A Rapid, Catalyst-Free, Three-Component Synthesis of Rhodanines in Water Using Ultrasound

Abstract

A green, efficient, rapid, high-yielding, catalyst-free method for the synthesis of rhodanines in water using ultrasonic irradiation is described. The procedure is straightforward and the rhodanine products are isolated by simple filtration.The use of water as a solvent has many advantages in organic processes and reactions, both in industry and in green chemistry applications. It is economical, non-toxic and environmentally friendly. The hydrophobic products produced when using water as the solvent are separable by extraction with an organic solvent. 1 Increasingly, ultrasound has been used in organic synthesis. 2 Compared with traditional methods, the use of ultrasound is more convenient and easily controlled. A large number of organic reactions can be carried out in higher yields and shorter times under mild ultrasonic irradiation conditions. [2][3][4][5] One of the main objectives of organic and medicinal chemistry is the design and synthesis of molecules having value as human therapeutic agents. 6 Rhodanines, in particular, are known to possess a wide spectrum of biological activity including the inhibition of targets such as HCV NS3 protease 6 and b-lactamase. 7 As a part of our ongoing research on the synthesis of heterocyclic compounds with medicinal applications, 8 and based on our previous study on the synthesis of rhodanine, 9 we became interested in the development of a green and practical method to synthesize rhodanines of potential pharmacological and biological interest via sonochemistry.Herein, we report a simple, efficient, one-pot method for the synthesis of rhodanine derivatives in high yields (86-94%) and in short times (3-5 minutes) using ultrasonic irradiation and water as the reaction medium.In order to evaluate the efficiency of this method the synthesis of rhodanine 3a, via reaction of dimethyl acetylenedicarboxylate (DMAD, 2a), carbon disulfide (CS 2 ) and benzylamine (1a) as a model system, was carried out in water using ultrasonic irradiation (US) or high-speed stirring (HSS) ( Table 1).To our surprise, the one-pot, three-component synthesis of rhodanine 3a in water as the solvent using ultrasonic irradiation was complete in three minutes, but the highspeed stirring method required a reaction time of one hour to go to completion (Figure 1). We next investigated the effect of various solvents on the synthesis of rhodanine 3a (model system) using ultrasonic irradiation and high-speed stirring. In each case reactions using the ultrasound method were complete within three minutes with the highest yield of 94% being obtained in Table

Ordered mesoporous SBA‐15/PrSO3Pd and SBA‐15/PrSO3PdNP as active, reusable and selective phosphine‐free catalysts in CX activation Heck coupling process

“…In 2009 and then 2010, Song and co‐workers reported SO 3 H‐functionalized mesoporous silicas such as Pd/SO 3 H‐MCM‐41, Pd/SO 3 H‐MCM‐48 and Pd/SO 3 H‐MSU‐1 and other Pd/SO 3 H mesoporous materials for direct synthesis of hydrogen peroxide from hydrogen and oxygen . Here, we fabricated covalently bonded sulfonic acid/SBA‐15 silica porous nanoreactor based on our previous reports [12h,j] . We then prepared various Pd‐based pre‐catalysts on the SBA‐15/SO 3 H using an ion‐exchange method and reduction of the Pd ions (Fig.…”

“…After hydrothermal preparation of SBA‐15, [12h] a mixture of calcined SBA‐15 (1 g) and (3‐mercaptopropyl)trimethoxysilane (1.75 g) in dry toluene (13 ml) was refluxed for 24 h. The product was filtered, and then dried under vacuum. The solid product was oxidized with H 2 O 2 (30%, excess) and two drop of H 2 SO 4 in methanol (20 ml) for 20 h [12h,j] . Then the mixture was filtered and washed with H 2 O.…”

“…As part of our ongoing programme involving organic CC and Cheteroatom bond forming and development of efficient and environmentally benign green methods in synthetic organic chemistry, our aim has been to investigate the design of catalysts to accomplish the desired Heck CC cross‐coupling with minimum by‐products and waste, as well as to decrease palladium leaching. Here, we present the results of an extended investigation of the activity and efficiency of a series of palladium‐supported functionalized SBA‐15 as a fast, waste‐free, green approach to the synthesis of unsymmetric biaryls.…”

Solvent‐Free and Catalysts‐Free Chemistry: A Benign Pathway to Sustainability

“…[63] In this work, the authors reported a one-pot procedure using aldehydes, amines, and diethylphosphite under ultrasound-assisted SF-CF conditions; aromatic amines yielded the best results (83-92 %). [65] The reaction was performed in water by simple mixing of dimethyl or ethyl acetylenedicarboxylate, carbon disulfide, and an amine; products were isolated in high yields (86-94 %) and in short reaction times (3-5 min) by straightforward filtration (Scheme 19). [64] The ultrasoundpromoted synthesis of rhodanine derivatives, of potential pharmacological and biological interest, was explored by Rostamnia and Lamei.…”

Synthesis and Synthetic Applications of Biologically Interesting Rhodanine and Rhodanine-Based Scaffolds

“…After our first report in 2009, later, we provided another green, but rapid and high-yielding method for the synthesis of alkyl rhodanines in water using ultrasonic irradiation [51]. The procedure was promoted by sonication.…”