Elemental Sulfur and Dimethyl Sulfoxide‐Promoted Oxidative Cyclization of Trifluoroacetimidohydrazides with Methylhetarenes for the Synthesis of 3‐Hetaryl‐5‐trifluoromethyl‐1,2,4‐triazoles

Abstract

Main observation and conclusion A metal‐free approach for the synthesis of 3‐hetaryl‐5‐trifluoromethyl‐1,2,4‐triazoles via sulfur/dimethyl sulfoxide‐promoted oxidative cyclization of readily available trifluoroacetimidohydrazides with methylhetarenes has been developed. This transformation proceeds in cascade sulfur‐mediated generation of thioaldehyde, condensation, intramolecular cyclization and oxidative aromatization sequence.

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).…”

Palladium-catalyzed four-component cascade carbonylative cyclization to access carbonyl-bridged bisheterocycles

“…1 Among them, oxindole and imidazole moieties constitute some of the highly privileged heterocyclic skeletons and exhibit broad-spectrum biological or pharmaceutical activities. 2 Considering the great importance and wide application of bis-heterocycles, numerous synthetic strategies have been developed over the past decade, which involved the direct cross-coupling of two heterocycle substrates, 3 the oxidative cyclization of bis-heteronucleophiles with active methylhetarenes 4 and transition metal-catalyzed cascade cyclization reactions. 5 The latter could realize formation of multiple bonds in a simple one-pot reaction to enable the synthesis of heterocycles with a high efficiency.…”

Regioselective Synthesis of 5-Trifluoromethyl 1,2,4-Triazoles via [3 + 2]-Cycloaddition of Nitrile Imines with CF3CN

“…Wu and co-workers reported a iodine-mediated annulation and a FeCl 3 -mediated cascade annulation of trifluoroacetimidoyl chlorides and hydrazones or hydrazides for the synthesis of 5-trifluoromethyl-1,2,4-triazoles ( Scheme 1 a) [ 29 , 30 ]. Wu and co-workers subsequently developed a metal-free oxidative cyclization and a copper-catalyzed intramolecular decarbonylative cyclization reaction of trifluoroacetimidohydrazides with methylhetarenes or isatins for the synthesis of 5-trifluoromethyl-1,2,4-triazoles [ 31 , 32 , 33 ] and 2-(5-trifluoromethyl-1,2,4-triazol-3-yl)aniline derivatives [ 34 ], respectively. Darehkordi and co-workers described the synthesis of 1,3-diaryl-5-(trifluoromethyl)-1 H -1,2,4-triazoles via the iodine-mediated intramolecular oxidative cyclization of N -(2,2,2-trifluoro-1-(arylimino)ethyl)benzimidamide intermediates, synthesized from the reaction of N -aryl-2,2,2-trifluoroacetimidoyl chlorides and benzamide hydrochloride derivatives ( Scheme 1 c) [ 35 ].…”