Preparation of meso-, (±)-, and optically active forms of 3,6-bis-(1-hydroxy-1-phenylpropyl)- and 3,6-bis-(1-hydroxy-1-phenylethyl)-1,2,4,5-tetrazines via a new synthesis of 1,2-dihydro-1,2,4,5-tetrazines from amidines

Abstract

The amidinium chlorides (IVa and b) were converted by the action of hydrazine hydrate into mixtures of the meso- and (±)-dihydrotetrazines (IIa and b), identical with those obtained from the more usual route via the imidate salts (IIIa and b). The dihydrotetrazines (IIa and b) were readily oxidised to the tetrazines (Ia and b). Fractional crystallisation of the tetrazines (Ia and b) or their dihydro-derivatives yielded pure samples of the meso- and (±)-compounds (Ia and b; IIa and b). The use of optically active amidinium chlorides (IVa and b) led to the formation of the optically active dihydrotetrazines (IIa and b) and tetrazines (Ia and b) by subsequent oxidation. Admixture of the (+)- and (–)-forms of compound (Ib) proved the (±)-tetrazine to be the lower-melting diastereoisomer. Absolute configurations and o.r.d. results for compounds (I) and (II) are also discussed.