Highly efficient synthesis of bis(indolyl)methanes in water

https://doi.org/10.1016/j.molcata.2007.05.024Get rights and content

Abstract

A simple, atom economy and highly efficient green protocol have been developed for synthesis of bis(indolyl)alkane by the reaction of indole derivatives with aldehydes and ketones in the presence of small amount of the heteropoly acids in water.

Graphical abstract

A simple, atom economy and highly efficient green protocol have been developed for synthesis of bis(indolyl)alkane by the reaction of indole derivatives with aldehydes and ketones in the presence of small amount of the heteropoly acids in water.

Introduction

There has been tremendous interest to develop highly efficient transformations for the preparation of organic compounds, as well as, biologically active materials, with potential application in the pharmaceutical or agrochemical industries, from the commercially available compounds. There is also a need for synthetic chemists to find new, efficient, and strategically important processes, which are environmentally benign and lead to the greater structural variation in a short period of time with high yields and simple work up procedure. For this reasons, over the last few year's enormous advances have been made to chemical processes to achieve the ultimate goal of hazard-free, waste-free, and energy-efficient synthesis [1]. In this context, organic reaction in water has played an important role in these processes and several organic reactions have been shown that are accelerate in water [2], [3], [4], [5], [6].

Indole framework is present in many substances commonly found in nature [7], [8], as well as in many compounds that show pharmacological and biological activities [9], [10], [11], [12]. The bis(indolyl)alkane moiety is also present in various natural products possessing important biological activity [13], [14], [15], [16], [17], [18]. Therefore, a number of synthetic methods for preparation of bis(indolyl)alkane derivatives have been reported in the literature by reaction of indole with various aldehydes and ketones in the presence of either a Lewis acid [19], [20] or a protic acid [21], [22], [23], [24], [25], [26], [27], [28], [29], [30].

In fact, the acids commonly used are generally toxic catalysts, difficult to handle, stoichiometric amount maybe needed, and require tedious aqueous work-up, along with the use of environmentally harmful organic solvents. In view of the importance of bis(indolyl)alkane derivatives, these problems were overcome to some extent by recently reported green methods under solvent-free conditions or using ionic liquids as reaction medium [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]. However, to the best of our knowledge, only few reports have been published for the synthesis of indole derivatives in water [37], [42], [43], [44], [45].

Section snippets

General procedure for preparation of bis(indolyl)methanes

To the mixture of indole (2 mmol), an aldehyde or a ketone (1 mmol), water (4 mL), H3PW12O40 (10 mg) or H3PMo12O40 (10 mg) was added and stirred vigorously at room temperature until the disappearance of the starting indole (1–8 h). When the reaction was complete, the reaction mixture was filtrate and washed with water. The crude product was analyzed by NMR and purified by recrystallization or column chromatography (EtOAc–petroleum ether) to afford the pure bisindole.

General procedure for preparation of di(1H-indol-3-yl)acetic acid (6)

To the mixture of indole (2 mmol),

Results and discussion

Due to the commercial availability, ease of handing, remarkably low toxicity, environmentally friendly, and economically feasible solid catalyst, organic reactions using heteropoly acids, HPAs, received more attention in recent years [46], [47], [48], [49]. In continuation of our ongoing interest in using water as reaction medium [50], [51], [52], [53], [54], [55], [56], we herein report the use of HPAs as catalysts in the electrophilic substitutions of indole and substituted indole with a

Conclusion

In conclusion, we have described a simple, convenient and efficient protocol for the synthesis of wide range of bis(1H-indol-3-yl)alkane in water. The simplicity, efficiency, mild reaction condition, high yields of products, easy work up procedure, and using very small amount of heteropoly acids make it the preferred procedure for the preparation of different kind of bis(1H-indol-3-yl)alkane. Another important feature of this methodology is the use of heteropoly acids as catalyst, water as

Acknowledgment

We are grateful to the Research Council of Sharif University of Technology for financial support.

References (57)

  • A.L. Smith et al.

    Biorg. Med. Chem. Lett.

    (2000)
  • Y. Liu et al.

    Tetrahedron Lett.

    (2000)
  • T. Walsh et al.

    Tetrahedron

    (2001)
  • J.D. Rainier et al.

    Tetrahedron Lett.

    (2000)
  • Y.M. Wang et al.

    J. Heterocycl. Chem.

    (1998)
  • H. Firouzabadi et al.

    J. of Mole. Catal. A

    (2006)
  • B.P. Bandgar et al.

    Tetrahedron Lett.

    (2003)
  • M. Chakrabarty et al.

    Tetrahedron Lett.

    (2002)
  • D.P. Chen et al.

    Tetrahedron Lett.

    (1996)
  • R. Nagarajan et al.

    Tetrahedron

    (2002)
  • X.L. Mi et al.

    Tetrahedron Lett.

    (2004)
  • L. Wang et al.

    Synlett

    (2005)
  • M.L. Deb et al.

    Tetrahedron Lett.

    (2006)
  • L.E. Briand et al.

    J. Appl. Catal. A

    (2003)
  • M.N. Timofeeva

    Apl. Catal. A.

    (2003)
  • B. Mirmashhori et al.

    J. Mol. Catal. A

    (2006)
  • N. Azizi et al.

    J. Organometallic Chem.

    (2006)
  • N. Azizi et al.

    Catalysis Commun.

    (2006)
  • T. Osawa et al.

    Mutat. Res.

    (1983)
  • D.J. Adams et al.

    Chemistry in Alternative Reaction Media

    (2004)
  • J.L. Chao

    Chem. Rev.

    (2005)
  • C.J. Li et al.

    Organic Reactions in Aqueous Media

    (1997)
  • M.C. Pirrung et al.

    J. Am. Chem. Soc.

    (2004)
  • K. Manabe et al.

    J. Am. Chem. Soc.

    (2002)
  • H. Firouzabadi et al.

    Adv. Synth. Catal.

    (2005)
  • R.A. Glennon

    J. Med. Chem.

    (1997)
  • M.G.N. Russell et al.

    J. Med. Chem.

    (2001)
  • H.-C. Zhang et al.

    Org. Lett.

    (2000)
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