Alkyne–azide click reaction catalyzed by metallic copper under ultrasound

Abstract

This protocol is for the ultrasound (US)-assisted 1,3-dipolar cycloaddition reaction of azides and alkynes using metallic copper (Cu) as the catalyst. The azido group is a willing participant in this kind of organic reaction and its coupling with alkynes is substantially improved in the presence of Cu(I). This protocol does not require additional ligands and proceeds with excellent yields. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) is generally recognized as the most striking example of 'click chemistry'. Reactions involving metals represent the favorite domain of sonochemistry because US favors mechanical depassivation and enhances both mass transfer and electron transfer from the metal to the organic acceptor. The reaction rate increases still further when simultaneous US and microwave irradiation are applied. The US-assisted click synthesis has been applied for the preparation of a wide range of 1,4-disubstituted 1,2,3-triazole derivatives starting both from small molecules and oligomers such as cyclodextrins (CDs). Using this efficient and greener protocol, all the adducts can be synthesized in 2-4 h (including work-up and excluding characterization). Click chemistry has been shown to be able to directly link chemistry to biology, thus becoming a true interdisciplinary reaction with extremely wide applicability.

Merging Metallic Catalysts and Sonication: A Periodic Table Overview

“…As depicted in Figure 1, both sonication alone (with a Ti horn) and simultaneous MW/US (pyrex horn) can be successfully employed [21,22]. Table 1.…”

“…Cyclodextrins form stable sandwich-type inclusion compounds with copper ions, giving rise to a green-grayish coloration that require time-consuming purifications using chelate agents [23]. Metallic copper as catalyst in dimethylformamide (DMF) at high temperature affords cyclodextrin-triazole derivatives (9 and 10, Scheme 3) as white powders, with only trace amounts of the metal [22]. Further extension of the same conceptual basis to imidazolium-functionalized alkynes led to positively charged triazole-bridged cyclodextrins (Scheme 4), which exhibit hybrid properties of cyclodextrins as encapsulating hosts and ionic liquids [24].…”

“…This protocol is much simpler and inexpensive than other catalysts employed for CuAAC reactions and works well in water, where the latter itself serves as ligand and metallic wastes are easily removed by filtration. As depicted in Figure 1, both sonication alone (with a Ti horn) and simultaneous MW/US (pyrex horn) can be successfully employed [21,22]. Table 1.…”

An Efficient Ultrasound-assisted Method for the Synthesis of 1,4-Disubstituted Triazoles

“…The disadvantage of the one-pot method is that the influence of ultrasound on the essential step of 1,3-dipolar cycloadditions can not be explored directly [12]. Cravotto chose only metallic copper as a catalyst for the investigation of the 1,3-dipolar cycloaddition in 1,4-dioxane/water with the help of ultrasound irradiation, however, a relatively high temperature was needed [13,14]. It is known that organic reactions in water are of great interest especially in relation to today's environmental concerns.…”

Optimization of biodiesel synthesis under simultaneous ultrasound-microwave irradiation using response surface methodology (RSM)

“…The main technical solutions for the difficulties faced in simultaneous ultrasound/microwave irradiation have been described by Cravotto and Cintas [19] and applied even for critical mixing involving metallic turnings [41].…”