Potassium 2-pyridonate, reaction with

The i-methyl-2-pyridone is salted out of the reaction mixture by the addition of 400-500 g. of anhydrous sodium carbonate to the well-stirred solution. When no more of the sodium carbonate dissolves, the stirring is discontinued and the yellow or brown oily layer containing most of the desired pyridone, together with some of the unreacted pyridinium salt, water, and inorganic salts, is separated from the aqueous mixture. The aqueous mixture is filtered (Note 2) to remove the excess sodium carbonate and the precipitated potassium or sodium ferrocyanide. The filtrate is divided into three portions, each of which is extracted twice with 200-cc. portions of technical iso-amyl alcohol (Note 3). The alcohol used for the second extraction of the first aqueous portion is satisfactory for the first extraction of a second aqueous portion, et cetera, so that a total volume of 800 cc. is used. The iso-amyl alcohol extracts are combined and added to the oily layer which was first separated from the reaction mixture. An aqueous layer usually appears and is separated and extracted with another 100-cc. portion of amyl alcohol. 

An interesting rearrangement of some 2,4-diazabicyclo[4,2,0]oct-7-ene-3,5-diones (138) by reaction with potassium i-butoxide gave the corresponding 2-pyridones and l,3-dioxo-l,2,3,4-tetra-hydropyrrolo[l,2-c]imidazoles (139) (Equation (12)) <83JOC2337). 

Pyridinium salts of type (57) are smoothly converted into iV-substituted pyridones (58) on reaction with pentyl nitrite and sodium methoxide, in an average yield of 64% (Scheme 24). 3-Phenacylpyridinium salts, e.g. (59), react with hydrazine and potassium hydroxide to give 4-alkyl-6-phenylpyridazines, e.g. (60), by a process involving ring-opening, ring-closure, and Wolff-Kishner reduction (Scheme 25). ... 

The amino function in 4-amino-3-halopyridines belraves unexceptionally. Thus 4-amino-3-diloropyridine gives the 3-chloro-4-pyridinediazonium salt dien treated with nitrous acid the diazonium salt decomposes in the presence of potassium iodide to yield 3-chloro-4-iodopyridine. 4-Amino-2,3,5,6-tetrafluoropyridine is a very weak base but it can be diazotized in 80% hydrofluoric acid. The diazonium salt is converted to 4-bromo-2,3,5,6-tetrabromopyridine with cuprous bromide, but its reaction with water or with A, lV-dimethylaniline are complex. 4-Amino-2-chloro-3-nitropyridine is not converted to 2-chloro-3-nitro-4-pyridone (K-97) on diazotization with mineral acids and sodium nitrite or with isoamyl nitrite in glacial acetic acid with the latter reagent 2-chloro-3-nitropyri-dine (K-98) is formed." Nitrous acid reacts with 4-amlno-2-pyridone to give 4-amino-3-nitroso-2-pyridone instead of the diazonium salt. ... 

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). 

Pyridone, potassium salt, benzylation of, 748 2-Pyridone, silver salt, 795 alkylation of, 745, 746 effect of electron withdrawing groups, 746 reaction with, halogenose,... 

Potassium/tert-butanol Reactions with trichloroacrylonitrile 3,4-Dichloro-2-pyridone ring... 

Marazano and co-workers have also applied the reactions of tryptamine with various Zincke salts, including 115 (Scheme 8.4.39), in the synthesis of pyridinium salts such as 116. This type of product is useful for further conversion to dihydropyridine or 2-pyridone derivatives. For example, in a different study, Zincke-derived chiral pyridinium salts could be oxidized site-selectively with potassium ferricyanide under basic conditions as a means of chiral 2-pyridone synthesis (117 —> 118, Scheme 8.4.40). 

Cyclic hydroxamic acids and V-hydroxyimides are sufficiently acidic to be (9-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the V-methoxy compound was readil3 obtained by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed by thermal isomeriza-tion of the corresponding 2-alkyloxypyridine V-oxides at 100°. 

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>. 

Only very powerful nucleophilic reagents such as HO-, NHJ, RLi, LAH, etc., react effectively at the ring carbon atoms of simple pyridines (c/. equation 22), and even then forcing conditions may be required. Oxidation of pyridine to 2-pyridone with potassium hydroxide, for example, requires a temperature of ca. 300 °C. Nevertheless, some of these reactions can be of very considerable synthetic importance, especially the classical Chichibabin reaction for the preparation of 2-amino, alkylamino and hydrazino heterocycles (equation 28). The sequence of substitution is C-2, then C-6 and finally C-4. The Chichibabin reaction also requires rather vigorous conditions and often proceeds in only moderate yield the simplicity of the approach, however, is such that it often represents the method of choice for the preparation of the requisite substituted heterocycle. 

Nucleophiles react particularly easily with quaternized azines and with pyrylium and thiopyrylium slats (cf. equation 23) typical examples, including the well-known reaction of pyridinium salts with hydroxide in the presence of potassium ferricyanide to give 2-pyridones, are summarized in equations (34)-(36) (note the rather unusual orientation of addition in the last case reaction normally occurs essentially exclusively a to the heteroatom if the position is free or occupied by a leaving group). 

It is known that 3-aminobenzo[6]furan can be prepared from o-cyanophenols and a-halogenocarbonyl compounds with subsequent Thorpe cyclization (73JPR779). The extension of this synthesis to heteroatom substituted benzo[6]furans is straightforward (76JPR313). The reaction of potassium salts of 3-cyano-2-pyridones (e.g. 27) with a-halogenocarbonyl compounds (esters, ketones) yields 2-alkoxy-3-cyanopyridines which can be cyclized in the presence of sodium ethoxide to give 3-aminofuro[2,3-6]pyridines (Scheme 6). 

Michael addition of the potassium enolate of cy-anacetamide (14) provided the precursor 55 of the pyridone 56. This intermediate was obtained by oxidation of 55 with t-BuOOH in the presence of 20 mol % SeOj on Si02. The addition of 10 % H2SO4 to the reaction mixture directly delivered the lactone 56. Lactones like 56 are not easy to reduce, but treatment with NaBH4/CeCl3 provided the diol 57 in 95 % yield. 57 could be easily converted to camptothecin by heating it to 115 °C in 60 % H2SO4 in EtOH. 

The oxidation of pyridinium salts with alkaline potassium ferricyanide provides a facile route to A -subslituted pyridones (Scheme 4.29a), although the sensitivity of pyridinium salts to nucleophilic attack may lead to ring fission reactions (Scheme 4.29b). 

Pyridones. 2-Halopyridines are converted into 2-pyridones when refluxed with potassium f-butoxide in f-butanol. The reaction presumably proceeds through the f-butyl ether. 3- and 4-Halopyridines do not undergo this transformation. ... 

A third synthesis (60) uses as starting material 3-nitro-4-pyridone which via 3-nitro-4-chloropyridine and 3-amino-4-methoxypyridine is converted to 3-cyano-4-methoxypyridine. The product of the reaction of this last compound with methyl sulfate is oxidized with potassium ferricyanide to ricinine. 

The hydroxy adducts can be oxidized into the Sn products. Indeed, the oxidative hydroxylation of Al-alkylpyridinium salts into pyridones is a well-known Sn transformation, as illustrated by the reaction of 3-methoxycarbonyl-l-methylpyridinium iodide with the hydroxide ion in the presence of potassium ferricyanide, affording the corresponding l-methyl-6-pyridone (Scheme 37) [2, 11, 139]. 

A -methyl-2-pyridone is prepared conveniently from pyridine by conversion to the quaternary methosulfate followed by oxidation with potassium ferricya-nide. Certain quinones with high redox potentials are reduced by -methylpyridonium methosulfate, but in these reactions A -methyl-2-pyridone could not be isolated. However, iV-methyl-2-pyridone is isolated when aqueous methylpyridinium hydroxide (XI-398) is treated with p-benzo-quinone. ... 

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