Condensation with 2-pyridones, 4-hydroxy

Pyrano-fused heterocycles, namely pyrano[3,2-f]quinoline-2,5(6//)-diones, pyrano[3,2-f]benzopyran-2,5(6//)-dione, and pyrano[3,2-f]pyridine-2,5(67T)-diones, have been efficiently prepared by the condensation of 4-hydroxy-2-(l//)-quinolines, 4-hydroxycoumarin, or 4-hydroxy-(17/)-pyridone with a-acetyl-y-butyrolactone or the sodium salt of a-formyl-y-butyro-lactone in the presence of ammonium acetate <1999JHC467>. 

Condensation of 4-hydroxy-6-methyl-2-pyridone with isobutylglyoxal in MeOH containing NaOMe yields quantitatively the Na salt of 155. Its diacetate,... 

Sym. double condensation of aldehydes with 4-hydroxy-2-pyridones... 

If 2-hydroxyacetophenone analogues such as 3-acetyl-4,6-dimethyl-2-pyridone and 4-acetyl-5-hydroxy-3-methyl-l-phenylpyrazole are used as the methylene component in the condensation with R COaEt in the presence of LiH in THE or dioxane, the reaction gives the corresponding R -containing p-diketones 132 and 134, whose dehydration under the action of concentrated H2SO4 affords 8-aza-2-(polyfluoroaIkyl) chromones 133 [58] and 6-(polyfluoroalkyl)-3-methyl-l-phenylpyrano[2,3-c] pyrazol-4(17/)-ones 135 [59] (Scheme 41). 

The most convenient synthesis of 6-hydroxy-2-pyridones is by the condensation of a P-ketoester, eg, ethyl acetoacetate, with an active methylene compound, eg, malonic ester, cyanoacetic ester, and an amine. The amine can be omitted if an acetamide is used and in some cases this modification results in a higher yield. 

A mixture of 5-oxo-3-methyl-5-cyclohexylpentene-2 acid 1-methyl ester and 5-oxo-3-methyl-5-cyclohexylpentene-3 acid 1-methyl ester was obtained by condensation of hexahydrobenzoyl chloride with p,p-dimethylacrylic acid methyl ester. 11.2 g of this mixture and a solution of 4.6 g of sodium acetate and 4 g of hydroxylamine hydrochloride were shaken for 20 hours at 25°C with a mixture of 8 ml of water and 15 ml methanol. Subsequently, a solution of 4 g of sodium hydroxide in 8 ml of water was then added, while cooling, shaken for 1 hour at room temperature. The mixture was extracted by means of benzene and the aqueous phase was acidified to reach a pH of 6. 3.5 g of l-hydroxy-4-methyl-6-cyclohexyl-2-pyridone were obtained melting point 144°C. 

The cyclization of the condensation product of 3-aminopyridine-l-oxide with diethyl ethoxymethylenemalonate (EMME) yields ethyl 4-hydroxy-1,7-naphthyridine-7-oxide-3-carboxylate (IX-108) the -oxide function need not be present if the o-positions of 3-aminopyridines are blocked. The Skraup reaction with 3-amino-2-pyridone yields l,7-naphthyridin-8-one. Several... 

The condensation of an aldehyde with ethyl cyanoacetate and ammonia to give 4-alkyl-3,5-dicyano-6-hydroxy-2-pyridone (XIl-198) probably proceeds through the oxidation of an intermediate glutaric acid imide -197). Only small amounts of the reduction products (XI-199)could be isolated. Additional pathways for the oxidation of W-197 to XII-198 were not excluded. ... 

These prodncts are formed through nucleophiUc attack followed by Claisen condensation (intermediate A), intramolecular cyclization and dehydration (intermediate B), and then by aromatization (after hydrolysis and decarboxylation) through involvement of the phenolic hydroxy group. At the same time, chromone 130a reacts with cyanoacetamide, A-methyl cyanoacetamide, and cyanoacetohydrazide in the presence of sodium ethoxide, affording 2-pyridones 212 in good yields [104] (Scheme 68). 

---