Pyridones, acidity nitration

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]. 

It is found in practice that for a number of compounds reacting ma the predominant species an almost horizontal plot is obtained. For compounds presumed to be nitrated via the free bases, such as 2,6-lutidine i-oxide and 3- and 5-methyl-2-pyridone, slopes of approximately unity are obtained. Since this type of plot allows for the incomplete ionisation of nitric acid, it can be used at higher acidities than plots using — ( H + logio Hjo) which break down when the condition is no longer true. 

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... 

The 2-nitration of 3-hydroxy- and 3-methoxy-pyridine in 85-96% sulphuric acid involves the conjugate acids, whilst the 3-nitration of 6-hydroxy and 6-methoxy-2-pyridone in 70-77 % sulphuric acid involves the free bases, which react at, or near to the encounter rate. ... 

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-... 

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). 

Several pieces of evidence can be used to determine whether the nitration of a given substrate occurs through the conjugate acid (SH+) or through the small amount of neutral substrate in equilibrium with it these approaches include the determination of the rate profile and comparisons with the reactivities of model compounds (Ridd, 1971b). From such evidence, it appears that a number of nitration reactions involve the small amount of neutral substrate in equilibrium with the conjugate acid the substrates include 2,6-dichloropyridine, pyridine-1-oxide, l-methylpyrazole-2-oxide, 3-methyl-2-pyridone, acetophenone and p-nitroaniline. These reactions have been reviewed recently (Hoggett et al., 1971 see especially Chap. 8). However, for the majority of these substrates, the... 

Pyridone is one of the compounds for which the encounter rate criterion for choosing between nitration via the free base or by the conjugate acid is ambiguous ( 8.2.3). 

Nitration of 2-pyridone, originally thought to give mainly 3-nitro-2-pyridone (47) together with some 3,5-dinitro-2-pyridone (48) and a trace of the 5-nitro derivative (49),123 was later shown to give a mixture of 47 and 48.124 Similarly, reaction of 6-methyl-2-pyridone with nitric acid in glacial acetic acid gave the product of nitration at C-3 (50).125 This preferential ortho-nitration is in marked contrast to... 

Pyridone undergoes mono- and dinitration at the /8-positions very readily.131-133 Nitration of 2,4-dihydroxypyridine (which probably exists in the 2-pyridone form, 55) occurs under very mild conditions and yields the 3-nitro product 56.134,135 If C-3 is blocked by a carb-ethoxyl group, nitration at C-5 takes place very readily.138,137 Unlike the monohydroxypyridines, which do not react with nitrous acid, 2,6-dihydroxypyridine (presumably mainly 6-hydroxypyrid-2-one) undergoes nitrosation at C-3.138... 

Nitration of pyridines via rearrangement of nitramines has been studied. 4-Amino-3-bromopyridine forms, with nitric acid, the nitramine 9.67 in 85% yield 9.67 rearranges in sulfuric acid to 4-amino-3-bromo-5-nitro-pyridine (9.68) in 97% yield (62RC967). The rearrangement of 2-nitrami-no-4-nitropyridine (9.69) to 2-amino-3,4-dinitropyridine is accompanied by the formation of 4-nitro-2-pyridone (64T81), subsequently shown to arise via nitrosation (79T2895). 

Pyridones, pyrones, and azinones. 2- and 4-Pyridone and their 1-alkyl derivatives are readily nitrated to form first the 3- or 5-mono- (H2S04/HN03, 30C) and then the 3,5-di-nitro derivatives. These nitrations involve reactions of the neutral pyridone species. The proportions of 3- and 5-nitration in 2-pyridone vary with the conditions. 3-Nitration is favored at low acidity and high temperature and 5-nitration by the reverse. 

Crystals of PPB are stable in air and dissolve in water to give a deep blue solution, which slowly bleaches with time. The blue color is enhanced and stabilized in the presence of nitric or perchloric acid (pH 1) and/or 0.1 Af sodium nitrate or perchlorate. In 0.1 M nitric acid PPB exhibits three optical spectroscopic bands at 680, 480, and 405 nm. The blue color is rapidly discharged in the presence of chloride ion and can be restored by removing chloride with silver nitrate. cu-Diammineplatinum a-pyridone blue is paramagnetic and exhibits strong ESR signals at room temperature, with g values of 2.37 and 1.99. 

A published synthesis of 3,4-diaminopyridine29 204 starts with nitration of 4-hydroxypyridine 207. This is a difficult reaction in spite of the electron-donating OH group because the compound is mostly a pyridone 206. Nevertheless a 74% yield of 208 can be achieved with a mixture of fuming nitric and sulfuric acids. 

Chloro-2-pyridone, 69 16-Chlorosteroids, 134 N-Chlorosuccinimide, 69-70 N-Chlorosuccinimide-silver nitrate, 185 Chlorosulfonic acid, 70 Chlorosulfonyl isocyanate, 70... 

Substitutions usually proceed via attack on the neutral pyridone, but in very strong acid, where there is almost complete 0-protonation, 4-pyridone undergoes a slower nitration, via attack on the salt, but with the same regioselectivity. ... 

Nitration of p-cymene by fuming nitric add leads to 2,4-dinitrotoluene.1184 Heating 1,6-dihydro-l-methyl-6-oxonicotinic acid with nitric acid (d 1.52) under reflux gives 1-methyl-3,5-dinitro-2(li/)-pyridone in good yield.1185 2,6-Dibromo-4-nitrosophenol is formed quantitatively from 3,5-dibromo-4-hydroxybenzoic acid and sodium nitrite in aqueous alcohol.166,1183 Nitrous acid replaces hydroxymethyl groups in phenols by nitro groups,1186 and diazonium salts replace them by diazo groups.1187... 

Activating substitutents, i.e. groups which can release electrons either inductively or mesomerically, make the electrophilic substitution of pyridine rings to which they are attached faster, for example 4-pyridone nitrates at the 3-position via the O-protonated salt. In order to understand the activation, it is helpful to view the species attacked as a (protonated) phenol-like substrate. Electrophilic attack on neutral pyridones is best visualised as attack on an enamide. Dimethoxypyridines also undergo nitration via their cations, but the balance is often delicate, for example 2-aminopyridine brominates at C-5, in acidic solution, via the free base. ... 

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