2-(Iodoethenyl)benzylamines as Potential Probes for Radical Intermediates Formed during Monoamine Oxidase Catalyzed Oxidations.
An attempt to trap radical intermediates during the monoamine oxidase (MAO) catalyzed oxidation of amines by intramolecular cyclization with an activated alkene that is built into the substrate was unsuccessful. (E)-2-(Iodoethenyl)benzylamine (3a) was shown to be a reversible inhibitor of MAO B, but the corresponding Z isomer (3b) was a good substrate. By GC-MS analysis, the expected radical trapping product, isoquinoline (5), was observed as one of two products in a 1:1 ratio. However, NMR analysis prior to GC-MS analysis showed no evidence of isoquinoline, suggesting that the isoquinoline was generated during gas chromatography. As a model for this GC-dependent reaction, the corresponding aldehyde, (Z)-2-(iodoethenyl)benzaldehyde (14), was treated with ammonia, and the product was analyzed by GC-MS; isoquinoline was detected. Likewise, the reaction of 14 with methylamine also produced isoquinoline by GC-MS analysis (but not by NMR analysis). These results are explained by electrocyclization of the corresponding imines at the elevated temperatures in the GC (Schemes 7 and 8). Substrate 3b and aldehyde 14 were recovered when the enzyme reaction products were chromatographed, although they were not detected by GC-MS. These products could arise via hydrolytic decomposition of the corresponding imine (17; Scheme 9). GC-MS analysis of 17 produced isoquinoline and (Z)-2-(iodoethenyl)benzyl iodide (18) in a 1:1 ratio; these are the two products observed in a 1:1 ratio after incubation of MAO with 3b and apparently arise from thermally induced electrocyclization and iodide ion cleavage (Scheme 9).
Wang
Xueqing
X
Department of Chemistry and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3113.
Silverman
Richard B.
RB