Pyridones from pyridinium salts

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. 

The mass spectrum from the pyridinium salt (171) has a molecular ion corresponding to loss of perchloric acid from the salt (79JA3607). The volatile species may be an ylide or more likely a vinylic elimination product since thermolysis of (171) is known to lead to a rapid generation of allylic pyridones (172). 

Both N-N and N-C bond fission occurs on irradiation of the hydrazone derivatives (191). The photodegradation of the phenylhydrazone and the hydrazone of benzil have also been described. a-Ketoiminyl radicals are formed on irradiation of oximino ketones at low temperature. A study of the photochemical decomposition of sulfamic esters and their use as initiators of cross-linking of a melamine resin have been described. The bispyridinyl radical (192) is formed by one electron reduction of the corresponding pyridinium salts. The irradiation of this biradical at 77 K results in C-N bond fission with the formation of benzene-1,3-diyl. The predominant products from the irradiation (X,> 340 nm) of (193) in methanol were identified as A -hydroxy-2-pyridone and (194) from the fission of the C-O bond. Other products were 2-pyridone, (195) and (196) that arise from O-N bond fission. The reaction is to some extent substituent dependent and a detailed analysis of the reaction systems has identified an intramolecular exciplex as the key intermediate in the C-O bond heterolysis. 

By the same procedure, dihydropyridine 244 was obtained from pyridone 243, prepared by oxidation of pyridinium salt 237 (78MI6). 

Taking into account that the properties of methiodides obtained from bases 1-methyl-IcP 86 and 3-methyl IcP 288 differ greatly not only from each other but also from the imidazolium salt 242, their structures were assumed to be those of pyridinium salts 235, 236 and 238. On the other hand, iodide 235 and quaternary salts 215 and 235 have similar UV spectra and this suggests their structures are that of A -5-alkyl halides. Samples of chloride 237 obtained by quaternization of 86 and by an alternative procedure from pyridone 243 proved to be identical (78MI4). 

Katritzky et al. have corrected an earlier report concerning the reaction of pyridinium carbamoyl methylide [generated from the salt (125) with base] with chalcone which leads to indolizine derivatives (126) rather than pyridones (127). There are many such reactions known, although dehydrogenation to indolizines usually occurs. 

The nitro group in quaternary salts of 4-nitropyridine is easily replaced. Recrystallization of the methiodide from undried acetone gives l-methyl-4-pyridone . Reaction of 4-nitropyridine with benzyl chloride yields 1-benzyl-4-pyridone, and with benzyl bromide, l-benzyl-3,5-dibromo-4-pyridone (nuclear bromination is thought to result from the oxidation of hydrobromic acid by nitrous acid) the experimental description suggests that in these reactions nucleophilic replacement of nitro by halide may occur initially . The consequences of the autoquaternization of 4-nitropyridine have already been mentioned. The formation of 4-hydroxypyridine from 4-nitropyridine and acetic anhydride a presumably involves the acetyl-pyridinium salt. 4-Nitropyridine 1-oxides give with acetic anhydride mainly 4-hydroxy-or 4-acetoxy-3-nitropyridine l-oxides sic but the presence... 

Ricinus communis.—The specific intermediates between nicotinic acid and ricinine are unknown a reasonable biosynthetic pathway is illustrated in Scheme 10. Robinson and co-workers have obtained a crude enzyme from R. communis seedlings, and resolved it by chromatography on DEAE-cellulose into three components, all of which catalysed the oxidation of 3-cyano-l-methylpyridinium perchlorate (43) to the pyridones (46) and (47). The optimum activity for ail these fractions was between pH 9.S and 10.S. The enzymes were relatively non-specific. All the following pyridinium salts were oxidized 3-formyl-l-methylpyridinium iodide, 3-nitro-l-methylpyridinium iodide, 3-acetyl-l-methylpyridinium iodide, 3-cyano-l-ethylpyridinium iodide, and l-benzyl-3-cyanopyridinium chloride. N-Methylnicotinamide, trigonelline sulphate, 1-methylpyridinium iodide, nicotinic acid, 1-methylquinolinium iodide, and 3-cyanopyridine, were not oxidized to any appreciable extent. 

Chloro-l-methylpyridinium iodide (1) reacts with a mixture of a carboxylic acid and an alcohol, in the presence of two equivalents of base, to form an ester (eq 1). The pyridinium salt (2) is formed rapidly by displacement of chloride from (1) by the carboxylate subsequent reaction with the alcohol results in formation of the ester, along with 1 -methyl-2-pyridone (3). A variety of solvents may be employed, but yields are highest in dichloromethane or pyridine. Tri-n-butylamine or Triethylanune are often used as base. The co-product (3) is insoluble in dichloromethane and so precipitates from this solvent. Good results are obtained even for hindered carboxylic acids and alcohols. 

Tlie existence of the ylide 19, which can formally be interpreted as the deprotonation product from the corresponding salt 7a, has been claimed by trapping chlorocarbene with pyridine during the laser-flash photolysis of e do-7-chlorodibenzo[n,c]bicyclo[4.1.0]heptane (18) (96JPC18426). Bromination of l-vinyl-2-pyridone (20) yields the bicyclic pyridinium bro-... 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

Improved procedures for the Chichibabin amination of pyridine derivatives have been reported (83JAP(K)58-208266, 83USP4386209, 83USP4405790). A general method has been developed for the conversion of 2-aminopyri-dines into 2-pyridones via 2-cthoxycarbonyl-l-(2-pyridyl)pyridinium ions 15. The pyridinium ions 15 are easily made from the 2-aminopyridines 14 and the corresponding pyrylium salt 13. On treatment with aqueous sodium hydroxide, pyridinium ions 15 are converted into the l-(substituted-2-pyridyl-carbonyl)-2-pyridones 16, which are readily hydrolyzed to the 2-pyridones 17 and the picolinic acid 18 (83JCS(P1)2623). 

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