Ring‐Chain Tautomerism of 3,5‐Disubstituted 5,6,7,8‐Tetrahydro‐3H‐3H‐[1,2,4]oxadiazolo[4,3‐c]pyrimidine, a Novel Heterocyclic Ring System

Abstract

~ ~The reaction of 3-aminopropionamide oxime (7) with two equiv. of benzaldehyde or of a substituted benzaldehyde gives cis-3,5-diaryl-5,6,?,8-tetrahydro-3H[l,2,4]oxadiazolo[4,3-c]-pyrimidines (cis-lla-c,e). According to 'H-, I3C-, and 15N-NMR studies these compounds form in solution a novel triple tautomeric equilibrium comprising cis-and trans-lla-c, e and 3-[2-(benzylidineamino)ethyl]-5-aryl-4,5-dihydro-1,2,4-oxadiazoles (10a-c, e). However, the solid obtained from ? and two equiv. of cinnamaldehyde proved to be an imine (log), which again formed in solution a similar triple tautomeric system analogously to the mutarotation of sugars. The structure of l l a and log was confirmed by X-ray crystallography.It is well known that in reversible intramolecular addition reactions cyclic stereoisomers may equilibrate in solution via open-chain intermediates. Mutarotation of sugars is a thoroughly studied example ') but similar ring-chain tautomeric systems have been observed with other ring systems, too, e. g. with nitrogen heterocycles2). These triple tautomeric equilibria generally correspond to the exo type 3, of Scheme 1.Our studies on ring-chain tautomerism and ring transformations of pyrimidines4) led to the discovery of [1,2,4]oxadiazol0[4,3-~]pyrimidines, a new heterocyclic ring system, which forms in solution a tautomeric system corresponding to the endo3) type in Scheme 1. To the best of our knowledge there has been no example reported so far for such a triple ring-chain tautomeric system involving amine addition to a C = N bond.Earlier we have described that in the reaction of 2-aminobenzamide oxime (1) with aldehydes (2) at room temperature 4-amino- Gonplves and co-workers found6' that in the reaction of the aliphatic analogue of 1, i. e. 3-aminopropionamide oxime (7), with one equiv. of aldehyde 2 the imines 8, while with two equiv. of 2 the (aminoethy1)oxadiazolines 10 are formed (Scheme 3). According to our own experiments in the reaction of one equiv. of benzaldehyde (2a) or its derivatives containing electron-attracting substituents (2b-d) imines 8a-d formed which equilibrate in solution with the pyrimidines 9. Both forms could be isolated in pure form and interconverted in solution. In contrast, in the case of cinnamaldehyde (Zg) and benzaldehydes containing electron-releasing substituents (Ze, 0 only the open-chain imine tautomers (8e-g) could be detected40 both in solution and in the solid state.In view of these findings4b.'' reinvestigation of the structure 10 proposed for the product of 7 and two equiv. of the aldehydes6) appears to be justified.