Florida State University Libraries Electronic Theses, Treatises and Dissertations The Graduate School 2005 Thermal and Photochemical Reactions of Acetylenes: I-Ortho-Effect in the Bergman Cyclization of Benzannelated Enediynes II- Photocycloaddition of Diaryl Acetylenes to Cyclic Dienes Mechanisms and Applications Tarek A. Zeidan Follow this and additional works at the FSU Digital Library. For more information, please contact [email protected] THE FLORIDA STATE UNIVERSITY COLLEGE OF ARTS AND SCIENCES THERMAL AND PHOTOCHEMICAL REACTIONS OF ACETYLENES: I-ORTHO-EFFECT IN THE BERGMAN CYCLIZATION OF BENZANNELATED ENEDIYNES II-PHOTOCYCLOADDITION OF DIARYL ACETYLENES TO CYCLIC DIENES MECHANISMS AND APPLICATIONS By TAREK A. ZEIDAN A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy Degree Awarded: Fall Semester, 2005 The members of the Committee approve the Dissertation of Tarek A. Zeidan defended on September 27th 2005 Igor V. Alabugin Professor Directing Dissertation Lloyd M. Epstein Outside Committee Member Jack Saltiel Committee Member Joseph B. Schlenoff Committee Member Approved: Naresh Dalal, Chair, Department of Chemistry and Biochemistry The Office of Graduate Studies has verified and approved the above named committee members. ii To my best friend, my partner, my soul mate...... Nadine & To Ahmed and Amal iii ACKNOWLEDGEMENTS During my few years at Florida State University, I had the opportunity to work and interact with several professors, staff, postdocs and graduate fellows. In these few lines I will try to acknowledge them and I apologize if I forget to mention anyone. First and foremost, I would like to thank my major professor, Igor V. Alabugin, for accepting me as a graduate student in his laboratory, for his continuous support, and for giving me the opportunity to be the first doctoral student to graduate from his laboratory. Professor Alabugin taught me many lessons and equipped me with the required basics to be able to start my scientific journey. I hope I will continue to live up to his expectations. Second, I am thankful to my committee members for their encouragement and help. I would like to express my gratitude to Professor Jack Saltiel for being by my side all the time, for his help and support, for his guidance in chemistry as well as in life and especially for believing in me. I am grateful to Professor Joseph B. Schlenoff for his support and encouragement and for allowing me to use instrumentation in his laboratory and to Professor Edwin E. Hilinski for his letters of recommendation. I am eternally thankful to Dr. Serguei V. Kovalenko who taught me everything I need to know in the laboratory. I will never forget our endless discussions every Friday afternoon. I would not have been able to go this far without his guidance, support and constructive critiques. Also, I am thankful to Dr. Marriappan Manoharan for his computational studies and everyone else in the Alabugin group. I am grateful to Professor Ronald Clark for teaching me about X-ray crystallography and acquiring all X-ray data described in this dissertation and to Dr. Ion Ghiviriga from the Department of Chemistry at the University of Florida for his help in some NMR experiments. I am also thankful to Dr. T. S. R. Krishna and Dr. Xeena Pillay from Professor Saltiel’s group for their assistance in some fluorescence experiments, to Dr. Jad Jaber for his assistance in acquiring some IR spectra, to Professor Kenneth A. Goldsby for use of electrochemistry equipment, to Dr. Bert van de Burgt for use of laser equipment and acquisition of Laser Flash Excitation spectra, to Professor Gregory Dudley and his lab members for lend ing me chemicals, Professor Naresh Dalal and Ms. Saritha Mellutla for providing some chemicals and to Professor Albert E. Steigman and Dr. Paul Giunta for teaching me how to use the DSC and SDT equipments. I am extremely grateful to Dr. Umesh Goli and Hank Henricks from the iv Biochemical Analysis and Synthesis Services laboratory (BASS Lab) for their help on HPLC, GC, MS and LC-MS and especially for their unconditional support. I am thankful to Dr. Joseph B. Vaughn and Steven E. Freitag from the NMR facility and to Dr. Tom Gedris for aquiring 19F and 13C NMR spectra. I would like to thank everyone in the administrative offices of the Department of Chemistry and Biochemistry at Florida State University, especially Ginger Martin, Cathy Flynn and Jacquelin Dulin (Jaquie). Also, I am thankful to Tia Williams, Tom Wages, Gary Poplin and Charlie Betts for computer support and Steve Leukanech from the illustration shop. I would like to thank Dr. Jean Chamoun for his support in illustration and graphics. I would not have completed this work without the support of my family (Nadine, Ahmed, Amal, Wael, Yassmine, Ola, Lama and Mohamad) and my friends (Jean and Maroun). v TABLE OF CONTENTS LIST OF SCHEMES ................................................................................................................. ix LIST OF FIGURES ................................................................................................................... xi LIST OF TABLES................................................................................................................... xiv ABSTRACT................................................................................................................................. xv CHAPTER I .................................................................................................................................. 1 INTRODUCTION ................................................................................................................... 1 The Bergman Cycloaromatization Reaction: The Beginnings ........................................... 1 Enediynes as Anticancer Antibiotics Drugs: Medical Significance and Limitations......... 1 Towards More Selective Enediyne Systems....................................................................... 3 The Bergman Cycloaromatization: Computational Studies ............................................... 7 Setting the Paradigm: A Theoretical Background .............................................................. 9 EXPERIMENTAL SECTION ................................................................................................ 11 Synthesis of Benzannelated Enediynes............................................................................. 11 Synthetic Procedures and Spectroscopic Details .............................................................. 12 Experimental Setup for Kinetic Studies............................................................................ 21 Kinetic Experiment for Different Concentration of Hydrogen-Atom Donor ................... 24 Experimental Setup for Differential Scanning Calorimetry Studies................................. 26 RESULTS .............................................................................................................................. 27 Differential Scanning Calorimetry Experiments .............................................................. 27 Effective Rate Constants of Ortho-Substituted Benzannelated Enediynes....................... 34 Activation Energies of Ortho-Substituted Benzannelated Enediynes .............................. 37 Effect of 1,4-Cyclohexadiene Concentration on the Effective Rate Constants................ 39 DISCUSSION........................................................................................................................ 41 Differential Scanning Calorimetry Kinetic Analysis........................................................ 41 Ortho-Substituted Benzannelated Enediynes.................................................................... 44 Effect of Concentration of 1,4-Cyclohexadiene on Rates and Activation Energies......... 47 Dissection of the Bergman Cyclization Kinetics.............................................................. 53 Ortho-Substituted Benzannelated Enediynes: Methoxy Substituent ................................ 54 CONCLUSIONS.................................................................................................................... 63 vi CHAPTER II............................................................................................................................... 65 INTRODUCTION ................................................................................................................. 65 Bergman Cyclization: The Photochemical Aspect ........................................................... 65 En Route to Novel Photochemical Reactions: From Bergman Cycloaromatization to C1C5 Cylization................................................................................................................ 67 Photochemical Cycloaddition of Acetylenes to 1,4-CHD: From Hydrogen/Electron Transfer to Cycloaddition ................................................................................................. 69 Photocycloaddition Reactions of Acetylenes: Literature Review .................................... 71 EXPERIMENTAL SECTION ................................................................................................ 78 Synthesis of Acetylenes .................................................................................................... 78 Synthetic Procedures and Spectroscopic Details .............................................................. 79 Determination of Quantum Yields.................................................................................