3- nitro-4-pyridone

The similarity of their rate profiles, and the similarity of their rate constants for nitration at a particular temperature and acidity show that 4-pyridone, i-methyl-4-pyridone, and 4-methoxypyridine are all nitrated as their cations down to about 85 % sulphuric acid. The same is true of 2-methoxy-3-methylpyridine. In contrast, 3- and 5-methyl-2-pyridone, i,5-dimethyl-2-pyridone and 3-nitro-4-pyridone all react... 

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

By contrast, the rate-acidity profiles for nitration of 3-nitro-4-pyridone, 3-and 5-methyl-2-pyridone and l,5-dimethyl-2-pyridone resemble each other and differ from the above-indicated reaction upon the free base, and correction of the observed rates to allow for the concentration of free base actually present gave rate-acidity profiles of the expected form the corrected entropies of activation then turned out to be positive. Furthermore, if the logarithms of the corrected rate coefficients obtained in media of low acidity were plotted against +log aHlQ, then slopes of near unity were obtained (see above, p. 18), but not otherwise. A similar result was obtained from the nitration data for 4-pyridone in media of low acidity suggesting that here it reacts as the free base. A further test which was applied was to calculate the concentration of nitronium ions in the various media and to correct the observed rate coefficients for this the logarithms of these coeffi-... 

Nitration of 4-pyridone takes place on the free base, except at high acidity where the protonated species is involved [68JCS(B)1477]. 4-Pyri-done is less reactive than 2-pyridone toward nitration (Table 9.7), a result which contrasts with hydrogen exchange where the reactivities are identical Table 9.1). As expected, nitration of 3-nitro-4-pyridone also occurs on the free base [68JCS(B) 1477]. From this work, partial rate factors of 10 10 to 10"12 were calculated for the monocations derived from 4-pyridone and 2- and 4-methoxypyridine deactivation by NH+ in these systems was estimated as >1013 [68JCS(B)1477]. 

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 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. ... 

Dibromo-l-methyl-4-pyridone has been prepared from Mmethyl-4-pyridone by modifications of an earber procedure. 7V- /i-Butyl)-2,6-di-methyl-4-pyridone is also brominated in acetic acid to the 3,5-derivative. 3-Nitro-4-pyridone and 2,6-dbnethyl-3-nitro-4-pyridone are halogenated at the 5-position to give 5-bromo- and 5-chloro-2,6-dimethyl-3-nitro-4-pyridone, which have been converted to the corresponding 4-chloropyridines for use in 7-carboline synthesis. 

A procedure has been described for the preparation of 3-nitro-4-pyridone from... 

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. 

Activated compounds such as 5-nitropyrimidin-2-one and 1-methyl-5-nitro-2-pyridone form the 2-chloro analogs with thionyl chloride 223b. 312b displacement of the —O—SO—Cl group. In reactions... 

Methyl-5-nitropyrimidm-4n//)-one reaas v/ith ketones in the presence of ammonittm salts to give 4,5-disubsdntted pyrimidmes or 5,6-disubsdntted 3-nitro-2-pyridones depending on reacdon condidons fEq. 10.83. ... 

Nitroenamines and related compounds have been used for synthesis of a variety of heterocyclic compounds. Rajappahas summarized the chemistry of nitroenamines (see Section 4.2).140 Ariga and coworkers have developed the synthesis of heterocycles based on the reaction of nitropyridones or nitropyrimidinone with nucleophiles. For example, 2-substituted 3-nitro-pyridines are obtained by the reaction of l-methyl-3,5-dinitro-2-pyridones with ketones in the presence of ammonia (Eq. 10.82).141... 

Methyl-5-nitropyrimidin-4(3f/)-one reacts with ketones in the presence of ammonium salts to give 4,5-disubstituted pyrimidines or 5,6-disubstituted 3-nitro-2-pyridones depending on reaction conditions (Eq. 10.83).142... 

The most efficient routes to the cationic oxazolo[3,2- ]pyridine ring system 351 rely on the method of Bradsher and Zinn <1967JHC66> involving the cyclocondensation of iV-phenacyl-2-pyridones 349 obtained by alkylation of readily available 2-pyridones 347 (Scheme 95). This method has been used by Babaev et al. to prepare a series of 6-nitro-oxazolo[3,2- ]pyridines 355 from 5-nitro-2-pyridone 352 in excellent yields <2003MOL460>. Similarly, tricyclic oxazolo[3,2- ]pyridines 359 have been prepared from the corresponding quinolin-2(177)-ones 356 <2003H(60)131>. 

In order to clarify the reaction mechanism, 6-deuterio-labeled 3,5-dinitro-l-methyl-2-pyridone (87, 1 mmol) was prepared and heated with cyclohexanone (2 mmol) and ammonia (10 mmol). A mixture of 2-deuterio- (88) and 4-deuterio-3-nitro-5,6,7,8-tetrahydroquinoline (89) was obtained in the ratio 58 42 (Scheme III.49). 

The electrophilic substitution of pyridones 187,192a, and 193 (Scheme 77) yields bromide 335 (91MI1, 92MI1), bis-compounds, such as 336a and b (87IJB1094), nitro derivatives 337 and 339, and allyl compounds 340a and b... 

Cyano, halo, amino, and nitro groups in the 2- or 4-position of pyridinium ions are susceptible to nucleophilic substitution. Treatment of these compounds with aqueous alkali gives the corresponding pyridones. Since this transformation is not the result of oxidation, it will not be further considered here. 

The role of the pyridone ring as a pharmacophore in cardiotonic agents such as amrinone (25-6) has been noted earlier very analogous activity is obtained with compounds in which the heterocylic ring is replaced by a pyridazinone. The synthesis of the first of these agents, pimobendan (35-6), starts with the acylation of the amino group in nitro-aniline (35-2) with anisoyl chloride (35-1) to give amide (35-3). 

A compound (40), isolated from the reaction between 2-chloro-5-nitro-pyridine and tert-butyl jV-hydroxycarbamate, has been shown to react with benzaldehyde to give 6-nitro-2-phenyl-triazolopyridine (41)53 5-nitro-2-pyridone acts as a leaving group. 

The triazole ring can be synthesized by reaction between a suitable pyridine (or piperideine) and an azide. Thus 5-nitro-2-pyridone (or N-substituted pyridones) and sodium azide give a 5-oxotriazolo[4,5-b]pyridine (94)182-184 whereas the enamine 95 reacts with p-nitrophenyl azide to give the hexahydro-l//-triazolo[4,5-c]pyridine 96.185,186... 

The nitration of 6-phenyl-2-pyridone (70% nitric acid or nitronium tetra-fluoroborate at RT) produces 3-nitro-6-phenyl-2-pyridone (up to 60% yield). However, nitration at 90°C with 70% nitric acid is reported to give 3-nitro-6-(4-nitrophenyl)-2-pyridone (36%), whereas at 90°C acetyl nitrate yields 50% of a mixture of 3- and 5-nitro-6-phenyl-2-pyridone (72KGS1374). 

Keywords Ammonium acetate Nitro compounds Pyridone Pyrimidinone Ring transformation... 

Nitropyrimidinone 3 has also electrophilic sites, the 2-and the 6-positions, which are attacked by amines to yield nitro enamines having a carbamoyl group 11 in good yields [28]. Nitroenamine 11 is converted to polyfunc-tionalized pyridone 12a upon treatment with sodium enolate of ethyl 3-oxobutanoate 13a [29]. 

Scheme 13 TCRT leading to pyrimidines and 3-nitro-2-pyridones...

The precipitated yellow solid during the reaction is 6-phenyl-3-nitro-2-pyridone 28g whose C2 - C3 - C4 unit is derived from the C4 - C5 - C6 unit of pyrimidinone 3. Another TCRT proceeds at the 4- and the 6-positions of pyrimidinone 3, which behaves as the synthetic equivalent of a-nitro-formylacetic acid 29. 

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