Hg(II) Complexes Constructed from Indazole Ligands as New Heterogeneous Catalyst for the Biginelli/Transesterification Reaction: Synthesis and Quantum-Chemical Investigations

Document Type : Research Article


Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I.R. IRAN


The present work deals with the synthesis, spectral characterization, DFT calculations, and catalytic activity of the new Hg(II) complexes derived from indazole ligands. The o-amino-ketones were obtained from the reduction of 6H-isoxazolo[4,3-e]indazoles as new heterocyclic ligands. Coordination of the ligands to Hg(II) cation led to the formation of new Hg(II) complexes. The IR, mass, and NMR spectra as well as the elemental analyses confirmed the structures of the new complexes. Furthermore, the DFT calculations at the B3LYP/6-311+G(d,p) level were used to gain further insight into the geometry of Hg(II) complexes. The catalytic activity of Hg(II) complexes as heterogeneous catalysts was studied for the synthesis of biologically active 3,4-dihydropyrimidin-2(1H)-one C5 ester (DHPMs), using classical Biginelli reaction followed by transesterification transformation. The results showed that the presented method gave the products good to excellent yields at reduced reaction time, which might be owing to the increased reactivity of the reactants on the surface area of Hg(II) complexes.


Main Subjects

[1] Sheykhan M., Yahyazadeh A., Rahemizadeh Z., Cu–EDTA-Modified APTMS-Fe3O4@SiO2 Core–Shell Nanocatalyst: A Novel Magnetic Recoverable Catalyst for the Biginelli Reaction, RSC Advances, 6(41): 34553-34563 (2016).
[2] González-Hernández E., Aparicio R., Garayoa M., Montero M.J., Sevilla M.Á., Pérez-Melero C., Dihydropyrimidine-2-thiones as Eg5 Inhibitors and L-Type Calcium Channel Blockers: Potential Antitumour Dual Agents, Med. Chem. Comm., 10(9): 1589-1598 (2019).
[3] Thipparapu G, Ajumeera R, Venkatesan V Novel Dihydropyrimidine Derivatives as Potential HDAC Inhibitors: In Silico Study, In Silico Pharmacology, 5(1): 1-9 (2017).
[4] Chioua M., Buzzi E., Moraleda I., Iriepa I., Maj M., Wnorowski A., Giovannini C., Tramarin A., Portali F., Ismaili L., López-Alvarado P., Tacripyrimidines, the First Tacrine-Dihydropyrimidine Hybrids, as Multi-Target-Directed Ligands for Alzheimer's Disease: European Journal of Medicinal Chemistry, 155: 839-846 (2018).
[5] Majellaro M., Jespers W., Crespo A., Núñez M.J., Novio S., Azuaje J., Prieto-Díaz R., Gioé C., Alispahic B., Brea J., Loza M.I., 3, 4-Dihydropyrimidin-2 (1 H)-ones as Antagonists of the Human A2B Adenosine Receptor: Optimization, Structure–Activity Relationship Studies, and Enantiospecific Recognition, Journal of Medicinal Chemistry, 64(1): 458-480 (2020).
[7] Shen P, Xu M., Yin D., Xie S., Zhou C., Li F., Halogenated Macroporous Sulfonic Resins as Efficient Catalysts for the Biginelli Reaction, Catalysis Communications, 77: 18-21 (2016).
[8] Phukan M., Kalita M.K., Borah R., A New Protocol for Biginelli (or Like) Reaction Under Solvent-Free Grinding Method Using Fe (NO3) 3.9 H2O as Catalyst, Green Chemistry Letters and Reviews, 3(4): 329-334 (2010).
[9] Bebout D.C., DeLanoy A.E., Ehmann D.E., Kastner M.E., Parrish D.A., Butcher R.J. Characterization of Mercury (II) Complexes of Bis [(2-pyridyl) methyl] Amine by X-Ray Crystallography and NMR Spectroscopy, Inorganic Chemistry, 37(12): 2952-2959 (1998).
[10] Tokdemir Öztürk S., Aksu P., Turan N., Buldurun K., Tanış E., Çolak N., Preparation, Spectral Characterization, ESR Measurements and DFT Calculations of Schiff Base Copper (II) Complex, Inorganic and Nano-Metal Chemistry, 51(11): 1546-1552 (2021).
[12] Pordel M., Sobhani S., Beyramabadi S.A., New Catalyst for Biodiesel Formation: Synthesis, Structural Elucidation and Quantum Chemical Calculations of New Ni (II) Complexes, Iran. J. Chem. Chem. Eng. (IJCCE), 40(2): 1751-1762 (2021).
[14] Turan N., Tanış E., Buldurun K., Çolak N., Synthesis, Structure, DFT Calculations, and in Silico Toxic Potential of Ni (II), Zn (II), and Fe (II) Complexes with a Tridentate Schiff Base, Russian Journal of General Chemistry, 91(8): 1572-1577 (2021).
[15] Das R., Giri S., Muliwa A.M., Maity A., High-Performance Hg(II) Removal Using Thiol-Functionalized Polypyrrole (PPy/MAA) Composite and Effective Catalytic Activity of Hg (II)-adsorbed Waste Material, ACS Sustainable Chemistry & Engineering, 5(9): 7524-7536 (2017).
[17] Awual M.R., Novel Nanocomposite Materials for Efficient and Selective Mercury Ions Capturing from Wastewater, Chemical Engineering Journal, 307: 456-465 (2017).
[18] Zhang X., Guo X., Yuan H., Jia X., Dai B., One-Pot Synthesis of a Natural Phenol Derived Fluorescence Sensor for Cu (II) and Hg (II) Detection, Dyes and Pigments, 155: 100-106 (2018).
[19] Cao Y., Luo C., Yang P., Li P., Wu C., Indazole Scaffold: A Generalist for Marketed and Clinical Drugs, Medicinal Chemistry Research, 30(3): 501-518 (2021).
[20] Wan Y., He S., Li W., Tang Z., Indazole Derivatives: Promising Anti-Tumor Agents, Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 18(9): 1228-1234 (2018).
[21] Dong J, Zhang Q, Wang Z, Huang G, Li S Recent Advances in the Development of Indazole-Based Anticancer Agents. Chem. Med. Chem., 13(15):1490-1507 (2018).
[22] Denya I., Malan S.F., Joubert J., Indazole Derivatives and their Therapeutic Applications: A Patent Review (2013-2017), Expert Opinion on Therapeutic Patents, 28(6): 441-453 (2018).
[23] Biginelli P., Gazz P., Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones, Chim. Ital., 23: 360-416 (1893).
[26] Peralta J.E., Scuseria G.E., Frisch M.J., Noncollinear Magnetism in Density Functional Calculations, Physical Review B, 75(12):125119 (2007).
[27] Lee C., Yang W., Parr R.G., Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density, Physical Review B, 37(2): 785 (1988).
[28] Hay P.J., Wadt W.R., Ab initio Effective Core Potentials for Molecular Calculations. Potentials for the Transition Metal Atoms Sc to Hg, The Journal of Chemical Physics, 82(1): 270-283 (1985).
[30] Vosburgh W.C., Cooper G.R., Complex Ions. I. The Identification of Complex Ions in Solution by Spectrophotometric Measurements, Journal of the American Chemical Society, 63(2): 437-442 (1941).
[31] Alikhani E., Pordel M., Beyramabadi S.A., New Zn(Li) Complexes Derived From Fluorescent Benzimidazoles: Synthesis, Spectral Characterization, Density Functional Theory Calculations, and Antibacterial Studies, Indian Journal of Heterocyclic Chemistry, 29(4): 311-318 (2019).
[33] Nagarajaiah H., Mukhopadhyay A., Moorthy J.N., Biginelli Reaction: An Overview, Tetrahedron Letters, 57(47): 5135-5149 (2016).
[34] Kalita H.R., Phukan P., CuI as Reusable Catalyst for the Biginelli Reaction, Catalysis Communications, 8(2): 179-182 (2016).
[35] Patil S., Jadhav S.D., Mane S.Y., Pineapple Juice as a Natural Catalyst: An Excellent Catalyst for Biginelli Reaction, International Journal of Organic Chemistry, 1(3): 125 (2011).