Picolinic acid hydrolysis

Picolinic acid has been generally prepared by the permanganate oxidation of a-picoline and isolated through the copper salt.1-2 3-4 5 In one instance,6 it was isolated directly as in the present procedure. It has recently been secured by the hydrolysis of w-trichloropicoline.7... 

N - Benzyl- N -p icolinoylpiperazine (EGYT-475, 4.88), a compound with potential antidepressant activity, underwent similar hydrolysis. After intravenous administration, picolinic acid (4.89) was one of its major urinary metabolites in rats the other product, A-benzylpiperazine (4.90) was also detected, but at much lower levels, since it was further transformed by A-de-benzylation [55], Since the products of direct hydrolysis of these cyclic tertiary amides (i.e., the corresponding secondary amines) were found at substantial levels, it appears that oxidative A-monodealkylation is not an essential step for hydrolysis in these compounds, in contrast to the findings for A,A-diethylbenzamide. This contradicts the hypothesis [52] (see above) that the steric bulk of the tertiary amide group impedes direct hydrolysis. Here, although the degree of steric bulk is at least comparable, direct hydrolysis clearly takes place. 

Fischer attempted the bromination of apoharmine in dilute sulfuric acid at room temperature and obtained a tetrabromo compound, which he did not characterize further. Treatment of l-benzoyl-2,5-dimethyl-4-azaindole with bromine in acetic acid at 25° gave the 3-bromo-l-benzoyl compound in 60% yield. On oxidation with permanganate it gave the same picolinic acid obtained before. Alkaline hydrolysis gave 3-bromo-2,5-dimethyl-4-azaindole (90%), also obtained by direct bromination of 2,5-dimethyl-4-azaindole in 60 % yield. 

Scheme 20.4 Ammoxidation of 3-picoline and hydrolysis of cyanopyridine to niacinamide (nicotinamide) and niacin (nicotinic acid). Adapted from [106].

In a few instances, not only methyl ketones but other alkyl ketones are degraded to shorter carboxylic acids resulting from halogenation of the methylene group adjacent to the carbonyl and subsequent hydrolysis [103, 160,1172]. The reaction between propiophenone and sodium hypobromite at 22-25 °C gives a 96% yield of benzoic acid [303]. Under similar conditions, 5-butyl-2-butyrylpyridine is converted into 5-butyl-a-picolinic acid in 79% yield [160]. Methyl 3-(a-pyridyl)propyl ketone yields not only the... 

The effects of divalent ions (Cu , Ni", Co" and Zn") on the hydrolysis of phthalate, succinate and acetate esters of 2-(hydroxymethyl)picolinic acid (54) have been studied to establish if strong bonding of the metal ion to the leaving group oxygen might enhance intramolecular carboxylate attack. With these esters, saturation conditions are observed at low metal ion concentrations... 

Recently, Ques ) reported that when o-aminophenol was added to pyrocatechase from Pseudomonas arvilla, ring cleavage occurred between C-l and C-6 yielding an intermediate which cyclized rapidly to picolinic acid. There was some hydrolysis of the intermediate but no cleavage between C-l and C-2 was observed. 

Fife, T.H., and T.J, Przystas. 1985. Divalent metal ion catalysis in the hydrolysis of esters of picolinic acid. Metal ion promoted hydroxide ion and water catalyzed reactions. J. Am. Chem. Soc. 107 1041-1047. 

The hydrolysis of coordinated nitriles has recently attracted some attention. A very facile hydrolysis of nitriles to the corresponding amides at platinum(IV) centers has been described.The complex [Cu(H2NCOCH2CONHNH2)Cl] is formed from the reaction NCCH2CONHNH2 the copper(II) both promotes the hydrolysis and is reduced to copper(I). The hydrolysis of 2-cyanopyridine to 2-pyridinecarboxamide is accelerated several hundred times by the copper(II) complexes of the ligands (21) and (22). In the case of the (22) some picolinic acid was formed, resulting from the intramolecular attack of alkoxide to yield an intermediate iminoester. ... 

A somewhat different approach coupled acid chloride 2.154 with 2.155 to give 2.1S6J Treatment with 7-picoline led to the rearranged product 2.157 in 84% overall yield from 2.154. Acid hydrolysis gave 8-oxo-9-aminononanoic acid, 2.158. 2.5.B. Pyrazoline Derivatives... 

Reaction of the m-nitrophenyl ester of pyridine-2,5-dicarboxylic acid with cyclodextrin (see Section 3) gives a picolinate ester [52] of a cyclodextrin secondary hydroxyl group (Breslow, 1971 Breslow and Overman, 1970) which will bind metal ions or a metal ion-pyridine carboxaldoxime complex. Such a complex will catalyse hydrolysis of p-nitrophenyl acetate bound within the cyclodextrin cavity leading to a rate constant approximately 2000-fold greater at... 

To prove their hypothesis, Bamford and Block (51) applied the diagnostic test previously designed by Gold and Jefferson (58) in their studies of hydrolysis of carboxylic anhydrides catalysed by tertiary bases. The technique employed involves the use of a series of tertiary bases having different relative abilities to assodate with Lewis acids and to act as Bronsted bases. Pyridine, a-picoline and 2,6-lutidine form... 

Nicotinic acid and nicotinamide, members of the vitamin B group and used as additives for flour and bread enrichment, and as animal feed additive among other applications, are made to the extent of 24 million pounds (nearly 11 million kilograms) per year throughout the world. Nicotinic acid (pyridine-3-caiboxylic acid), also called niacin, has many uses. See also Niacin. Nicotinic acid is made by the oxidation of 3-picolme or 2-mcthyl-5-cthylpyridine (the isocinchomcnc acid produced is partially deearboxylated). Alternatively, quinoline (the intermediate quinolinic acid) is partially deearboxylated with sulfuric add in the presence of selenium dioxide at about 300° C or with nitric acid, or by electrochemical oxidation. Nicotinic acid also can be made from 3-picoline by catalytic ammoxidation to 3-cyanopyridine, followed by hydrolysis. 

Condensation of y-picoline with mesoxalic ester yielded 4-(j8,j8-diethoxycarbonylvinyl)pyridine (35). The unsaturated ester (35) was hydrogenated with platinum catalyst to form 36 which was treated with bromine. 4-(j8-Bromo-j8,j8-diethoxycarbonylethyl)-piperidine (37) was obtained and was cyclized with pyridine to 2,2-die th 0 xycarbony 1 quinuclidine (38). Hydrolysis of 38 and partial decarboxylation gave quinuclidine-2-carboxylic acid (39). 

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