A-Methyl pyridone

N-Methyl-4-hydroxy-2-quinolone 183 in a three-component reaction gives spiro pyrano[3,2-c]qionoline-2-ones (02MI2), but indolones 213 with 4-hydroxy-6-methyl-2-pyridone 177 react in a complicated way (97BCJ1625). Ethoxycarbonyl-methylene indolone (Z = COOEt) forms pyrans 224, while dicyano analogs (Z = CN) yield substituted quinoline 225 (Scheme 85). 

Nitration of 2-pyridone, originally thought to give mainly 3-nitro-2-pyridone (47) together with some 3,5-dinitro-2-pyridone (48) and a trace of the 5-nitro derivative (49),123 was later shown to give a mixture of 47 and 48.124 Similarly, reaction of 6-methyl-2-pyridone with nitric acid in glacial acetic acid gave the product of nitration at C-3 (50).125 This preferential ortho-nitration is in marked contrast to... 

With alkyl groups in the 2- or 4-positions, however, the reaction may take a completely different course, resulting in side-chain oxidation. Thus, when 2-picoline A-oxide is heated with acetic anhydride, some 6-methyl-2-pyridone is indeed formed, but the main product is 2-pyridylmethyl acetate (172).397,400 4-Picoline A-oxide and acetic anhydride give 4-pyridylmethyl acetate (173) and... 

The only homoleptic cage described above is [Copfchpjig] 45, and therefore one might conclude that, in the absence of other influences, pyridonates favour structures based on tetrahedra. However, structures featuring pyridonates are found in virtually all the categories, chiefly due to the coordinative flexibility of the ligands. There is also a marked difference between the coordination chemistry of the 6-chloro- and 6-methyl-2-pyridonate ligands, due to electronic factors which influence the coordi-... 

An aq. soln. of NaN02 dropped with ice-salt cooling and mechanical stirring into a soln. of 2-amino-6-methylpyridine in H2S04, at a rate to keep the temp, below 5 , stirred an additional hr. below 10°, finally heated to 90 on a steam bath 6-methyl-2-pyridone. Y 92.8%. (F. e. s. R. Adams and A. W. Schrecker, Am. Soc. 71, 1186 (1949).)... 

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). 

A second excellent method of introducing a mercapto substituent consists of treating 6-methyl-2-pyridone (X-110) with P2SS. Oxidation with concentrated... 

Diazomethane reacted with 4-carboxy-3-cyano-6-methyl-2-pyridone (X-140) in the expected manner to form the methyl ester (X-141). Further treatment of X-141 with diazomethane led to a mixture of 0- (X-142) and A -methyl (X-143)... 

Trichloroacrylonitrile and ethyl a-alkylacetoacetates (XII-80) give XII-81, which cyclizes vifli sulfuric acid to 5-alkyl-3,4-dichloro-6-methyl-2-pyridones (Xn-82). ... 

Diketene and glycine in a basic solution ve 3-acetyl-1-carboxymethylene-4-hydroxy-6-methyl-2-pyridone (XII-189) by a reaction path in which dehydroacetic acid is not an intermediate. However, W-acetoacetylglycine was not detected. Deacylation of XII-189 to XII-190 occurs in sulfuric acid. 

Acetylacetone and malonyl chloride give 5-acetyl-4-hydroxyd-methyl-2-pyrone (XII-253), a positional isomer of dehydroacetic acid, which reacts with aqueous ammonia or aqueous methylamine to form XII-254 (R = H, CHs), which can also be prepared from the enamine of acetylacetone and carbon suboxide (see Section I.3.E., p. 635). The //-methylpyridone XII-2S4 (R = CH3) is deacetylated to 4-hydroxy-l,6-dimethyl-2-pyridone with sulfuric acid however, W-254 (R = H) was not deacetylated under these conditions. Acetylacetone and carbon suboxide give 8-acetyl-4-hydroxy-7-methylpyrano-[4,3-6] pyiane-2,5-dione (XI-255) with catalytic amounts of sulfuric acid. This is also formed from acetylacetone and malonyl chloride or from carbon suboxide and the intermediate 5-acetyl-4-hydroxy-6-methyl-2-pyrone (XU-253). 3,5-Diacetyl-4-hydroxy-6-methyl-2-pyrone (XI-256) can be formed by acetylation of XII-253 with acetic acid and phosphorus oxychloride or by degradation of XII-255. 3,5-Diacetyl-4-hydroxy-6-methyl-2-pyridone can... 

A -benzyloxy-2-pyridone even at ambient temperature. For example, a compound previously described as 2-benzyloxy-6-methylpyridine-l-oxide (XII451) was later shown to be l-benzyloxy-6-methyl-2-pyridone. The... 

The monoanion of 6-methyl-2-pyridone is not sufficiently acidic to form a satisfactory dipotassium salt when treated with two equivalents of potassium amide. It does, however, react with / -butyllithjum in tetrahydrofuran or ether to give the dilithio salt, which condenses readily with carbonyl compounds e.g., to give the tertiary alcohol XII-538 in 94% yield. Less conveniently, the dehydration product of XII 538 was prepared from the dipotassium salt of XII-527 (R H) via XU-536 (R = CgHs). 4-Methyl-and 3-methyl-2pyridones as... 

The course of alkylation of 2- and 6-substituted-3-pyridinols is subject 10 a steric effect. Sodium salts of 3-pyridinol in ethanol are N-alkylated by methyl bromo- or iodoacetate. However, 2-bromo-3-pyridinol is N-alkylated by methyl and ethyl iodide in dimethylformamide but is 0-alkylated by haloacetates to XII-563 (Rj = Br, R = H). 2-Bromo-6-methyl-3-pyridinol (XH-562, Rj = Br, R = CH3) is A-alkylated by methyl and ethyl iodide and 6>-alkylated by diazomethane, but reacts with bromoacetic acid in chlorobenzene to give 3-hydroxy-6-methyl-2-pyridone (XII-565), possibly via 2-(a-bromoacetoxy)-6-methyl-3-pyridinol (XII-S64). With 6-methyl-2-methylthio-3-pyridinol (XII-562 Rj = CH3S, R = CH3), A-alkylation should be favored electronically, particularly by electron release by the 2-methylthio group. However, quaternization is difficult even with the simple alkyl halides and only 0-alkylation is observed when methyl iodoacetate is used. ... 

Pyridone, 6-methyl-2-pyridone, 5,6-tetramethylene-2-pyridone, and 5,6-dimethyl-2-pyridone give the products of 1,2-addition to dimethyl acetyl-enedicarboxylate. A -Methyl-2-pyridone gives Mmethylphthalimide, which is probably formed by decomposition of the Diels-Alder adduct XII-706. ... 

Hydroxy-3- (a-iminoethyl)-6-methyl-2-pyridone, preparation by autocondensation of acetoacetamide, 641... 

Wijaya, K., Moers, O., Blaschette, A. and Jones, P.G., Polysulfonylamines, CXII - a novel solid-state aspect of 2-pyridones Isolation and x-ray structures of bis(2-pyridone)hydrogen(l) and bis(6-methyl-2-pyridone)hydrogen(l) dimesylamides, Z. Naturforsch. B 54 (5), 643-648 (1999). 

A suspension of 5-phenyl-6-methyl-2-pyridone-3-carboxylic acid in excess oxalyl chloride and somewhat more than 2 equivalents of phosphorus oxide chloride... 

Piperidine and pyridine added at room temp, to a stirred soln. of 4-hydroxy-6-methyl-2-pyridone in methanol-ethanol, after 5 min. isovaleraldehyde added drop-wise during 3 min., and refluxed 16 hrs. product. Y 80%. F. e. s. J. A. Findlay et al.. Can. J. Chem. 54, 270 (1976). 

A new route for the functionalization of the methyl group of 6-methyl-2-pyridone has been described by Greenwald and Zirkle [17]. When 2-benzyloxy-6-methylpyridine was oxidized... 

It is not clear whether the conversion of 6-methyl-2-pyridone into 3,5-dibromo-6-methyl-2-pyridone by N-bromosuccinimide in carbon tetrachlorides ll is a radical or electrophilic substitution. There is, however, evidence that under conditions favouring radical substitution, bromination of nuclear methyl groups in pyridones occursi s. ... 

It is found in practice that for a number of compounds reacting ma the predominant species an almost horizontal plot is obtained. For compounds presumed to be nitrated via the free bases, such as 2,6-lutidine i-oxide and 3- and 5-methyl-2-pyridone, slopes of approximately unity are obtained. Since this type of plot allows for the incomplete ionisation of nitric acid, it can be used at higher acidities than plots using — ( H + logio Hjo) which break down when the condition is no longer true. 

The procedure for preparing 6-hydroxynicotinic acid is also based on a method described by von Pechmann. 6-Hydroxynico-tinic acid has also been prepared by decarboxylation of 6-hy-droxy-2,3-pyridinedicarboxylic acid by heating 6-hydra-zinonicotinic acid or its hydrazide with hydrochloric acid by the action of carbon dioxide on the sodium salt of a-pyridone at 180-200 and 20 atmospheres by heating the nitrile of 6-chlo-ronicotinic acid with alcoholic sodium hydroxide or hydrochloric acid from 6-aminonicotinic acid and by the prolonged action of concentrated ammonium hydroxide on methyl cou-malate. ... 

In 1931 Ing pointed out that formula (II) and (III) do not contain methyl or potential methyl groups in j ositions 6 and 8 which they occupy in cytisoline. Further, a partially reduced quinoline ought to oxidise easily to a benzenecarboxylic acid and so far the only simple oxidation, products recorded from cytisine were ammonia, oxalic acid and isovaleric acid. Distillation of cytisine with zinc dust or soda-lime yields pyrrole and pyridine, but no quinoline. On these grounds Ing suggested that cytisine should be formulated without a quinoline nucleus, and that the reactions which indicate the presence of an aromatic nucleus in the alkaloid can be accounted for by an a-pyridone ring. This a-pyridone nucleus can... 

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