Ambident oxidative ring closure of semicarbazones

Abstract

Oxidative cyclisation of a series of substituted benzaldehyde semicarbazones, with bromine in acetic acid in the presence of base or with lead tetra-acetate, yields 2-amino-1,3,4-oxadiazoles. With bromine in the absence of base there is a competition between cyclisations involving nitrogen and oxygen atoms, and the main products are triazolones arising from ring closure at a nitrogen atom. Ring closure at an oxygen atom appears to involve a nitrilimine intermediate as the product governing species, whereas the ring closure at nitrogen appears to be a carbonium-ion reaction. A methyl group at N-2 in the semicarbazone systems prevents the formation of a nitrilimine species and confines the subsequent cyclisation reaction to nitrogen atom attack. The rates of bromination (in 70%) acetic acid at 20 °C of a similar series of benzaldehyde semicarbazones proved to be independent of the bromine concentration. The slow step in the reaction measured was the syn–anti isomerisation of the semicarbazone. We favour a mechanism for this process involving rotation about the CN bond, in light of (a) data on the effect of substituents on the rate of isomerisation and (b) comparison with related systems.