University of Texas at El Paso DigitalCommons@UTEP Open Access Theses & Dissertations 2015-01-01 SynThesis of Benzofused-p-indolequinones from 1,4-naphthoquinone and selective N- Debenzylation by Dess-Martin Periodinane Quang Huynh Luu University of Texas at El Paso, [email protected] Follow this and additional works at: https://digitalcommons.utep.edu/open_etd Part of the Organic Chemistry Commons Recommended Citation Luu, Quang Huynh, "SynThesis of Benzofused-p-indolequinones from 1,4-naphthoquinone and selective N-Debenzylation by Dess- Martin Periodinane" (2015). Open Access Theses & Dissertations. 885. https://digitalcommons.utep.edu/open_etd/885 This is brought to you for free and open access by DigitalCommons@UTEP. It has been accepted for inclusion in Open Access Theses & Dissertations by an authorized administrator of DigitalCommons@UTEP. For more information, please contact [email protected]. SYNTHESIS OF BENZOFUSED-P-INDOLEQUINONES FROM 1,4-NAPHTHOQUINONE AND SELECTIVE N-DEBENZYLATION BY DESS-MARTIN PERIODINANE QUANG HUYNH LUU Department of Chemistry APPROVED: Katja Michael, Ph.D., Chair Shizue Mito, Ph.D. Carl Dirk, Ph.D. Siddhartha Das, Ph.D. Charles Ambler, Ph.D. Dean of the Graduate School SYNTHESIS OF BENZOFUSED-P-INDOLEQUINONES FROM 1,4-NAPHTHOQUINONE AND SELECTIVE N-DEBENZYLATION BY DESS-MARTIN PERIODINANE By QUANG HUYNH LUU, B. ENG. THESIS Presented to the Faculty of the Graduate School of The University of Texas at El Paso in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Department of Chemistry THE UNIVERSITY OF TEXAS AT EL PASO August 2015 AKNOWLEDGEMENT First and foremost, my special thanks go to my mentor, Dr. Shizue Mito, who not only gives me her full support, both academically and socially, but also inspires me to pursue my dream of becoming a professor. Working with her is a particularly precious experience. It is also my pleasure and honor to have Dr. Michael, Dr. Dirk, and Dr. Das as my committee members. Their useful advices have kept me on the right track and helped me progressing with my research more than I could do by myself. Moreover, I owe my deep gratitude to Dr. Michael, Dr. Villagrán, Dr. Pannell, and their labs for unconditionally supporting me during the hardest moments. Especially, the Department of Chemistry will always have my great appreciation for continuously providing me teaching assistantship and important equipments throughout my time at UTEP. In addition, I would like to thank my talented undergraduate students, especially Jorge D. Guerra, Cecilio M. Castañeda, and Jong Saunders (Baek). This thesis would not be possible without their enthusiastic contribution and hard work. Finally, I am blessed to have my dear friends at UTEP, Dr. Kalagara and Karen Ventura, as well as my beloved family, who always believe in me and do not hesitate to provide me with the most convenient condition so that I can concentrate on my work. Quang H. Luu iii TABLE OF CONTENTS AKNOWLEDGEMENT ................................................................................................................ iii TABLE OF CONTENTS ............................................................................................................... iv LIST OF FIGURES ....................................................................................................................... vi LIST OF SCHEMES..................................................................................................................... vii LIST OF TABLES .......................................................................................................................... x ABBREVIATIONS ....................................................................................................................... xi CHAPTER 1: ULTRASOUND ASSISTED ONE-POT SYNTHESIS OF BENZOFUSED-P-INDOLEQUINONES FROM 1,4-NAPHTHOQUINONE AND α- AMINOACETALS ......................................................................................................................... 1 1.1. Introduction .......................................................................................................................... 1 1.1.1. Oxidation of indoles ...................................................................................................... 2 1.1.2. Cyclization of quinones ................................................................................................. 6 1.1.3. Miscellaneous methods................................................................................................ 13 1.2. Results and discussion ........................................................................................................ 15 1.3. Conclusion .......................................................................................................................... 28 1.4. Experimental details and spectroscopic data ...................................................................... 29 References ................................................................................................................................. 81 iv CHAPTER 2: SELECTIVE OXIDATIVE N-DEBENZYLATION OF TERTIARY AND SECONDARY AMINES BY DESS-MARTIN PERIODINANE ............................................... 85 2.1. Introduction ........................................................................................................................ 85 2.1.1. N-dealkylation using Cytochromes P-450 and other enzyme-derived species: .......... 85 2.1.2. N-Dealkylation using metal complexes: ...................................................................... 86 2.1.3. N-Dealkylation using non-metal reagents: .................................................................. 92 2.2. Results and discussion: ...................................................................................................... 95 2.3. Conclusion:....................................................................................................................... 103 2.4. Experimental procedure and spectral data ....................................................................... 104 References ............................................................................................................................... 131 CHAPTER 3: SYNTHESIS OF PYRIDAZINEDIONES, QUINONE DIMERS, AND POLYQUINONES ...................................................................................................................... 133 3.1. Synthesis of pyridazinediones from alkynes and diformyl hydrazine: ............................ 133 3.2. Synthesis of naphthoquinone dimers: .............................................................................. 138 3.3. Synthesis of polyquinones:............................................................................................... 141 References ............................................................................................................................... 146 CURRICULUM VITA...............................................................................................................147 v LIST OF FIGURES Figure 1. 1. Natural products containing indolequinone structures ................................................ 2 Figure 1. 2. Medicinal compounds synthesized from indolequinone precursors ........................... 2 Figure 2. 1. Compounds inert to N-debenzylation by CAN ......................................................... 92 Figure 2. 2. Effect of substituent on acidity of H ....................................................................... 97 Figure 2. 3. Structures of DMP, IBX, and monoacetate iodinane 140 ....................................... 100 Figure 3. 1. Syn and anti conformation of 1,4-naphthoquinone dimer ....................................... 139 vi LIST OF SCHEMES Scheme 1. 1. Synthesis of BE 10988 by Moody et al. .................................................................... 4 Scheme 1. 2. Oxidation of indoles to indolequinones by dichromate reagent ................................ 6 Scheme 1. 3. Yamashita’s utilization of Sonogashira coupling reaction in the synthesis of indolequinones ................................................................................................................................ 9 Scheme 1. 4. Formation of indolequinones using Ce(IV) and Mn(III) ........................................ 10 Scheme 1. 5. Preparation of indolequinone precursor to marine alkaloid tsitsikammamine A by Delfourne and co-workers............................................................................................................. 12 Scheme 1. 6. Indolequinones 55 synthesized by quinone–amine cyclization followed by dehydration ................................................................................................................................... 13 Scheme 1. 7. Synthesis of indolequinone 57 from tryptamine and 2-methoxynaphthoquinone .. 13 Scheme 1. 8. Planned synthesis of isoquinolinoles 72.................................................................. 16 Scheme 1. 9. Alternate synthesis of 69a ....................................................................................... 16 Scheme 1. 10. Planned Synthesis of heterocycles 75 ................................................................... 17 Scheme 1. 11. Planned synthesis of indolequinone 80 ................................................................. 18 Scheme 1. 12. Mechanism of indolequinone 82 formation .......................................................... 21