Click Chemistry – How to Enhance Click Reactions with Sonication

Click chemistry reactions such as copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions can greatly benefit from the application of power ultrasound. Sonochemical effects increase yield and conversion rate. Additionally, the overall efficiency of click chemistry reactions is improved. As a technique of green chemistry, ultrasonication contributes to more efficient and environmental-friendlier chemical reactions.

Ultrasonically Promoted Copper-Catalyzed Azide-Alkyne Cycloaddition

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is renown as the most important and prominent example of click chemistry reactions. Cravotto and colleagues from the Univerisity of Turin (Italy) have developed a protocol for an ultrasound-assisted 1,3-dipolar cycloaddition reaction of azides and alkynes using metallic copper (Cu) as catalyst. The azido group is a willing participant in this kind of organic reaction. The coupling capacity of the azido group with alkynes is substantially improved in the presence of Cu(I) and sonication promotes the click reaction.

Sonochemically enhanced click chemistry: The copper-catalyzed cycloaddition with phenylacetylene is improved by ultrasonication.
(Study and graphic: © Cintas et al., 2010)

Advantages of Sonochemical Reactions

Ultrasonic synthesis (sono-synthesis) has emerged as one of the most appreciated intensifying techniques in chemistry due to multiple advantages. Sonochemically promoted reactions excel conventional agitated or thermal-based methods with respects to reaction rate, yield, operational simplicity, purity of the products, energy efficiency etc. It is scientifically demonstrated that the use of power ultrasound can promote chemical reactions, and can decrease reaction time as well as unwanted side reactions. As an alternative green source of energy, sonication makes many chemical reactions environmental-friendlier as less reactants, milder solvents, and less energy are required.

Sonochemical Copper-Catalyzed Organic Reactions

The beneficial effects of ultrasound and sonochemistry to reactions involving metals are well-known. Sonication promotes mechanical removal of passivating layers and enhances both mass transfer and electron transfer from the metal to the organic acceptor.
The ultrasound-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.
(cf. Cintas et al., 2010)

Time-Saving Click Chemistry due to Ultrasonically Accelerated Reaction Kinetics

The implementation of ultrasound can accelerate slow chemical reactions, which take normally several hours in batch mode. Due to significantly improved reaction kinetics, the reaction time can be reduced to several minutes. Using an ultrasonic flow reactor can considerably improve the yields, obtain time savings and thereby resulting in great efficacy of conventionally slow syntheses.

High-Performance Ultrasonicators for Sonochemically Enhanced Click Reactions

Hielscher Ultrasonics designs, manufactures and distributes high-performance probe-type ultrasonicators, sonochemical reactors and accessories for sophisticated sonochemical processes. With ultrasonic processors ranging from 50 watts to 16,000 watts per probe (sonotrode / horn), Hielscher is able to offer you the most suitable sonochemical setup for your chemical reaction.
Hielscher ultrasonicators are recognized for their quality, reliability and robustness. Hielscher Ultrasonics is an ISO certified company and put special emphasis on high-performance ultrasonicators featuring state-of-the-art technology and user-friendliness. Of course, Hielscher ultrasonicators are CE compliant and meet the requirements of UL, CSA and RoHs.

The table below gives you an indication of the approximate processing capacity of our ultrasonicators: