6- Methylpyridine-2-carboxylic acid

The nature of the base, CmHijN, varies. When produced from pure Mupinine, m.p. 68-9°, it furnishes on oxidation only 3-methylpyridine-2-carboxylic acid (XV) and pyridine-2 3-dicarboxylic acid. If, however, lupinine, m.p. 63-3°, is used, the resulting pyridine base on oxidation furnishes in addition 2-n-butylpyridine-6-carboxylic acid (XVI) and 6-methylpyridine-2-carboxylic acid (XVII). The conclusion is drawn that lupinine, m.p. 63-3°, is a mixture of 1-lupinine (XI) with aZlolupinine (XII), each of these components furnishing its own lupinane (XIII and XIV), and that these two lupinanes contribute to the final degradation product, the tertiary pyridine base, CioHuN, the two isomerides 2-w-Ijutyl-3-inethylpyridine (XVIII) and 2-w-butyl-6-raethylpyridine (XIX) respectively. These interrelationships are shown by the following scheme —... 

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). 

Radical chlorination of 2,6-lutidine with thionyl chloride at 120° gives 2,6-di-(trichloromethyl) pyridine, and 2-methylpyridine-carboxylic acids behave similarly256,... 

Heating 6-[(2-carboxylphenyl)amino]-5-cyano-2-methylpyridine-3-carboxylate in refluxing POCI3 afforded 6-cyano-8-ethoxycarbonyl-9-methyl-ll//-pyrido[2,T3]quinazolin-ll-one, but in PPA at 135-145°C 2-methyl-3-ethoxycarbonyl-4-methyl-5-oxo-5,10-dihydrobenzo(3)-l,8-napthyridine-9-carboxylic acid formed <2004CHE510>. 

Ethyl pyridine-2-acetate and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with w-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

The reaction of 6-methylpyridine-3-carboxylic acid methyl ester with N,0-dimethylhydroxylamine and isopropyl-magnesium chloride in toluene gives the N-methoxyamide derivative (x), which is reduced with diisobutyl aluminium hydride (DIBAL) to afford 6-methylpyridine-3-carbaldehyde (xi). The reaction of the aldehyde (xi) with a phosphite provides the diphenyl phosphonate derivative, which is condensed with 4-(methylsulfonyl)benzaldehyde in the presence of potassium fe/f-butoxide in HF to yield the enimine (xii). Finally, this compound is hydrolyzed with HCI to yield the ketosulfone (ix). 

Alternatively the oxidation of 4 -(methylsulfonyl) acetophenone with S8 and morpholine produces the 2-(4-(methylsulfonyl)phenyl)acetic acid ethyl ester (xiv), which is condensed with 2-methylpyridine-3-carboxylic acid methyl ester by means of terf-butyl magnesium chloride in hot tetrahydrofurane to give the ketosulfone (ix). 

Alkyl derivatives of heterocyclic compounds may be oxidized to carboxylic acids, for example, methylpyridines and methylpyridine N-oxides by superoxide ions, generated electrochemically in DMF.57... 

Mendel44 found that reaction of 2-aminopyridine-3-carboxylic acid with ethyl acetoacetate or ethyl benzoylacetate gave rise to a decarboxylated product (36 R1 = Me, Ph R = R2 = H), whereas with ethyl 4,4,4-tri-fluoroacetoacetate, the product was ethyl 2-aminopyridine-3-carboxylate. Yale51 obtained 3-benzoyl-2-hydroxy-4-oxo-4ff-pyrido[ 1,2-a] pyrimidine in 4- 5%, yield from 2-amino-3-methylpyridine and ethyl benzoylacetate in diethylbenzene. 

Okamoto et a/.156 cyclized the dinitriles (86 R = CN, R2 = H) by heating in 15° hydrochloric acid to obtain pyrido[l,2-a]pyrimidine-3-carboxylic acids (89 R2 = H). 2-Aminopyridinium chloride and ethoxymethylene-malononitrile at 110CC yielded 3-cyano-4-imino-4H-pyrido[l,2-a]pyrimi-dine (87 R1 = R2 = H, X = NH) and compound 91. Under similar conditions, 2-amino-3-methylpyridine gave a noncyclized product of type 91. 

Picolinic acid (pyridine-2-carboxylic acid). Equip a 3-litre three-necked flask with a thermometer, sealed stirrer unit and a reflux condenser (Liebig pattern with a wide inner tube). Place a solution of lOOg (106ml, 1.08mol) of 2-methylpyridine in 1 litre of water in the flask and heat to 70 °C on a water bath. Add 450 g (2.84 mol) of potassium permanganate in 10 equal portions through the condenser over a period of 3-4 hours maintain the temperature at 70 °C for the first five additions and at 85-90 °C for the last five. Make each... 

The structure and numbering system for pyridine are given in Section 11.21, where we are also told that pyridine is aromatic. Oxidation of 3-methylpyridine is analogous to oxidation of toluene. The methyl side chain is oxidized to a carboxylic acid. 

C7H7N03 2-hydroxy-6-methylpyridine-3-carboxylic acid 38116-61-9 514.86 45 314 2 10776 C7H8FN 4-fluoro-N-methylaniline 459-59-6 408.65 35.181 2... 

In contrast, reductions of V-methylpyridine 2- and 3-carboxylic acids in acidic solution led only to the corresponding alcohols [14], although the difference may have been that reductions of the latter were performed until all carboxylate was consumed, whereas in the earlier work electrolysis was stopped after 2 F/mol was passed. An extensive evaluation of V-methylpyridine 3-carboxylic acid by polarography and cyclic voltammetry over a wide pH range gave evidence for dimer formation in both acidic and basic solution, although no product isolation was attempted [15]. 

---