Metal‐Free Synthesis of 5‐Trifluoromethyl‐1,2,4‐Triazoles from Iodine‐Mediated Annulation of Trifluoroacetimidoyl Chlorides and Hydrazones

Abstract

A metal-free approach for the synthesis of 5-trifluoromethyl-1,2,4-triazoles from trifluoroacetimidoyl chlorides and hydrazones has been achieved under aerobic oxidative conditions. The reaction proceeds through a cascade base-promoted intermolecular CÀ N bond formation and iodinemediated intramolecular CÀ N bond oxidative coupling sequence. The protocol features broad substrate scope and can be scaled up to gram scale.

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

“…Based on the results from the mechanistic investigations and in previous literatures, [10,13] a plausible reaction mechanism was proposed as depicted in Scheme 4. Initially, the base‐mediated C−N bond coupling of trifluoroacetimidoyl chloride 1 with hydrazide 2 generated amidine derivative 5 .…”

“…In this context, trifluoroacetimidoyl halides have been frequently applied as versatile building blocks in synthetic organofluorine chemistry [9] . Very recently, our group reported an iodine‐mediated annulation reaction of trifluoroacetimidoyl chlorides and hydrazones to prepare a variety of 5‐trifluoromethyl‐1,2,4‐triazoles in good yields (Scheme 1e) [10] . Nevertheless, the hydrazones derived from aliphatic aldehydes were not applicable to the reaction, so 3‐alkyl‐fluorinated 1,2,4‐triazoles could not be furnished.…”

“…Nevertheless, the hydrazones derived from aliphatic aldehydes were not applicable to the reaction, so 3‐alkyl‐fluorinated 1,2,4‐triazoles could not be furnished. As a continuation of our ongoing research on the synthesis of trifluoromethyl‐containing N ‐heterocycles, [10,11] we herein present an FeCl 3 ‐mediated cascade annulation of trifluoroacetimidoyl chlorides and hydrazides to produce structurally diverse 5‐trifluoromethyl‐1,2,4‐triazoles under mild conditions (Scheme 1f).…”

“…[9] Very recently, our group reported an iodine-mediated annulation reaction of trifluoroacetimidoyl chlorides and hydrazones to prepare a variety of 5-trifluoromethyl-1,2,4-triazoles in good yields (Scheme 1e). [10] Nevertheless, the hydrazones derived from aliphatic aldehydes were not applicable to the reaction, so 3-alkyl-fluorinated 1,2,4-triazoles could not be furnished. As a continuation of our ongoing research on the synthesis of trifluoromethyl-containing N-heterocycles, [10,11] we herein present an FeCl 3 -mediated cascade annulation of trifluoroacetimidoyl chlorides and hydrazides to produce structurally diverse 5-trifluoromethyl-1,2,4-triazoles under mild conditions (Scheme 1f).…”

“…Optimization of reaction conditions. [a] , entries[6][7][8][9][10]. Further examination towards reaction temperature demonstrated that the low temperature was detrimental to the reaction and the elevated temperature had a marginal influence on the reaction with the slight decrease of the reaction efficiency(Table 1, entries[11][12][13].…”