Pyridones Knoevenagel reaction

The second target, 4-oxo-4H-l-benzopyran-3-carboxylic acids (3) were obtained by Jones oxidation of or hydrolysis of the 3-carbonitrile derivatives ( ) described below (14). The third target, 3-(4-oxo-4H-1-benzopyran-3)acrylic acids (4) were synthesized generally by the Knoevenagel reaction of 3-carboxaldehydes (2) with malonic acid ( 1 ). In the meantime, it was found that the 3-carboxaldehydes ( ), which were able to function as P-dialdehyde compounds, were attacked by amide groups in some cases, to give 2(IH)-pyridone derivatives after condensation with malonic acid derivatives. Thus, condensation of 2 with malonodiamide in pyridine gave initially acrylamide derivatives which were converted into 3-carbamoyl-5-(2-hydroxybenzoyl)-2(IH)-pyridones ( ) (24) ... 

Snider et al. have synthesised the antiinsectan ( )-leporin [496] 7-26 using the domino-Knoevenagel-hetero Diels-Alder sequence. The intermediate 1-oxa-1,3-butadiene 7-25 was formed in situ by condensation of the pyridone 7-23 and the dienal 7-24. Subsequently, a hetero Diels-Alder reaction occurred accompanied by minor side reactions. Thus, the desired cycloadduct 7-27 was formed only in moderate yield as 5 1 mixture with its trans-fused diastereomer (Fig. 7-6). Functionalisation of the nitrogen atom yielded the natural product. A similar reaction sequence occurred in the synthesis of the structurally related free radical scavenger ( )-pyridoxatin, however, in this approach the hetero Diels-Alder reaction represented only a side reaction competing with the desired intramolecular ene reaction [497]. 

Cyanoacetamides yield a-cyanoacrylamides (124) stereoselectively upon reaction with aldehydes and nonselectively with ketones under standard Knoevenagel conditions. a-Cyanoacrylamides (124) are also obtained by partial hydrolysis of methylenemalonodinitriles. With 1,3-diketones, e.g. acetyl-acetone, pyridones like (125) are formed upon reaction with cyanoacetamides. Base-catalyzed dimerization of a-cyanoacrylamides (124) yields piperidones. ... 

Vinyl ketones, ethyl cyanoacetate and atnncaiixin acetate give 4,6-disubsti-tuted 3-cyano-2-pyridones (XU-142) by a reaction path that includes a Michael addition and a dehydrogenation. The intermediate 3,4-dihydro-2-pyridones were not detected. When benzylideneacetophenone was used in benzene, the reaction proceeded by a Knoevenagel condensation and it was possible to isolate the intermediate 3-cyano-5,6-dihydro-4,6-diphenyl-2-pyridone, which was dehydrogenated to MI-142 by boiling in acetone. ... 

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