Pyridone reactions with

Carbomethoxy-4,6-dihydroxy-l-methyl-2-pyridone, reaction with PCI5, 787... 

Because of the increased importance of inductive electron withdrawal, nucleophilic attack on uncharged azole rings generally occurs under milder conditions than those required for analogous reactions with pyridines or pyridones. Azolium rings are very easily attacked by nucleophilic reagents reactions similar to those of pyridinium and pyrylium compounds are known azolium rings open particularly readily. 

Bis(trifluoromethyl)-substituted pyrimidines are also available fromtrifluoro-acetonitrde on reaction with enamines and ynamines [d ] With dimethylami-nocrotonates, a cyclocondensation takes place to give 2-pyridones. 5-Cyano-6-trifluoromethyluracil is available via a similar route [95] (equation 18)... 

Fluoro and 3- or 5-nitro-2-chloropyridine A-oxides may be converted to the corresponding l-benzoyloxy-2-pyridones by reaction with benzoic acid alone. 

The overall conversion of a 2-furyl ketal to a 6-substitutod l-hydroxy-2-pyridone (79) can be effected by electrolysis in methanol followed by reaction with hydroxylamine. A Grignard reagent can... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

The addition of 2-butenyl(triisopropoxy)titanium was applied in the total synthesis of the pyridone fragment of the antibiotics aurodox and efrotomycin57. 2-Alkenyltitanium(IV) reagents exhibit outstanding simple diastereoselectivity in reactions with methyl ketones52,58 (see Table 2). 

Kuzuya M., Noguchi A. The Nature of Substituent Effects on Tautomeric Equilibria of 2-Pyridones and Their Reactions Trends Org. Chem. 1991 2 73-92 Keywords chemo- and regiochemistry of Diels-Alder reactions with benzyne,... 

Pyridones can also be converted to 2-chloropyridines by exchanging the carbonyl functionality using phosphoroxychloride (POCI3) [72]. A combination of N-halosuccinimides and triphenylphosphine has also been applied to introduce halogens in this position [73]. The carbonyl functionality in 2-pyridones makes these systems reactive towards nucleophiles as well, which add in 1,4-reactions with displacement of halides [74]. The use of transition metal mediated couplings like Heck, and Suzuki have also been successfully applied on halogenated 2-pyridones (d. Scheme 10) [36,75]. 

Wetai Ion Analysis. We have reported a sensitive trace-metal analysis based upon HPLC separation of p-aminophenyl EDTA chelates and fluorescence detection by postcolumn reaction with fluorescamine (23). An application of the pyridone chemistry already discussed leads to a fluorescent-labeled EDTA (VIII). 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

Mixed O, N donor molecules are truly extensive and structurally diverse, and only a few selected examples will be presented. In line with other 2-substituted pyridine analogs reported in this chapter, it is worthwhile noting the chemistry of 2-pyridone (or 2-hydroxypyridine, Hopy), which can form O-bonded monodentate complexes such as Co(Hopy)4(N03)2, but as the monoanion is an effective chelate ligand, forming Co(opy)2 and Co(bpy)(opy)2 compounds.454 An unusual solid state melt reaction with Co(OAc)2 yields the dodecanuclear cluster Co12 (OH)6(OAc)6(opy )12.455... 

The reaction of l-(2-pyridyl)-3,5-dinitro-2-pyridone 14 with ethyl sodio acetoacetate or diethyl sodio acetone-dicarboxylate gave a mixture of N-(2-pyridyl)nitroacetamide 15, phenol derivatives 16, and a low yield of 2-oxo-2,5-dihydropyrido[1,2-b [ 1,2,4]triazine 4-oxide 17 (79TL1393). The mechanism of the reaction is shown in Scheme 5. 

Scheme 13.6 Reactions of 2-pyridone (PYOH) with di-iodine...

O-Protection of this 2-pyridone was followed by lithiation to give 271 with BuLi and i-PriNH followed by reaction with a diastereoisomeric mixture of the aldehyde 272. Oxidation gave a diastereoisomeric mixture of the ketones 273 whose deprotection yields a stereoisomeric mixture of 255. 

The presence of the enamino moiety in 2-amino-4H-pyrans accoimts for their ability to undergo recyclizations into various pyridones, 1,4-dihy-dropyridines, and 2H-pyrones-2. To some extent, properties of 2-amino-4H-pyrans in reactions with nucleophiles can be compared to those of pyrillium salts (68T5059,80T697) because they also tend to form recyclized products. Reactions proceed in the presence of bases or acids. Naphthopyrans 133 form 2-alkoxypyridines 261 on the action of sodium alcoholates or ethanolic NaOH (79M115) (Scheme 101). 

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