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Enantiomeric Chromatographic Separations and Ionic Liquids Jie Ding Iowa State University

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Enantiomeric Chromatographic Separations and Ionic Liquids Jie Ding Iowa State University Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2005 Enantiomeric chromatographic separations and ionic liquids Jie Ding Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Analytical Chemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, Medicinal Chemistry and Pharmaceutics Commons, Medicinal-Pharmaceutical Chemistry Commons, and the Organic Chemistry Commons Recommended Citation Ding, Jie, "Enantiomeric chromatographic separations and ionic liquids " (2005). Retrospective Theses and Dissertations. 1725. https://lib.dr.iastate.edu/rtd/1725 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Enantiomeric chromatographic separations and ionic liquids by Jie Ding A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Analytical Chemistry Program of Study Committee: Daniel W. Armstrong, Major Professor Lee Anne Willson Robert S. Houk Jacob W. Petrich Richard C. Larock Iowa State University Ames, Iowa 2005 Copyright © Jie Ding, 2005. All rights reserved. UMI Number: 3200412 Copyright 2005 by Ding, Jie All rights reserved. INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. UMI UMI Microform 3200412 Copyright 2006 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 ii Graduate College Iowa State University This is to certify that the doctoral dissertation of Jie Ding has met the dissertation requirements of Iowa State University Signature was redacted for privacy. Major Professor Signature was redacted for privacy. or the Major Program Ill This dissertation is dedicated to My husband: FuminLi My son: Brad H. Li My parents: Chuzhang Ding and Yuanying Yin My parents-in-law: Hongji Li and Xiucong Xin IV TABLE OF CONTENTS ACKNOWLEDGEMENTS viii INTRODUCTION: THESIS ORGANIZATION 1 PART ONE. ENANTIOSELECTIVE CHROMATOGRAPHY 3 CHAPTER 1. OVERVIEW: DIRECT SEPARATION OF ENANTIOMERS USING GAS AND LIQUID CHROMATOGRAPHY 4 1.1. Introduction 4 1.2. Gas Chromatography Chiral Stationary Phases 5 1.2.1. Amino acid based chiral stationary phases 5 1.2.2. Metal-Ligand complex chiral stationary phases 6 1.2.3. Derivatized cyclodextrin bases chiral stationary phases 8 1.2.4. Chiral ionic liquids as chiral stationary phases 13 1.3. Liquid Chromatography Chiral Stationary Phases 14 1.3.1. 7i-complex chiral stationary phases 14 1.3.2. Macrocyclic chiral stationary phases 16 1.3.2.1. Crown ether-based chiral stationary phases 16 1.3.2.2. Cyclodextrins and cyclodextrin derivatives 17 1.3.2.3. Macrocyclic glycopeptide chiral stationary phases 20 1.3.3. Polymeric chiral stationary phases 21 1.3.3.1. Proteins 21 1.3.3.2. Polysaccharide chiral stationary phases 23 1.3.3.3. Synthetic polymeric chiral stationary phases 26 1.4. Summary 28 References 28 CHAPTER 2. SEPARATION OF RACEMIC SULFOXIDES AND SULFINATE ESTERS ON FOUR DERIVATIZED CYCLODEXTRIN CHIRAL STATIONARY PHASES USING CAPILLARY GAS CHROMATOGRAPHY 36 Abstract 36 2.1. Introduction 3 7 2.2. Experimental 38 2.2.1. Apparatus 38 2.2.2. Chemicals and reagents 39 2.2.3. Elution orders and absolute configuration assignments 42 2.2.4. Calculations 43 2.3. Results and Discussion 43 2.3.1. Group I (chiral sulfoxides #1-7) 43 2.3.2. Group II (chiral sulfoxides #8-13) 44 2.3.3. Group III (chiral sulfinate esters #14-20) 45 2.3.4. Group IV (chiral sulfoxides #21-23) 48 2.3.5. Group V (chiral sulfoxides #24-25) 48 V 2.3.6. Elution order investigation 49 2.4. Concluding Remarks 51 Acknowledgement 51 References 51 CHAPTER 3. EVALUATION OF ETHOXYNONAFLUOROBUTANE AS A SAFE AND ENVIRONMENTALLY FRIENDLY SOLVENT FOR CHIRAL NORMAL-PHASE LC-ATMOSPHERIC PRESSURE CHEMICAL IONIZATION/ELECTROSPRAY IONIZATION-MASS SPECTROMETRY 55 Abstract 55 3.1. Introduction 56 3.2. Experimental 58 3.2.1. Reagents and solvents 58 3.2.2. HPLC and MS instrumentation 58 3.2.3. Columns and mobile phases 59 3.2.4. Ionization and MS acquisition conditions 59 3.3. Results and Discussion 60 3.3.1. Using the MS-compatible normal-phase solvent, ENFB (HFE-7200) 60 3.3.2. Limits of detection for APCI-MS and ESI-MS versus UV detection using heptane and ENFB containing mobile phases 64 3.3.3. Effect of Flow-rate and Sensitivity for APCI and ESI-MS detection 65 3.3.4. Effect of Modifier on Chromatographic Parameters 68 3.3.5. Effect of Modifier on APCI-MS Sensitivity 69 3.4. Conclusions 69 Acknowledgements 71 References 71 PART TWO. GENERAL PROPERTITY STUDIES OF IONIC LIQUIDS USING INVERSE GAS CHROMATOGRAPHY 74 CHAPTER 4. HISTORICAL REVIEW OF IONIC LIQUIDS 75 4.1. Introduction 75 4.2. Preparation of ionic liquids 76 4.3. Applications of ionic liquids 79 4.3.1. Ionic liquids in organic synthesis and catalysis 79 4.3.2. Ionic liquids in liquid-liquid extraction 80 4.3.3. Ionic liquids in gas-liquid chromatography 81 4.3.4. Ionic liquids in matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) 82 4.4. Summary 84 References 85 VI CHAPTER 5. CHARACTERIZING IONIC LIQUIDS ON THE BASIS OF MULTIPLE SOLVATION INTERACTIONS 88 Abstract 88 5.1. Introduction 88 5.2. Experimental Section 93 5.3. Results and Discussion 96 5.3.1. Ionic liquid model 100 5.3.2. Organic synthesis 101 5.3.3. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry 103 5.3.4. Gas chromatography stationary phases 103 5.4. Conclusions 106 Acknowledgement 107 References 107 CHAPTER 6. AN EXAMINATION OF IONIC LIQUID-ALKANE INTERACTIONS : EVIDENCE OF A SOLVOPHOBIC EFFECT 111 Abstract 111 6.1. Introduction 111 6.2. Experimental 113 6.2.1. Chemicals 113 6.2.2. Capillary columns 113 6.2.3. Apparatus 114 6.2.4. Protocol 114 6.3. Theory 115 6.3.1. Entropy 116 6.3.2. Enthalpy 119 6.4. Results and Discussion 122 6.4.1. Entropy changes 124 6.4.2. Enthalpy changes 126 6.5. Conclusions 128 References 130 PART THREE. CHIRAL IONIC LIQUIDS: SYNTHESIS AND APPLICATIONS 135 CHAPTER 7. OVERVIEW: CHIRAL IONIC LIQUIDS: SYNTHESIS AND APPLICATIONS 136 Abstract 136 7.1. Introduction 136 7.2. Synthesis of chiral ionic liquids (CILs) 137 7.2.1. Prelude to CILs 137 7.2.2. The appearance of CILs 139 7.3. Applications of chiral ILs 151 vii 7.4. Future outlook 153 Literature cited 154 CHAPTER 8. CHIRAL IONIC LIQUIDS AS STATIONARY PHASES IN GAS CHROMATOGRAPHY 158 Abstract 158 8.1. Introduction 158 8.2. Experimental Section 160 8.2.1. Materials 160 8.2.2. Methods 160 8.3. Results and Discussion 161 8.4. Conclusions 166 Acknowledgement 166 References 166 CHAPTER 9. USE OF CHIRAL IONIC LIQUIDS AS SOLVENTS FOR THE ENANTIOSELECTIVE PHOTOISOMERIZATION OF DIBENZOBICYCLO[2.2.2]OCTATRIENES 169 Abstract 169 Text 170 Acknowledgements 174 References 174 Appendix 176 CHAPTER 10. GENERAL CONCLUSIONS 182 viii ACKNOWLEDGEMENTS If time went back to 1993 when I was a freshman in chemistry department, at Xiamen University, P.R.C., I probably would not have imagined I would pursue my Ph.D. in United States. However, things happened like just by chance yet seemed to be logic in nature. Twelve years have passed, and I would like to say that it was a wise decision to major in chemistry, and went oversea to pursue my Ph.D. degree. I am myself amazed how much I have learnt about chemistry, especially chromatographic enantiomeric separations and ionic liquids, merits of being a strong and firm person, and abilities to deal with difficulties from not only research but also life in general. I am sure all the experiences I had here at Iowa State University will benefit my life henceforward. It would be almost impossible to express my thanks to everyone who helped me to achieve academic success. I will simply comment that Iowa State University is a great place for advanced study. In the meanwhile, I would like to say a few words to people I interacted most often and closely. First of all, I would like to thank Dr. Armstrong, my major professor, for his guidance and mentoring in the past five years. His dedication to science and insight in front of challenges has sparked my passion toward research. His great patience to students, wealthy knowledge in science, and excellent lecturing skills, has motivated my enthusiasm in teaching. His kind support and understanding made my life in Ames as an international student much easier and more delightful. Dr. Armstrong is a great scientist! Honestly, I am really grateful to have him as my advisor, and I am proud to be able to meet his high research criteria. I greatly appreciate the help and friendship of past and present Armstrong's group members, postdocs, visiting scientists, and friends whom I have met in Ames. Special thanks go to Lingfeng He for teaching me how to coat capillary GC columns, and Jared L.
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