Pyridones, hydrogenation

During the synthesis of 2-pyridones, hydrogenation-hydrogenolysis of the ketone intermediate was performed on different catalysts (Scheme 4.24).56,57... 

In solid 2-pyridone, hydrogen bonding is of the NH 0 type. " 6-Chloro-2-pyridinol exists as the pyridinol tautomer in the solid state and forms hydrogen bonded dimers of the OH-N type. Molecular weight determinations in chloroform show that concentrated solutions of 4-methyl-, 4-phenyl-, 3,4-trimethylene-, and 3,4-tetramethylene-6-chloro-2-pyridone contain mainly hydrogen bonded dimers. ... 

Wijaya, K., Moers, O., Blaschette, A. and Jones, P.G., Polysulfonylamines, CXII - a novel solid-state aspect of 2-pyridones Isolation and x-ray structures of bis(2-pyridone)hydrogen(l) and bis(6-methyl-2-pyridone)hydrogen(l) dimesylamides, Z. Naturforsch. B 54 (5), 643-648 (1999). 

Electron-deficient alkenes add stereospecifically to 4-hydroxy-THISs with formation of endo-cycloadducts. Only with methylvinyl-ketone considerable amounts of the exo isomer are produced (Scheme 8) (16). The adducts (6) may extrude hydrogen sulfide on heating with methoxide producing 2-pyridones. The base is unnecessary with fumaronitrile adducts. The alternative elimination of isocyanate Or sulfur may be controlled using 7 as the dipolarenOphile. The cycloaddition produces two products, 8a (R = H, R = COOMe) and 8b (R = COOMe, R =H) (Scheme 9) (17). Pyrolysis of 8b leads to extrusion of furan and isocyanate to give a thiophene. The alternative S-elimi-nation can be effected by oxidation of the adduct and subsequent pyrolysis. 

The same convention is used when a ring =C— is transformed to a carbonyl group, an operation that requires a hydrogen atom to be affixed to another position, as in (123) and (124). This convention does not imply added hydrogen, but only locates one whose presence is already required. Thus 2-pyridone implies C5H5NO and is a fully adequate name when it is not desired to distinguish between (123) and (124) or a mixture of the two. 

The mechanism of recognition of most supramolecular entities (such as abiotic receptors) is the formation of several hydrogen bonds. Since heterocyclic tautomers possess both strong HBA and HBD properties (see Sections III,G, V,D,2, and VI,G), they are often used for this purpose. For instance, the hydrogen bond network formed by 5,5 -linked bis(2-pyridones) has been used by Dickert to obtain sensors (96BBG1312). 

Unexpectedly strong intermolecular hydrogen bonding has been reported by IR spectroscopic studies for tetrahydro-4,7-phenanthroline-l,10-dione-3,8-dicarboxylic acids, which exist in the oxo-hydroxy form 165 in both solid state and in solution [78JCS(CC)369].Tlie conclusion was based on comparison of B-, C-, and D-type bands for 165 and their dimethyl esters (detection of hydrogen bonding) and on analysis of IR spectra in the 6 /xm region (pyridine- and pyridone-like bands). 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Since 2-pyridone (24a, Table 3) exists as an equilibrium mixture with 2-hydroxy-pyridine (25a)14), it is difficult to isolate 24a in a pure state. However, the complexation method using inclusion hosts is applicable for the isolation of keto-form 24a in a pure state. For example, 24a was isolated by inclusion complexation (1 2 complexes) with 1 (26a) (Table 3) and with 3 (27a) (mp 151-153 °C), respectively. Both 26a and 27a do not contain the enol form (25a). The structure of 26a was studied by X-ray crystal analysis (Figs. 7, 8)12>. Inclusion of the keto-form is understandable, because 1 and 3 form more stable hydrogen bonds with the carbonyl oxygen of the... 

---