An Efficient Green Approach for the Synthesis of Structurally Diversified Spirooxindoles Using Sulfonic Acid Functionalized Nanoporous Silica (SBA-Pr-SO3H)

Document Type: Research Article


1 Department of Chemistry, Alzahra University, P.O. Box 1993891176 Tehran, I.R. IRAN

2 School of Chemistry, University of Tehran, P.O. Box 14155-6455 Tehran, I.R. IRAN


One-pot multicomponent reaction between isatin, barbituric acid, and 6-amino-1,3-dimethyl uracil was investigated in the presence of sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H) and resulted in the formation of spirooxindole dipyrimidines. Spirooxindole unit is found in many natural products and biologically active molecules and 1,4-dihydropyridines are an important class of compounds with interesting biological activities such as vasolidator, antitumor, antidiabetic, bronchodilator and anti-atherosclerotic activities. Excellent yields and short reaction timesare related to the highefficiency of SBA-Pr-SO3H that the reactions take place easily in its nano-pores. Mild reaction conditions and easy work-up procedures are other advantages of this green method.


Main Subjects

[1] Orru R.V., Ruijter E., “Synthesis of Heterocycles via Multicomponent Reactions II”, Vol. 2: Springer-Verlag Berlin Heidelberg, (2010).
[2] Gu Y., Multicomponent Reactions in Unconventional Solvents: State of the Art, Green Chem., 14: 2091-2128 (2012).
[3] Liang B., Kalidindi S., Porco J.A., Stephenson C.R.J., Multicomponent Reaction Discovery: Three-Component Synthesis of Spirooxindoles, Org. Lett., 12: 572-575 (2010).
[4] Bhaskar G., Arun Y., Balachandran C., Saikumar C., Perumal P.T., Synthesis of Novel Spirooxindole Derivatives by One Pot Multicomponent Reaction and their Antimicrobial Activity, Eur. J. Med. Chem., 51: 79-91 (2012).
[5] Lo M.M.C., Neumann C.S., Nagayama S., Perlstein E.O., Schreiber S.L., A Library of Spirooxindoles Based on a Stereoselective Three-Component Coupling Reaction, J. Am. Chem. Soc., 126: 16077-16086 (2004).
[6] Galliford C.V., Scheidt K.A., Pyrrolidinyl-Spirooxindole Natural Products as Inspirations for the Development of Potential Therapeutic Agents, Angew. Chem. Int. Ed., 46: 8748-8758 (2007).
[7] Deppermann N., Thomanek H., Prenzel A.H.G.P., Maison W., Pd-Catalyzed Assembly of Spirooxindole Natural Products: A Short Synthesis of Horsfiline, J. Org. Chem., 75: 5994-6000 (2010).
[8] Trost B.M., Brennan M.K., Asymmetric Syntheses of Oxindole and Indole Spirocyclic Alkaloid Natural Products, Synthesis, 2009: 3003-3025 (2009).
[9] Cheng D., Ishihara Y., Tan B., Barbas III C.F., Organocatalytic Asymmetric Assembly Reactions: Synthesis of Spirooxindoles via Organocascade Strategies, ACS Catal., 4: 743-762 (2014).
[10] Lashgari N., Mohammadi Ziarani G., Badiei A., Zarezadeh-Mehrizi M., Application of Sulfonic Acid Functionalized SBA-15 as a New Nanoporous Acid Catalyst in the Green One-Pot Synthesis of Spirooxindole-4H-pyrans, J. Heterocycl. Chem., 51: 1628-1633 (2014).
[11] Ball-Jones N.R., Badillo J.J., Franz A.K., Strategies for the Enantioselective Synthesis of Spirooxindoles, Org. Biomol. Chem., 10: 5165-5181 (2012).
[12] Goldmann S., Stoltefuss J., 1,4-Dihydropyridines: Effects of Chirality and Conformation on the Calcium Antagonist and Calcium Agonist Activities, Angew. Chem. Int. Ed., 30: 1559-1578 (1991).
[13] Morshed S.R.M., Hashimoto K., Murotani Y., Kawase M., Shah A., Satoh K., Kikuchi H., Nishikawa H., Maki J., Sakagami H., Tumor-Specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines, Anticancer Res., 25: 2033-2038 (2005).
[14] Briede J., Stivrina M., Vigante B., Stoldere D., Duburs G., Acute Effect of Antidiabetic 1,4-Dihydropyridine Compound Cerebrocrast on Cardiac Function and Glucose Metabolism in the Isolated, Perfused Normal Rat Heart, Cell Biochem. Funct., 26: 238-245 (2008).
[15] Stout D.M., Meyers A., Recent Advances in the Chemistry of Dihydropyridines, Chem. Rev., 82: 223-243 (1982).
[16] Melero J.A., van Grieken R., Morales G., Advances in the Synthesis and Catalytic Applications of Organosulfonic-Functionalized Mesostructured Materials, Chem. Rev., 106: 3790-3812 (2006).
[17] Pouretedal H.R., Basati S., Characterization and Photocatalytic Activity of ZnO, ZnS, ZnO/ZnS, CdO, CdS and CdO/CdS Nanoparticles in Mesoporous SBA-15, Iran. J. Chem. Chem. Eng. (IJCCE), 34: 11-19 (2015).
[18] Mohammadi Ziarani G., Lashgari N., Badiei A., Sulfonic Acid-Functionalized Mesoporous Silica (SBA-Pr-SO3H) as Solid Acid Catalyst in Organic Reactions, J. Mol. Catal. A: Chem., 397: 166-191 (2015).
[20] Wight A.P., Davis M.E., Design and Preparation of Organic−Inorganic Hybrid Catalysts, Chem. Rev., 102: 3589-3614 (2002).
[22] Mohammadi Ziarani G., Shakiba Nahad M., Lashgari N., Badiei A., Facile Microwave-Assisted Synthesis of 2-Aryloxazolo[4,5-b]pyridines Using SBA-Pr-NH2, J. Nanostruct. Chem., 5: 39-44 (2015).
[23] Mohammadi Ziarani G., Badiei A., Azizi M., Zarabadi P., Synthesis of 3,4-Dihydropyrano[c] Chromene Derivatives Using Sulfonic Acid Functionalized Silica (SiO2PrSO3H), Iran. J. Chem. Chem. Eng. (IJCCE), 30: 59-65 (2011).
[24] Mohammadi Ziarani G., Mousavi S., Lashgari N., Badiei A., Shakiba M., Application of Sulfonic Acid Functionalized Nanoporous Silica (SBA-Pr-SO3H) in the Green One-pot Synthesis of Polyhydroacridine Libraries, Iran. J. Chem. Chem. Eng. (IJCCE), 32: 9-16 (2013).
[25] Gholamzadeh P., Mohammadi Ziarani G., Lashgari N., Badiei A., Asadiatouei P., Silica Functionalized Propyl Sulfonic Acid (SiO2-Pr-SO3H): An Efficient Catalyst in Organic Reactions, J. Mol. Catal. A: Chem., 391: 208-222 (2014).
[26] Mohammadi Ziarani G., Badiei A.R., Khaniania Y., Haddadpour M., One Pot Synthesis of Polyhydroquinolines Catalyzed by Sulfonic Acid Functionalized SBA-15 as a New Nanoporous Acid Catalyst under Solvent Free Conditions, Iran. J. Chem. Chem. Eng. (IJCCE), 29: 1-10 (2010).
[27] Khalafi-Nezhad A., Mohammadi S., Magnetic, Acidic, Ionic Liquid-Catalyzed One-Pot Synthesis of Spirooxindoles, ACS Comb. Sci., 15: 512-518 (2013).
[29] Khalafi-Nezhad A., Shahidzadeh E.S., Sarikhani S., Panahi F., A New Silica-Supported Organocatalyst Based on L-proline: An Efficient Heterogeneous Catalyst for One-Pot Synthesis of Spiroindolones in Water, J. Mol. Catal. A: Chem., 379: 1-8 (2013).