0-Methylpicolinic acid

The formation of hydrated cobalt(n) complexes of pyridine carboxylic acids and the subsequent thermal decomposition to lower hydrates has been documented.82,83 Cobalt(n) halides react with 6-methylpicolinic acid (6-mpaH), picolinic acid (paH), nicotinic acid (naH), and pyridine-2,6-dicarboxylic acid (2,6-py) to form Co(6-mpa) (6-mpaH)X (X = Cl, Br, or NCS), Co(naH)nX2 (n = 2, X = Cl, Br n = 3, X = NCS), and Co(pa)(paH)X, EtOH (X = Cl, Br, or NCS) which are all probably octahedral.83 6-Methylpicolinic acid also formed Co(6-mpaH)4X2,2HX (X = Cl or Br) which were formulated [(6-mpaH)2H]2[CoX4], since the electronic spectra show absorptions characteristic of tetrahalogenocobaltate(n) ions.83... 

The use of picolinic and 6-methylpicolinic acids in a Mitsunobu reaction has been advocated because the resultant esters are readily cleaved by copper(II) (Scheme 22.6). The advantage is that ester cleavage occurs under neutral conditions, which minimizes the risk of elimination even with base-sensitive systems.9... 

Azaindoles are more stable to air oxidation than indoles, are stable to mild reagents like silver oxide and selenium dioxide, but are readily attacked by permanganate. In the structure proof of 7-aza-indole, Kruber oxidized the 1-benzenesulfonyl derivative with potassium permanganate in acetone solution to obtain 2-(benzene-sulfonyl)aminonicotinic acid. The 1-acetyl and 1-benzoyl derivatives gave inconsistent results, which Kruber attributed to their ease of hydrolysis. l-Benzoyl-2,5-dimethyl-4-azaindole and its 3-substituted derivatives give 3-benzamido-6-methylpicolinic acid with permanganate oxidation. ... 

Good evidence for nitration at the 3-position was provided by Clayton and Kenyon. l-Benzoyl-2,5-dimethyl-4-azaindole was nitrated in 60 % yield, and followed with potassium permanganate oxidation in aqueous acetone gave 3-benzamido-6-methylpicolinic acid. Alkaline hydrolysis of the nitration product gave 3-nitro-2,5-dimethyl-4-azaindole (85% yield), which was also obtained by direct nitration of 2,5-dimethyl-4-azaindole in low yield. In addition, reduction gave the 3-amino compound, which was identical to that obtained by catalytic reduction of the product formed by coupling the azaindole with benzenediazonium chloride. 

A solution of 10 g 6-methylpicolinic acid (73 mmol) and 10.0 g n-heptaldehyde (87 mmol) in 60 mL / -cymene was refluxed for 25 h, after which carbon dioxide evolution ceased (90% of theoretical). The cooled solution was extracted with 2 M HCl (2 x 50 mL), the combined acid extracts were alkalinized and extracted with ether, and the ether extract was dried and distilled to give 24% l-(6 -methyl-2 -pyridyl)-l-heptanol, b.p. 122-124°C (2 mmHg). 

A stirred mixture of 6-methylpicolinic acid N-oxide and acetic anhydride warmed 18 hrs. at 60-65°, then heated 5 hrs. at 90-100° with 6 N HCl 6-methyl-2-pyridone. Y 84%. Y. Murakami and J. Sunamoto, Bull. Chem. Soc. Japan 42, 3350 (1969). 

An interesting variant on this scheme to form alkylpyridinecarboxylic acids by nitric acid oxidation has been described by Czech workers starting with 2,4- or 2,6-lutidine these bases are condensed with formaldehyde to yield unsymmetrical j3-(hydroxyethyl)methylpyridines. Nitric acid oxidation now occurs preferentially at the hydroxylated side chain yielding the corresponding methylpicolinic acids. Thus, 2,4-lutidine (X-60) is converted to a separable mixture of 4-(/3-hydroxyethyl)-2-methylpyridine (X-61), 4-[tris(hydroxy-methyl)methyl]-2-methylpyridine (X-62), and 2-( -hydtoxymethyl)4-methyl-pyridine (X-63). Nitric acid oxidation yields 2-methylpyridine-4-carboxylic acid (X-64) from X-61 and X-62, and 4-methylpyridine-2-carboxylic acid (X-65) from X-63. A similar reaction sequence carried out with 2,6-lutidine (X-66) affords ultimately 6-methylpyridine-2-carboxylic acid (X-67). 

Preparation of substituted pyridinecarboxyUc acid 1-oxides by means of H-abstraction is reported by Abramovitch and others. Thus, treatment of the lithium derivative of 4-chloropyridine-l-oxide or 4-chloro-3-methylpyridine-l-oxide with CO2 gave the corresponding 4-chloro- and 4-chloro-5-methylpicolinic acid-1-oxides. Under the same conditions, 4-picoline-l-oxide gave the 2,6-di-carboxylic acid. 

The product of rearrangement of 6-methylpicolinic acid-1-oxide (XII-431) and acetic anhydride, previously characterized as 2-acetoxymethylpyridine, has been shown to be 6-acetoxy-2-picoline (XII-432). The observation that 2-picoline-l-oxide (XII426), the decarboxylation product of XII431, gives mainly 2-acetoxymethylpyridine indicates that decarboxylation, N-0 cleavage, and acetoxylation of XI1431 at C-2 are concerted. " ... 

Acetoxy-2-picoline, 716 from 6-methylpicolinic acid-1-oxide, 716... 

These compounds readily undergo the desired addition-cyclization with carbon disulphide directly in ethanol at room temperature, no condensing agent being required. A-Methylpicolinic acid amidrazone produces the expected 2-(2-pyridyl)-4-methyl-l,3,4-thiadiazoline-5-thione... 

Kiss E, Garribba E, Micera G, Kiss T, Sakiuai H. 2000. Ternary complex formation between VO(IV)-picolinic acid or VO(IV)-6-methylpicolinic acid and small blood serum bioligands. J Inorg Biochem 78 97-108. 

The Hammick reaction (p. 163) provides some evidence for this view. Kinetic data for the decarboxylation of picolinic and methylpicolinic acids are given in Table 6,3. Methyl groups have the expected effect, but the results and those for reaction in a range of solvents do not permit choice between the zwitterion (10) and the form (11) as the entity undergoing decarboxylation" . 

Table 14. Stability constants for normal and protonated complexes of Pu(VI) with picolinic, methylpicolinic and nicotinic acids (7=0.01, r=298K) [43],...

Picolinic Add Metabolism. Picolinic acid is converted to its glycine conjugate when administered to mammals. - Birds use ornithine in place of glycine. The mechanism of the condensation is not known, but presumably it resembles the formation of hippuric acid, in which a CoA derivative of the carboxyl group is the acylating agent. A-Methylpicolinic... 

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