4-Aryl 2-quinolinones, formation

An efficient one-pot procedure for the synthesis of 4-aryl-8-arylidene-5,6,7,8-tetrahydro-2-quinolinones 66 has been developed by Yen and co-workers [54] based on a cyclocondensation reaction of W-ethoxycarbonylmethylpyridinium chloride with an aromatic aldehyde and cyclohexanone. The microwave-assisted (domestic microwave oven) MCR resulted in the formation of compound 66 in high yields (Scheme 50). 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

The oxidative aromatization of tetrahydro-5(l/f)-quinolinones and tetrahydropyrido [2,3-fif]pyrimidin-4(//)-one withpara-benzaldehydes as oxidants in NaOEt/EtOH results in the formation of the corresponding quinolone and aryl methanol because of the hydride transfer from tetrahydroquinoline to arylaldehydes during the oxidation process. The yield of the products basically depends on the substituents with -l-M effect attached to the para position of benzene rings connected to the 2- and 4-positions of the hydro-quinolinone moiety and substituents with -I effect attached to the aryl aldehydes. 

A recent example of the application of Suzuki reactions to introduce diversity is shown by the synthesis of 4-carbon-based substituted quinoli-nones [118]. There are limited methods for the synthesis of such derivatives and the outlined solid phase approach involved the synthesis of a resin-bound 3-methoxycarbonyl 4-tosyl quinolinone and subsequent Suzuki coupling with several aryl boronic acids and cleavage (Scheme 43). One drawback was the formation of hydrolysis byproducts, lowering the yield. 

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