3-Acetyl-4-methyl-2 -pyridones

From monoalkylammobutenones and diketene at —5°C in benzene 3-acetyl-4-methyl-2(l//)-pyridones 300 are formed via the intermediate amides 299 (80MI1). 

The reactions of 2-substituted 6-methyl-4/7-l,3-oxazin-4-ones 98 with isoxazole ketones 99 in the presence of potassium / -rt-butoxide furnished 3-acetyl-5-(3-methylisoxazol-5-yl)-2-pyridones 101 in good to excellent yields (Scheme 14). The formation of 2-pyridones 101 presumably proceeds via nucleophilic addition of the methylene carbon of 99 to the carbon atom at position 2 of the l,3-oxazin-4-ones 98, followed by ring opening to give the acetoacetyl intermediates 100, which are transformed into 101 by intramolecular aldol condensation <2005H(66)299>. 

Kato et al,94 reported that 2-amino-6-methylpyridine and diketene did not yield 4-oxo-4/f-pyrido[l,2-a]pyrimidines but instead yielded 2-acetyl-acetamido-6-methylpyridine and pyridone or pyrone derivatives. 2-Methyl-4-oxo-4H-pyrido[l,2-a]pyrimidine (47) and its 8-methyl derivative have also been prepared from 2-aminopyridine and 2-amino-4-methylpyridine with N,N-dimethyl-3-aminocrotonamide95 or with acetoacetamide45 in yields of 5 and 39°,. respectively. 

CR(Q(262)1017>. The nucleophilic reactivity of the oxygen atom has been observed in the acetylation by acetic anhydride of 2-aryl- and 2-heteryl-A2-thiazolin-4-ones (Scheme 136). 2-Alkoxy and 2-methyl derivatives of A2-thiazolin-4-one (196) react with OPCl3 to yield thiazolylphosphoric esters (197) which have insecticidal uses (Scheme 137). An example of the electrophilic reactivity of the C-4 atom is the easy formation of oxime and phenylhydrazone derivatives. 5-Aryl-A2-thiazolin-4-one (198) gives the 1,3-dipolar cycloaddition product (199) with methyl fumarate and methyl maleate (Scheme 138). Under similar conditions, treatment of (198) with dimethyl acetylenedicarboxylate (DMAD) yields a thiophene derivative (202) when R = Ph and a pyridone derivative (203) when R = H (Scheme 139). The proposed mechanism involves the formation of a mesoionic intermediate (200) which reacts in a cycloaddition with a second molecule of DMAD, yielding (201), the decomposition of which depends on the R substituent. 

Hydroxylamine converts pyran-2-ones into pyridine JV-oxides by attack at the 1,2-bond for example, the pyran-2-one (278), obtained by heating 3-acetyl-4-hydroxy-6-methyl-pyran-2-one (dehydroacetic acid) and DMF dimethyl acetal in xylene, reacts with two moles of hydroxylamine under mild conditions to give the pyrano[2,3-6]pyridine JV-oxide (279) (77JHC931). Hydrazine converts pyran-2-ones into l-amino-2-pyridones (78JHC759). 

Kato et reported that 2-amino-6-methylpyridine and diketene did not yield 4-oxo-4//-pyrido[l,2-a]pyrimidines but instead yielded 2-acetyl-acetamido-6-methylpyridine and pyridone or pyrone derivatives. 2-Methyl-... 

Among examples of lactam-lactim tautomerism pyridine derivatives 98a, 98b, and 100 have been proven to be pyridones on the basis of their IR spectra, whereas UV and IR spectra suggest the aminopyridine structure 101 (63BCJ633). Spectral data similarly confirm the existence of substance 31a (Scheme 57) in the 4-hydroxy-2-pyridone form rather than the 2,4-dihydroxypyridine form 234 (74BCJ1750). Consequently, its acetylation by acetic anhydride/pyridine at 130 °C or methylation yield N,0-disubstituted derivatives 235a and 235b, respectively. Acetylation at 100 °C, however, leads to 0,0 -disubstitution (236). 

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. 

Aminotropolone and diketene form 3-acetyl-4-hydroxy-6-methyl-l-(tropo-lon-4-yl)-2-pyridone (MI-193) and N-(tropolon-4-yl)-2,6-dimethyI-4-oxo-4/f-pyran-3-carboxamide(Xn-194). ... 

Treatment of a-unsubstituted-iV-(2-pyridyl)acetoacetamides with triethyl orthoformate and zinc chloride dn ethanol gives 3-acetyl-6-methyl-l -(2-pyridyl)-5-( -2-pyridylcarboxamido)-2-pyridone (XII-201). ... 

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... 

Acetyl-2-methyl-l-phenylethylpyridinium perchlorate when treated with aqueous sodium hydroxide gives the anhydro base that forms 5-acetyl-1-phen-ethyl-2-pyridone (Xn-421) with potassium permanganate in acetone. ... 

Pyridinols and pyridones are sometimes prepared by dehydrogenation of hydropyridinols. For example, the available 1-phenyl- and 1-methyl-5,6-dihydro-2-pyridones (XII460 R - CH3, C6Hs) are readily dehydrogenated to the pyridones with palladium-on-carbon. y-Acetyl- and 7-benzoyl-7-phenylbutyro-... 

Acetyl-4-hydroxy-6-methyl-2-pyridone and dimethyl sulfate in sodium methoxide give the iV-methyl-2-pyridone (40%) but diazomethane causes 0-methylation (52%). ... 

Hydroxy-2-pyridones form 4-acetoxy-2-pyridones readily. 4-Acetoxy-l, 6-di-methyl-2-pyridone and 4-acetoxy-5-acetyl-6-methyl-2-pyridone have been prepared employing acetic anhydride. 4-Acetoxy-6-methyl-l-phenyl-2-pyridone has been formed with phosphoryl chloride and acetic acid. Methyl citrazinate (XI-597) and acetic anhydride give methyl 2,6-diacetoxyisonicotinate. ... 

Acetyl-2,6-dimethyl-4-pyridone and sodium h)rpobromite form 3-acetyl-5-bromo-2,6-dimethyl-4-pyridone (XII-6S8), which then gives 3,5-dibromo-2,6-di-methyl-4-pyridone (XII-659)... 

Acetyl-4-hydroxy-6-methyl-2-p5nidone and phosphoryl chloride in acetic acid give 3,5-diacetyl-4 hydro3 -6-methyl-2-pyridone (XII-689). 4-Hydroxy-6-methyl-2-pyridone (XD-690, R = H), l,6-dimethyl-4-hydror -2-pyridone... 

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. ... 

Acetyl-4-hydroxy-6-methyl-2-pyridone oxime, 641 5 -Acetyl-4-hydroxy-6-methyl-2-pyridone, 634 acetylation, 658, 816 N-alkylation with dimethyl sulfate, 765... 

Acetyl-4-hydroxy-6-phenyl-2-pyridone, 635 from 5-acetyl-4-hydroxy-6-phenyl-(2tf)-2-pyrone, 658 5-benzoyl-4-hydroxy-6-methyl-(2f )-2-pyrone, 658... 

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