IJOC  Vol.3 No.2 , June 2013
New Greener Alternative for Biocondensation of Aldehydes and Indoles Using Lemon Juice: Formation of Bis-, Tris-, and Tetraindoles

This work presents a new greener alternative for biocondensation of aldehydes and indoles for the synthesis of bis- and tris(indolyl)methanes catalyzed by lemon juice (Citrus limon) in good yields under ultrasound irradiation in aqueous ethanol. Various substituted aldehydes with indoles under this reaction condition are elucidated. Also, tetraindolyl compounds were prepared using terephthaldialdehyde by following the same protocol. This method is an environmentally benign, efficient reaction, which requires shorter reaction time and simple experimental and work-up procedures.

Cite this paper: R. Pal, "New Greener Alternative for Biocondensation of Aldehydes and Indoles Using Lemon Juice: Formation of Bis-, Tris-, and Tetraindoles," International Journal of Organic Chemistry, Vol. 3 No. 2, 2013, pp. 136-142. doi: 10.4236/ijoc.2013.32015.

[1]   R. J. Sundberg, “The Chemistry of Indoles,” Academic Press, New York, 1996.

[2]   M. Shiri, M. A. Zolfigol, H. G. Kruger and Z. Tanbakouchian, “Bis- and Trisindolylmethanes (BIMs and TIMs),” Chemical Reviews, Vol. 110, No. 4, 2010, pp. 2250-2293. doi:10.1021/cr900195a

[3]   C. A. Bradfield and L. F. Bjeldanes, “Structure-Activity Relationships of Dietary Indoles: A Proposed Mechanism of Action as Modifiers of Xenobiotic Metabolism,” Journal of Toxicology and Environmental Health, Vol. 21, No. 3, 2003, pp. 311-323. doi:10.1080/15287398709531021

[4]   M. Chakrabarty, N. Ghosh, R. Basak and Y. Harigaya, “Dry Reaction of Indoles with Carbonyl Compounds on Montmorillonite K10 Clay: A Mild, Expedient Synthesis of Diindolylalkanes and Vibrindole A,” Tetrahedron Letters, Vol. 43, No. 22, 2002, pp. 4075-4078. doi:10.1016/S0040-4039(02)00682-2

[5]   A. K. Mallik, R. Pal and T. K. Mandal, “Facile Formation of Bis(3-indolyl)methylarenes by Iodine-Catalyzed Reaction of Indole with α,α'-Bis(arylmethylene)ketones and α-Substituted Arylmethyleneketones in Dry Ethanol,” Indian Journal of Chemistry, Vol. 46B, No. 12, 2007, pp. 2056-2059.

[6]   R. J. Sundberg, “The Chemistry of Indoles,” Academic Press, New York, 1970.

[7]   M. Roomi and S. MacDonald, “Reductive C-Alkylation II,” Canadian Journal of Chemistry, Vol. 48, No. 1, 1970, pp. 39-143. doi:10.1139/v70-019

[8]   D. M. Pore, U. V. Desai, T. S. Thopate and P. P. Wadgaonkar, “A Mild, Expedient, Solventless Synthesis of Bis(indolyl)alkanes Using Silica Sulfuric Acid as a Reusable Catalyst,” Arkivoc, Vol. xii, 2006, pp. 75-80. doi:10.3998/ark.5550190.0007.c09

[9]   C. Ramesh, J. Banerjee, R. Pal and B. Das, “Silica Supported Sodium Hydrogen Sulfate and Amberlyst-15: Two Efficient Heterogeneous Catalysts for Facile Synthesis of Bisand Tris(1H-indol-3-yl)methanes from Indoles and Carbonyl Compounds,” Advanced Synthesis & Catalysis, Vol. 345, No. 3, 2003, pp. 557-559. doi:10.1002/adsc.200303022

[10]   K. R. M. Naidu, S. I. Khalivulla, P. C. R. Kumar and O. Lasekan, “KHSO4-SiO2 Catalyzed Facile Synthesis of Bis(indolyl)methanes,” Organic Communications, Vol. 5, No. 3, 2012, pp. 150-159.

[11]   J. T. Li and S. F. Sun, “Synthesis of Diindolylmethanes (DIMs) Catalyzed by Sillicotungstic Acid by Grinding Method,” E-Journal of Chemistry, Vol. 7, No. 3, 2010, pp. 922-926. doi:10.1155/2010/986980

[12]   G. A. Meshram and V. D. Patil, “Simple and Efficient Method for Synthesis of Bis(indolyl) Methanes with Cu(BF4)2·SiO2 Under Mild Conditions,” Synthetic Communications, Vol. 40, No. 1, 2010, pp. 29-38. doi:10.1080/00397910902916064

[13]   J. S. Yadav, B. V. S. Reddy, C. V. S. R. Murthy, G. M. Kumar and C. Madan, “Lithium Perchlorate Catalyzed Reactions of Indoles: An Expeditious Synthesis of Bis(indolyl)methanes,” Synthesis, Vol. 5, 2001, pp. 783787. doi:10.1055/s-2001-12777

[14]   R. Nagarajan and P. T. Perumal, “InCl3 and In(OTf)3 Catalyzed Reaction: Synthesis of 3-Acetyl Indoles, BisIndolylmethanes and Indolylquinoline Derivatives,” Tetrahedron, Vol. 58, No. 6, 2002, pp. 1229-1232. doi:10.1016/S0040-4020(01)01227-3

[15]   S. J. Ji, S. Y. Wang, Y. Zhang and T. P. Loh, “Facile Synthesis of Bis(indolyl)methanes Using Catalytic Amount of Iodine at Room Temperature under Solvent-Free Conditions,” Tetrahedron, Vol. 60, No. 9, 2004, pp. 20512055. doi:10.1016/j.tet.2003.12.060

[16]   G. V. M. Sharma, J. J. Reddy, P. S. Lakshmi and R. P. Krishna, “A Versatile and Practical Synthesis of Bis(indolyl)methanes/Bis(indolyl)glycoconjugates Catalyzed by Trichloro-1,3,5-triazine,” Tetrahedron Letters, Vol. 45, No. 41, 2004, pp. 7729-7732. doi:10.1016/j.tetlet.2004.08.084

[17]   R. Nagarajan and P. T. Perumal, “Electrophilic Substitution of Indoles Catalyzed by Triphenyl Phosphonium Trichlorate: Synthesis of 3-Acetyl Indoles and Bis-Indolylmethane Derivatives,” Synthetic Communications, Vol. 32, No. 1, 2002, pp. 105-109. doi:10.1081/SCC-120001515

[18]   C. J. Li and T. H. Chan, “Organic Reactions in Aqueous Media,” John Wiley & Sons, New York, 1997.

[19]   A. Kamal and A. A. Qureshi, “Syntheses of Some Substituted Di-indolylmethanes in Aqueous Medium at Room Temperature,” Tetrahedron, Vol. 19, No. 4, 1963, pp. 513-520. doi:10.1016/S0040-4020(01)98540-0

[20]   S. Kumar, I. S. Grover and J. S. Sandhu, “A Practical, Clean and Green Synthesis of Vibrindole and Bis(indolyl)methanes Catalyzed by Alum [KAl(SO4)2·12H2O] in Water,” Indian Journal of Chemistry, Vol. 48B, No. 4, 2009, pp. 585-589.

[21]   A. K. Mallik, R. Pal, C. Guha and H. Mallik, “A Convenient, Eco-friendly, and Efficient Method for Synthesis of Bis(3-indolyl)methanes on Water,” Green Chemistry Letters and Reviews, Vol. 5, No. 3, 2012, pp. 321-327. doi:10.1080/17518253.2011.630027

[22]   D. Chen, L. Yu and P.-G. Wang, “Lewis Acid-Catalyzed Reactions in Protic Media: Lanthanide-Catalyzed Reactions of Indoles with Aldehydes or Ketones,” Tetrahedron Letters, Vol. 37, No. 26, 1996, pp. 4467-4470. doi:10.1016/0040-4039(96)00958-6

[23]   S. Mishra and R. Ghosh, “Ecofriendly and Sustainable Efficient Synthesis of Bis(indolyl)methanes Based on Recyclable Brønsted (CSA) or Lewis (ZrOCl2·8H2O) Acid Catalysts,” Indian Journal of Chemistry, Vol. 50B, No. 11, 2011, pp. 1630-1636.

[24]   M. L. Deb and P. J. Bhuyan, “An Efficient and Clean Synthesis of Bis(indolyl)methanes in a Protic Solvent at Room Temperature,” Tetrahedron Letters, Vol. 47, No. 9, 2006, pp. 1441-1443. doi:10.1016/j.tetlet.2005.12.093

[25]   R. Ghorbani-Vaghei, H. Veisi, H. Keypour and A. A. Dehghani-Firouzabadi, “A Practical and Efficient Synthesis of Bis(indolyl)methanes in Water, and Synthesis of Di-, Tri-, and Tetra(bis-indolyl)methanes under Thermal Conditions Catalyzed by Oxalic Acid Dihydrate,” Molecular Diversity, Vol. 14, No. 1, 2010, pp. 87-96. doi:10.1007/s11030-009-9150-z

[26]   S. Y. Wang and S. J. Ji, “Facile Synthesis of Bis(indolyl)methanes Catalyzed by Ferric Dodecyl Sulfonate [Fe(DS)3] in Water at Room Temperature,” Synthetic Communications, Vol. 38, No. 8, 2008, pp. 1291-1298. doi:10.1080/00397910701873318

[27]   T. J. Mason, “Practical Sonochemistry,” Ellis Horwood, New York, 1991.

[28]   J. T. Li, S. X. Wang, G. F. Chen and T. S. Li, “Some Applications of Ultrasound Irradiation in Organic Synthesis,” Current Organic Synthesis, Vol. 2, No. 3, 2005, pp. 415-436. doi:10.2174/1570179054368509

[29]   X. F. Zeng, S. J. Ji and S. Y. Wang, “Novel Method for Syntheis of Unsymmetrical Bis(indolyl)alkanes Catalyzed by Cerric Ammonium Nitrate (CAN) under Ultrasonic Irradiation,” Tetrahedron, Vol. 61, No. 43, 2005, pp. 10235-10241. doi:10.1016/j.tet.2005.08.040

[30]   J. T. Li, H. G. Dai, W. Z. Xu and T. S. Li, “An Effficient and Practical Synthesis of Bis(indolyl)methanes Catalyzed by Aminosulfonic Acid Under Ultrasound,” Ultrasonics Sonochemistry, Vol. 13, No. 1, 2006, pp. 24-27. doi:10.1016/j.ultsonch.2004.12.004

[31]   S. Y. Wang, S. J. Ji and X. M. Su, “A Meldrum’s Catalyzed Bis(indolyl)methanes in Water Under Ultrasonic Condition,” Chinese Journal of Chemistry, Vol. 26, No. 1, 2008, pp. 22-24.

[32]   J. T. Li, X. H. Zhang and Y. L. Song, “Efficient Synthesis of Bis(indolyl)methanes Catalyzed by Silicotungstic Acid Under Ultrasound Irradiation,” International Journal of Chem Tech Research, Vol. 2, No. 1, 2010, pp. 341-345. doi:10.1002/cjoc.200890029

[33]   J. T. Li, M. X. Sun, G. Y. He and X. Y. Xu, “Efficient and Green Synthesis of Bis(indolyl)methanes Catalyzed by ABS in Aqueous Media Under Ultrasound Irradiation,” Ultrasonics Sono-chemistry, Vol. 18, No. 1, 2011, pp. 412-414. doi:10.1016/j.ultsonch.2010.07.016

[34]   R. Pal, S. Khasnobis and T. Sarkar, “First Application of Fruit Juice of Citrus Limon for Facile and Green Synthesis of Bisand Tris(indolyl)methanes in Water,” Chemistry Journal, Vol. 3, No. 1, 2013, pp. 7-12.

[35]   R. Pal, “Micro-wave-assisted Eco-Friendly Synthesis of Bis-, Tris(indolyl)methanes and Synthesis of Di-bis(indolyl)methanes Catalyzed by Fruit Juice of Citrus Limon Under Solvent-free Conditions,” IOSR Journal of Applied Chemistry, Vol. 3, No. 4, 2013, pp. 1-8. doi:10.9790/5736-0340108