Catalytic Preparation of 1-Aryl-Substituted 1,2,4-Triazolium Salts

Abstract

1,4-Diaryl- and 1-aryl-4-alkyl-substituted 1,2,4-triazolium salts are convenient air-stable precursors to carbenes used both as organocatalysts or as ligands for transition metal complexes. Traditionally, they are prepared via a multistep synthetic pathway with the low-yielding formation of the triazolium ring occurring in the last step. We have developed an alternative two-step synthesis involving the conversion of a primary amine or aniline derivative to the corresponding 4-substituted triazole followed by a copper-catalyzed arylation with diaryliodonium salts. This transition metal-catalyzed arylation can be carried out under mild conditions in acetonitrile and is tolerant toward both water and oxygen. Additionally, the high functional group tolerance of the protocol described here gives easy access to triazolium salts containing heterocyclic substituents or sulfides.

Synthesis of Benzo[4,5]thiazolo[2,3-c][1,2,4]triazole Derivatives via C-H Bond Functionalization of Disulfide Intermediates

“…Triazole, 3a , was prepared according to the literature procedure shown in Scheme 2 [ 46 , 48 ]. While the p -methoxybenzyl-protected aniline, 2a , could be obtained in this case by protecting 2-mercaptoaniline, 1a , under argon atmosphere, the lack of commercial availability of substituted 2-mercaptoanilines required the development of a different synthesis route.…”

Oxidative Cyclization of 4‐(2‐Mercaptophenyl)‐Substituted 4H‐1,2,4‐Triazolium Species to Tricyclic Benzothiazolium Salts

“…As previously reported, diaryliodonium salts offer the possibility of selectively arylating the N-1 position of 4- www.eurjoc.org substituted triazoles containing other nucleophilic atoms. [57] To explore the limits of the electron-donating and electron-withdrawing effects on the oxidative cyclization reaction, we synthesized a range of N-arylated triazolium salts 2 a-g by reacting 1 with a variety of diaryliodonium salts prepared by known literature procedures. [58,59] We found that carrying out the copper-catalyzed quaternization of triazole 1 gave the best isolated yields when the reaction was carried out in the presence of 1.1 equivalents instead of 1.5 equivalents of the diaryliodonium salt and the reaction time was increased from 4 h to overnight (Scheme 2).…”

“…As previously reported, diaryliodonium salts offer the possibility of selectively arylating the N‐1 position of 4‐substituted triazoles containing other nucleophilic atoms [57] . To explore the limits of the electron‐donating and electron‐withdrawing effects on the oxidative cyclization reaction, we synthesized a range of N ‐arylated triazolium salts 2 a – g by reacting 1 with a variety of diaryliodonium salts prepared by known literature procedures [58,59] .…”

“…In this report we demonstrate a three‐step synthesis of N ‐substituted tricyclic thiazolium salts 4 from triazole 1 (Scheme 1). Triazole 1 was prepared according to a literature procedure in 69 % yield [47,57] . Arylation or alkylation of triazole 1 gave the triazolium species 2 which upon deprotection to the free thiol 3 was observed to cyclize under oxidative conditions thereby leading to the tricyclic product 4 .…”

“…4‐(2‐((4‐methoxybenzyl)thio)phenyl)‐4H ‐ 1,2,4‐triazole ( 1 ) was prepared on a 100 mmol scale in 69 % yield according to a literature procedure [47,57] …”