One-Pot Three Component Domino Reaction for the Synthesis of Novel Isoxazolo[2,3-c][1,3,5]Thiadiazepin-2-Ones Catalyzed by PTSA—A Green Chemistry Approach


The synthesis of novel isoxazolo[2,3-c][1,3,5]thiadiazepin-2-ones has been achieved in excellent yields by one-pot three-component Domino reaction without the production of toxic waste products by using p-toluene sulfonic acid (PTSA) as a Lewis acid catalyst. PTSA plays a crucial role in the success of the reaction, as well as for increasing reaction rate.

Share and Cite:

Rajanarendar, E. , Venkateshwarlu, P. , Krishna, S. , Reddy, K. and Thirupathaiah, K. (2015) One-Pot Three Component Domino Reaction for the Synthesis of Novel Isoxazolo[2,3-c][1,3,5]Thiadiazepin-2-Ones Catalyzed by PTSA—A Green Chemistry Approach. Green and Sustainable Chemistry, 5, 107-114. doi: 10.4236/gsc.2015.53014.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kappe, C.O. (2000) Recent Advances in the Biginelli Dihydropyrimidine Synthesis. New Tricks from an Old Dog. Accounts of Chemical Research, 33, 879-888.
[2] Zhu, J. and Bienayne, H. (2005) Multi-Component Reactions. Wiley-VCH-Wenkein, Germany.
[3] Ramon, D.J. and Yus, M. (2005) Asymmetric Multi-Component Reactions (AMCRs): The New Frontier. Angewandte Chemie International Edition, 44, 1602-1634.
[4] Volla, C.M.R., Atodiresei, I. and Rueping, M. (2014) Catalytic C-C Bond Forming Multi-Component Cascade or Domino Reaction: Pushing the Boundaries of Complexity in Asymmetric Organocatalysis. Chemical Reviews, 114, 2390-2431.
[5] Stevens, M., Pannecouque, C. and De Clercq, E. (2003) Inhibition of Human Immunodeficiency Virus by a New Class of Pyridine Oxide Derivatives. Antimicrobial Agents and Chemotherapy, 47, 2951-2957.
[6] Menendez, J.C. (2006) Multicomponent Reactions. Synthesis, 15, 2624.
[7] Bertozzi, F., Gustafsson, M. and Olsson, R. (2002) A Novel Metal Iodide Promoted Three-Component Synthesis of Substituted Pyrrolidines. Organic Letters, 4, 3147-3150.
[8] Bagley, M.C., Cala, J.W. and Bower, J. (2002) A New One-Pot Three-Component Condensation Reaction for the Synthesis of 2,3,4,6-Tetrasubstituted Pyridines. Chemical Communications, 6, 1682-1683.
[9] Huma, H.Z.S., Halder, R., Kalra, S.S., Das, J. and Iqbal, J. (2002) Cu(I)-Catalyzed Three Component Coupling Protocol for the Synthesis of Quinoline Derivatives. Tetrahedron Letters, 43, 6485-6488.
[10] Domling, A. and Ugi, I. (2000) Multicomponent Reactions with Isocyanides. Angewandte Chemie International Edition, 39, 3168-3210.<3168::AID-ANIE3168>3.0.CO;2-U
[11] Yu, L., Chen, B. and Huang, X. (2007) Multicomponent Reactions of Allenes, Diaryl Diselenides, and Nucleophiles in the Presence of Iodosobenzene Diacetate: Direct Synthesis of 3-Functionalized-2-Arylselenyl Substituted Allyl Derivatives. Tetrahedron Letters, 48, 925-927.
[12] Khosropour, A.R., Khodaei, M.M. and Moghannian, H. (2005) A Facile, Simple and Convenient Method for the Synthesis of 14-Alkyl or Aryl-14-H-Dibenzo[a,j]xanthenes Catalyzed by pTSA in Solution and Solvent-Free Conditions. Synlett, No. 6, April, 955-958.
[13] Nadaraj, V., Selvi, S.T. and Sasi, R. (2006) Microwave-Assisted Synthesis of Quinoline Alkaloids: 4-Methoxy-1-Methyl-2-Quinolinone and Its Analogs. Arkivoc, 2006, 82-89.
[14] Maluindarante, M.P.D. and Wimalsena, K. (1998) Detailed Characterization of p-Toluenesulfonic Acid Monohydrate as a Convenient, Recoverable, Safe, and Selective Catalyst for Alkylation of the Aromatic Nucleus. The Journal of Organic Chemistry, 3, 2858-2866.
[15] Longhi, K., Moreira, D.N., Marzari, M.R.B., Floss, V.M., Bonacorso, H.G., Zanatta, N. and Martins, M.A.P. (2010) An Efficient Solvent-Free Synthesis of NH-Pyrazoles from β-Dimethylaminovinylketones and Hydrazine on Grinding. Tetrahedron Letters, 51, 3193-3196.
[16] Kazuo, O. and Yoh-Ichi, M. (1992) Synthesis and Antiarrhythmic Activity of 2, 5-Disubstituted 2,3-Dihydro-1,2,5-Benzothiadiazepin-4(5H)-One-1,1-Dioxides. Chemical & Pharmaceutical Bulletin, 40, 2442-2447.
[17] Kidwai, M., Sapra, P., Misra, P., Saxena, R.K. and Singh, M. (2001) Microwave Assisted Solid Support Synthesis of Novel 1,2,4-Triazolo[3,4-b]1,3,4-Thiadiazepines as Potent Antimicrobial Agents. Bioorganic & Medicinal Chemistry, 9, 217-220.
[18] Anusha, D., Rubig, S. and Sarita, K. (2006) Microwave Enhanced Solid Support Synthesis of Fluorine Containing Benzopyrano-Triazolo-Thiadiazepines as Potent Antifungal Agents. Bioorganic & Medicinal Chemistry, 14, 1303-1308.
[19] Geeta, A.S., Vijayaraj, R., Kumar, T.R. and Anand, R.S. (2011) Synthesis of Certain 3-Pyridyl [1,2,4]Triazolo[3,4-b][1,3,4] Thiadiazepines and Evaluation of Their Possible Biological Activities. International Journal of Research in Pharmaceutical and Biomedical Sciences, 2, 155-159.
[20] Daidone, G., Raffa, D., Maggio, B., Plescia, F., Cutuli, V.M.C., Mangano, N.G. and Caruso, A. (1999) Synthesis and Pharmacological Activities of Novel 3-(Isoxazol-3-yl)-Quinazolin-4(3H)-One Derivatives. Archiv der Pharmazie, 332, 50-54.
[21] Talley, J.J., Brown, D.L., Carter, J.S., Graneto, M.J., Koboldt, C.M., Masferrer, J.L., Perkins, W.E., Rogers, R.S., Shaffer, A.F., Zhang, Y.Y., Zweifel, B.S. and Seibert, K. (2000) 4-[5-Methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, Valdecoxib: A Potent and Selective Inhibitor of COX-2. Journal of Medicinal Chemistry, 43, 775-777.
[22] Li, W.T., Hwang, D.-R., Chen, C.-P., Shen, C.-W., Huang, C.-L., Chen, T.-W., Lin, C.-H., Chang, Y.-L., Chang, Y.-Y., Lo, Y.-K., Tseng, H.-Y., Lin, C.-C., Song, J.-S., Chen, H.-C., Chen, S.-J., Wu, S.-H. and Chen, C.-T. (2003) Synthesis and Biological Evaluation of N-Heterocyclic Indolyl Glyoxylamides as Orally Active Anticancer Agents. Journal of Medicinal Chemistry, 46, 1706-1715.
[23] Rajanarendar, E., Govardhan Reddy, K., Shivarami Reddy, A. and Nagi Reddy, M. (2012) Brownsted Ionic Liquid [HMim]BF4 Promoted Simple and Efficient One-Pot Green Synthesis of Isoxazolyl-1,3-Benzoxazines at Ambient Temperature. Green Chemistry Letters and Reviews, 5, 699-705.
[24] Rajanarendar, E., Nagi Reddy, M. and Ram Murthy, K. (2010) Multi-Component Synthesis of Methylene Bis-Isoxazolo[4,5-b]Pyridine-N-Oxides. Chinese Chemical Letters, 21, 927-930.
[25] Rajanarendar, E., Venkateshwarlu, P. and Ram Krishna, S. (2012) Ceric Ammonium Nitrate Catalyzed One-Pot Synthesis of Novel Isoxazolyl-Hexahydroquinindolinones Cerammoniumnitrat Katalysierten One-Pot Synthese von Neuartigen Isoxazolyl-Hexahydroquinindolinones. Heterocyclic Letters, 2, 283-289.
[26] Rajanarendar, E., Thirupathaiah, K., Ram Krishna, S. and Kishore, B. (2013) Green Chemistry Approach to Fast and Highly Efficient One-Pot Synthesis of Bis-Isoxazolyl-1,2,5,6-Tetrahydropyridine-3-Carboxylates. Green and Sustainable Chemistry, 3, 9-18.
[27] Rajanarendar, E., Goverdhan Reddy, K. and Ram Krishna, S. (2015) A Facile One-Pot Synthesis of Highly Functionalized Isoxazolyl Imidazo[1,2-a]Pyridines through CuI-Promoted Cyclization. Journal of Heterocyclic Chemistry, 52, 660-668.
[28] Rajanarendar, E., Nagi Reddy, M., Govardhan Reddy, K. and Rama Krishna, S. (2012) L-Proline Catalyzed Efficient One-Pot Three-Component, Aza-Diels—Alder Reactions on Nitrostyryl Isoxazoles: A Facile Synthesis of New Isoxazolyl Tetrahydroquinolines and Isoxazolo[2, 3-a] Pyrimidines. Tetrahedron Letters, 53, 2909-2913.
[29] Rajanarendara, E., Nagi Reddy, M. and Raju, S. (2011) An Efficient One-Pot Synthesis of Polyhydroquinolines via Hantzsch Condensation Using L-Proline as Catalyst. Indian Journal of Chemistry—Section B, 50B, 751-755.
[30] Rajanarendar, E., Nagi Reddy, M. and Shaik, F.P. (2011) An Efficient One Pot Three Component Synthesis of New Isoxazolyl Polyhydroacridine-1,8-Diones in an Ionic Liquid Medium. Indian Journal of Chemistry—Section B, 50B, 245-252.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.