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Ansa Thesis Bushra MULTICOMPONENT REACTIONS FOR THE SYNTHESIS OF HETEROCYCLIC COMPOUNDS A THESIS SUBMITTED FOR THE AWARD OF THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY BY ANSA MADEEHA ZAFAR DEPARTMENT OF CHEMISTRY THE ISLAMIA UNIVERSITY OF BAHAWALPUR PAKISTAN 2015 i In the Name of Allah, the Most Merciful, the Most Kind ii Dedicated To My teachers, parents, family and my friends Samina Aslam and Bushra Jabeen Who are always a source of strength and guidance iii Certificate It is hereby certified that the work presented by Ansa Madeeha Zafar D/O Zafar Iqbal Bhatti in this thesis entitled “ Multicomponent reactions for the synthesis of heterocyclic compounds” was successfully carried out under my supervision. Prof. Dr. Misbahul Ain Khan (Supervisor) Professor Emeritus Department of Chemistry The Islamia University of Bahawalpur iv Declaration I, Ansa Madeeha Zafar , hereby declare that the work in this thesis is original. To the best of my knowledge, it contains no material written by another person or previously published except where due acknowledgement or reference has been made. Ansa Madeeha Zafar v Preface The present thesis is an effort to put on record our efforts to further the chemistry of Pyridines and pyrimidines through applications of MCR (Hantzch and Biginelli reactions). The central theme was the use of arylfuran-2-carbaldehydes. Attempts were made to exhaustively use of a couple of substrates (Active methylene compounds) but rather to demonstrate the utility of these reactions by diversifying the reactants to demonstrate their feasibility for such reactions. This approach makes available diverse novel molecules which can act as scaffolds for building up further heterocycles by careful and appropriate modifications of the functionalities offered during these reactions. Thus a vast series of molecules be custom made in future for biological studies and their QSAR analyses.We had wished to duly characterize all the synthesized compounds by the usual physical, spectroscopic (NMR & MS) and their elemental analyses but unfortunately due to non availability of analytical services and financial constraints partially due to HEC’s revised policies it had not been possible in totto . However it was still strived to get the maximum analytical data for most of the new products. Where it was not feasible these compounds were characterized through their spectral data (NMR and/or Mass spectra through fragmentation patterns). These mass spectral fragmentational data were very helpful for the identification of a series of compounds.The dihyropyridines and dihydropyrimidones (and thiones) were aromatized by way of oxidation by DMSO, CaOCl and other means to provide fully aromatized pyridines and pyrimidines yet offering other molecules available for manipulation, another contribution to heterocyclic chemistry. The results of these efforts are presented in this thesis. Ansa Madeeha Zafar vi ABSTRACT vii Diverse 5-arylfuran-2-carbaldehydes were prepared and subsequently utilized in MCR reactions to obtain various derivatives of dihydropyridines utilizing Hantzsch method and then these dihydropyridines were aromatized by using DMSO, DMSO/HNO 3 and CaOCl as oxidizing agents. A number of dihydropyrimidines derivatives were also prepared by using Biginelli reaction with these 5-arylfuran-2-carbaldehydes and these were also aromatized by using only CaOCl as oxidizing agent. For these syntheses a variety of “active methylenes” were used such as acetophenones, acetoacetanilides and even ethyl cyanoacetate in some cases. The characterization of the compounds was mostly carried out by using Mass, IR, 1H, 13 CNMR spectroscopy and by CHN microanalysis. Ar Ar 3 3 R R R3 R3 2 2 R N R 2 2 H R N R Dihydropyridines pyridines Ar=Aryl Furan, R2=Me, Ph, R3=H, COOEt, COCH , CONHAr etc 3 Ar Ar 1 R OOC H R1OOC N N 2 2 R N X R N X H H Dihydropyrimidines pyrimidines 2 1 Ar=Aryl Furan, R =Me, Ph, R =H, COOEt, COCH3, CONHAr etc X=O, S viii ACKNOWLEDGMENT All praises for Allah Almighty who is the most beneficent, the most merciful. He bestowed all his blessings on me and made me able to complete this task. All praises for our prophet Muhammad (PBUH) who enlightened human hearts with the love of God. I acknowledge the opportunity given to me by The Islamia University of Bahawalpur, Pakistan and HEC, Pakistan for a Ph.D. scholarship. Without their support, this study would not have been possible. My special humble respect, utmost gratitude and reverence go to my research supervisor Professor Dr. Misbahul Ain Khan. His support has always been a motivation in completing my Ph.D. work. His support, guidance and advice were always with me at every step. He was always there for me in every problem and difficult situation. I have no words to say thanks or to acknowledge him. I honor and respect the prayers and support of my parents especially my mother, who always stands by me in every problem of my life. A special word of thanks to the Chairman, Department of Chemistry The Islamia University of Bahawalpur, for providing Laboratory facilities during research work. I am also indebted to all my respected teachers who had always been there whenever I needed their help. I am especially thankful to those who were directly involved in my grooming at the university. Their constant help has made these years of my life at IUB a rewarding experience. Here, I would not keep any pause in saying that I am deeply grateful to my dear friends for their support especially Dr. Samina Aslam, Noreen Aslam, Meharzadi Noreen Shahi, Shazia ix Noreen, Warda Hassan, Rizwana Mustafa, Bushra Jabeen and Musarrat Jabeen. I shall always be thankful to them. I am also grateful to the Higher Education Commission of Pakistan for financial support under the indigenous Scholarship Scheme. Not the least of all, my gratitude and thanks to all my other colleagues, library, laboratory, administrative staff and all others who have helped me in my research work. Ansa Madeeha Zafar x Publication The following original paper has been published based on the research work of the thesis. Ansa Madeeha Zafar, Saira Qureshi, Muhammad Naeem Khan, Muhammad Azad, Munawar Ali Munawar and Misbahul Ain Khan, Asian Journal of Chemistry; Vol. 25, No. 6 ( 2013 ), 3244-3246.
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