Organic Chemistry Portal
Organic Chemistry Highlights

Ultrasound Chemistry

Saturday, September 5, 2009
Ricardo A. W. Neves Filho, Diogo R. M. Moreira
Universidade Federal de Pernambuco

Part 3: Facile synthesis of amines, amides, imines and hydrazones promoted by ultrasound irradiation

High yielding ultrasound mediated three-component synthesis of substituted propargylamines

Sreedhar and co-workers from Indian Institute of Chemical Technology have described a mild one-pot, three-component synthesis of substituted propargylamines by using ultrasound irradiation (Tetrahedron Lett. 2005, 46, 7019. DOI: 10.1016/j.tetlet.2005.08.047) In this A3-coupling reaction, the sound waves promote a fast addition of metallic acetylides to imides that have been generated in situ. The acoustic protocol has been employed successfully for synthesizing 15 propargylamines in high yields. It has been found that 4- or 3-methoxybenzaldehyde substrates were weakly reactive under such conditions, thus their use resulted in poor conversions. The use of ultrasound irradiation has decreased the reaction time as well as the use of large amount of copper catalyst in comparison to conventional procedures. Moreover, in this method, commonly used organic solvents have been replaced by water, thus it may be considered as an eco-friendly protocol. In the light of these findings, He and co-workers have found that this protocol of an A3-coupling reaction also works well under microwave irradiation (Synth. Commun. 2007, 37, 849. DOI: 10.1080/00397910601131320).

First high-yielding ultrasound-mediated synthesis of functionalized amides

Recently, the group of Srivastava from Federal University of Pernambuco, Brazil, has reported a new clean, one-pot synthesis of secondary amides from carboxylic acids and amines by employing ethyl chloroformate as coupling agent and ultrasound irradiation. (Ultrasonics Sonochem. 2009, 16, 737. DOI: 10.1016/j.ultsonch.2009.04.006). The protocol has been used to synthesize fourteen amides in moderate to good yields in 1 h of total reaction time. The reaction has worked well when employing aliphatic, aromatic as well as heteroaromatic carboxylic acids. A large number of structurally different amines have also been tested, and it was found that the reaction can be performed with either alkylamines or anilines. Nonetheless, just one limitation of the presented method has been found: the hindered adamantanamine did not undergo the reaction. The use of sound wave activation has been found to be essential because when the reaction was carried out by using conventional stirring, no changes in the starting materials took place.

Ultrasound-mediated preparation of functionalized imines

Guzen and coworkers from State University of São Paulo (Brazil) have reported a quick and cost-effective alternative for the synthesis of symmetrical and unsymmetrical imines in high yields and E stereoselectivity, by using unmodified silica as catalyst and ultrasound irradiation (Tetrahedron Lett. 2007, 48, 1845. DOI: 10.1016/j.tetlet.2007.01.014). The advantageous properties of the silica rather than other solid catalysts are in terms of yields, costs, reaction conditions, and also quantities of reactants. The efficiency of this method was attributed to the ability of ultrasonic irradiation to increase the available surface of silica, at the same time, pushing up the solubility of reactants in ethanol. The scale-up of the method has been investigated and it was found that even at 50 mmol scale the reactions have worked well. Furthermore, silica-gel catalyst has been used many times with remarkable results and only slight loss of catalytic activity. Therefore, the abovementioned approach is quite attractive for the preparation of imines on laboratory or industrial scale.

High yielding synthesis of aromatic hydrazones through ultrasonication

The arylhydrazone unit is widely used in pharmaceutical compositions and consequently, the search for quick and mild syntheses of such important compounds has been the focus of research in many research groups. In the light of this scenario, Jarikote and co-workers from National Chemical Laboratory (India) have developed a novel protocol for the catalyst-free synthesis of substituted arylhydrazones by employing sonication as the energy source. (Ultrasonics Sonochem. 2003, 10, 45. DOI: 10.1016/S1350-4177(02)00100-1). In fact, the reaction of arylhydrazines and aldehydes or ketones under ultrasound irradiation at room temperature has been employed for synthesizing 12 products in high yields (90-96%) in just 1 h of reaction time. The method presented a large scope of applications but, as a drawback, it demands the use of an argon atmosphere, since low conversion of starting materials took place without using such an inert gas.

High yielding preparation of aromatic thiosemicarbazones and analogues

Leite and co-workers from Federal University of Pernambuco (Brazil) have described a rapid, diastereoselective (only E-isomers) and easy synthesis of aromatic thiosemicarbazones using ultrasound irradiation at room temperature (Tetrahedron Lett. 2008, 49, 1538. DOI: 10.1016/j.tetlet.2007.12.103). Although the reactants were insoluble in water, ultrasound irradiation increased their solubility, thus an efficient and fast condensation of carbonyl compounds with thiosemicarbazide was observed. Moreover, this protocol has also been successfully applied for synthesizing aromatic semicarbazones as well as guanyl hydrazones in good yields, while under conventional heating, lower conversions are observed after 1 h of reaction time. As a limitation, no conversion has been observed by using benzophenone as substrate.

Hetero-Michael reactions of substituted aminofuran-2-one derivatives via ultrasound irradiation

Recently, an interesting protocol for the hetero-Michael reactions to give substituted aminofuran-2-one derivatives has been disclosed by Arcadi, Alfonsi and Marinelli from University of L’Aquila-Via Vetoio (Italy). The reaction of alkyl 4-hydroxy-2-alkynoates with primary or secondary amines under neutral conditions and ultrasound irradiation at r.t. afforded highly functionalized aminofuran-2-ones in yields ranging from 50-90%. Moreover, when these reactions were performed with conventional stirring, lower conversions were always observed, even under prolonged reaction times (Tetrahedron Lett. 2009, 50, 2060. DOI: 10.1016/j.tetlet.2009.02.106).

R. A. W. N. Filho, D. R. M. Moreira, Org. Chem. Highlights 2009, September 5.