Pyridinecarboxylic acids oxidation

Pyridine 210 is oxidized by 20% nitric acid at the acetyl group to 2-methyl-5-pyridinecarboxylic acid, while its ozonation gives cinchomeronic acid [pyridine-2,5-dicarboxylic acid (215)] (75DIS) which is decarboxylated (200°C, 2 h) to nicotinic acid 216 in 97% yield (75DIS). 

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. 

In a similar manner, 2,4,6-trisubstituted 3-pyridinecarboxylic acid esters have been prepared using a mixture of a, 3-ketoesters, propargylic alcohols, ammonium acetate and Mn02. The reaction proceeds by oxidation of the propargylic alcohol to the corresponding ketone, which reacts with the enamine being formed from the like loos lor and ammonium acetate. For this domino process, normal heating at 70 °C was used. 

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]. 

Ozonolysis of alkenylpyridines gives pyridinecarbaldehydes (61JOC4912) and the latter also result from oxidation of 2- and 4-methylpyridines with iodine and dimethyl sulfoxide (70JOC841) or with selenium dioxide, although this last method also gives pyridinecarboxylic acids (69MI20600, 69MI20602). 

Pyridinecarboxylic acids also result from the oxidation of alkylpyridines with potassium permanganate (55OS(3)740), nitric acid, and chromium trioxide in sulfuric acid (Scheme 60) (71S31). Alkylquinolines can be oxidized at the side chain with potassium dichromate and sulfuric acid. 

The chemistry of aryl groups attached to the 7r-deficient heterocycles is unexceptional and much as might be expected. Thus, electrophilic substitution of phenylpyridines occurs exclusively in the phenyl ring. 4-Phenylpyridine gives mononitration products in the ratio o m p, 20 33 47 (68JCS(B)862, 71JCS(B)712). The oxidation of phenylpyridines can lead to either a pyridinecarboxylic acid or benzoic acid. 

The vibrational spectra of [ZnL L ] (LH = 2-pyridinecarboxylic acid A-oxide V = H20 or D20) indicate coordination through the A-oxide oxygen and the carboxylate group-504 In contrast, the complexes with 3-pyridinecarboxylic acid A-oxide and pyridine-4-carboxylic acid A-oxide are polymeric multinuclear species.505 Crystal structures of [ZnL4(NCS)2] (L = 3-pyridine-A,A-diethylcarboxamide)506 and [ZnL2(H20)2(HC02)2] (L = 3-pyridinecarbox-amide)507 have been reported. 

Nicotinic acid has been prepared by the oxidation of nicotine with nitric acid.1 It has also been prepared by the action of potassium permanganate upon /3-picoline, nicotine, lutidine, /3-phenyl pyridine, and /3-dipyridyl2 and by the action of chromic acid upon nicotine and /3-phenyl pyridinecarboxylic acid.3... 

Anodic oxidation of alkylpyridines to pyridinecarboxylic acids is an old but viable synthetic procedure, usually giving the desired product in reasonable yield. In contrast to catalytic air oxidation, which works best for making... 

Stamicarbon217> claims the use of anion exchange membranes in divided cells for the electrochemical oxidation of alkylpyridines to the corresponding pyridinecarboxylic acids. Finally, Takeda 218) has used the principle of paired synthesis in a divided cell for the simultaneous generation of synthetic intermediates. 

Oxidation of pyridinecarboxylic acids.1 Reaction of a pyridinecarboxylic acid or the ester with 10% F2 in N2 results in oxidation to the corresponding 2-pyridone in 50-75% yield. An N-fluoropyridinium salt is probably an intermediate. 

The oxidative cleavage of carbon-carbon double bonds has been reviewed by StewartIn general, carboxylic acids are produced under acidic conditions. However, since many alkenes lack sufficient solubility in water, cosolvents such as pyridine, acetone or acetic acid have often been used to bring the oxidant and reductant into contact For example, a good yield of 2,6-diphenyl-4-pyridinecarboxylic acid was obtained from the reaction depicted in equation (29). Table 9 contains additional examples. 

C6H5BrN202 4-bromo-3-nitroaniline 53324-38-2 25.00 1.7656 2 6833 C6H5N03 3-pyridinecarboxylic acid 1-oxide 2398-81-41 53.33 1.3510 2... 

Chromic acid and potassium permanganate are more powerful oxidizing agents than nitric acid they usually convert all side chains into carboxyl groups. Like benzene homologs, alkylpyridines can also be oxidized, yielding pyridinecarboxylic acids, e.g., isonicotinic acid from 4-ethylpyridine ... 

Oxidation of coniine with chromic acid produces butyric acid (115, 124), while dehydrogenation of the alkaloid with silver acetate converts it to abase, conyrine (125), which is also obtained from coniine hydrochloride by distillation with zinc dust (126). Conyrine, CgHnN, is a colorless, fluorescent oil, b.p. 166-168°, which forms a chloroplatinate and an aurichloride it can be converted back to coniine by reduction with hydriodic acid, it behaves on methylation like a pyridine base, and further, it gives rise on oxidation to a-pyridinecarboxylic acid. Therefore, conyrine is a 2-propylpyridine (XCIV) while coniine is a 2-propylpiperidine (XCV) (126), in which the side chain is normal since conyrine is not identical with 2-isopropylpyridine (127). 

---