1- Fluoro-2-pyridone

Fluoro-2-pyridone was prepared by a Balz-Schiemann reaction on 4-amino-2-methoxypyridine followed by Me3Sil. BF as counterion gave a better yield than PF 6 (85JHC145). 

Trifluoromethyl [ F]hypofluorite Acetyl [ F]hypofluorite Perchloryl f Flfluoride Xenon d/[ F]fluoride 1-[ F]Fluoro-2-pyridone AZ-f FlFluoropyridinium triflate A/-[ F]Fluoro-A/-alkylsulphonamides Bromo [ F]fluoride... 

F]Fluoro-2-pyridone was prepared in about 20% radiochemical yield (50% being the maximum feasable yield) by bubbling P F]F2 through a solution of 2-trimethylsilyloxypyridine in CFCI3 (freon-11) at low temperature (Scheme 8) [82]. 

Carbanions in the form of organomagnesium, -sodium, or -lithium salts have been fluorinated with various reagents, including perchloryl [ F]fluoride, 1-[ F]fluoro-2-pyridone, A/-[ F]fluoropyridinium triflate and A/-[ F]fluoro-A/-alkylsulphonamides. 

M. Constantinou, F.l. Aigbirhio, R.G. Smith, C.A. Ramsden, V.W. Pike, Xenon difluoride exchanges fluoride under mild conditions A simple preparation of [ F]xenon difluoride for PET and mechanistic studies, J. Am. Chem. Soc. 123 (2001) 1780-1781. F. Oberdorfer, E. Hofmann, W. Maier-Borst, Preparation of a new fluorine-18-labelled precursor 1-[ F]fluoro-2-pyridone, Appl. Radiat. Isot. 39 (1988) 685-688. 

Fluoro-2-pyridone is readily prepared by reaction of 5% fluorine in nitrogen and 2-trimethylsiloxypyridine in trichloro-fluoromethane at -78°C the pyridone is a selective fluorinating reagent. 5 The novel 3-substituted pyridine (43) is formed when... 

Although a very powerful reagent for electrophiUc fluorinations, the J -fluoro compounds [83] (fluoro-pyridones, fluoro-J -sulfonamides) have not been widely used in fluorine-18 chemistry probably because they are prepared from F-fluorine. 

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 copper-catalysed V-arylation of diazinones by aryl halides, but mainly using 2-fluoro-4-iodoaniline, was described as part of a paper devoted primarily to pyridones. Pyrazin-2-one, pyrimidin-4-one and pyridazin-3-one all reacted successfully but pyrimidin-2-one failed to give any product <06TL7677>. 

Electrochemical fluorination of pyridine in the presence of a source of fluoride ion gave 2-fluoropyridine in 22% yield (85M11). With xenon difluoride, pyridine formed 2-fluoropyridine (35%), 3-fluoropyridine (20%), and 2,6-difluoropyridine (11%) in a reaction unlikely to be a conventional electrophilic substitution. Xenon hexafluoride has also been used (76JFC179). With cesium fluoroxysulfate at room temperature in ether or chloroform, the major product was 2-fluoropyridine (61 and 47%, respectively). Some 2-chloropyridine was also formed in chloroform solution. In methanol the entire product was 2-methoxypyridine (90TL775). Fluorine, diluted with argon in acetic acid, gave a 42% yield of the 5-fluoro derivative of l-methyl-2-pyridone [82H( 17)429],... 

Acyl-2-fluoro-l,4-dihydropyridines 149, easily synthesized by alkylation of 2-fluoropyridinium salts, undergo hydrolysis to form dihydro-2-pyridones 150 in which only the more stable 3,4-/ra t-isomer is formed. 1,4-Dihydropyridines 149 can also be oxidized with DDQ to form 2-pyridones 151 (Scheme 40) <2002JOC7465, 2000CC2459>. 

The stabilities of pyridine-2- and -4-diazonium ions resemble those of aliphatic rather than benzenoid diazonium cations. Benzenediazonium ions are stabilized by mesomerism which involves electron donation from the ring, but such electron donation is unfavorable in 2- and 4-substituted pyridines. On formation, pyridine diazonium cations normally immediately react with the aqueous solvent to form pyridones. However, by carrying out the diazotization in concentrated HC1 or HBr, useful yields of chloro- and bromopyridines 752 can be obtained. Iodinated pyridines can be obtained in good yield using the Sandmeyer reaction. Aminopyridazines and -pyrazines, 2- and 4-aminopyrimidines, and amino-1,2,4-triazines behave similarly. Nucleophilic fluorination via the BalzSchiemann reaction of diazonium fluoroborates yields fluoropyridines, including 2-fluoropyridines. Fluoroborates can also be converted into fluoro compounds by ultraviolet irradiation. 

Like pyridones, oxy-diazines are readily deprotonated under mild conditions, to give ambident anions which can be alkylated conveniently by phase-transfer methods, alkylation usually occurring at nitrogen. " M-Arylations of uracils also proceed in this way with, for example, l-fluoro-4-nitrobenzene."" 3-Pyridazinones alkylate cleanly on N-2 under phase-transfer conditions," but the regiochemistry of uracil alkylation is sometimes difficult to control (see also below). Uracils are sufficiently acidic to take part in Mitsunobu reactions." ... 

Fluoropyridine, which is rapidly converted into Ar-(4-pyridyi)-4-pyridone in aqueous solution, has been prepared by diazotization of 4-aminopyri ne in fluoro-boric acid solution with sodium nitrite, followed by neutralization at — 20°C and distillation alternatively, diazotization may be achieved in anhydrous hydrofluoric acid followed by thermal decomposition of the diazonium fluoride at 50 °C with isolation of the 4-fluoropyridine with an organic solvent. The latter method has been applied to the preparation of 2,6-difluaropyridine from 2,6-diamino-pyridine. The 6-fluoro-derivatives of a large number of 3- and 5-nitro- and 3,5-... 

A nitro group in the 2- or 4-position of the pyridine ring is susceptible to nucleophilic substitution under relatively mild conditions, and in these reactions it competes with a 3- or 5-halogen. 3-Halo-4-nitropyridines (halo = Cl, Br, I) react with aqueous barium or potassium hydroxide to form 3-halo-4-pyridones and with alkoxides to form 4-alkoxy-3-halopyridines. However, 3-fluoro-4-nitropyridine is converted to 4-nitro-3-pyridinol or 3-alkoxy-4-nitropyri-dines. The corresponding iV-oxides react similarly. (See Section 1.6.A., p. 688). 

Biftmctional catalysis of the reaction between fluoro-2,4-dinitrobenzene and piperidine and chloro-2,4-dinitrobenzene and piperidine by 2-pyridone, but not by iV-methyl-2-pyridone, has been reported. 2-Pyridone has been evaluated as... 

Cyano-6-hydroxy-2-pyridones, by cyclization, 625 3-Cy suio-6-hydroxy-4-tri f luoro-methyl-2-pyridone, 624 3-Cyano-6-hydroxy-4-tri fluoro-methyl-2-pyridone, 625... 

Cyano-6-methy1-4-tri fluoro-methyl-2-pyridone, conversion to the Vitamin Bg, analog, 622 synthesis, 622... 

S-Sthyl-2-picolin6, oxidation with nitric acid, 3 3-Eth /lp>/ridina, formation from reduction of 3-py-ridylacetonitrile, 367 3-Ethylpyridine, 702 conversion to iV-methy 1-2-pyridones, 702 direct amination of, 702 N-Ethyl-2-pyridone, from an arylazopyridinium fluoro-borate, 710... 

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