepared by the condensation of picolinic acid (2-pyridinecarboxylic acid) with 2,6-xylidine which on methylation with dimethyl sulphate in xylene yields the corresponding N-methyl derivative. This when subjected to platinum-catalysed hydrogenation in active aeetie aeid followed by alkalinization yields mepivacaine base, which is then dissolved in an inert solvent and made to react with an equimolar amount of hydrochloric acid. 

Intermolecular hydrogen bonding has been observed by infrared spectroscopy for nicotinic and isonicotinic acid, while the expected intramolecular phenomenon was observed with picolinic acid. Spectral abnormalities of the carboxylate ion absorption at 1640 cm" and 1380 cm" have been recorded. The infrared spectra of isomeric pyridinecarboxylic acid-1-oxides have been reported and Hammett a values determined for the 4- (o = 0.2S) and 3- (a = 1.18) positions. ... 

A -Oxides of pyridinecarboxylic acids are prepared by oxidation of their potassium salts in hydrogen peroxide/acetic acid. (See also Chapter IV.) The A-oxides, particularly those derived from isocinchomeronic acid, are reputed to inhibit the decomposition of peracids. ... 

A reaction deals with the preparation of 4-halogenated pyridinecarboxylic acids (X-240) from 4-nitronicotinic acid-1-oxide (X-239) by explosive interaction with phosphorous trichloride or tribromide The requisite formation of nitrosyl chloride is not recorded. The 4-iodoacid (X-240, X = I) was prepared from the chloro-acid with hydrogen iodide. The authors also report... 

A dinuclear complex with bridging 4,4 -biphenylene and two 3-pyridinecarboxylic acid ligands bonded to each of the Pt atoms forms macrocycle 344 by strong intermolecular hydrogen bonding between the carboxylic acids a linear polymer is also obtained. 

Amphoteric property a-amino acid 1.0, aminobenzoic acid 0.5, pyridinecarboxylic acid 0.5 Dummy variable for the presence of p-lactam Summation of numbers of carbon and halogen atoms weighted by C, 1.0 F", 0.5 Cl, I.O Br, 1.5 and 1, 2.0 Dummy variable for the presence of intramolecular hydrogen bonds as ortho-OH and —CO—R, —OH and NH,... 

Freifelder, M. Hydrogenation of pyridinecarboxylic acids with platinum catalyst. J. Org. Chem. 1962,27, 4046. 

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