Pd-Catalyzed Synthesis of 1,2,4-Triazoles

Significance

Reported here is the four-component synthesis of 5-(hetero)aryl-1,2,4-triazoles 3 by the carbonylative coupling of amidines 1 to aryl iodides. The acyl amidine intermediates 2 are proposed to undergo an in situ hydrazinolysis to give products 3. The best results were obtained using Pd(OAc)₂/Xantphos with Et₃N in DMF under atmospheric pressure of CO. The scope of the reaction was well explored, affording various 1,2,4-triazoles in moderate to good yields. This reaction can also be performed using amidrazones 4 to obtain 1,2,4,-triazoles 5; however, amidrazones 4 are not as commercially available compared to amidines 1. As an application, the synthesis of ­deferasirox, an active pharmaceutical ingredient, was realized in one step and 41% yield from 2-iodophenol, 2-hydroxybenzamidine and 4-hydrazinobenzoic acid.