Synthesis of 4-aminopyrimidines from 1,2,4-oxadiazoles. Part 4. A novel heterocyclic rearrangement: formation of 4-hydroximinohexahydropyrimidines from 3-(2-aminoethyl)-4,5-dihydro-1,2,4-oxadiazoles

Abstract

The 4,5-dihydro derivatives of 3-(2-aminoethyl)-5-substituted-1,2,4-oxadiazoles 1 have been prepared. These derivatives 8a–d rearrange readily, but in contrast to compounds 1, not to pyrazoles, but to 2-aryl-1-benzyl-4-hydroximinohexahydropyrimidines 9a–d. Studies on the mechanism of the 1→2 azole–azole, and the novel 8→9 azole–azine, rearrangements revealed that the site of the side chain nitrogen attack is controlled by the presence or absence of a delocalized π-electron system in the starting azole ring. Compound 9a and benzaldehyde gave cis- and trans-6-benzyl-3,5-diphenyl-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-c]pyrimidines 16 and 17, respectively. The structures of 9a, 16 and 17 were confirmed by X-ray crystallography.