Pyridin-2-ones carboxylation

An example of this type of cyclization is the formation of 3-nitro-l,5-naph-thyridin-4(lH)-one (4) from 3-(/3-nitroethylideneamino)pyridine 2-carboxylic acid (3) by heating in acetic anhydride [56JCS(I)212]. No yields are given. 

Treatment of 3-phenylperhydro[l, 3]oxazolo[3,2-a]pyridine-5-carboxylates 303 and 304 with BF3 Et20 in THE, followed by reduction with NaBD4 afforded 6-deutero-4-phenylperhydropyrido[2,1 -c][l, 4]oxazin-1 -ones 220 and 222 (97JA6446). 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

The demetalating abilities of buffer species depend on both their structures and their acidities. Thus, while pyridine-2-carboxylic (picolinic) acid catalyzes the demetalation even of the rather inert lm, its 3- and 4-isomers (nicotinic and isonicotinic acids) are inactive. The difference is rationalized to result from the ability that only coordinated picolinic acid has to deliver a proton to an amidato nitrogen in an intramolecular manner. The reaction order in picolinic acid equals one for la and two for lm. For lm, inactive pyridine and nicotinic acid speed up the demetalation in the presence of picolinic acid (Fig. 8). 

Nicotinamide (8.45) and nicotinic acid (8.46, niacin)—which have also been referred to as vitamin B3 or B5—are simple pyridine-3-carboxylic acid derivatives occurring in liver, yeast, and meat. In the form of nicotinamide-adenine dinucleotide (NAD" ) or its phosphorylated form (NADP+), nicotinamide is the most important electron carrier in intermediary metabolism. Unlike FAD, it adds a hydride ion (i.e., one pair of electrons and one hydrogen) only. 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

Two derivatives of nicotinamide (pyridine-3-carboxylic amide), one of the B2 vitamins, nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ), serve as redox coenzymes. Of the three heterocyclic ring systems found in these coenzymes, i.e. those of purine, ribose and pyridine, it is the pyridine portion that is reactive in redox reactions. Biologically, two oxidation states are important the oxidized form, NAD(P)+, and the 1,4-dihydro isomer of the two-electron reduced form, NAD(P)H (Scheme 1). Nicotinamide coenzymes interconvert between these two oxidation states in... 

Picolinic acid (pyridine 2-carboxylic acid) is the prototype for this type of ligand. Pyridine itself does not react favorably with vanadate, nor do the 3 and 4 pyridine carboxylates. At first sight, one would expect that 2-hydroxypyridine would react favorably with vanadate, but this is not true. There are two likely explanations for this. First, the 2-hydroxypyridine exists predominantly as the keto tautomer, so the effective concentration of the hydroxylate is low. The keto form of the ligand can be expected to be much less reactive than the hydroxyl form. Second, the formation... 

A mixture of 2 ml of morpholine, 3 ml of dimethylformamide and 10 ml of water was heated to 60°C and under stirring the equal molecular quantity of 6-isopropyl-4-oxo-4H-l-benzopyran-3-carbonitrile was added for 5 minutes. The mixture was heated at that temperature for one hour and the resultant precipitate was filtered, rained with water recrystallized from acetic acid and washed with chloroform. By the above procedure was obtained 2-amino-6-isopropyl-4-oxo-4H-l-benzopyran-3-carboxaldehyde melting at 206°-208°C. A mixture of 4 ml ethyl cyanoacetate, 50 ml of ethanol, 5 ml of piperidine and the equal molecular quantity of 2-amino-6-isopropyl-4-oxo-4H-l-benzopyran-3-carboxaldehyde was refluxed for 30 minutes and, after cooling, the crystalline precipitate was filtered and washed with chloroform. By above procedure was obtained ethyl-2-amino-7-isopropyl-l-azaxanthone-3-carboxylate, melting after recrystallization from ethanol at 243°-244°C. A mixture of 10 ml of acetic acid and 10 ml of 55% sulfuric acid the equal molecular quantity and 2-ethyl-amino-7-isopropyl-l-azaxanthone-3-carboxylate was stirred at 130°C for 4 hours and, after water was added, the precipitate was collected by filtration and recrystalllized from dimethylformamide to give the 2-amino-7-(l-methylethyl)-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carboxylic acid, melting point 300°C. 

Amino-l,5-naphthyridin-4 (1 //)-one (21) underwent diazotization to 3-diazo-nio-l,5-naphthyridin-4(1//)-one chloride (22) (substrate, Me2NCHO, 0°C, Me2CHCH2CH2ONO [, HCI/btOH [ 75%), which on irradiation gave 177-pyrrolo[3,2-b]pyridine-3-carboxylic acid hydrochloride (23) [substrate, AcOH, H20, 0°C, hv (arc lamp), h %].722... 

Amino-l,5-naphthyridin-4 (1 //)-one gave crude 3-diazonio-l,6-naphthyridin-4(l//)-one chloride (HC1, NaN02, 5°C, 12 h) and thence 3-diazonio-l,6-naphthyridin-4-olate (26) (NaHC03, Et20 70% overall) 726 subsequent irradiation caused ring contraction to pyrrolo [3,2-[Pg.133]

Amino-l,7-naphthyridin-4(l//)-one (10) underwent diazotization to give 4-oxo-3,4-dihydro-l,7-naphthyridin-3-ylidendiazonium chloride hydrochloride (11) (NaN02, HC1, 0°C 80%) and subsequent ring contraction on irradiation to afford pyrrolo[2,3-c]pyridine-3-carboxylic acid (12) (AcOH, H20, hv,... 

In several multidentate ligands associating one carboxylate and pyridine/imidazole moieties, the coordination involves both the N and O atoms. Dimeric, but also trimeric, or polymeric complexes can be formed in which metal centers are linked by one or two oxygen of the carboxylate moiety of the ligand. 

Picolines.—The three isomeric mono-methyl pyridines are known as picolines. One of these is obtained by heating strychnine with lime. From them by oxidation pyridine mono-carboxylic acids are obtained... 

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