Efficient C-O and C-N Bond Forming Cross-Coupling Reactions Catalyzed by Core-Shell Structured
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Efficient C-O and C-N bond forming cross-coupling reactions catalyzed by core-shell structured Cu/Cu2O nanowires Thesis by Ahmed Elshewy In Partial Fulfillment of the Requirements For the Degree of Master of Science King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia December 2013 2 The thesis of Ahmed Elshewy is approved by the examination committee. Committee Chairperson: Prof. Kuo-Wei Huang, Assistant Professor of Chemical Sciences, Division of Physical Sciences and Engineering Committee Member: Prof. Jorg Eppinger, Assistant Professor of Chemical Sciences, Division of Physical Sciences and Engineering Committee Member: Prof. Zhiping Lai, Associate Professor of Chemical and Biological Engineering, Division of Physical Sciences and Engineering 3 ABSTRACT Efficient C-O and C-N bond forming cross-coupling reactions catalyzed by core-shell structured Cu/Cu2O nanowires Ahmed Elshewy Oxygen and Nitrogen containing compounds are of utmost importance due to their interesting and diverse biological activities. The construction of the C-O and C–N bonds is of significance as it opens avenues for the introduction of ether and amine linkages in organic molecules. Despite significant advancements in this field, the construction of C-O and C–N bonds is still a major challenge for organic chemists, due to the involvement of harsh reaction conditions or the use of expensive catalysts or ligands in many cases. Thus, it is a challenge to develop alternative, milder, cheaper and more reproducible methodologies for the construction of these types of bonds. Herein, we introduce a new efficient ligand free catalytic system for C-O and C-N bond formation reactions. 4 TABLE OF CONTENTS Page EXAMINATION COMMITTEE APPROVALS FORM ................................. 2 ABSTRACT.............................................................................................................................. 3 ACKNOWLEDGMENTS ................................................................................................. 6 LIST OF ABBREVIATIONS ........................................................................................ 7 LIST OF FIGURES ............................................................................................................. 9 LIST OF TABLES ............................................................................................................. 10 Chapter 1: INTRODUCTION .................................................................................. 11 1.1 Ullmann and C-O coupling ................................................................ 14 1.2 C-N bond formation ................................................................................ 19 Chapter 2: BACKGROUND ....................................................................................... 21 2.1 C-O bond formation ................................................................................ 22 2.2 C-N bond formation ................................................................................ 24 Chapter 3: RESULTS AND DISCUSSION ........................................................ 26 3.1 Optimization of base ............................................................................. 26 3.2 Optimization of solvent ...................................................................... 27 3.3 Optimization of reactant equivalents ....................................... 28 3.4 Optimization of reaction time in C-O bond formation .......................................................................................................................................... 29 5 3.5 Catalyst scope in C-O bond formation ..................................... 30 3.6 C-O bond formation in phenol synthesis .............................. 34 3.7 C-N bond formation ............................................................................... 36 3.8 Optimization of reaction time in C-N bond formation 36 3.9 Catalyst scope in C-N bond formation ..................................... 37 3.10 Heterogeneous vs. Homogenous mechanism ............... 39 3.11 Catalyst recyclability and SEM analysis ............................. 41 Chapter 4: CONCLUSION .......................................................................................... 44 Chapter 5: MATERIALS AND METHODS ...................................................... 45 5.1 Preparation and Characterization of Cu-based catalysts .................................................................................................................... 45 5.2 Typical Procedure For the activity experiments ............. 47 REFERENCES ..................................................................................................................... 56 6 ACKNOWLEDGMENTS This Master thesis was carried out under the guidance of Professor Kuo-Wei Huang at King Abdullah University of Science and Technology. At the very last step of that journey, I want to acknowledge and express my deepest appreciation for the support I received from many people during the process of preparing my Master thesis. First and foremost, I would like to extend my sincere gratitude to my research advisor, Professor Kuo-Wei Huang, for his support and excellent guidance during this research work. He has been a great mentor to me, constantly providing me challenging tasks while enriching my knowledge with his exceptional insights in chemistry. I sincerely appreciate his confidence and trust on me and the multitude of little advices he has given me, not only with chemistry, but also with life. It is really my great pleasure and honor to have you as my mentor. 7 LIST OF ABBREVIATIONS DCM = dichloromethane DMSO = dimethyl sulfoxide DMF = dimethyl formamide eq. = equivalents FG = functional group GC = gas chromatography h = hour HRTEM = high resolution transmission electron microscope m = meta M = metal MAOS = microwave-assisted organic synthesis Me = methyl min = minute MS = mass spectroscopy ICP-OES = Inductively coupled plasma atomic emission spectroscopy Nu = nucleophile NMP = N-methyl-2-pyrrolidine NMR = nuclear magnetic resonance o = ortho R = organic substituent SEM = scanning electron microscope TEM = transmission electron microscope THF = tetrahydrofuran 8 TLC = thin layer chromatography X = Halogen (Cl, Br, I) 9 LIST OF FIGURES Figure Page 1. Possible catalytic cycle driven by Cu……………………………….................................13 2. A) an example of Glaser coupling B) Mizorogi-Heck reaction…………………………………………………….……………....14 3. Structure of PCBs...................................................................................................................15 4. Examples of biologically active compounds with ether linkage........................15 5. The accumulated number of published articles involving organic and inorganic microwave assisted synthesis 1970-1999...........................................18 6. Two illustrating equations for Ullmann reaction………………………….…............21 7. Reaction profile of C-O bond formation with iodobenzene and phenol.........30 8. Reaction profile of C-N bond formation with iodobenzene and aniline….….37 9. Proposed Catalytic Cycle…………………………………………………………………...…...41 10. Catalyst recyclability………………………………………………………….….……………..42 11. SEM images for the catalyst before (left) and after (right) the reaction…..43 12. SEM image of blank Cu foam………………………………………………………………...46 13. HRTEM image of the sample Cu/Cu2O nanowires………………………………….47 10 LIST OF TABLES Table Page 1. Comparison of main advantages/disadvantages of homogenous vs. heterogenous catalytic systems…………………...........................................................16 2. Optimization of the Base and comparison between conventional and microwave conditions ………………………..………………………………………….....26-27 3. Effect of different solvents on reaction yield............................................................28 4. Effect of phenol amount on reaction yield……………………………........................29 5. Synthesis of diaryl/alkyl-aryl ethers via Cu/Cu2O catalyzed coupling of iodobenzene derivatives and various substituted phenols/alcohols…....31-32 6. Effect of halogen substitution on the reaction yield under the same conditions………………………………………………………………………………………..32-33 7. Optimization of solvent and base for phenol synthesis………………………….34 8. Optimization of reaction conditions for phenol synthesis...……………………35 9. Optimization of conditions for diphenyl amine synthesis………………………36 10. Synthesis of di/tri-amines via Cu/Cu2O catalyzed coupling of iodobenzene and various substituted amines…………………………...……….37-38 11 Chapter 1: INTRODUCTION ’’Organic synthesis is considered, to a large extent, to be responsible for some of the most exciting and important discoveries of the twentieth century in chemistry, biology and medicine and continues to fuel the drug discovery and development processes with myriad processes and compounds for new medical breakthroughs and applications.’’ Stating that, K. C. Nicolaou1 displayed the great importance of synthetic organic chemistry over the last two centuries since Wöhler’s synthesized urea in 1828. He also pointed out the issues that organic chemists are facing in the twenty-first century which concisely are to respond to an ever-growing demand for new, efficient and environmentally friendly methods to perform chemical transformations.2 Among these transformations or synthetic reactions, the carbon-carbon and carbon- heteroatom bond formation are surely of high importance, as unique tools for the synthesis of complex