Sonochemically Improved Diels-Alder Reactions
Diels-Alder reactions are widely used for chemical syntheses, where atomic carbon-carbon bonds must be formed. Ultrasonication and its sonochemical effects are highly efficacious in driving and promoting Diels-Alder reactions resulting in higher yields, significantly reduced reaction time and at the same time being part of environmental-friendly green chemistry.
Sonochemically-Enhanced Diels-Alder Reaction for Green Chemistry
The Diels-Alder reactions are chemical reactions, in which bonds between carbon atoms are formed. The Diels-Alder reaction is classified as a thermally-allowed [4+2] cycloaddition [π4s + π2s]. Since ultrasound-assisted organic synthesis is a green and efficient synthetic route, which enhances reaction rates, yields, and the selectivity of reactions, sonication is a simple and reliable technique used widely in laboratories and industrial production. Often, the sonochemically promoted route facilitates organic transformation at ambient conditions which otherwise require drastic conditions of temperature and pressure, which helps to save energy costs and turns the chemical synthesis into a saver procedure.
Ultrasonic Diels-Alder Reaction using Deep Eutectic Solvents
Deep eutectic solvents (DES) are solutions of Lewis or Brønsted acids and bases which form a eutectic mixture. Since deep eutectic solvents are non-flammable, possess low vapour pressures and toxicity, and are often made from natural compounds, they are a saver, more environmental-friendly solvent alternative. Ultrasonication and deep eutectic solvents are known to work synergistically together and are therefore used for chemical synthesis as well as in ultrasonic extraction. The use of deep eutectic solvents is beneficial in ultrasonically promoted Diels-Alder reactions, too. For instance, sonication is used to promote the Diels-Alder reaction using N-ethylmaleimide as dienophile, changing the nature of the diene in deep eutectic solvents (DES) under both conventional heating and ultrasonic activation.
Using ultrasonic activation in combination with deep eutectic solvents proved beneficial providing good yields in drastically reduced reaction times.
General Procedure for Diels-Alder Reaction using DES and Sonication
Ultrasonically-promoted Diels-Alder reactions were carried out by inserting the ultrasonic probe (sonotrode / horn) in the reaction vessel. Using an ultrasonic probe with 0.5 cm diameter tip, the nominal output power was 70 W. Reactions were performed at 40°C applying sonication inpulse mode with 5 sec ON and 20 sec OFF cycles. The ultrasonically intensified Diels-Alder reaction gave good yields in a much shorter time than under silent conditions (70 min and 24 h for sonochemical and silent reactions, respectively).
In order to evaluate the energy efficiency of the sonochemically-intensified Diels-Alder reaction, the energy consumption for the silent and the ultrasonically-promoted Diels-Alder reaction were compared. The calculations gave a consumption of 35,094 kJ/g for the silent reaction and 28.4 kJ/g for ultrasonically-assisted reaction (ultrasonic horn with an output power of 70 W net energy), respectively. This results in a 99% of energy saved for the sonochemically-driven Diels-Alder reaction. All these observations strongly suggest that the combined use of deep eutectic solvents (DES) and ultrasonication irradiation is an efficient and energy saving methodology for important synthetic processes like Diels-Alder reaction. (Marullo et al., 2020)
The Effect of Various Deep Eutectic Solvents in Combination with Sonication
Best results for ultrasonically-promoted Diels-Alder reaction were achieved, when the deep eutectic solvents [ChCl]:[Fru] and [TBACl]:[EG] are used as solvents. Using [ChCl]:[Fru] and [TBACl]:[EG] as solvents afforded significant reductions in reaction time as well as significant improvements in yield (for [TBACl]:[EG] 73% and 87%, and for [ChCl]:[Fru] 23 and 75% under silent and sonochemical conditions, respectively).
In some cases, namely when [TBPCl]:[EG], [ChCl]:[Gly], and [AcChCl]:[EG] are used as solvents, the yields are comparable to those obtained under silent conditions, but the rate of the chemical process is still drastically improved by sonication.
Sonication works very well with low vapour pressure and viscous solvents like ionic liquids (ILs) since these conditions facilitate the generation of more inetnse cavitation effects. Since deep eutectic solvents possess similar physical properties to ionic liquids, they can be suitably used in conjunction with ultrasonication. The combined interplay of deep eutectic solvents (DES) and sonication significantly decreases the energetic demand of the Diels-Alder reaction. Sigmificant reductions in reaction time from 24 h to 70 min can be observed whilst affording very good yields. In regards to process efficiency, this means that the combined use of deep eutectic solvents (DES) and ultrasonication allows to process an amount of materials 10 times higher than under silent conditions. (Marullo et al., 2020)
Ultrasonic Diels-Alder Reaction of Oxabicyclic Alkenes
Wei and colleagues (2004) showed that ultrasonication promoted the Diels–Alder reaction of substituted furans with reactive dienophiles such as dimethyl acetylenedicarboxylate (DMAD) and dimethyl maleate afforded functionalized oxabicyclic alkenes in good yields. The ultrasonically-promoted reaction of regiospecific furano Diels-Alder cycloaddition of 2-vinylic furans with DMAD furnished functionalized oxabicyclic alkenes in good yield.
Sonochemically Improved Cycloaddition Reactions
Bravo and colleagues (2006) described a series of sonochemical cycloadditions involving either cyclopentadiene or 1,3-cyclohexadiene with carbonyl dienophiles in an imidazolium-based ionic liquid as reaction medium. They demonstrated that ultrasonication does effectively improve these cycloaddition reactions resulting in higher yields and/or reduced reaction times when compared with the corresponding silent reactions. For instance, for simple α,β- unsaturated dienophiles such as methyl vinyl ketone or acrolein the effects of ultrasonic activation are obvious. For example, methyl vinyl ketone gives rise to 89% yield within 1 h of mild sonication, while the silent reaction afforded only 52% within the same reaction time.
Ultrasonicators at Any Size for Sonochemically Promoted Diels-Alder Reactions
Hielscher Ultrasonics designs, manufactures and distributes high-performance ultrasonic probe-type homogenizers and sonochemical equipment for the integration into chemical systems such as synthesis and catalysis reactions. Hielscher ultrasonicators are used world-wide as reliable tool to promote, intensify, accelerate and improve chemical reactions.
Hielscher Ultrasonics’ ultrasonic processors are available at any size from small lab devices to large industrial processors for batch and flow chemistry applications. Precise adjustment of the ultrasonic amplitude – the most important parameter for sonochemical applications – allows to operate Hielscher ultrasonicators at low to very high amplitudes and to fine-tune the amplitude exactly to the required ultrasonic process conditions of the specific chemical reaction system.
Hielscher’s ultrasonic generator feature a smart software with automatic data protocolling. All important processing parameters such as ultrasonic energy, temperature, pressure and time are automatically stored onto a built-in SD-card as soon as the device is switched on.
Process monitoring and data recording are important for continuous process standardization and product quality. By accessing the automatically recorded process data, you can revise previous sonication runs and evaluate the outcome.
Another user-friendly feature is the browser remote control of our digital ultrasonic systems. Via remote browser control you can start, stop, adjust and monitor your ultrasonic processor remotely from anywhere.
Contact us now to learn more about our high-performance ultrasonic homogenizers can improve your organic synthesis reaction such as Diels-Alder reactions, Mannich reactions or Michael addition amongst many others!
The table below gives you an indication of the approximate processing capacity of our ultrasonicators:
|Batch Volume||Flow Rate||Recommended Devices|
|1 to 500mL||10 to 200mL/min||UP100H|
|10 to 2000mL||20 to 400mL/min||UP200Ht, UP400St|
|0.1 to 20L||0.2 to 4L/min||UIP2000hdT|
|10 to 100L||2 to 10L/min||UIP4000hdT|
|n.a.||10 to 100L/min||UIP16000|
|n.a.||larger||cluster of UIP16000|
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Literature / References
- Salvatore Marullo, Alessandro Meli, Francesca D’Anna (2020): A Joint Action of Deep Eutectic Solvents and Ultrasound to Promote Diels-Alder Reaction in a Sustainable Way. ACS Sustainable Chem. Eng. 8, 2020. 4889-4899.
- Wei K, Gao H, Li WZ. (2004): Facile Synthesis of Oxabicyclic Alkenes by Ultrasonication-Promoted Diels-Alder Cycloaddition of Furano Dienes. Journal of Organic Chemistry 69(17), 2004. 5763-5765.
- Bravo, José; Lopez, Ignacio; Cintas, Pedro; Silvero, Guadalupe; Arévalo, María (2006): Sonochemical cycloadditions in ionic liquids. Lessons from model cases involving common dienes and carbonyl dienophiles. Ultrasonics Sonochemistry 13, 2006.. 408-414.
- Suslick, Kenneth S.; Hyeon, Taeghwan; Fang, Mingming; Cichowlas, Andrzej A. (1995): Sonochemical synthesis of nanostructured catalysts. Materials Science and Engineering: A. Proceedings of the Symposium on Engineering of Nanostructured Materials. ScienceDirect 204 (1–2): 186–192.
- Suslick, Kenneth S.; Didenko, Yuri ; Fang, Ming M.; Hyeon, Taeghwan; Kolbeck, Kenneth J.; McNamara, William B.; Mdleleni, Millan M.; Wong, Mike (1999): Acoustic cavitation and its chemical consequences. In: Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 357, No. 1751, 1999. 335-353.