Formation of optically active 1,2,4-triazoles from the reactions of optically active N-arylmandelamidrazones with trialkyl ortho esters or aldehydes

Abstract

A series of optically active N-arylmandelamidrazones has been prepared, either by the action of a substituted hydrazine on ethyl (–)-mandelimidate hydrochloride or by direct resolution of the (±)-amidrazone via the (+)- and (–)-mandelic acids. Reactions of these amidrazones with trialkyl ortho esters led to optically active 1,3-disubstituted and 1,3,5-trisubstituted 1,2,4-triazoles. The reaction of N-arylmandelamidrazone salts with ortho esters is, however, more complex, the 1,2,4-triazole products either being identical with those formed from the amidrazone bases or having undergone O-alkylation along with racemisation to the benzylic centre. A mechanism is proposed for this alkylation process. The reaction of optically active amidrazones with aldehydes is also complex, aliphatic aldehydes apparently yielding optically active 1,2,4-triazoles but aromatic aldehydes giving either optically active or racemised products, depending on the amidrazone used. Absolute configurations have been assigned to both amidrazones and triazoles by chemical means and also, tentatively, by comparison of c.d. spectra.