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

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 N 1 -alkylidene carboxamidrazones were studied. O -Peracylated N 1 -(β- d -glycopyranosylmethylidene)-arenecarboxamidrazones were prepared from the corresponding glycosyl cyanides and amidrazones by Raney-Ni® reduction in the presence of NaH 2 PO 2 . 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 NH 4 OAc in AcOH. Under the same conditions O -perbenzoylated N 1 -arylidene- C -(β- d -glucopyranosyl)-formamidrazones gave the expected 1,2,4-triazoles as minor products only. N 1 -Arylidene-arenecarboxamidrazones were also transformed into 3,5-diaryl-1,2,4-triazoles with NBS/NH 4 OAc in AcOH indicating high functional group tolerance and general applicability of the method.