Synthesis of 5-aryl-3-C-glycosyl- and unsymmetrical 3,5-diaryl-1,2,4-triazoles from alkylidene-amidrazones

Abstract

Among 1,2,4-triazole derivatives with versatile biological activities 3-C-glucopyranosyl-5-substituted-1,2,4-triazoles belong to the most efficient inhibitors of glycogen phosphorylase, and are thus potential antidiabetic agents. In seeking new synthetic methods for this class of compounds oxidative ring closures of N¹-alkylidene carboxamidrazones were studied. O-Peracylated N¹-(β-D-glycopyranosylmethylidene)-arenecarboxamidrazones were prepared from the corresponding glycosyl cyanides and amidrazones by Raney-Ni® reduction in the presence of NaH₂PO₂. Bromination of the so obtained compounds by NBS gave hydrazonoyl bromide type derivatives which were ring closed to 3-C-glycosyl-5-substituted-1,2,4-triazoles in pyridine or by NH₄OAc in AcOH. Under the same conditions O-perbenzoylated N¹-arylidene-C-(β-D-glucopyranosyl)-formamidrazones gave the expected 1,2,4-triazoles as minor products only. N¹-Arylidene-arenecarboxamidrazones were also transformed into 3,5-diaryl-1,2,4-triazoles with NBS/NH₄OAc in AcOH indicating high functional group tolerance and general applicability of the method.