SYNTHESIS of PYRIDINES by USING METAL OXIDES on ZIRCONIA SUPPORT AS CATALYSTS By

SYNTHESIS OF PYRIDINES BY USING METAL OXIDES ON ZIRCONIA SUPPORT AS CATALYSTS by SEBENZILE BEAUTY SHABALALA Submitted in fulfillment of the academic requirements for the degree of Master of Science in the Chemistry, School of Chemistry & Physics College of Agriculture, Engineering and Science University of KwaZulu-Natal Durban May 2017 As the candidate’s supervisor I have approved this thesis for submission Supervisor: Prof. Sreenkantha Jonnalagadda Signed:……………………….. Date: ………. Co-Supervisor: Prof. Werner Van Zyl Signed:……………………….. Date: ……… i ABSTRACT In recent years, there has been a concern for the development and design of sustainable chemical routes, which resulted in Green Chemistry, a concept that became popularized in the 1990s with the intention to reduce pollution. It encouraged the planning of chemical processes to attain a final product that would, amongst other things, use the same amount of input materials, the use of green solvents as well as the use of environmentally friendly materials, which are non- toxic. Multicomponent reactions (MCRs) have become very attractive subjects in organic synthesis due to the formation of C-C and C-hetero atoms in a one-pot synthesis. They have emerged as processes with considerable ecological interest as they address the fundamental principles of synthetic efficiency and reaction design. This arises from minimization of waste, time, energy, and cost. In this study, heterogeneous catalysts with an increased activity have been synthesized and applied as easily recoverable catalysts, and focused on the effect of heterogeneous catalysts reaction’s parameters on the catalytic activity and selectivity of 1, 4- dihydropyridines synthesis. Heterocyclic structures are commonly useful templates for the design and improvement of potent and specific biologically active agents. Pyridines and their derivatives form an important class of heterocyclic compounds and owing to their properties are desired in many different fields, such as natural products, pharmaceuticals, and functionalized materials. They also show a wide range of biological properties, such as antibacterial, antioxidant, antiviral, anticancer, anticonvulsant and antihypertension activity. Pyridines are also known for their anti- inflammatory activity and can act as antagonist’s inhibitors. This study is based on the development efficient and environmental-friendly techniques and routes for the synthesis of heterocyclic compounds (pyridines), in the presence of variety of reusable catalysts. The synthesis of functionalized 1,4-dihydropyridine derivatives by the incorporation of dimethylacetylenedicarboxylate, 4-fluoroaniline, malononitrile with various substituted ii benzaldehydes using Sm2O3/ZrO2 as catalyst with ethanol as solvent and at room temperature has been achieved with (87-96%) yields. A CeO2/ZrO2 heterogeneous catalyst was employed for the synthesis of pyridine derivatives via a one-vessel, four-component reaction consisting of substituted benzaldehyde, malononitrile, dimethylacetylenedicarboxylate and dimethylaniline. Eleven compounds were synthesized giving yield of (87-95%). An efficient four component/one-pot protocol was developed for synthesis of functionalized pyridine derivatives by reacting dimethylacetylenedicarboxylate, 4-bromoaniline, malononitrile with various substituted benzaldehydes in the presence of Y2O3/ZrO2 as catalyst. Excellent yield of (88-95%) were obtained. The noteworthy advantages of this basic method are the use of ethanol as a solvent, excellent yields and shorter reaction times. Most catalysts were reusable for up to seven cycles. Powder X-ray diffraction, TEM, SEM and N2 adsorption/desorption analysis techniques were employed for the structural interpretation of the catalysts. The identity of target products were established and confirmed by diverse spectral (1H NMR, 13C NMR, 15N NMR, FT-IR and HRMS) techniques. iii DECLARATIONS DECLARATION 1 - PLAGIARISM I, Sebenzile Beauty Shabalala, declare that 1. The research reported in this thesis, except where otherwise indicated is my original research. 2. This thesis has not been submitted for any degree or examination at any other university. 3. This thesis does not contain other persons’ data, pictures, graphs or other information, unless specifically acknowledged as being sourced from other persons. 4. This thesis does not contain other persons' writing, unless specifically acknowledged as being sourced from other researchers. Where other written sources have been quoted, then: a. Their words have been re-written but the general information attributed to them has been referenced b. Where their exact words have been used, then their writing has been placed in italics and inside quotation marks, and referenced. 5. This thesis does not contain text, graphics or tables copied and pasted from the Internet, unless specifically acknowledged, and the source being detailed in the thesis and in the References sections. Signed: ……………………………………………………………………………… iv DECLARATION 2 - PUBLICATIONS DETAILS OF CONTRIBUTION TO PUBLICATIONS that form part and/or include research presented in this thesis (include publications, submitted, in press and published and give details of the contributions of each author to the experimental work and writing of each publication) 1. Sebenzile Shabalala, Suresh Maddila, Werner E. van Zyl and Sreekantha B Jonnalagadda, A facile, efficacious and reusable Sm2O3/ZrO2 catalyst for the synthesis of functionalized 1,4- dihydropyridine derivatives. Catalysis Communications, (79) 21–25, 2016. http://dx.doi.org/10.1016/j.catcom.2016.02.017 My contribution: All the pyridines and derivatives were synthesized and characterized by me under the supervision of Prof. Jonnalagadda (Supervisor), Prof van Zyl (Co- author) and Dr. S. Maddila (Postdoctoral fellow working under Prof. Jonnalagadda) and drafted the article. 2. Sebenzile Shabalala, Suresh Maddila, Werner E. van Zyl and Sreekantha B Jonnalagadda, Sustainable CeO2/ZrO2 catalyst for the green synthesis of highly functionalized 1,4-dihydropyridine-2,3-dicarboxylate derivatives. (Revised manuscript submitted to Current Organic Synthesis) My contribution: Synthesis and characterization of all compounds and derivatives were done by me under the supervision of Prof. Jonnalagadda (Supervisor) Prof van Zyl (Co- author) and Dr. S. Maddila (Postdoctoral fellow working under Prof. Jonnalagadda) and drafted the article. 3. Sebenzile Shabalala, Suresh Maddila, Werner E. van Zyl and Sreekantha B Jonnalagadda, An innovative and simple protocol for the synthesis of 1,4-Dihydropyrines using a highly stable and efficient Y2O3/ZrO2 catalyst (submitted to a journal for publication) My contribution: Synthesis of all compounds and their derivatives as well as the characterization were done by me under the supervision of Prof. Jonnalagadda (Supervisor) Prof van Zyl (Co-author) and Dr. S. Maddila (Postdoctoral fellow working under Prof. Jonnalagadda) and drafted the article. Signed:…………………………………………………………………………………………..... v ACKNOWLEDGEMENTS I would first like to thank the Sovereign God Jesus Christ for keeping and humbling me until this day and the scripture, which kept me going Mattew 6:33 "But seek ye first the kingdom of God, and his righteousness; and all these things shall be added unto you". I thank my supervisors Professors S.B. Jonnalagadda and W.E. van Zyl for the opportunity and guidance that they gave me throughout the research and write up. I really appreciate it. The University of KwaZulu-Natal, I acknowledge it for the platform it has given me to do the research as well as Prof. S.B. Jonnalagadda, for bursary given from his NRF grant holder funds. It was not going to be easy without that bursary. I would like to convey my warmest gratitude to Dr Suresh Maddila, who has guided me from day one until the end. He has been such a wonderful research adviser; he assisted in every possible means one could offer. This one goes to my research group members Gracious Shabalala, who did not only share a lab with me but also became a loving and caring sister to me. Surya Narayana Maddila, who assisted me in various ways, as well as the rest of the research group members, Vuyolwethu Ndabankulu, Bhekumuzi Gumbi and Mlungisi Sithole. Special thanks to my parents, Pheneas Shabalala and Gugu Shabalala, as well as my fiancé Siyabonga Mbatha. They have been supporting me emotionally, financially and mentally. They were there through all the hardships and challenges I went through. Thank you vi CONFERENCE PARTICIPATION 1. Sebenzile Shabalala, Suresh Maddila, Werner E. van Zyl and Sreekantha B Jonnalagadda “A facile, efficacious and reusable Sm/ZrO2 catalyst for the synthesis of functionalized 1,4-dihydropyridine derivatives”. (Oral presentation at the 42nd National Convention of the South African Chemical Institute Conference 29 Nov. - 4th December, 2015 at Elangeni Hotel, Durban 2. Sebenzile Shabalala, Suresh Maddila, Werner E. van Zyl and Sreekantha B Jonnalagadda “Sustainable CeO2/ZrO2 catalyst for the green synthesis of highly functionalized 1,4-dihydropyridine-2,3-dicarboxylate derivatives” (Poster presentation at the College of Agriculture, Engineering and Science Research day, 29th November 2016, Howard Campus, UKZN. vii LIST OF ABBREVIATIONS Abbreviations 3-CR Three component reaction 1HNMR Proton Nuclear Magnetic Resonance 13CNMR Carbon-13 Nuclear Magnetic Resonance °C Degrees Celcius ArH Aromatic ring proton BET Brunauer - Emmett - Teller Calcd Calculated C-C Carbon - Carbon bond CDCl3 Deuterated Chloroform

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