A Convenient FeCl₃‐Mediated Synthesis of 5‐Trifluoromethyl‐1,2,4‐triazoles from Trifluoroacetimidoyl Chlorides and Hydrazides

Abstract

A low cost FeCl 3-mediated cascade annulation of trifluoroacetimidoyl chlorides and hydrazides for the efficient synthesis of 5trifluoromethyl-1,2,4-triazoles has been developed. The transformation proceeds through a cascade base-promoted intermolecular CÀ N bond formation and FeCl 3-mediated intramolecular dehydration sequence under mild conditions. The protocol exhibits many notable features and can be readily scaled up to gram scale.

Synthesis of 3H-1,2,4-Triazol-3-ones via NiCl2-Promoted Cascade Annulation of Hydrazonoyl Chlorides and Sodium Cyanate

“…Encouraged by the excellent viability of the cyanate anion in transition-metal-catalyzed cross-coupling reactions and our continuous interest in the efficient synthesis of structurally diverse N -heterocycles, we herein report a general and atom-economical approach for the preparation of biologically valuable 1,2,4-triazol-3-ones from the nickel-mediated cascade annulation of hydrazonoyl chlorides and sodium cyanate (Scheme e). Hydrazonoyl chlorides have frequently been applied as a versatile building block to build diverse heterocycles .…”

Trifluoromethylated Amidrazone Derivatives as Key Compounds for the Synthesis of 4-Aryl-3,5-bis(trifluoromethyl)-4H-1,2,4-triazoles

“…Therefore, due to the presence of 1,2,4-triazole moiety in drug compounds and pesticides and also of their biological importance, the exploration of new and efficient methods with excellent yield to synthesize versatile trifluoromethylated 1,2,4-triazoles is very important. 30,31 Oxidative cyclization reaction of trifluoroacetimidohydrazides with 4-picoline (Scheme 1a), 32 Dglucose (Scheme 1b), 20 2-methylquinoline (Scheme 1c), 33 and acetophenone (Scheme 1d), 15 are some of the important methods for the synthesis of 2-trifluoromethylated 1,2,4-triazole derivatives, which are reported in the literature. Also, 2,4-bis(trifluoromethylated) derivatives were synthesized by two different methods: 1) multicomponent reaction of trifluoroacetic anhydride, sulfanilamide, and hydrazine hydrate (Scheme 1e), 28 and 2) reaction of primary amines with 3,5-bis(trifluoromethyl)-1,3,4-oxadiazoles or 2,5-dichloro-1,1,1,6,6,6-hexafluoro-3,4-diazahexa-2,4dienes under various reaction conditions (Scheme 1f).…”

Synthesis of 3-Trifluoromethyl-1,2,4-triazolines and 1,2,4-Triazoles via Tandem Addition/Cyclization of Trifluoromethyl N-Acylhydrazones with Cyanamide

“…In recent years, the synthetic protocols employing different trifluoromethyl synthons have emerged as widespread strategies to construct 3-trifluoromethyl-1,2,4-triazoles. For instance, trifluoroacetimidoyl halides were used to react with hydrazones or hydrazides to afford many 3-trifluoromethyl-1,2,4-triazole derivatives (Scheme , a) . Trifluoroacetimidohydrazides were other trifluoromethyl building blocks to be reacted with aryl iodides, methylhetarenes, or methyl ketones, respectively, to produce a series of 3-trifluoromethyl-1,2,4-triazoles (Scheme , b) .…”