PREPARATION OF HETEROATOM-SUBSTITUTED 1,3-THIAZOLES AS BUILDING BLOCKS FOR LIQUID CRYSTAL SYNTHESIS A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Alan M. Grubb December, 2011 Dissertation written by Alan M. Grubb B.S., Marietta College, USA, 2005 Ph.D., Kent State University, USA, 2011 Approved by , Chair, Doctoral Dissertation Committee Dr. Paul Sampson , Chair, Doctoral Dissertation Committee Dr. Alexander Seed , Members, Doctoral Dissertation Committee Dr. Robert Twieg Dr. Soumitra Basu Dr. Brett Ellman Dr. Philip Bos Accepted by , Chair, Department of Chemistry Dr. Michael Tubergen , Dean, College of Arts and Sciences Dr. John R. D. Stalvey ii TABLE OF CONTENTS LIST OF FIGURES ......................................................................................................... vi LIST OF SCHEMES ....................................................................................................... ix LIST OF TABLES ........................................................................................................ xvii LIST OF ABBREVIATIONS ....................................................................................... xix ACKNOWLEDGMENTS ........................................................................................... xxiv CHAPTER 1. INTRODUCTION ................................................................................... 1 1.1. Introduction to smectic C* liquid crystal phases ....................................................... 1 1.2. General structure of ferroelectric liquid crystals ....................................................... 9 1.3. Use of sulfur-based heterocycles in liquid crystals.................................................. 11 1.4. Rationale for targeting alkoxy-1,3-thiazole-based liquid crystals ........................... 14 1.5. Reactivity of 1,3-thiazole rings ................................................................................ 20 1.6. Overview of dissertation goals................................................................................. 22 CHAPTER 2. SYNTHESIS OF 5-ALKOXY-1,3-THIAZOLE LIQUID CRYSTAL TARGETS ....................................................................................................................... 23 2.1. Literature approaches to 5-alkoxy-1,3-thiazoles...................................................... 23 2.2. Synthesis of 5-alkoxy-1,3-thiazole-containing liquid crystals via a Lawesson’s reagent-mediated ring closing strategy ............................................................................. 25 CHAPTER 3. DIHALO-1,3-THIAZOLES AS BUILDING BLOCKS FOR ORGANIC SYNTHESIS ................................................................................................ 31 3.1. Introduction to dihalo-1,3-thiazoles as building blocks for organic synthesis ........ 31 3.2.1. Literature approaches to 2,5-dibromo-1,3-thiazole (3.3) ...................................... 31 3.2.2. A new approach for the preparation of 2,5-dibromo-1,3-thiazole (3.3) ............... 33 iii 3.3.1. Literature approaches to 2,5-dichloro-1,3-thiazole (3.8) ...................................... 36 3.3.2. A new approach for the preparation of 2,5-dichloro-1,3-thiazole (3.8) ................ 36 3.4.1. Literature approaches to 2,4-dibromo-1,3-thiazole (3.11) .................................... 37 3.4.2. A new approach for the preparation of 2,4-dibromo-1,3-thiazole (3.11) ............. 38 3.5.1. Introduction to mixed dihalo-1,3-thiazole building blocks ................................... 39 3.5.2. Literature approaches to mixed 2,5-dihalo-1,3-thiazoles ..................................... 40 3.5.3. New approaches for the preparation of mixed 2,5-dihalo-1,3-thiazoles ............... 42 3.5.4. Alternative approach to the preparation 5-bromo-2-iodo-1,3-thiazole (3.18) ...... 49 CHAPTER 4. SYNTHESIS OF 2-ALKOXY-1,3-THIAZOLE LIQUID CRYSTAL TARGETS ....................................................................................................................... 51 4.1. Literature approaches to 2-alkoxy-1,3-thiazoles...................................................... 51 4.2. Preparation of 2-alkoxy-1,3-thiazole-containing liquid crystal targets via selective SNAr chemistry of 2,5-dibromo-1,3-thiazole (3.3) ........................................................... 53 CHAPTER 5. 4-FLUORO-1,3-THIAZOLE LIQUID CRYSTALS ......................... 73 5.1. Rationale for targeting 4-fluoro-1,3-thiazole-based liquid crystals ......................... 73 5.2. Literature approaches to 4-fluoro-1,3-thiazoles ....................................................... 75 5.3. De novo approaches to 4-fluoro-1,3-thiazoles ......................................................... 78 5.4. Halogen-metal exchange approaches leading to 4-fluoro-1,3-thiazoles .................. 84 5.5. Fluorination via nucleophilic sources of fluorine .................................................... 95 5.6. Preparation of 4-fluoro-1,3-thiazole-containing liquid crystal targets via fluorination using electrophilic aromatic substitution ........................................................................ 100 CHAPTER 6. 2- AND 5-CARBOXY-1,3-THIAZOLE LIQUID CRYSTALS ...... 115 6.1. Rationale for targeting 2- and 5-carboxy-1,3-thiazole-based liquid crystals ......... 115 6.2. Synthesis of 5-carboxy-1,3-thiazole-based liquid crystals via selective Suzuki coupling of 2,5-dibromo-1,3-thiazole (3.3) .................................................................... 115 iv 6.3. Attempted synthesis of 2-carboxy-1,3-thiazole-based liquid crystals ................... 119 CHAPTER 7. TRANSITION TEMPERATURES AND COMPARISON OF LIQUID CRYSTALLINE TARGETS ........................................................................ 129 7.1.1. Liquid crystalline properties of synthesized alkoxy-4-cyanophenyl-1,3-thiazole- based liquid crystals ........................................................................................................ 129 7.1.2. Comparison of alkoxy-4-cyanophenyl-1,3-thiazole-based liquid crystals ......... 133 7.2.1. Liquid crystalline properties of synthesized 1,3-thiazole containing (S)-4-(1- methylheptyloxy)phenyl-based liquid crystals ............................................................... 136 7.2.2. Comparison of (S)-4-(1-methylheptyloxy)phenyl-based liquid crystals ............ 141 CHAPTER 8. ELECTRO-OPTICAL STUDIES ...................................................... 150 8.1. Determination of pitch in relation to temperature .................................................. 150 8.2. Determination of polarization current .................................................................... 151 8.3. Determination of tilt angle ..................................................................................... 153 8.4. Determination of switching time ........................................................................... 155 CHAPTER 9. CONCLUSIONS .................................................................................. 158 CHAPTER 10. EXPERIMENTAL ............................................................................ 163 10.1. Experimental for Chapter 2 .................................................................................. 164 10.2. Experimental for Chapter 3 .................................................................................. 191 10.3. Experimental for Chapter 4 .................................................................................. 197 10.4. Experimental for Chapter 5 .................................................................................. 220 10.5. Experimental for Chapter 6 .................................................................................. 265 CHAPTER 11. REFERENCES .................................................................................. 273 v LIST OF FIGURES Figure 1.1: Typical ordering of common mesophases. ....................................................... 1 Figure 1.2: McMillan’s model for the origin of tilted smectic phases. ............................... 2 Figure 1.3: Wulf’s model for the origin of tilted smectic phases. ...................................... 3 Figure 1.4: Schematic arrangement of molecules for the achiral smectic C phase (top) and the chiral smectic C* phase (bottom). ................................................................................. 4 Figure 1.5: Helical structure of the smectic C* phase. ....................................................... 6 Figure 1.6: General structure of ferroelectric liquid crystals. ............................................. 9 Figure 1.7: Central linkages which promote formation of the smectic C phase. .............. 10 Figure 1.8: Terminal groups which promote formation of the smectic C phase. ............. 10 Figure 1.9: Previously synthesized liquid crystalline targets containing sulfur-based heterocycles....................................................................................................................... 11 Figure 1.10: Strength and orientation of the dipole moments for thiophene, fluorothiophene, 1,3-thiazole, and 1,3,4-thiadiazole rings. .............................................. 12 Figure 1.11: Angle formed between the substituents of 2,5- and 2,4-substituents in sulfur- based heterocycles. ........................................................................................................... 12 Figure 1.12: Numbering system for the 1,3-thiazole ring.