Copper-Catalyzed One-Pot Synthesis of 1,2,4-Triazoles from Nitriles and Hydroxylamine

A simple
and efficient copper-catalyzed one-pot synthesis of substituted
1,2,4-triazoles through reactions of two nitriles with hydroxylamine
has been developed. The protocol uses simple and readily available
nitriles and hydroxylamine hydrochloride as the starting materials
and inexpensive Cu­(OAc)2 as the catalyst, and the corresponding
1,2,4-triazole derivatives are obtained in moderate to good yields.
The reactions include sequential intermolecular addition of hydroxylamine
to one nitrile to provide amidoxime, copper-catalyzed treatment of
the amidoxime with another nitrile, and intramolecular dehydration/cyclization.
This finding provides a new and useful strategy for synthesis of 1,2,4-triazole
derivatives.