Direct Access to 1,3,5-Trisubstituted 1H-1,2,4-Triazoles from N-Phenylbenzamidines via Copper-Catalyzed Diamination of Aryl Nitriles

Abstract

A copper-catalyzed formation of C-N/N-N bonds using Nphenylbenzamidines with aryl nitriles has been developed and affords a route to 1,3,5-trisubstituted 1H-1,2,4-triazoles in moderate to excellent yields. The method is operationally simple and environmentally benign with a large substrate scope available and represents an economical path for numerous C-N/N-N bond formations.

C,N‐Diarylformamidines as Valuable Building Blocks in the Synthesis of Heterocyclic Compounds

“…Derivatives of 1,2,4-triazole play a key role in medicinal chemistry, in particular, there are reviews of antitumor and antiviral activities. [51] In his 2016 publication, Zhang L. et al [52] reported the possibility of synthesizing 1,3,5-trisubstituted 1H-1,2,4-triazoles from readily available N-phenylbenzamidines 1 and arylnitriles 74 (Scheme 59).…”

“…In his 2016 publication, Zhang L. et al [52] . reported the possibility of synthesizing 1,3,5‐trisubstituted 1 H ‐1,2,4‐triazoles from readily available N ‐phenylbenzamidines 1 and arylnitriles 74 (Scheme 59).…”

Electrochemical Cyclization of Hydrazones and Amidines To Access Trisubstituted 1,2,4-Triazoles

“…[2] Among the classical approaches, the hydrazones or in situ generated hydrazones from the combination of hydrazines and aldehydes occur intermolecular cyclization with amine derivatives to afford a series of polysubstituted 1,2,4-triazoles. [3] In 2016, our group had introduced a copper-catalyzed N-Phenylbenzamidines and arylnitriles to access 1,3,5trisubstituted 1H-1,2,4-triazoles. [4] A base-promoted annulation of trifluoroacetohydrazonoyl chlorides with imidates were also developed to synthesize trifluoromethyl-1,2,4-triazoles.…”

“…3 In 2016, our group introduced a copper-catalyzed reaction of N-phenylbenzamidines with aryl nitriles to access 1,3,5-trisubstituted 1H-1,2,4-triazoles. 4 A base-promoted annulation of trifluoroacetohydrazonoyl chlorides with imidates was also developed to synthesize trifluoromethyl-1,2,4-triazoles. 5 Moreover, Zhang and co-workers have described an efficient base-mediated cyclization of nitriles with hydrazines to directly form 1,3,5-trisubstituted 1,2,4-triazoles.…”