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|Título:||Chemical and microsomal oxidation of tertiary amides|
regio- and stereoselective aspects
|Editora:||ROYAL SOC CHEMISTRY|
|Citação:||JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2. - n. 8 (2001), p. 1299-1305|
|Resumo:||The conformationally restricted tertiary amides N-methyl-2-pyrrolidone 6, N-methyl-2-piperidone 7 and N-methyl-epsilon -caprolactam 8 were oxidised by 5,10,15,20-tetraphenylporphyrinatoiron(III) chloride/tert-butyl hydroperoxide (TPPFe/(BuOOH)-O-t) and by phenobarbital-induced rat liver microsomes. The products were the N-demethylated lactams together with the analogous N-methylimides and norimides. For the TPPFe/(BuOOH)-O-t reaction ring oxidation is preferred to N-demethylation, paralleling the relative stabilities of the corresponding intermediate carbon-centred radicals as calculated by the AM1 semi-empirical method. In contrast, the microsomal reaction of the N-methyllactams strongly favours N-demethylation, demonstrating that hydrogenatom abstraction from the alkyl group Z to the amide carbonyl oxygen atom is preferred. The chiral tertiary amides N-methyl-N-(1-phenylethyl)benzamide 9 and N-methyl-5-phenyl-2-pyrrolidone 10 were also oxidised by TPPFe/(BuOOH)-O-t and by phenobarbital-induced rat liver microsomes. Using TPPFe/(BuOOH)-O-t, loss of the secondary alkyl group of 9 is preferred by a factor of ca. 6. Similarly, ring oxidation of 10 is favoured over demethylation by a factor of 9. For the microsomal reaction of (R)-9 dealkylation is preferred over demethylation by a factor of 1.7, whereas for (S)-9 demethylation is favoured by a factor of 1.25. For the microsomal reaction of (R)-10 and (S)-10 ring oxidation at the 5-position of the pyrrolidone ring is preferred over demethylation by factors of ca. 4 and 9 for the two isomers, respectively, and the (S)-enantiomer undergoes ring oxidation 2-3 times more readily than the (R)-enantiomer. For both 9 and 10 there is negligible stereochemical influence of the chiral centre upon the N-demethylation reaction. The results show that the stereochemical preference of the microsomal N-dealkylation reaction is modest.|
|Aparece nas colecções:||FF - Produção Científica 2000-2009|
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