Mechanistic Insights into Copper(I)‐Catalyzed Azide‐Alkyne Cycloadditions using Continuous Flow Conditions

Abstract

Abstract:The copper-catalyzed azide-alkyne cycloaddition (CuAAC, "click chemistry") was studied employing copper-in-charcoal (Cu/C) and a variety of copper metal sources as "heterogeneous" catalysts. The type and pretreatment conditions of the different copper sources on the CuAAC were investigated. In addition, the effect of copper leaching from the catalyst over time and in dependence on the reaction mixture composition was studied by ICP-MS analysis in the continuous flow mode. These investigations confirm a "homogeneous" mechanism and suggest surface layer copper(I) oxide as the catalytically active species in CuAAC chemistry involving zerovalent copper metal.

Synthesis of 1,2,3-triazole-linked galactohybrids and their inhibitory activities on galectins

“…32 Various flow techniques for elimination of copper traces have been developed as well. 30,33 Careful control of copper content is necessitated by aspects such as limits on heavy metals in pharmaceutically active compounds, 30 product stability 34 and inhibition of enzymes by copper ions. 35,36 Nevertheless, there are not many examples where the residual copper has been analyzed in the carbohydrate-triazole conjugates which were obtained via CuAAC reaction.…”

Flow Technology for Organometallic-Mediated Synthesis

“…Kappe and coworkers reported some examples of click chemistry in flow [55]. Copper metal and copper-on-charcoal (Cu-C) were suitable sources of "heterogeneous" catalysts for the azide-alkyne cycloaddition (CuAAC).…”

Bifunctional Derivatives of (Thia)calix[4]-arenes with Terminal Double and Triple Bonds: Synthesis and Azide-Alkyne Click Reactions

“…[19] бензил-азид [20] и п-нитрофенилазид [21] синтезировали по литературным методикам. Общая методика получения триазолов 11-14: К смеси каликсарена (8а или 10) и азида (соотношение каликсарен:азид = 1:3), растворенных в смеси толуола и триэ-тиламина (3.5 и 0.5 мл на 0.1 г каликсарена, соответственно), добавляли иодид меди(I) (0.003 г, 0.0157 ммоля на 0.1 г каликс-арена).…”