A NEW LATE-STAGE LAWESSON’S CYCLIZATION STRATEGY TOWARDS THE SYNTHESIS OF ARYL 1,3,4-THIADIAZOLE-2-CARBOXYLATE ESTERS A thesis submitted to the Kent State University Honors College in partial fulfillment of the requirements for Departmental Honors by Michael Joseph Schmidt August, 2013 TABLE OF CONTENTS LIST OF FIGURES.............................................................................................................v LIST OF TABLES...........................................................................................................viii ACKNOWLEDGEMENTS................................................................................................ix CHAPTER 1. INTRODUCTION.......................................................................................1 1.1 Introduction to liquid crystals and their phases...............................1 1.1.1 Liquid crystal phases........................................................................2 1.1.2 Interaction of liquid crystals with electric fields and polarized light..................................................................................5 1.2 Ferroelectric liquid crystals (FLCs) and their applications in liquid crystals displays (LCDs)....................................................8 1.2.1 Molecular structure of ferroelectric liquid crystals........................12 1.3 The synthesis of 1,3,4-thiadiazoles in liquid crystal materials......15 1.3.1 Ring-forming approaches to 1,3,4-thiadiazoles and other five-membered aromatic S-heterocycles........................................16 1.3.2 Ring-modifying approaches to 1,3,4-thiadiazoles and other five-membered aromatic S-heterocycles........................................25 1.4 Goals and scope of the current work..............................................31 2. RESULTS AND EXPERIMENTAL DISCUSSION................................33 2.1 Attempted application of alkyl 1,3,4-thiadiazole-2-carboxylate ester/thioester methodology to the preparation of aryl esters........33 iii 2.1.1 Introduction to previously established method for the synthesis of alkyl 1,3,4-thiadiazole-2-carboxylate esters and thioesters: complications from thiadiazole decarboxylation...........................33 2.1.2 Early studies towards the preparation of alkyl 1,3,4-thiadiazole-2- carboxylate esters...........................................................................35 2.1.3 First use of sodium 1,3,4-thiadiazole-2-carboxylate salt...............38 2.1.4 Preparation of the sodium 5-(4-octyloxyphenyl)-1,3,4-thiadiazole- 2-carboxylate salt (45)...................................................................42 2.1.5 Synthesis of 4-alkoxyphenols (63a-c)...........................................45 2.1.6 Attempted preparation of aryl 1,3,4-thiadiazole-2-carboxylate esters 48 using previously developed esterification approach.......46 2.2 Reevaluation of the synthesis of aryl 1,3,4-thiadiazole-2- carboxylate esters...........................................................................51 2.2.1 Synthesis of 4-alkoxyphenyl oxalyl chlorides 67..........................52 2.2.2 Synthesis of 4-alkoxyphenyl (N’-(4-octyloxyphenylcarbonyl) hydrazinecarbonyl)formates 68a-c................................................54 2.2.3 Synthesis of 4-alkoxyphenyl 5-(4-octyloxyphenyl)-1,3,4- thiadiazole-2-carboxylates 48 via late-stage Lawesson’s cyclization......................................................................................57 2.3 Liquid crystalline properties of 5-(4-octyloxyphenyl)-1,3,4- thiadiazole-2-carboxylate esters 48a-c..........................................60 2.4 Potential future work......................................................................62 3. EXPERIMENTAL DETAILS...................................................................64 3.1 General considerations...................................................................64 3.2 Experimental details and schemes.................................................65 REFERENCES..................................................................................................................90 iv LIST OF FIGURES Figure 1.1: Schematic showing the N, SmA, and SmC phases...........................................3 Figure 1.2: Schematic of the SmC* phase...........................................................................5 Figure 1.3: Schematic of light polarization..........................................................................7 Figure 1.4: Polarization/external field relationship for (a) paraelectic and (b) ferroelectric material................................................................................................................................9 Figure 1.5: The off (a)/on (b) states of an SSFLC cell......................................................10 Figure 1.6: The on (a)/off (b) states of a TN cell...............................................................11 Figure 1.7: General structure of ferroelectric materials. X = terminal dipolar groups, Y = central linkage, Z = chiral end group, L = lateral substituent, C = central core................13 Figure 1.8: Series of central and terminal links in Sm LCs...............................................13 Figure 1.9: General structure of potential mesogen targets in the Seed/Sampson research group..................................................................................................................................14 Figure 1.10: The dipole and bend angles in some sulfur heterocycles..............................15 Figure 1.11: General cyclization approach to 5-membered S-heterocyclic aromatic compounds.........................................................................................................................16 Figure 1.12: Proposed cyclization mechanism of 1,4-dicarbonyl compounds to 1,3,4- thiadiazoles using Lawesson’s reagent (modified from Ozturk).......................................17 Figure 1.13: Parra’s complementary approaches to 2,5-diaryl-1,3,4-thiadiazole columnar LCs (reproduced from Parra).............................................................................................19 Figure 1.14: Han’s use of Lawesson’s reagent for a study of 2,5-diaryl-1,3,4- thia/oxadiazole based liquid crystals (reproduced from Han)...........................................20 Figure 1.15: A usefully divergent pathway to 1,3,4-Thiadiazoles and 1,2,4-Triazoles by Kurzer et al. (reproduced from Kurzer).............................................................................22 v Figure 1.16: Lebrini and coworkers’ use of microwaves in the synthesis of symmetrical 2,5-diaryl-1,3,4-thiadiazoles (reproduced from Lebrini)...................................................23 Figure 1.17: Han’s use of microwaves in Lawesson’s cyclizations (reproduced from Han)....................................................................................................................................24 Figure 1.18: Rao’s use of sequential bromination/SNAr chemistry (reproduced from Rao)....................................................................................................................................26 Figure 1.19: Selective Sonogashira coupling approach by Lehmann and coworkers...........................................................................................................................27 Figure 1.20: Parra’s synthesis of some chiral Schiff-base containing 1,3,4-Thiadiazole- bassed liquid crystals (reproduced from Parra).................................................................28 Figure 1.21: Lachances’s synthesis of 2-bromo-5-cyano-1,3,4-thiadiazole......................29 Figure 1.22: Tanaka’s chemoselective thiazole synthesis.................................................29 Figure 1.23: Methodology toward 1,3,4-thiadiazole-2-carboxylate esters previously established by our group which has not been extensively explored for aryl ester synthesis....................................................................................................................31 Figure 1.24: General scheme of target molecules in this work..........................................32 Figure 2.1: Several proposed pathways for thiadiazole decarboxylation (reproduced from Spinelli)..............................................................................................................................35 Figure 2.2: Bradley’s pathway to 2-hydro-1,3,4-thiadiazoles (reproduced from Bradley)...............................................................................................37 Figure 2.3: General strategy toward 1,3,4-thiadiazole-2-carboxylate esters first attempted by Bradley, later optimized by Sybo..................................................................................39 Figure 2.4: Modifications by Wallace and Gans to Bradley/Sybo’s approach to 1,3,4- thiadiazole-2-carboxylate esters and thioesters.................................................................41 Figure 2.5: Reproduction of work by Bradley/Sybo, followed by attempted elaboration to aryl esters...........................................................................................................................42 vi Figure 2.6: TLC analysis (10% EtOAc in petroleum ether) of the results of column chromatography of the ethyl ester (44)..............................................................................44 Figure 2.7: Synthesis of 4-alkoxyphenols 63.....................................................................46 Figure 2.8: Decarboxylated