Catalyst and Solvent-Free Microwave Assisted Expeditious Synthesis of 3-Indolyl-3-hydroxy Oxindoles and Unsymmetrical 3,3-Di(indolyl)indolin-2-ones


A simple and efficient method for the synthesis of 3-indolyl-3-hydroxy oxindoles and unsymmetrical 3,3-di(indolyl)indolin-2-ones using microwave irradiation without catalyst and solvent is described. A series of 3-indolyl-3-hydroxy oxindoles and unsymmetrical 3,3-di(indolyl)indolin-2-ones have been synthesized in very short reaction times of 5 and 10 minutes and in yields ranging from 31% to 98% and from 53% to 78% respectively. This method offers a significant advantage over the conventional methods in terms of simplicity and shorter reaction time. To the best of our knowledge compounds N-allyl-3-hydroxy-3-(1-methyl-indol-3-yl)indolin-2-one (6c), N-allyl-3-hydroxy-3-(5-methoxy-indol-3-yl)indolin-2-one (8c), N-benzyl-3-hydroxy-3-(1-methyl-indol-3-yl) indolin-2-one (10c), N-propargyl-3-hydroxy-3-(1-methyl-indol-3-yl)indolin-2-one (13c), N-propargyl-3-hydroxy-3-(5-methoxy-indol-3-yl)indolin-2-one (14c), 3-(5-methoxy-1H-indol-3-yl)-3-(1H-indol-3-yl)indolin-2-one (1e), 3-1-methyl(5-methoxy-1H-indol-3-yl)-3-(1H-indol-3-yl)indolin-2-one (2e), 3-1-allyl(5-methoxy-1H-indol-3-yl)-3-(1H-indol-3-yl)indolin-2-one (3e), 3-1-benzyl(5-methoxy-1H-in- dol-3-yl)-3-(1H-indol-3-yl)indolin-2-one (4e) and 3-1-(prop-2-ynyl)(5-methoxy-1H-indol-3-yl)-3(1H-indol-3-yl)indolin-2-one (5e) are reported here for the first time. All the compounds are characterized by IR, 1H, 13C NMR and HRMS.

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Vuram, P. , Kabilan, C. and Chadha, A. (2015) Catalyst and Solvent-Free Microwave Assisted Expeditious Synthesis of 3-Indolyl-3-hydroxy Oxindoles and Unsymmetrical 3,3-Di(indolyl)indolin-2-ones. International Journal of Organic Chemistry, 5, 108-118. doi: 10.4236/ijoc.2015.52012.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Paira, P., Hazra, A., Kumar, S., Paira, R., Sahu, K.B., Naskar, S., Saha, P., Mondal, S., Maity, A., Banerjee, S. and Mondal, N.B. (2009) Efficient Synthesis of 3,3-Diheteroaromatic Oxindole Analogues and Their in Vitro Evaluation for Spermicidal Potential. Bioorganic & Medicinal Chemistry Letters, 19, 4786-4789.
[2] Subba Reddy, B.V., Rajeswari, N., Sarangapani, M., Prashanthi, Y., Ganji, R.J. and Addlagatta, A. (2012) Iodine-Catalyzed Condensation of Isatin with Indoles: A Facile Synthesis of Di(indolyl)indolin-2-ones and Evaluation of Their Cytotoxicity. Bioorganic & Medicinal Chemistry Letters, 22, 2460-2463.
[3] Pajouhesh, H., Parson, R. and Popp, F.D. (1983) Potential Anti-convulsants VI: Condensation of Isatins with Cyclohexanone and Other Cyclic Ketones. Journal of Pharmaceutical Sciences, 72, 318-321.
[4] DeLorbe, J.E., Jabri, S.Y., Mennen, S.M., Overman, L.E. and Zhang, F.L. (2011) Enantioselective Total Synthesis of (+)-Gliocladine C: Convergent Construction of Cyclotrypta-mine-Fused Polyoxopiperazines and a General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors. Journal of the American Chemical Society, 133, 6549-6552.
[5] Guo, C., Song, J., Huang, J.-Z., Chen, P.-H., Luo, S.-W. and Gong, L.-Z. (2012) Core-Structure-Oriented Asymmetric Organocatalytic Substitution of 3-Hydroxyoxindoles: Application in the Enantioselective Total Synthesis of (+)-Folicanthine. Angewandte Chemie-International Edition, 51, 1046-1050.
[6] Berens, U., Brown, J.M., Long, J. and Selke, R.D. (1996) Synthesis and Resolution of 2,2'-Bis-diphenylphosphino [3,3']biindolyl, a New Atropisomeric Ligand for Transition Metal Catalysis. Tetrahedron: Asymmetry, 7, 285-292.
[7] Kumar, V.P., Reddy, V.P., Sridhar, R., Srinivas, B., Narender, M. and Rao, K.R. (2008) Supramolecular Synthesis of 3-Indolyl-3-hydroxy Oxindoles under Neutral Conditions in Water. Journal of Organic Chemistry, 73, 1646-1648.
[8] Jafarpour, M., Rezaeifard, A., Gazkar, S. and Danehchin, M. (2011) Catalytic Activity of a Zirconium (IV) Schiff Base Complex in Facile and Highly Efficient Synthesis of Indole Derivatives. Transition Metal Chemistry, 36, 685-690.
[9] Sarrafi, Y., Alimohammadi, K., Sadatshahabi, M. and Norozipoor, N. (2012) An Improved Catalytic Method for the Synthesis of 3,3-Di(indolyl)oxindoles Using Amberlyst 15 as a Heterogeneous and Reusable Catalyst in Water. Monatshefte für Chemie, 143, 1519-1522.
[10] Jafarpour, M., Rezaeifard, A. and Gorzin, G. (2011) Enhanced Catalytic Activity of Zr(IV) Complex with Simple Tetradentate Schiff Base Ligand in the Clean Synthesis of Indole Derivatives. Inorganic Chemistry Communications, 14, 1732-1736.
[11] Kamal, A., Srikanth, Y.V.V., Khan, M.N.A., Shaik, T.B. and Ashraf, M. (2010) Synthesis of 3,3-Diindolyl Oxyindoles Efficiently Catalysed by FeCl3 and Their in Vitro Evaluation for Anticancer Activity. Bioorganic & Medicinal Chemistry Letters, 20, 5229-5231.
[12] Azizian, J., Mohammadi, A.A., Karimi, N., Moham-madizadeh, M.R. and Karimi, A.R. (2006) Silica Sulfuric Acid a Novel and Heterogeneous Catalyst for the Synthesis of Some New Oxindole Derivatives. Catalysis Communications, 7, 752-755.
[13] Alinezhad, H., Haghighi, A.H. and Salehian, F. (2010) A Green Method for the Synthesis of Bis-Indolylmethanes and 3,3’-Indolyloxindole Derivatives Using Cellulose Sulfuric Acid under Solvent-Free Conditions. Chinese Chemical Letters, 21, 183-186.
[14] Saffar-Teluri, A. (2014) Boron Trifluoride Supported on Nano-SiO2: An Efficient and Reusable Heterogeneous Catalyst for the Synthesis of Bis(indolyl)methanes and Oxindole Derivatives. Research on Chemical Intermediates, 40, 1061-1067.
[15] Sarrafi, Y., Al-imohammadi, K., Sadatshahabi, M. and Norozipoor, N. (2012) An Improved Catalytic Method for the Synthesis of 3,3-Di(indolyl)oxindoles Using Amberlyst 15 as a Heterogeneous and Reusable Catalyst in Water. Monatshefte für Chemie—Chemical Monthly, 143, 1519-1522.
[16] Karimi1, N., Oskooi1, H., Heravi, M., Saeedi, M., Zakeri, M. and Tavakoli, N. (2011) On Water: Bronsted Acidic Ionic Liquid [(CH2)4SO3HMIM][HSO4] Catalysed Synthesis of Oxindoles Derivatives. Chinese Journal of Chemistry, 29, 321-323.
[17] Azizian, J., Mohammadi, A.A., Karimi, A.R. and Mohammadizadeh, M.R. (2004) KAl(SO4)2.12H2O as a Recyclable Lewis Acid Catalyst for Synthesis of Some New Oxindoles in Aqueous Media. Journal of Chemical Research, 2004, 424-426.
[18] Yadav, J.S., SubbaReddy, B.V., Uma, G.K., Meraj, S. and Prasad, A.R. (2006) Bismuth (III) Triflate Catalyzed Condensation of Isatin with Indoles and Pyrroles: A Facile Synthesis of 3,3-Diindolyl- and 3,3-Dipyrrolyl Oxindoles. Synthesis, 2006, 4121-4123.
[19] Feng, G.L., Geng, L.J. and Zhang, H.L. (2009) Facile Synthesis of 3,3-Di(indolyl)indolin-2-one Derivatives Catalyzed by ZrO2/S2O82- Solid Superacid under Grinding Condition. Chemical Journal on Internet, 11, Article ID: 111001pe.
[20] Chakrabarty, M., Sarkar, S. and Harigaya, Y. (2005) A Facile Clay-Mediated Synthesis of 3,3-Diindolyl-2-indolinones from Isatins. Journal of Chemical Research, 8, 540-542.
[21] Deb, M.L. and Bhuyan, P.J. (2009) Water-Promoted Synthesis of 3,3’-Di(indolyl)oxindoles. Synthetic Communications, 39, 2240-2243.
[22] Praveen, C., Ayyanar, A. and Perumal, P.T. (2011) Practical Synthesis, Anticonvulsant, and Antimicrobial Activity of N-Allyl and N-Propargyl Di(indolyl)indolin-2-ones. Bioorganic & Medicinal Chemistry Letters, 21, 4072-4077.
[23] Wang, S.Y. and Ji, S.J. (2006) Facile Synthesis of 3,3-Di(heteroaryl)indolin-2-one Derivatives Catalyzed by Ceric Ammonium Nitrate (CAN) under Ultrasound Irradiation. Tetrahedron, 62, 1527-1535.
[24] Moghadam, K.R., Kiasaraie, M.S. and Amlashi, H.T. (2010) Synthesis of Symmetrical and Unsymmetrical 3,3-Di(indolyl)-indolin-2-ones under Controlled Catalysis of Ionic Liquids. Tetrahedron, 66, 2316-2321.
[25] Nikpassand, M., Mamaghani, M., Tabatabaeian, K. and Samimi, H.A. (2010) An Efficient and Clean Synthesis of Symmetrical and Unsymmetrical 3,3-Di(indolyl)indolin-2-ones Using KSF. Synthetic Communications, 40, 3552-3560.
[26] Shanthi, G., Lakshmi, N.V. and Perumal, P.T. (2009) A Simple and Eco-Friendly Synthesis of 3-Indolyl-3-hydroxy Oxindoles and 11-Indolyl-11H-indeno[1,2-b]quinoxalin-11-ols in Aqueous Media. ARKIVOC, 2009, 121-130.
[27] Meshram, H.M., Kumar, D.A., Goud, P.R. and Reddy, B.C. (2010) ChemInform Abstract: Triton B Assisted, Efficient, and Convenient Synthesis of 3-Indolyl-3-hydroxy Oxindoles in Aqueous Medium. Synthetic Communications, 40, 39-45.
[28] Hosseini-Sarvari, M. and Tavakolian, M. (2012) Preparation, Characterization, and Catalysis Application of Nano-Rods Zinc Oxide in the Synthesis of 3-Indolyl-3-hydroxy Oxindoles in Water. Applied Catalysis A: General, 441-442, 65-71.
[29] Khorshidi, A. and Tabatabaeian, K.J. (2011) An Ultrasound-Promoted Green Approach for the Synthesis of 3-(Indol- 3-yl)-3-hydroxyindolin-2-ones Catalyzed by Fe(III). Journal of the Serbian Chemical Society, 76, 1347-1353.
[30] Makarem, S., Fakhari, A.R. and Mohammadi, A.A. (2012) Electro-Organic Synthesis of Nanosized Particles of 3-Hydroxy- 3-(1H-indol-3-yl)indolin-2-one Derivatives. Monatshefte für Chemie—Chemical Monthly, 143, 1157-1160.
[31] Srihari, G. and Murthy, M.M. (2011) Kaolin/KOH Is an Efficient Heterogeneous Catalyst for the Synthesis of 3-Hydroxy-3-indolyl Oxindoles. Synthetic Communications, 41, 2684-2692.
[32] Deng, J., Zhang, S., Ding, P., Jiang, H., Wang, W. and Li, J. (2010) Facile Creation of 3-Indolyl-3-hydroxy-2-oxindoles by an Organocatalytic Enantioselective Friedel-Crafts Reaction of Indoles with Isatins. Advanced Synthesis & Catalysis, 352, 833-838.
[33] Hanhan, N.V., Sahin, A.H., Chang, T.W., Fettinger, J.C. and Franz, A.K. (2010) Catalytic Asymmetric Synthesis of Substituted 3-Hydroxy-2-oxindoles. Angewandte Chemie International Edition, 49, 744-747.
[34] Prathima, P.S., Rajesh, P., Rao, J.V., Kailash, U.S., Sridhar, B. and Rao, M.M. (2014) “On Water” Expedient Synthesis of 3-Indolyl-3-hydroxy Oxindole Derivatives and Their Anticancer Activity in Vitro. European Journal of Medicinal Chemistry, 84, 155-159.
[35] Lakhdar, S., Westermaier, M., Terrier, F., Goumont, R., Boubaker, T., Ofial, A.R. and Mayr, H. (2006) Nucleophilic Reactivities of Indoles. The Journal of Organic Chemistry, 71, 9088-9095.

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