Acidity continued pyridones

TABLE X-5. Hydroxypyridine (or Pyridone) Carboxylic Acids (continued)... 

In the second instance, two approaches seem to be worthy of special note. The synthetic utility of elemental phosphorus based on it acting as a radical trap appears to be quite valuable, but additional effort is required to determine the variability of the source of the organic free radicals. (Is there some other, more efficacious, source of organic free radicals that works better with this system than acylated iV-hydroxy-2-pyridones ) The other approach that appears ripe for development is the hydrolysis/elimination with "phosphorates" derived from the oxidative addition of white phosphorus to alkenes. We look forward to the continued development of such facile approaches toward the preparation of fundamental phosphonic acids. 

N-Hydroxythiopyridone is purchased from the Olin Corp. as an aqueous 40% solution of sodium 2-pyridinethiol-1-oxide (sodium omadine). Sodium omadine (1 L) is diluted with water (H2O, 600 mL) and the solution cooled to 0°C. Hydrochloric acid (350 mL) is added dropwise over a 20-min interval with continuous stirring and cooling for a further 20 min. The resulting suspension containing N-hydroxythio-pyridone is filtered and the solid is washed with H2O (2 L). The N-hydroxythiopyridone is dried over sodium hydroxide or potassium hydroxide under reduced pressure and... 

Cavalleri et al. (219) studied the cycloaddition of thioisomiinchnones with 5-amino-4-methylene-l,2,3-triazolines. The resulting cycloadducts afford 2-pyridones with Raney Ni or 8-thia-6-azabicyclo[3.2.1]octanes with acid. Kato has continued his extensive exploration of cycloaddition studies of mesoionic heterocycles with atypical dipolarophiles. Thus, whereas thioisomiinchnone (320) gave a complex mixture with 6,6-dimethylfulvene (119), it reacted with 2-tert-butyl-6,6-dimethylfulvene to afford 321 in 17% yield (151,152). The cycloaddition of 320 with benzocyclobutadiene was much cleaner to give 322 in 70% yield (114). 

TABLE XII-44. 2-Pyridone Carboxylic Acids and Derivatives (Continued)... 

Fohlisch reported in 1971 the use of enaminones derived from the reaction of dimethyIformamide acetal with the methyl group of acetophenones in a convenient synthesis of chromanones (12). It was found that upon refluxing o-hydroxyacetophenone in the presence of dimethylformamide acetal and xylene, with continuous removal of the methanol formed in the reaction, an 80% yield of the intermediate enaminone 12 was obtained. Treatment of 12 with dilute acid then gave the desired chromanone 13 in 71% yield. Thus, to utilize this reaction in our synthesis of dihydropyrano[2,3-b]pyridines, the acetyl-pyridone 15 was chosen as our starting compound. 

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