Publicação
Chemical and microsomal oxidation of tertiary amides
| dc.contributor.author | Iley, J | |
| dc.contributor.author | Tolando, R | |
| dc.contributor.author | Constantino, L | |
| dc.date.accessioned | 2015-12-30T10:17:56Z | |
| dc.date.available | 2015-12-30T10:17:56Z | |
| dc.date.issued | 2001 | |
| dc.description.abstract | 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. | |
| dc.format | application/pdf | |
| dc.identifier.citation | JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2. - n. 8 (2001), p. 1299-1305 | |
| dc.identifier.doi | http://dx.doi.org/10.1039/b102731j | |
| dc.identifier.issn | 1472-779X | |
| dc.identifier.uri | http://hdl.handle.net/10451/21323 | |
| dc.language.iso | eng | |
| dc.publisher | ROYAL SOC CHEMISTRY | |
| dc.subject | Chemistry, Organic | |
| dc.subject | Chemistry, Physical | |
| dc.title | Chemical and microsomal oxidation of tertiary amides | |
| dc.title | regio- and stereoselective aspects | |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 1305 | por |
| oaire.citation.startPage | 1299 | por |
| oaire.citation.title | JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2 | por |
| oaire.citation.volume | n. 8 (2001) | por |
| rcaap.rights | restrictedAccess | |
| rcaap.type | article |