Pyridone methides

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

The anhydro bases, e.g. (61), formed by deprotonation of 2- and 4-alkylquinolinium salts, are more stable than the pyridone methides and are usually isolable. They are reactive enamines and some typical chemistry is shown in Scheme 50. 

Proton loss from a- and y-alkyl groups on a cationic (pyridinium, pyrylium or thiinium) ring is comparatively easy. The resulting unstable and highly reactive neutral anhydro-bases or pyridone methides cf. 645) can be isolated by using 10M sodium hydroxide, but are generally used directly. 

The A// values obtained as described in Scheme 20 demonstrate that 2-pyridone and 2-pyridinethione retain most of the aromatic resonance energy of pyridine, and that 2-pyridone imine is also strongly aromatic, while 2-pyridone methide is much less so. 

Lithium cyclopentadienylide with benzyl pyridinium chloride gives i the pyridone methide (85) (see below and p. 328). 

Like its lithium analogue, sodium cyclopentadienylide gives, with quaternary pyridinium salts, pyridone methides of the type (85)The same and related reagents yield analogous products by reaction with 2- and 4-bromo-l-alkylpyridinium salts , with 4-methoxy- or 4-phenoxy-1-alkylpyridinium salts . ... 

The acylation of G-alkyl groups in quaternary pyridinium salts has not otherwise been reported, but pyridone methides undergo substituted acylations with phenyl isocyanate and isothiocyanate. Some products of such reactions are recorded in Table 6.7. Some interesting examples of methide acylations are shown S ... 

The pyridone methide generated from 2-picoline methiodide by sodium methoxide 56d or piperidine s gives the bis-cyanoethyl derivative (35)... 

The dipole moments of the analogous dibenzo- and tetraphenyl-sesquiful-valenes182 are essentially smaller than those of the tropones. There is effectively no ring current in pyridone-2-methide, while 2-pyridone is said to have about 25% of the aromaticity of benzene.183... 

An elegant new synthesis of polycyclic heteroaromatic compounds via quinone-methide intermediates is illustrated in Scheme 60. The required quinone-methides have also been generated from hydroxy-pyridones and -coumarins, and these have been allowed to react with a wide selection of aromatic amines. ... 

G—GE[3 >0=G—OH], and resembles the splitting of 1-phenacyl-pyridinium salts (p. 390). Other examples are known743, 877 Although methide formation must occur in these reactions the methide is not considered to play a part in pyridone formation743. 

Cook, M., Katritzky, A., Linda, P., and Tack, R. (1972) Aromaticity and tautomerism. Part 1. The aromatic resonance energy of 2-pyridone and the related thione, methide, and imine.. Chem. Soc., Perkin Trans. 2, 1295-1301. 

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