An efficient and practical synthesis of bis(indolyl)methanes catalyzed by aminosulfonic acid under ultrasound
Introduction
Indole derivatives are found abundantly in a variety of natural plants and exhibit various physiological properties and are potentially bioactive compounds. Bis(indolyl)methanes and bis(indolyl)ethanes are important derivatives of indole. Bis(indolyl)methanes (BIM) are the most active cruciferous substances for promoting beneficial estrogen metabolism in woman and men [1]. BIM increase the body’s natural metabolism of hormones and promote good estrogen (2-hydroxyestrogen). This indole antioxidant is patented for alleviating symptoms of fibromyalgia. BIM is effective in the prevention of cancer due to its ability to modulate certain cancer causing estrogen metabolites [2]. Scientists have demonstrated that BIM induces apoptosis in human cancer cells and may also normalize abnormal cell growth associated with cervical dysplasia. Thus indole and its derivatives have been a topic of research interest [3].
The acid-catalyzed reaction of electron-rich heterocyclic compounds with p-dimethylaminobenzaldehyde is known as Ehrlich test for π-electron excessive heterocycles such as pyrroles and indoles. The analogous reaction of indole with other aromatic or aliphatic aldehydes and ketones produces azafulvenium salts, which can undergo further addition with the second indole molecule to afford BIM [4]. Protic acids as well as Lewis acids [5] are known to promote these reactions. Lanthanide triflates are also found to catalyze these reactions [6]. However, in spite of their potential utility, some of the reported methods suffer from drawbacks such as long reaction times, expensive catalysts, low yields and cumbersome product isolation procedures.
Aminosulfonic acid has been extensively used as a catalyst for many organic reactions, such as the esterification of carboxylic acids, the oxidation of aromatic aldehydes to carboxylic acids, the preparation of amines by decarbonylation of carboxamides with sodium hypochlorite and the synthesis of anthroquinonecarboxamides from anthroquinonecarboxylic acids, synthesis of dihydropyrimidinones via condensation of aldehydes, β-keto esters and urea [7].
Ultrasound has increasingly been used in organic synthesis in the last three decades. Compared with traditional methods, the procedure is more convenient and easily controlled. A large number of organic reactions can be carried out in higher yields, shorter reaction time or milder conditions under ultrasound irradiation [8]. Herein, we wish to report an efficient and practical synthesis of BIM catalyzed by aminosulfonic acid under ultrasound irradiation (Scheme 1).
Section snippets
Apparatus and analysis
Melting points were uncorrected. 1H NMR spectra were measured on a Bruker ADVANCE 400 (400 MHz) spectrometer using TMS as internal standard and CDCl3 or CD3COCD3 as solvent. Sonication was performed on a Shanghai Branson-CQX ultrasonic cleaner (with a frequency of 25 kHz and a nominal power of 250 W). The reaction flask was located in the maximum energy area in the cleaner, where the surface of reactants is slightly lower than the level of the water, and addition or removal of water was used to
Result and discussion
As shown in Table 1, the effects of different catalysts, such as AlCl3, ZnCl2, Montmorillonite clay K-10, silica sulfuric acid on the reaction were examined. Among these catalysts, aminosulfonic acid is found to be an excellent catalyst in terms of conversion and reaction time. So, we chose aminosulfonic acid as the catalyst for synthesis of BIM under ultrasound irradiation.
We studied the influence of the amount of the catalyst on the reaction time and yield. As shown in Table 2, increasing the
Conclusion
In conclusion, aminosulfonic acid was found to be a cheap, novel, convenient and efficient catalyst for the synthesis of BIM from indole and some carbonyl compounds under ultrasound irradiation.
Acknowledgements
The project was supported by Educational Ministry of China and Natural Science Foundation of Hebei Province (203107), PR China.
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