THE UNIVERSITY OF HULL Novel Materials for Nematic Mixtures Being a Thesis submitted for the Degree of Doctor of Philosophy In the University of Hull By Richard John Kiddle MSci (Hons) (Durham), AMRSC February 2005 Summary of Thesis submitted for the degree of PhD by Richard John Kiddle Msci (Hons) (Durham), AMRSC on Novel Materials for Nematic Mixtures The primary aim of this thesis was to generate nematic liquid crystals of low viscosity and negative dielectric anisotropy through single components and mixtures. The most effective way of increasing the negative dielectric anisotropy of a system is by employing the use of materials possessing large lateral dipole moments. To accomplish this many novel materials based on the highly successful 1,2-difluorobenzene group have been synthesised and characterised. Difluoroterphenyls and difluorophenylnaphthalenes are known to have the required properties, so the primary aim of this work was to expand the library of such compounds. In order to obtain lower viscosity; compounds with benzodioxinanes, dioxaborinane, and benzodioxaborinane units were also targeted. Non-linear cores are known to promote the formation of nematic phases over smectic, so a few compounds based on the benzofuran and 2,5-diphenyl thiophene cores were synthesised. Additionally, chiral dopants based on the lactate linking group were targeted as part of the programme to confer a high helical twisting power to nematic mixtures. Many of the materials synthesised possess the desirable properties of low melting points wide nematic ranges, and medium to high birefringence, in addition to high negative dielectric anisotropy. As a multitude of the new materials have novel structural components, novel synthetic methodologies were developed successfully in order to achieve them. Publications The following publications contain material from this thesis: R. J. Kiddle, M. Hird, British Liquid Crystal Society Annual Conference, Manchester, UK, 2004. Poster presentation: “Terphenyls of Negative Dielectric Anisotropy and High Birefringence”. R. J. Kiddle, M. Hird, Royal Society of Chemistry Materials Section, Sheffield, UK, 2003. Poster presentation: “Ortho-Difluorophenylnaphthalenes for Nematic Mixtures of Negative Dielectric Anisotropy and High Birefringence”. R. J. Kiddle, M. Hird, British Liquid Crystal Society Annual Conference, Cambridge, UK, 2003. Oral presentation: “Ortho-Difluorophenylnaphthalenes for Nematic Mixtures of Negative Dielectric Anisotropy and High Birefringence”. M. R. Friedman, R. J. Kiddle, K. J. Toyne, M. Hird, 19th International Liquid Crystal Conference, Edinburgh, UK, 2002. Poster presentation: “Benzo[b]furan as a novel core in thermotropic liquid crystals”. Acknowledgements I would like to express my sincere thanks and appreciation to Dr. M. Hird for his valued help, advice and supervision throughout the course of this research programme, and Professor J. W. Goodby for providing an excellent research group. I also wish to thank the Department of Chemistry of The University of Hull for the provision of research facilities, and to QinetiQ (Malvern) for financial support. Throughout my education my family have selflessly given me support, particularly my late Grandfather, to whom this thesis is dedicated; I cannot thank them enough. Abbreviations and Conventions The following abbreviations and conventions are used throughout this work. Physical Properties Bp = boiling point Mp = melting point lit. = literature value I = isotropic liquid Cr = crystalline state E = crystalline E phase N = nematic phase SmA = smectic A phase SmC = smectic C phase An asterisk (*) after the phase indicates chirality e.g. N* is a chiral nematic phase Structural Information s = singlet d = doublet dd = doublet of doublets ddd = doublet of doublets of doublets t = triplet ddt = doublet of doublets of triplets td = triplet of doublets tt = triplet of triplets q = quartet dt = doublet of triplets sext = sextet quin = quintet m = multiplet sept = septet GLC = gas-liquid chromatography TLC = thin-layer chromatography DSC = differential scanning calorimetry MS = mass spectrometry NMR = nuclear magnetic resonance IUPAC nomenclature conventions are used as a guide in the naming of compounds, except where more familiar, common, or trivial names are used. 1,4-disubstituted cyclohexyl rings are in all cases in the trans formation. Synthetic Information DCC = N,N'-dicyclohexylcarbodiimide DCM = dichloromethane DMAP = (4-N-dimethylamino)pyridine DME = 1,2-dimethoxyethane DMF = N,N-dimethylformamide PMHS = poly(methylhydrosiloxane) PPA = polyphosphoric acid PTSA = para-toluenesulphonic acid THF = tetrahydrofuran MBS = (S)-(+)-2-methylbutylsulphanyl All reaction solvents are written in italics. In some cases a reagent will also be the reaction solvent, here the formula of the reagent will appear in italics. Novel compounds prepared by the author are referenced as a number in bold typeface, e.g. 2. Known compounds are denoted as a number both underlined and in bold, e.g. 2, and referenced. Contents 1: Introduction 1 1.1: General Aspects of Liquid Crystals 2 1.1.1: The Historical Aspect 2 1.1.2: The Classification of Mesophases 3 1.2: Thermotropic Liquid Crystals 1.2.1: Thermodynamic Behaviour of Calamitic Thermotropic Liquid 5 Crystals 1.2.2: The Nematic and Cholesteric Mesophases 6 1.2.3: The Smectic Mesophases 9 1.2.4: The Disordered Crystal Mesophases 11 1.3: Some Physical Properties of Calamitic Liquid 14 Crystals 1.3.1: Dielectric Anisotropy 14 1.3.2: Birefringence (Optical Anisotropy) 15 1.3.3: Elastic Constants 16 1.3.4: Viscosity 17 1.4: The Application of Liquid Crystals in Display Devices 19 1.4.1: Twisted Nematic Displays 19 1.4.2: Supertwisted Nematic Displays 21 1.4.3: Active Matrix Displays 22 1.4.4: Electrically Controlled Birefringence Displays 22 1.4.5: Materials Requirement for Liquid Crystal Displays 24 1.5: Summary 30 1.6: References 31 2: Research Objectives 2.1: Aims of the Work 34 35 2.1.1: Materials for the Vertically-Aligned Nematic (VAN) device 35 2.1.2: Chiral Dopants 38 2.2: References 3: Experimental 3.1: Experimental-General Notes 39 40 41 3.1.1: Assessment and Physical Characterisation of Materials 41 3.1.2: Chromatographic Techniques 42 3.1.3: Spectroscopic Techniques 42 3.1.4: Starting Materials 43 3.1.5: Solvents 43 3.1.6: Miscellaneous 43 3.2: Synthetic Schemes 44 3.3: Experimental Procedures 80 3.3.1: Scheme 1 80 3.3.2: Scheme 2 84 3.3.3: Scheme 3 86 3.3.4: Scheme 4 88 3.3.5: Scheme 5 91 3.3.6: Scheme 6 93 3.3.7: Scheme 7 97 3.3.8: Scheme 8 98 3.3.9: Scheme 9 104 3.3.10: Scheme 10 118 3.3.11: Scheme 11 126 3.3.12: Scheme 12 128 3.3.13: Scheme 13 130 3.3.14: Scheme 14 131 3.3.15: Scheme 15 137 3.3.16: Scheme 16 143 3.3.17: Scheme 17 145 3.3.18: Scheme 18 145 3.3.19: Scheme 19 146 3.3.20: Scheme 20 150 3.3.21: Scheme 21 155 3.3.22: Scheme 22 159 3.3.23: Scheme 23 161 3.3.24: Scheme 24 165 3.3.25: Scheme 25 166 3.3.26: Scheme 26 169 3.3.27: Scheme 27 174 3.3.28: Scheme 28 175 3.3.29: Scheme 29 176 3.3.30: Scheme 30 178 3.3.31: Scheme 31 180 3.3.32: Scheme 32 181 3.3.33: Scheme 33 182 3.3.34: Scheme 34 183 3.3.35: Scheme 35 187 3.3.36: Scheme 36 188 3.3.37: Scheme 37 189 3.3.38: Scheme 38 191 3.3.39: Scheme 39 192 3.3.40: Scheme 40 194 3.3.41: Scheme 41 195 3.3.42: Scheme 42 196 3.4: Discussion of Synthetic Routes and Methods Employed 199 3.4.1: Convergent Synthesis Methodology 199 3.4.2: Preparation of Aryl Intermediates (Schemes 1-7) 203 3.4.3: Preparation of Terphenyls (Schemes 8-13) 205 3.4.4: Preparation of 2,6-Disubstituted Napthalene Materials 206 (Schemes 14-18) 3.4.5: Preparation of Benzodioxinane Materials (Schemes 19-28) 209 3.4.6: Preparation of 8-Fluoro-6-(2-fluoro-4-propoxyphenyl)-2-(4- 214 propylcyclohexyl)benzodioxinane (Scheme 29) 3.4.7: Preparation of 5-Heptyl-2-(4’-heptyl-biphenyl-yl) pyrimidine (Scheme 30) 214 3.4.8: Preparation of 2-(2,3-Difluorobiphenyl-4-yl)-[1,3,2]- 215 dioxaborinane Materials (Scheme 31) 3.4.9: Preparation of 2,5-Bis-(4-phenyl)thiophene Materials 215 (Schemes 32 and 33) 3.4.10: Preparation of 2,5-Diphenylbenzofuran Materials 216 (Scheme 34) 3.4.11: Preparation of Chiral Dopants (Schemes 35-42) 3.5: Experimental References 4: Materials Evaluation 4.1: Terphenyls 216 219 222 223 4.2.1: Introduction 223 4.1.2: Mesomorphism of 2’,3’-Difluoroterphenyls 228 4.1.3: Mesomorphism of 2,3-Difluoroterphenyls 235 4.1.4: Mesomorphism of Terphenyls with No Lateral Groups 238 4.1.5: Mesomorphism of Terphenyl Mixtures 239 4.1.6: Photomicrographs 243 4.2: 2,6-Phenylnaphthalenes 247 4.1.1: Introduction 247 4.2.2: Mesomorphism of 2,3-Difluorophenylnaphthalenes 249 4.2.3: Mesomorphism of 2-Fluorophenylnaphthalene 252 and Phenylnaphthalene Compounds 4.2.4: Mesomorphism of a 253 2,3-Difluorobiphenylnaphthalene Compound 4.3: Benzodioxinanes 254 4.3.1: Introduction 254 4.2.2: Mesomorphism of 2,3-Difluorophenylbenzodioxinanes 256 4.3.3: Mesomorphism of 2-Fluorophenylbenzodioxinanes 258 and Phenylbenzodioxinane Compounds 4.3.4: Mesomorphism of 2,3-Difluorobiphenylbenzodioxinanes 260 4.3.5: Mesomorphism of Laterally Substituted 262 and Unsubstituted 2,6-Bisphenylbenzodioxinanes 4.3.6: Mesomorphism of Laterally Substituted 264 and Unsubstituted 6-Phenyl-2-cyclohexylbenzodioxinanes 4.4: Biphenylpyrimidines 266 4.4.1: Introduction 266 4.4.2: Mesomorphism of Biphenylpyrimidine Compounds 267 4.5: Difluorobiphenyldioxaborinanes 268 4.5.1: Introduction 268 4.5.2: Mesomorphism of Difluorobiphenyldioxaborinanes 269 4.6: Bis-(4-phenyl)thiophenes 270 4.6.1: Introduction 270 4.6.2: Mesomorphism of Bis-(4-phenylthiophenes 271 4.7: Diarylbenzo[b]furans 273 4.7.1: Introduction 273 4.2.2: Mesomorphism of Diarylbenzo[b]furan Compounds 274 4.8: Chiral Dopants 275 4.8.1: Introduction 275 4.8.2: Mesomorphism of Chiral Dopants 276 4.9: References 5: Summary and Conclusions 278 281 5.1: General Summary and Conclusions 282 5.2: Materials for Vertically-Aligned Nematic (VAN) 283 Applications 5.2.1: Difluoroterphenyls 283 5.2.2: Difluorophenylnapthalenes 284 5.2.3: Benzodioxinanes 284 5.2.4: Other Core Units 286 5.3: Chiral Dopants 287 5.4: Physical Properties 288 5.5: References 289 1 Chapter One: Introduction 2 1.1: General Aspects of Liquid Crystals Liquid crystals (also called mesogens), exhibit a state of matter intermediate between a crystalline solid and an isotropic liquid. As their name implies, they possess physical properties associated with both the disordered liquid phase and the ordered crystal phase. What follows is a general introduction to the history, physical properties and applications of liquid crystals. 1.1.1: The Historical Aspect The first liquid crystal, nerve myelin, was identified by Virchow in 1854 [1]. Mettenheimer later observed that myelin was double refracting, indicating that the liquid possessed properties normally observed only in crystalline materials [2]. It is now known that myelin is a lyotropic (solvent induced) liquid crystal. The first thermotropic (thermally induced) liquid crystal was discovered by Reinitzer, who in a paper submitted on 3rd May 1888, described his observations of the coloured phenomena occurring in melts of cholesteryl acetate and cholesteryl benzoate [3]. In addition, he noted the “double melting” behaviour of cholesteryl benzoate, whereby the crystals transformed at 145.5 °C into a cloudy fluid, which clarified upon further heating to 178.5 °C. Reinitzer knew of the excellent work of Otto Lehmann in the field of polarisation microscopy, and asked him to advise on the optical behaviour of the cholesteryl esters [4]. This interaction led to an agreement that the materials were homogenous systems, and the term liquid crystal was used for the first time [5]. A large number of mesophases were subsequently discovered, and were classified into the three basic types: smectic, nematic, and chlolesteric by Friedel in 1922 [6]. Today, cholesterics are known as chiral nematics with no need that they be derived from cholesterol, and the existence of several polymorphic smectic forms is recognised; Friedel identified only one, the smectic A phase. 3 The commercial value of liquid crystals was not realised until 1964, when Fergason reported that colour changes in chiral nematic liquid crystals could be used in surface thermography and in the detection of atmospheric pollution [7]. In 1968, Heilmeier first used the dynamic scattering effect in an electro-optical liquid crystal device at room temperature [8, 9]. In the early 1970’s the twisted nematic (TN) effect was demonstrated by Schadt, Helfrich, and Fergason independently [10, 11]. This started the development of today’s liquid crystal display devices. In 1970, Gray obtained a research grant from the UK Ministry of Defence for work on liquid crystal materials of positive dielectric anisotropy, this research led to the synthesis of the now famous cyanobiphenyls [12]. These materials are the first stable compounds to exhibit the nematic phase at room temperature as single components or in mixtures, which are suitable for use in twisted nematic display devices. Commercial mixtures of biphenyls are still widely used in display devices today, despite having been discovered over thirty years ago. Many other structurally similar two- and three-ring compounds have been subsequently synthesised and assessed for their ability to generate a nematic phase and for their physical properties. 1.1.2: The Classification of Mesophases Liquid crystals can be classified into two main categories, according to the mode of their formation. If the liquid crystalline state is formed by heating from the solid, or by cooling the isotropic liquid, then it is termed a thermotropic liquid crystal. Lyotropic mesophases are formed by the addition of a solvent, usually water, to a suitable amphiphile. The nature of the phase formed is dependent on the concentration of the amphiphile and the temperature. A number of different mesophases are often observed over a given concentration range. The classification of liquid crystals is summarised in Figure 1.1.2.1. Thermotropic liquid crystals are divided according to molecular shape: spherical, discotic, or calamitic. These may be sub-divided according to the degree of order of the phase. High molecular mass compounds, polymers, organometallics and dendrimers can also be classified in this way. However, exceptional cases exist; sanidic compounds can give rise to calamitic liquid 4 crystal behaviour, and ellipsoid compounds have shown columnar “discotic” phases. A phasmidic substance has a shape intermediate between ellipsoid and discoid and can exhibit both columnar and calamitic mesophases. The scope of this work focuses solely on thermotropic, calamitic mesophases, therefore lyotropic, and non-calamitic thermotropic systems are not discussed in detail. Liquid Crystals Thermotropic Spherical Plastic Lyotropic Discoid Cubic Nematic Calamitic Nematic Columnar Figure 1.1.2.1: A classification of liquid crystals. Smectic Soft Crystals 5 1.2: Thermotropic Liquid Crystals 1.2.1: Thermodynamic Behaviour of Calamitic Thermotropic Liquid Crystals Figure 1.2.1.1: The melting behaviour of calamitic thermotropic liquid crystals. Figure 1.2.1.1 represents the melting behaviour of calamitic thermotropic liquid crystals. Heating a crystal causes the thermal motions of the component molecules to increase in intensity. At the melting point, the molecules have sufficient energy to overcome the lattice enthalpy, and the lattice breaks apart. In a non-mesogenic material, heating the crystal (T 1 ) causes a complete loss of ordering and an isotropic liquid results. In a liquid crystalline material, there is a stepwise loss of molecular ordering in the transition from the crystalline 6 state to an isotropic liquid; this is entirely due to the anisotropy of intermolecular forces arising from the dichotomous molecular structure of such compounds. If the initial breakdown of the crystal lattice occurs between the ends of the long axis of the molecules (T 2 ) a smectic phase results. In the transition from a smectic phase to a nematic phase (T 4 ) the molecules lose positional ordering, but retain orientational ordering. Further heating causes loss of orientational order, resulting in an isotropic liquid (T 6 ). If the material possesses smectic morphology only, then an increase in temperature will result in complete loss of the remaining molecular ordering, forming an isotropic liquid (T 5 ). Conversely, a mesogen may not show a smectic state; in this case, heating from the crystal causes a loss of all positional ordering and only orientational ordering remains (T 3 ). In a pure compound, transitions between mesophases and a mesophase to isotropic liquid phase are deemed reversible, occurring at a very similar temperature upon heating and cooling. The temperature at which a compound recrystallises is often well below the melting point, due to supercooling. In some cases a mesophase is only exhibited below the melting point of a compound in the supercooling region; this is termed a monotropic phase, and is denoted by round brackets. An enantiotropic phase is one, which occurs above the melting point. 1.2.2: The Nematic and Cholesteric Mesophases The nematic phase is the least ordered liquid crystal phase. There is no lamellar arrangement, only short range translational order in all directions. However, there exists a quasi-long range orientational ordering of the molecules along the long-molecular axis, which forms a statistically parallel arrangement of molecules with a common axis called the director (n). In the bulk phase, there are as many molecules pointing in one direction relative to the director as there are pointing in the opposite direction, the molecules have a disordered head-to-tail arrangement (n = -n). Thus, the phase has rotational symmetry relative to the direction, the phase is uniaxial. The molecules in the nematic phase possess a high degree of mobility and are relatively free to rotate about their long axes and to some degree about their short axes. The relaxation times for rotations about the short axes are 7 much longer (~105 to 106 times per second) than those about the long axes (~1011 to 1012 times per second). The degree to which the molecules are aligned along the director is termed the order parameter of the phase, and is given by the following expression [13]: S = ½<3cos2θ-1> Where θ is the angle made between the long axis of the individual molecule and the director. The angular brackets denote an averaged value taken over all molecular orientations. An order parameter of zero implies that the phase has no order at all (isotropic liquid), whereas a value of one indicates that the phase is perfectly ordered (crystalline solid). In a nematic phase, the value of S is typically between 0.4 and 0.7, indicating that the molecules are considerably disordered. Different mesophases have characteristic values of S. In addition, S varies with temperature. When a nematic phase is composed of chiral molecules, or a chiral dopant is added to a normal nematic phase, a chiral nematic (cholesteric) phase is induced. The chiral nematic phase has the orientational order of an achiral nematic, but this orientational ordering is skewed at a slight angle throughout the phase, resulting in the formation of a helix. The pitch length (p) of the helix is defined as the distance along the helical axis over which the average direction of molecular orientation rotates through an angle of 360°. The pitch length can vary greatly, from less than 0.1 μm to infinity. An increase in temperature causes the pitch length to reduce, because an increase in thermal energy causes an increase in the change in the angle of the molecular orientation. The phase can selectively reflect light when the pitch length is approximately equal to the wavelength of incident light. Therefore, the selective reflection of colours can occur if the wavelength is in the visible region. As the pitch length is temperature dependent, an increase or decrease in temperature will cause a change in the colour of the reflected light. 8 Director Pitch Length Figure 1.2.2.1: The structure of the chiral nematic phase. 9 1.2.3: The Smectic Mesophases The smectic phase is characterised by layered or lamellar ordering, caused by long range intermolecular forces along the short axes of the molecules. There are different variations on the smectic phase (A, B, C, F, I). They are identified by the orientation of the long molecular axis and correlations within the layers. The alphabetical order merely indicates the chronological order of discovery. The most common smectic phases are the smectic A phase and the more ordered smectic C phase. In the smectic A phase the molecules are arranged in layers so that their long axes are on average perpendicular to the layer planes. Like the nematic phase, the molecules are undergoing rapid reorientaional motion about both the long and short molecular axes. The molecules are arranged so that there is no translational periodicity in, or in between the planes of the layers. Therefore, there is only short range hexagonal ordering, extending over a few molecules. The layer spacing is slightly shorter than the molecular length. n n θ Smectic A Smectic C Figure 1.2.3.1: The structure of the smectic A and smectic C phases. In the smectic C phase the constituent molecules are arranged in diffuse layers where the molecules are tilted at a temperature-dependent angle (θ) with respect to the layer planes. Like the smectic A phase, the molecules within the layers are hexagonally close-packed 10 with respect to the director of the phase, over short distances. Over large distances the molecules are randomly packed. The smectic A phase has D ∞ symmetry and is optically uniaxial, whereas the smectic C phase has C 2h symmetry and is weakly optically biaxial. The chiral smectic C has a helical twist similar to that of the cholesteric phase, but with a higher degree of order [14]. Other, more ordered smectic phases have been documented, these are the smectic B (hexatic), smectic F, smectic I, and the alternating smectic C phase, (SmC alt , sometimes called smectic O) [15]. In the smectic B (hexatic), smectic F, and smectic I phases, the molecules possess long range order along the layer normal. Within the layers, the molecules have short range order, but the correlation length is of an order of magnitude longer than in the smectic A, or C phases. • • • • • • • • • • Smectic B • • • • Smectic F • • • • • • • Smectic I Figure 1.2.3.2: The structure of the smectic B, smectic F and smectic I phases. 11 The molecules in the smectic B phase are packed in a hexagonal array, and orientated orthogonal to the layer normal. The phase is very similar to, but more ordered than, the smectic A phase. In a similar way, the smectic I phase is analogous to the smectic C phase, but the molecules are tilted towards the apex of a quasi-hexagonal array. In the smectic F phase, the molecules are tilted towards the side of the hexagonal array. n Figure 1.2.3.3: The structure of the alternating tilt smectic C phase. The difference between the alternating smectic C phase and the standard C phase is that in the SmC alt phase, the tilt direction appears to flip from layer to the next, producing a zigzag layer arrangement. The orientational ordering is long range but there is no long range positional correlation of the molecules between layers. The chiral alternating smectic C phase is antiferroelectric [16]. 1.2.4: The Disordered Crystal Mesophases The B, E, G, J, H and K phases are disordered crystals. They are characterised by long range translational order in three dimensions. Unlike ordered crystalline structures, however, as with other phases, the molecules are undergoing rapid rotation about their long axes. This rapid rotation has led to these phases being described as anisotropic plastic crystals. The B phase is identical to the smectic B phase, but in the hexatic B phase the out of the plane order is only short range, whereas the crystal B phase has long range periodic order in three dimensions. 12 In the same way the J and G phases are crystalline modifications of the smectic I and F phases, respectively [17, 18]. In the molecules within the E phase are arranged in rectangular symmetry (conferring biaxiality) with their long axes perpendicular to the layer planes, forming a herringbone array. The distance between molecules is too short to allow full reorientational motion, so the rotation is of an oscillatory nature. The H and K phases are equivalent to the crystal E phase, expect for the molecules being titled with respect to the layer planes [19]. The packing arrangement is monoclinic, and the tilt is towards the short edge of the packing array in the H phase. In the K phase the tilt is towards the long edge. As in the E phase the reorientational motion is oscillatory in nature. 13 B, E • • • • • G, J, H, K • • • • • • • • • • • • • • G • B • • • • • • • • • • • • J · · · · · · H Figure 1.2.4.1: The structure of the disordered crystal mesophases. · · E · · · · · · · · · · · · · K 14 1.3: Some Physical Properties of Calamitic Liquid Crystals 1.3.1: Dielectric Anisotropy A material that is polarisable, but non-conducting is referred to as dielectric. Non-polar molecules may acquire an induced dipole moment in an electric field as the field causes a distortion in the electronic distributions and nuclear positions. In a polar molecule a permanent dipole moment is present; this is due to the partial charges on the atoms in the molecule, which arises from differences in electronegativity. Any existing dipole moments are modified by an applied electric field. Since uniaxial liquid crystals are anisotropic in nature, such a medium will have two dielectric permittivities. It is usual to discuss the dielectric anisotropy of a liquid crystalline material as defined by: ∆ε = ε  - ε ⊥ Where ε  is the permittivity along the long molecular axis, parallel to the director, and ε ⊥ is the permittivity perpendicular to the long molecular axis and to the director. For electrooptic display devices, ∆ε is a quantity of paramount importance, as its magnitude directly determines the strength of the interaction between a liquid crystal and an applied electric field. The sign of ∆ε also determines the geometry of display devices; under a large applied field the director aligns so that the larger dielectric constant lies parallel to the field. Obtaining negative ∆ε materials is more difficult than for positive ∆ε materials; this is because there are infinite axes perpendicular to the director along which the dipole may lie, only one of which may be parallel to the electric field. Furthermore, a strong dipole moment is usually resident in a substituent group, the lateral disposition of which may adversely affect liquid crystal phase stability and drastically raise the viscosity of the system. This situation is illustrated in figure 1.3.1.1, where compound 2 has two lateral cyano groups and an ester moiety, but has half the value of ∆ε, as compound 1, which has one terminal cyano group. 15 NC CN C5H11 O C5H11 CN C5H11 O 1 2 Cr 23 N 35 I Cr 99 N 112 I ∆ε = +22 ∆ε = -11.5 Figure 1.3.1.1: Compounds with positive and negative dielectric anisotropy [12, 20]. 1.3.2: Birefringence (Optical Anisotropy) In an anisotropic medium, a ray of light entering with a propagation direction other than parallel to the optical axis is divided into two rays which travel through the material at different velocities, and therefore have different refractive indices. This phenomenon is called double refraction or birefringence. The two emerging rays are polarised in planes perpendicular to one-another, and are called the ordinary (coupled to the molecular optic axis), and the extraordinary ray (which is perpendicular to the optic axis), and will have refractive indices n o and n e respectively. A liquid crystal is an anisotropic medium, in which the optic axis is defined by the director. Most liquid crystals are uniaxial, or have sufficiently small optical biaxiality that it can be neglected, and the optical anisotropy (maximum birefringence) is defined as: ∆n = n e - n o and for most purposes it may be taken that ∆n ∝ S where S is the order parameter of the mesogenic phase. 16 Birefringence is largely determined by the presence of aromatic rings and π-bonded terminal or linking groups in the liquid crystal molecule, see Figure 1.3.1.1. C5H11 CN C3H7 OC2H5 1 3 Cr 23 N 35 I Cr 42 N (38) I ∆ n = 0.237 ∆ n = 0.10 C3H7 OC2H5 4 Cr 49 N 50 I ∆ n = 0.05 Figure 1.3.2.1: Compounds with high, medium and low birefringence [12, 21, and 22]. 1.3.3: Elastic Constants In liquid crystal electrooptic devices, it is the operation of an electric field on the dielectric anisotropy of the fluid and aligns the molecules into the ‘on state’, while the ‘turn-off’ is usually driven by elastic forces. The elastic behaviour of liquid crystals is very weak compared to that of solids (about 10-11 N), and is difficult to detect by mechanical means [23]. However, the elastic torques are sufficient to drive the realignment of the liquid crystal director in a time scale of the order of milliseconds. The elastic behaviour of liquid crystals is not dimensionally equivalent to solids; all deformations are curvatures and can be expressed as a combination of the splay (k 11 ), twist (k 22 ) and bend (k 33 ) of the director, where the absolute values indicate the tendency to resist the deformation. 17 The absolute values of elastic constants help to determine the relaxation speed of display devices, it is the ratios of the elastic constants, particularly k 33 / k 11 that are more important, because of their effect on the shape of electro-optic switching curve in displays. A low value of k 33 / k 11 , which is desirable in many display modes, can best be achieved by increasing the length to width ratio of the core unit of molecules, by excluding lateral substituents, and by increasing the lengths of terminal chains. N C3H7 F C3H7 N 5 6 Cr 53 N [7] I Cr 85 N 145 I k33 / k11 = 1.24 k33 / k11 = 1.99 Figure 1.3.3.1: Materials with a small and large k 33 / k 11 ratio [24, 25]. 1.3.4: Viscosity The response time (τ = τ on + τ off ) of liquid crystal displays is limited by the viscosity of the fluid [26]: τ on = γ d2 2 / V 2th ) - 1) π 2 K1 ((Von γ d2 τ off = π K1 K 1 = “splay” elastic constant, γ = rotational viscosity, d = cell spacing. Five independent viscosities are required to characterise a liquid crystal: three of these (known as the Miesowics viscosities) represent conventional shear flow with different 18 dispositions of the director to the shear direction, the fourth represents director rotation and the fifth coupling between the director and the flow pattern [27]. The bulk viscosity of a nematic phase depends on the direction of flow of each molecule with respect to the director, averaged out over the whole sample. The bulk viscosity is dependent on the order parameter of the nematic phase, and therefore decreases with a temperature increase (approximately by a factor of 3-5 over 20 °C), except close to the clearing point, where the viscosity increases significantly. Viscosity can be minimised by reducing the polarity and polarisability of the molecule, and by using short terminal groups and omitting lateral substituents. C5H11 CN C7H15 F 7 Cr 96 N 219 I γ1 = 1338 mPa 8 Cr 36 N [-56] I γ1 = 27 mPa Figure 1.3.4.1: Materials with small and large viscosities [28, 29]. 19 1.4: The Application of Liquid Crystals in Display Devices There are a large variety of uses for liquid crystals, but only the application of the nematic phase in electro-optic display devices will be considered. 1.4.1: Twisted Nematic Displays The twisted nematic (TN) effect was discovered in 1970 by Schadt, Helfrich, and Fergason, this led to the development of the twisted nematic cell [10, 11]. The cell consists of two transparent glass plates coated with thin layers of indium-tin oxide (ITO) and unidirectionally buffed polyimide on their inner surfaces. The polyimide layer is used to achieve a macroscopic orientation of the liquid crystal director. The two glass plates are held apart at a distance of approximately 6-10 μm by spacers. The rubbing directions of each glass plate are arranged perpendicular to each other. The cell is then filled with a nematic liquid crystal and is cooled from the isotropic phase into the nematic phase. Owing to the boundary conditions the nematic phase will be come aligned parallel to the rubbing direction of each glass plate and consequently the director will undergo a twist of 90° over the layer surface. A small amount of chiral nematic dopant is added, and a pretilt angle of about 1° applied at the boundaries, this is to minimise reversed twist defects and reversed tilt defects. Polariser sheets are attached to the outer surfaces of each glass plate, with the polarizing axis parallel to the rubbing directions. Plane polarised light is guided through 90° by the molecules in the nematic phase and passes through the cell, exiting through the second polarizer. This effect is based on an experiment by Mauguin in 1911, which showed that the polarisation of light follows a slowly varying directional change of the optical axis [30]. This configuration, the so-called normally white (NW) mode, the display appears bright when no voltage is applied to the cell. The application of an electric field across the cell re- 20 orients the molecules with their long axis towards the layer normal, expect for the surface region where the homogenous alignment is retained. This surface alignment induces relaxation back to the 90° twist state on removal of the field. In the ON state no light can pass though the cell, which therefore appears black. Figure 1.4.1.1: The principle of operation of the TN device. The normally white mode is used as a transmissive mode with additional backlight in active matrix addressing (TFT) displays, or as a reflective mode, by using a reflective sheet at the back of the cell in calculators and watches. If both polarisers are orientated parallel to the rubbing directions of the cell, a black appearance in the unactivated state, and a bright appearance in the activated state results. This is the normally black (NB) mode, and mainly used in automotive applications. 21 1.4.2: Supertwisted Nematic Displays In 1982 it was found that an electrooptical configuration with an infinite slope can be realised for a LCD with a twist angle of about 270° [31, 32]. As this twist angle is much larger than the twist angle of about 90° for the twisted nematic (TN) effect, the expression “supertwisted” devices was coined. Such a large twist can be induced by quite a large amount of a chiral dopant, for example, a twist angle of 270° corresponds to a cell spacing (d) / pitch (p) ratio of 0.75. The twist angle is also constrained by the rubbing directions, and hence a certain d/p range is allowed for one twist angle. For a fixed concentration (c) of a chiral material, the pitch (p) can be derived from the helical twisting power (HTP) of the dopant [33]: HTP = 1 / (c x p) The HTP depends on the molecular structures of the dopant guest as well as that of the nematic host [34-36]. A general structure-HTP relation is not known. Typically, the chiral dopants have a different structure to the calamitic molecules of the nematic host [37, 38]. The structure of a single-layer STN cell is similar to that of the TN cell. However, the basic principal of standard STN LCDs results in interference colours in either the on or off state. The colours can be changed by using a selective polariser, or colour filter but normally it is impossible to produce a black and white appearance. The interference colours of STN-LCDs can be overcome by retardation compensation, this is the principle of the double layer super twisted nematic display, (DL)STN-LCD [39]. In this device the interference colour of a STN cell is compensated by a second STN cell with opposite helical twist sense, but otherwise identical properties. However, double layer STN displays require a very precise cell gap spacing, which leads to increased production costs. Compared to the TN-LCDs, the high twist angle of STN displays has resulted in an improvement of the viewing angle and of the response time-voltage characteristics. The 22 steep electrooptic characteristic of STN cells means that multiplexing is possible, and the first liquid crystal TV, based on double layer STN technologies was demonstrated in 1987. 1.4.3: Active Matrix Displays In a liquid crystal cell, the ITO layers on both of the glass substrates are patterned in order to generate conductive areas in which the liquid crystal orientation can be modified by an applied electric field. These active areas are separated by nonconductive areas. Low information content displays (watches and calculators) are usually addressed directly by an individual connection between each pixel and an electrode. Higher information displays require matrix addressing. In active matrix addressed TN-LCDs, the multiplexing action is decoupled from the TNLCD by adding a non-linear switching element integrated into each pixel. The non-linear switching element can be a semiconductor in the form of a metal-insulator-metal (MIM), diode, or a thin-film-transistor (TFT). TFTs are most commonly used as they offer the best performance. The voltage levels in the select and non-select states are not restricted, so the performance of a TFT driven TN display does not deteriorate with increasing number of picture elements. Active matrix TN-LCD devices offer good contrast, fast response times and a wide range of viewing angles. Because of this they are used in the fabrication of colour TV and laptop screens, the colour being introduced by the use of RGB colour filters, located in the inner surface of the non-active matrix planes of the cell, under the ITO electrode layer. 1.4.4: Electrically Controlled Birefringence Displays The electrically controlled birefringence (ECB) effect was first described in 1971, but at that time, could not compete commercially with the TN effect [40-42]. The ECB-LCD needs homeotropic surface alignment of the molecules, and the nematic materials must have negative dielectric anisotropy. Both of these conditions had been difficult to meet in the past. The principle of the ECB-LCD is shown in figure 1.4.4.1. 23 Figure 1.4.4.1: The principle of operation of the ECB device. The molecules are aligned homeotropically in the “off state” with a small pretilt angle of about 1° from the glass normal to give uniform switching. There is no birefringence as the light is parallel to the optic axis. When crossed polarisers are aligned at 90° to the molecular tilt direction, the “off state” appears dark, and transmission of the “on state” is given by [43]: T = T ο x (sin2 π x ((∆n x θm x d) / λ)) Where ∆n x θm ~ (∆n / 2) x θm2 For small tilt angles, ∆n is the birefringence of the liquid crystal material, θm is the tilt angle of the molecules at the centre of the cell for a given voltage, and d is the cell thickness. 24 The transmission is greatest when: ∆n x θm x d = λ / 2 A small change in the molecular tilt across the cell (which is caused by a small variation in the applied voltage) generates a significant change in the transmission. The resulting steep electro-optic characteristic qualifies the ECB effect for LCDs driven at high multiplex ratios [44, 45]. Compared to the TN effect, the ECB effect offers three advantages for TFT addressed displays: a higher contrast, a wider viewing angle, faster switching, and a more stable grey scale [46]. Modern ECB devices (now called the vertically-aligned nematic (VAN) device) have a compensation layer, characterised by negative birefringence; this is to prevent off-axis light bleeding. A multidirectional pretilt is also used to improve viewing angle. 1.4.5: Materials Requirement for Liquid Crystal Displays The quality of any liquid crystal display is strongly determined by the physical properties of the mesogenic material. To achieve the highest display quality it is essential to select and optimise the materials for the given LC cell parameters and requirements. However, it is impossible to find one single liquid crystalline material which fulfils all the materials requirements. Therefore, mixtures of up to twenty components are usually used in LCDs. All LC display devices require the following: 1) Stable, colourless materials, for operation at room temperature 2) Low-voltage operation 3) Operation over a wide temperature range 4) Materials with a low value of k 33 / k 11 5) Materials with low viscosity 25 In addition, the different types of liquid crystal display require LC mixtures of very specific values of dielectric anisotropy, birefringence and clearing point. An overview of the most important nematic LCDs in production today is presented in table 1.4.5.2 [47]. All are based on a TN cell, except for the IPS device, which is based on an interdigital electrode arrangement, and the VA-TFT device, which is based on the ECB cell. Figure 1.4.5.1: Applications of Liquid Crystal Displays. 26 Technology Applications Materials Characteristics Requirements Standard PC monitors, ∆ε 4-6 Well established technology; use of AM-LCD notebook compensation films for improvement (5V/4V computers ∆n 0.085-0.10 T NI 80-120 °C driver) Low of viewing angle independence of contrast ∆ε 10-12 V tn Notebook AM-LCD computers, (3.3 V/2.5 V PDAs, driver) camera ∆n 0.085-0.10 T NI ~70 °C AM-LCD; lower power consumption; very sensitive towards impurities of the liquid crystal material view finders Reflective Video games, ∆ε 4-8 No TFT small reduction of power consumption by up computers, ∆n 0.06-0.07 T NI ~80 °C backlight required, therefore to ~90 %; relatively low brightness PDAs. and contrast In-Plane PC monitors, ∆ε 12-16 Very wide viewing angle and superior Switching TV. picture quality; nitrile based materials (IPS) VA-TFT T NI ~80 °C can also be used PC monitors, ∆ε ~ - 4.5 Very wide viewing angle and superior TV. picture quality, large size; very high Plasma TV Addressed advertising LCD (PALC) ∆n ~0.075 ∆n ~0.08 T NI ~70 °C ∆ε <0 ∆n ~0.08 T NI ~70 °C contrast and fast switching time Large size (1 m diagonal); very good picture quality and fast switching time Table 1.4.5.2: The material requirements for commercial active matrix LCDs [47]. 27 Figure 1.4.5.3 shows materials used in modern, standard active matrix displays. Compounds with terminal halogens are used to provide the required ∆ε value, as cyanobased materials cannot be used due to their low voltage-holding ratio. Compounds 11-14 have an additional, lateral fluoro group in order to augment the molecular dipole moment [48]. C5H11 Cl C5H11 F 9 10 Cr 32 I Cr 34 I F F C5H11 F C5H11 F 11 12 Cr 46 N 105 I Cr 46 N 124 I F F F F C3H7 C3H7 13 Cr 25 SmB 53 N 119 I 14 Cr 39 N 104 I Figure 1.4.5.3: Examples of materials used in standard TN and AM-LCDs [47]. As stated previously, AM-LCDs based on the vertically aligned nematic (VAN) cell require dielectrically negative liquid crystals, typically these materials are based on the 1,2difluorobenzene unit. Several examples are shown in figure 1.4.5.4. 28 F F C5H11 F CH3 F C5H11 OC2H5 15 16 Cr 49 (N 13) I Cr 14 I F F C5H11 F CH3 F C5H11 OC2H5 18 17 Cr 67 N 145 I F Cr 79 (SmB 78) N 185 I F F C5H11 OC2H5 19 Cr 74 SmA 86 N 171 I F C2H5 C3H7 20 Cr 73 N 115 I Figure 1.4.5.4: Examples of materials used in VA-TFT devices [47]. The materials shown in figures 1.4.5.3 and 1.4.5.4 are used for their dielectric anisotropy values. This basic property is often accompanied by relatively low clearing temperatures, or high rotational viscosities. In order to improve the operating temperature range of the display, and to adjust the birefringence and dielectric anisotropy to the exact specifications dictated by the display design, often less polar compounds are used to tune the liquid crystal mixture. Some commonly used examples of such materials are shown in figure 1.4.5.5. 29 C3H7 C2H5 C3H7 C3H7 21 22 Cr 1 I Cr 64 SmB 82 N 132 I O C3H7 C5H11 O 23 24 Cr -9 SmB 52 N 63 I C5H11 Cr 23 N 37 I C5H11 25 Cr 13 SmB 164 N 170 I C3H7 C5H11 OCH3 26 Cr 53 SmB 72 I Figure 1.4.5.5: Examples of materials used in liquid crystal mixtures [47]. 30 1.5: Summary Thermotropic liquid crystals have been studied since the 19th century; and are classified today into nematic and the various polymorphs of the smectic phase. A typical liquid crystal material can display one or more of these phases. The physical properties of liquid crystals are temperature and pressure dependent as well as depending on the type of liquid crystal state. Liquid crystal phases are anisotropic, and the most important properties of the nematic state, for display devices are dielectric anisotropy, birefringence, elastic constants and viscosity. Most commercial electro-optic displays are based on the nematic phase. The twisted nematic (TN), supertwisted nematic (STN), and electrically controlled birefringence (ECB) devices are the most common. These devices all have different material requirements which can be realised by the use of mixtures of mesomorphic compounds possessing the desired properties. 31 1.6: References 1. R. Virchow, Virchows Arch. Path. Anat. Physiol., 1854, 6, 571. 2. C. Mettenheimer, Corr. Blatt d. Vereins gem. Arb. z. Forderung d. wissenschaftl. Heilkunde, 1857, 24, 331. 3. F. Reinitzer, Monatsh. Chem., 1888, 9, 421. 4. H. Kelker, P. M. Knoll, Liq. Cryst., 1989, 5, 19. 5. O. Lehmann, Z. Phys. Chem., 1889, 4, 462. 6. G. Friedel, Annales de Physique, 1922, 18, 273. 7. J. L. Fergason, Sci. Amer., 1964, 211, 77. 8. G. H. Heilmeier, L. A. Zanoni, L.A. Barton, Proc. IEEE, 1968, 56, 1162. 9. G. H. Heilmeier, L. A. Zanoni, L.A. Barton, Appl. Phys. Lett., 1968, 13, 46. 10. M. Schadt and W. Helfrich, Appl. Phys. Lett., 1971, 18, 127; Swiss Patent 532261, 1970. 11. J. L. Fergason, U.S. Patent 3918796, 1971. 12. G. W. Gray, K. J. Harrison, J. A. Nash, Eletron. Lett., 1973, 9, 130. 13. S. Dumrongrattana, C. C. Huang, Phys. Rev. Lett., 1986, 56, 464. 14. H. R. Brand, P. E. Cladis, P. L. Finn, Phys. Rev. A., 1988, 38, 2132. 15. A-M. Levelut, C. Germain, P. Keller, L. Liebert, J. Billard, J. Phys., 1983, 44, 623. 16. N. Hiji, A. D. L. Chandani, S. Nishiyama, Y. Ouchi, H. Takezoe, A. Fukuda, Ferroelectrics, 1988, 85, 99. 17. A-M. Levelut, J. Doucet, M. Lambert, J. Phys., 1974, 35, 773. 18. J. Doucet, P. Keller, A-M. Levelut, P. Porquet, J. Phys. Lett., 1978, 39, 548. 19. P. A. C. Gane, A. J. Leadbetter, P. G. Wrighton, Mol. Cryst. Liq. Cryst., 1981, 66, 247. 20. H. Schad, S. M. Kelly, Mol. Cryst. Liq. Cryst., 1986, 75, 133. 21. R. Eidenschink, J. Krause, L. Pohl, German Patent DE-OS 2636684, 1978. 22. R. Eidenschink, G. W. Gray, K. J. Toyne, A. E. F. Wachtler, Mol. Cryst. Liq. Cryst. (Lett.), 1988, 5, 177. 32 23. J. Grupp, Phys. Lett., 1983, 99A, 373. 24. H. Zaschke, German Patent DE 2429093, 1975. 25. M. Schadt, R. Buchecker, A. Villinger, Liq. Cryst., 1990, 7, 519. 26. A. Raviol, W. Stille, G. Strobl, J. Chem. Phys., 1995, 103, 3788. 27. M. Miesowicz, Nature, 1935, 136, 261. 28. R. Eidenschink, J. Krause, L. Pohl, German Patent DE-OS 2701591, 1978. 29. R. Eidenschink, L. Pohl, European Patent 14840, 1980. 30. C. Maugium, Bull. Soc. Fr. Min., 1911, 34, 71. 31. C. M. Waters, E. P. Raynes, British Patent GB 2123163B, 1984. 32. Y. Kando, T. Nakagomi, S. Hasagawa, German Patent DE 3403259 A1, 1985. 33. H. Finkelmann, H. Stegemeyer, Ber. Bunsenges. Phys. Chem., 1978, 82, 1302. 34. H. Finkelmann, H. Stegemeyer, Ber. Bunsenges. Phys. Chem., 1974, 78, 869. 35. W. J. A. Goossens, Mol. Cryst. Liq. Cryst., 1970, 12, 237. 36. B. W. Van der Meer, G. Vertogen, Phys. Lett., 1979, 71A, 486. 37. H. Stegemeyer, H. J. Kersting, W. Kuczynski, Ber. Bunsenges. Phys. Chem., 1987, 91, 3. 38. G. Gottarelli, G. P. Spada, Mol. Cryst. Liq. Cryst., 1985, 123, 377. 39. K. Katoh, Y. Endo, M. Akatsuka, M. Ohgawara, K. Sawada, Jap. J. Appl. Phys., 1987, 26, L 1784. 40. M. Schiekel, K. Fahrenschon, Appl. Phys. Lett., 1971, 19, 391. 41. G. Labrunie, J. Robert, J. Appl. Phys., 1973, 44, 4869. 42. S. Matsumoto, M. Kawamoto, K. Mizunoya, J. Appl. Phys., 1976, 47, 3842. 43. J. Duchene, Displays, 1986, 7, 3. 44. J. Robert, F. Clerc, SID ’80 Digest Tech. Papers, 1980, 30. 45. H. Schad, SID ’82 Digest Tech. Papers, 1982, 244. 46. J. F. Clerc, J. C. Deutsch, Proc. Eurodisplay ’87, London, 1987, p 111. 47. P. Kirsch, M. Bremer, Angew. Chem. Int. Ed., 2000, 39, 4216. 48. Y. Goto, T. Ogawa, S. Sawada, S. Sugimori, Mol. Cryst. Liq. Cryst., 1991, 209, 1. 49. R. Eidenschink, Kontakte (Darmstadt), 1979, 1, 15. 33 50. K. Praefcke, D. Schmidt, G. Heppke, Chem. Zeit., 1980, 104, 269. 51. M. Schadt, R. Buchecker, A. Villinger, Liq. Cryst., 1990, 7, 519. 52. M. A. Osmann, L. Revesz, Mol. Cryst. Liq. Cryst., 1980, 56, 157. 53. N. Carr, G. W. Gray, Mol. Cryst. Liq. Cryst., 1985, 124, 27. 34 Chapter Two: Research Objectives 35 2.1: Aims of the Work 2.1.1: Materials for the Vertically-Aligned Nematic (VAN) device Vertically Aligned Nematic (VAN) devices require materials of a high optical anisotropy (birefringence) and a negative dielectric anisotropy. This device, given the recent availability of suitable negative dielectric anisotropy materials, offers much potential for large TFT addressed displays [1]. The standard TFT driver requires an operating voltage under six volts. As a consequence the dielectric anisotropy of the nematic mixture has to be at least -3, taking the corresponding elastic constants into consideration. The first VAN devices had a switching time from black to white of 25 ms; this is not sufficient to realise full moving pictures [2]. The required optical path (d x ∆n) of this device is about 0.3 µm, for currently used cell gaps, a nematic mixture with a ∆n value of 0.08 is required. In order to improve the switching time, smaller cell gaps are required (3 μm or less), therefore liquid crystals with quite a high (greater than 0.08) optical anisotropy are required. A liquid crystal with negative dielectric anisotropy can be achieved by the introduction of a lateral polar group into the molecular structure. Molecules with a lateral cyano substituent have a very high negative ∆ε. However, this group has a large van der Waals volume, leading to a significant deterioration of the clearing point as well as to a major increase in the viscosity of the system. In addition, 2,3-dicyanophenyl compounds are only poorly soluble in liquid hosts and have poor photostability; they also have low resistivity [3]. Accordingly, other types of lateral substituents have been utilised [4, 5]. Now fluorine is most significant and most widely used. Its high electronegativity (the highest of any element, 4.0) in combination with its small size (the smallest van der Waals radius expect for hydrogen), 1.47 angstroms means that the fluoro substituent can exert a significant, but not too drastic effect on the molecular breadth to allow tailoring of the melting point and liquid crystal phase morphology. Lateral substituents are useful for the formation of nematogens, since they disrupt lamellar packing, thus reducing smectic phase stabilities. 36 Therefore QuietiQ, who sponsored this work require compounds based on the highly successful 1,2-difluorobenzene group [6-8]. Difluoroterphenyls (27, 28) and difluorophenylnaphthalenes (29) are known to have the necessary properties so the primary aim of this work is to expand the library of such compounds [9-11]. In order to obtain lower viscosity; compounds with benzodioxinane (30, 31), dioxaborinane (32), and benzodioxaborinane (33) units are also targeted. Additionally, non-linear cores are known to promote the formation of nematic phases over smectic, so a few compounds based on the benzofuran (34) and 2,5-diphenyl thiophene (35) cores are desired [12, 13]. Relatively high clearing points of nematic phases are observed when the chains of terminal groups are short and have odd numbers of atoms, so most of the target compounds have chains of three or five atoms in length. Alkoxy terminal chains are desirous as the polarity of the oxygen atom will increase the overall negative dielectric anisotropy of the system. However, the alkoxy chain will increase the viscosity, relative to an alkyl group, so dialkyl compounds are needed for inclusion in mixtures. Furthermore, target compounds will include an alkylsulphanyl terminal chain to provide a high birefringence [14]. In order to compare physical and mesogenic properties ‘parent’ compounds (with no lateral substituents) were also prepared. 37 F F F R1 R2 R1 R2 28 27 R F 1 F F O 29 30 O F R1 F R2 O O B O R1 R2 32 O B R2 O F F R1 31 F O F R1 R2 F F R1 O 33 34 F 1 R F F S F R1 35 Figure 2.1.1.1: Generic molecular structures of target compounds R2 R2 38 2.1.2: Chiral Dopants Dopants incorporating an optically active centre are used extensively in mixtures with nematic hosts for electrooptic display device applications. These chiral dopants have been used for many years to induce a certain handedness to prevent the formation of reverse twist defects in TN cells, as well as to compensate the temperature dependence of the threshold voltage [15-19]. In order to adjust and stabilise the desired angle of twist in STN devices chiral dopants are also necessary [20-22]. It is for these reasons that it is commercially important to synthesise new chiral dopants that are characterised by short pitches and good solubility in nematic hosts. Chemical, thermal and photochemical stability is also vital. Compounds containing two mesogenic groups joined by a flexible spacer group derived from lactic acid have been made previously for ferroelectric applications [23]. It was thought that similar compounds, with the lactate group as a spacer, or as a terminal group would be applicable to nematic systems Additionally, research on diesters derived from the optically active diol, (R,R)-2,3butandiol has shown the diesters to have high helical twisting powers (HTP) when used as dopants in suitable nematic mixtures [24]. It is for this reason that such materials are prepared as part of this work. 39 2.2: References 1. D. Pauluth, K. Tarumi, J. Mater. Chem., 2004, 14, 1219. 2. K. Ohmuro, S. Kataoka, T. Sasaki, Y. Koike, SID Dig. Tech. Pap., 1997, 845. 3. M. A. Osman, Mol. Cryst. Liq. Cryst., 1982, 82, 295. 4. M. A. Osman, Mol. Cryst. Liq. Cryst., 1985, 28, 45. 5. P. J. Collings and M. Hird, ‘Introduction to Liquid Crystals – Chemistry and Physics’, Chapter 3 (eds., G. W. Gray, J. W. Goodby and A. Fukuda), Taylor and Francis, London, 1997. 6. V. Reiffenrath, J. Krause, A. Wachtler, G. Weber, U. Finkenzeller, European Patent EP-B 0364538, 1988. 7. P. Kirsch, V. Reiffenrath, M. Bremer, Synlett, 1999, 4, 389. 8. M. Klasen, M. Bremer, Angew. Chem. Int. Ed., 2000, 39, 4216. 9. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, J. Chem. Soc., Perkin. Trans. 2, 1989, 2041. 10. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1990, 191, 1. 11. G. W. Gray, K. J. Toyne, D. Lacey, M. Hird, World Patent 90108119, 1990. 12. M. R. Friedman., Ph.D. Thesis, The University of Hull, England, 2001. 13. R. Cai, E. T. Samulski, Liq. Cryst., 1991, 9, 5, 617. 14. M. Hird, A. J. Seed, K. J. Toyne, J. W. Goodby, G. W. Gray, and D. G. McDonnell, J. Mater. Chem., 1993, 3, 851. 15. G. W. Gray, K. J. Harrison, J. A. Nash, E. P. Raynes, Electronic Lett., 1973, 9, 616. 16. G. W. Gray, D. G. McDonnell, Electronic Lett., 1975, 11, 556. 17. G. W. Gray, D. G. McDonnell, Mol. Cryst. Liq. Cryst., 1976, 37, 189. 18. M. Schadt, W. Helfrich, Appl. Phys. Lett., 18, 127. 19. P. R. Gerber, Phys. Lett. A., 1980, 78, 285. 20. T. J. Scheffer, J. Nehring, Appl. Phys. Lett., 1984, 45, 1021. 21. M. Schadt, F. Leenhouts, Proc. SID, 1978, 28, 275. 22. U. Finkenzeller, H. J. Plach, Mol. Cryst. Liq. Cryst. Lett., 1988, 6, 87. 23. M. Marcos, A. Omenat, J. L. Serrano, Liq. Cryst., 1993, 13, 6, 843. 24. S. M. Kelly, M. Schadt, H. Seiberle, Liq. Cryst., 1992, 11, 5, 761. 40 Chapter Three: Experimental 41 3.1: Experimental-General Notes 3.1.1: Assessment and Physical Characterisation of Materials Transition Temperatures Transition temperatures of final products and melting points of intermediates were determined optically using an Olympus BH-2 polarising microscope with a Mettler FP52 hot stage linked to an FP5 temperature control unit. Where low temperature microscopy was necessary, a Zeiss BIN polarising microscope with a Linkam TP91 hotsatge controller and LNP1 cooling pump was used. Measurements made in this way are accurate to ±1 °C Differential Scanning Calorimetry (DSC) The transition temperatures were confirmed using Differential Scanning Calorimetry (Perkin-Elmer 7 Series/Windows thermal analysis software). A static nitrogen atmosphere was used in the furnace and an empty gold pan was used as the reference. Indium metal was used for calibration. All the transistion temperatures quoted in this chapter are the DSC values. Optical Rotation (OR) Optical rotation was determined by an Optical Activity Ltd. AA-10 automatic polarimeter. In all cases the sample solvent was chloroform. 42 3.1.2: Chromatographic Techniques Gas-Liquid Chromatography (GLC) A Chrompack CP9001 gas chromatograph fitted with a WCOT fused silica column (10 m x 0.25 mm) and flame ionisation detector was used, linked to a 486 PC workstation using Summit for Windows software. Thin-Layer Chromatography Merck 60 F254 plates were used. Detection was by UV fluorescence (254 nm and 365 nm). Column Chromatography Flash (pressurised) or gravity chromatography was carried out using Merck Kieselgel C60 230-240 mesh silica gel. 3.1.3: Spectroscopic Techniques Nuclear Magnetic Resonance Spectroscopy (NMR) Conformation of the structures of intermediates and products was obtained by using a JEOL Lamada 400 FT (400 MHz). Tetramethylsilane was used as the internal standard in all cases. Mass Spectrometry (MS) Mass spectra were recorded using a Finnegan-MAT 1020 GS-MS spectrometer. 43 3.1.4: Starting Materials Materials were obtained from Aldrich, Avocado, Fluorochem, Kingston Chemicals, Merck or Lancaster Synthesis. (S)-(+)-1-Bromo-2-methylbutane was obtained from Aldrich and has a chemical purity of 99+ % and an optical purity of >99 % ee, with an optical rotation of [α]D21° +4.5° (5 g/ml, chromoform). (2R,3R)-(-)-Butane-2,3-diol was obtained from Aldrich and has a chemical purity of 97+ % and an optical purity of >99 % ee, with an optical rotation of [α]D23° -13.2° (neat). 3.1.5: Solvents All solvents were used without further purification for column chromatography and in reaction mixtures unless otherwise stated. Dry tetrahydrofuran (THF) was obtained by distillation over potassium metal under a dry nitrogen atmosphere with benzophenone indicator. Toluene was dried over sodium wire. Dichloromethane (DCM) was distilled over phosphorus pentoxide. Pyridine was dried over anhydrous potassium hydroxide. Anhydrous N,N-Dimethylformamide (DMF) was obtained from Aldrich, a transfer line was used to dispense the solvent. 3.1.6: Miscellaneous The proton NMR and mass spectra of the products from the boronic acid preparations are not reported; as these products are a mixture of dimeric, trimeric anhydrides and adducts with THF. The basic conditions used in the subsequent coupling reactions permit the use of these products as well as the free acid. Tetrakis(triphenylphosphine)palladium(0) was prepared according to the literature procedure [1]. 44 3.2: Synthetic Schemes Scheme 1 Br 1 Br 2 R1 = C2H5 3 R1 = C4H9 4 R1 = C6H13 5 R1 = C8H17 Br 6 R2 = C3H7 7 R2 = C5H11 8 R2 = C7H15 9 R2 = C9H19 B(OH)2 10 R2 = C3H7 11 R2 = C5H11 12 R2 = C7H15 1a O R1 1b R2 1c R 2 1a R1COCl / AlCl3, bromobenzene. 1b NH2NH2 / KOH, DCM. 1c (i) Mg , THF, (ii) B(OMe)3, (iii) 10% HCl. 45 Scheme 2 HS Br 13 Br 14 R = C2H5 15 R = C4H9 16 R = (S)-2-methylbutyl B(OH)2 17 R = C2H5 18 R = C4H9 2a RS 2b RS 2a RBr, K2CO3, butanone. 2b Mg, THF, (ii) B(OMe)3, (iii) 10% HCl. Scheme 3 HO Br 19 Br 20 R = C2H5 21 R = C4H9 22 R = C6H13 23 R = C8H17 B(OH)2 24 R = C2H5 25 R = C4H9 3a RO 3b RO 3a RBr, K2CO3, butanone. 3b Mg, THF, (ii) B(OMe)3, (iii) 10% HCl. 46 Scheme 4 F HO Br 26 Br 27 R = C3H7 28 R = C4H9 29 R = C6H13 30 R = C8H17 B(OH)2 31 R = C3H7 32 R = C4H9 33 R = C6H13 34 R = C8H17 4a F RO 4b F RO 4a RBr, K2CO3, butanone. 4b (i) nBuLi, THF, (ii) B(OMe)3, (iii) 10% HCl. 47 Scheme 5 F F 35 HO 5a F F 36 R = C2H5 37 R = C3H7 38 R = C4H9 F 39 R = C2H5 40 R = C3H7 41 R = C4H9 RO 5b F RO B(OH)2 5a RBr, K2CO3, butanone. 5b (i) nBuLi, THF, (ii) B(OMe)3, (iii) 10% HCl. 48 Scheme 6 F F 42 6a F F 43 R1 = C2H5 44 R1 = C4H9 45 R1 = C6H13 F 46 R2 = C3H7 47 R2 = C5H11 48 R2 = C7H15 F 49 R2 = C3H7 50 R2 = C5H11 51 R2 = C7H15 HO R1 6b F R2 6c F R2 B(OH)2 6a (i) n-BuLi, THF; (ii) R1-CHO. 6b (i) P2O5; (ii) H2, Pd/C, hexane. 6c (i) nBuLi, THF; (ii) B(OMe)3; (iii) 10% HCl. 49 Scheme 7 F F 42 7a F F 52 R = C2H5 53 R = C4H9 RS 7b F RS F B(OH)2 54 R = C2H5 55 R = C4H9 7a (i) n-BuLi, THF; (ii) RSSR. 7b (i) nBuLi, THF; (ii) B(OMe)3; (iii) 10% HCl. 50 Scheme 8 F F 42 8a F F B(OH)2 R 8b F 56 F 57 R = C3H7 58 R = C5H11 59 R = C7H15 60 R = C9H19 61 R = SC2H5 62 R = SC4H9 63 R = MBS F 64 R = C3H7 65 R = C5H11 66 R = C7H15 67 R = C9H19 68 R = SC2H5 69 R = SC4H9 70 R = MBS R 8c F R Br 6 R = C3H7 7 R = C5H11 8 R = C7H15 9 R = C9H19 14 R = SC2H5 15 R = SC4H9 16 R = MBS B(OH)2 MBS = (S)-(+)-2-methylbutylsulphanyl 8a (i) nBuLi, THF; (ii) B(OMe)3; (iii) 10% HCl. 8b Pd(PPh3)4, Na2CO3, DME, H2O. 8c (i) nBuLi, THF; (ii) B(OMe)3; (iii) 10% HCl. 51 Scheme 9 F 64 R1 = C3H7 66 R1 = C7H15 67 R1 = C9H19 68 R1 = SC2H5 69 R1 = SC4H9 70 R1 = MBS F R1 B(OH)2 R2 9a F R1 F R2 Br 6 R2 = C3H7 7 R2 = C5H11 8 R2 = C7H15 9 R2 = C9H19 14 R2 = SC2H5 20 R2 = OC2H5 21 R2 = OC4H9 22 R2 = OC6H13 23 R2 = OC8H17 71 R1 = C3H7, R2 = C3H7 72 R1 = C3H7, R2 = C5H11 73 R1 = C3H7, R2 = C9H19 74 R1 = C3H7, R2 = OC2H5 75 R1 = C3H7, R2 = OC4H9 MBS = (S)-(+)-2-methylbutylsulphanyl 76 R1 = C3H7, R2 = OC6H13 77 R1 = C3H7, R2 = OC8H17 78 R1 = C7H15, R2 = C3H7 79 R1 = C7H15, R2 = C7H15 80 R1 = C7H15, R2 = SC2H5 81 R1 = C9H19, R2 = C9H19 82 R1 = C9H19, R2 = OC8H17 83 R1 = SC2H5, R2 = C3H7 84 R1 = SC2H5, R2 = C5H11 85 R1 = SC2H5, R2 = C9H19 86 R1 = SC4H9, R2 = C3H7 87 R1 = SC4H9, R2 = C5H11 88 R1 = SC4H9, R2 = C7H15 89 R1 = SC4H9, R2 = C9H19 90 R1 = MBS, R2 = C5H11 91 R1 = MBS, R2 = C7H15 92 R1 = MBS, R2 = OC4H9 93 R1 = MBS, R2 = OC6H13 9a Pd(PPh3)4, Na2CO3, DME, H2O. 52 Scheme 10 Br 94 Br 95 R1 = C3H7 96 R1 = C5H11 97 R1 = C7H15 98 R1 = C9H19 10a R1 F 10b R2 F R1 F B(OH)2 39 R2 = OC2H5 41 R2 = OC4H9 49 R2 = C3H7 54 R2 = SC2H5 55 R2 = SC4H9 F R2 99 R1 = C3H7, R2 = OC2H5 100 R1 = C5H11, R2 = C3H7 101 R1 = C5H11, R2 = OC4H9 102 R1 = C3H7, R2 = SC2H5 103 R1 = C3H7, R2 = SC4H9 104 R1 = C5H11, R2 = SC2H5 105 R1 = C5H11, R2 = SC4H9 106 R1 = C7H15, R2 = SC2H5 107 R1 = C7H15, R2 = SC4H9 108 R1 = C9H19, R2 = SC2H5 109 R1 = C9H19, R2 = SC4H9 10a (i) Acid Chloride, AlCl3, DCM; (ii) PMHS. 10b Pd(PPh3)4, Na2CO3, DME, H2O. 53 Scheme 11 18 B(OH)2 C4H9S I 11a C4H9S Br Br 111 F 11a R F C4H9S 110 F B(OH)2 F R 112 R = C3H7 113 R = C5H11 114 R = C7H15 11a Pd(PPh3)4, Na2CO3, DME, H2O. 49 R = C3H7 50 R = C5H11 51 R = C7H15 54 Scheme 12 C7H15 Br 97 B(OH)2 115 12a C7H15 12b R C7H15 Br 7 R = C5H11 15 R = SC4H9 R 116 R = C5H11 117 R = SC4H9 12a (i) Mg, THF; (ii) B(OMe)3; (iii) 10% HCl. 12b Pd(PPh3)4, Na2CO3, DME, H2O. Scheme 13 R1 95 R1 = C3H7 97 R1 = C7H15 Br 13a R1 R2 B(OH)2 R2 118 R1 = C3H7, R2 = OC2H5 119 R1 = C7H15, R2 = SC2H5 13a Pd(PPh3)4, Na2CO3, DME, H2O. 17 R2 = SC2H5 24 R2 = OC2H5 55 Scheme 14 HO Br 120 Br 121 R1 = C2H5 122 R1 = C4H9 14a R1O F 14b R 1O R2 F F B(OH)2 39 R2 = OC2H5 41 R2 = OC4H9 49 R2 = C3H7 50 R2 = C5H11 F R2 123 R1 = OC2H5, R2 = C3H7 124 R1 = OC2H5, R2 = C5H11 125 R1 = OC2H5, R2 = OC2H5 126 R1 = OC2H5, R2 = OC4H9 127 R1 = OC4H9, R2 = C3H7 128 R1 = OC4H9, R2 = C5H11 129 R1 = OC4H9, R2 = OC2H5 130 R1 = OC4H9, R2 = OC4H9 14a = R1Br, K2CO3, butanone. 14b = Pd(PPh3)4, Na2CO3, DME, H2O. 56 Scheme 15 15a HO Br Br OBn 120 131 15b C3H7 OBn 132 OH 133 OTf 134 15c C5H11 15d C5H11 F R F 15e B(OH)2 39 R = OC2H5 41 R = OC4H9 49 R = C3H7 50 R = C5H11 54 R = SC2H5 55 R = SC4H9 F C5H11 F R 135 R = C3H7 136 R = C5H11 137 R = OC2H5 138 R = OC4H9 139 R = SC2H5 140 R = SC4H9 15a = BnBr, K2CO3, butanone. 15b = (i) n-BuLi, ZnCl; (ii) C3H7CCH, Pd(PPh3)4, THF. 15c = H2, Pd/C, ethanol. 15d = (TfO)2O, pyridine. 15e = Pd(PPh3)4, Na2CO3, LiCl, DME, H2O. 57 Scheme 16 C4H9O 121 Br R 16a C4H9O 10 R = C3H7 25 R = OC4H9 B(OH)2 R 141 R = C5H11 142 R = OC4H9 16a = Pd(PPh3)4, Na2CO3, DME, H2O. Scheme 17 C4H9O Br 121 F 17a C3H7O B(OH)2 F C4H9O OC3H7 143 17a = Pd(PPh3)4, Na2CO3, DME, H2O. 31 58 Scheme 18 C4H9O Br 121 F 18a F C3H7 F C 4H 9O F C3H7 144 18a = Pd(PPh3)4, Na2CO3, DME, H2O. B(OH)2 64 59 Scheme 19 OH 145 OH Br 19a O R Br 1 O 146 R1 = C3H7 147 R1 = C5H11 148 R1 = C7H15 19b R2 O R 2 B(OH)2 R1 O 149 R1 = C3H7, R2 = C3H7 150 R1 = C3H7, R2 = OC4H9 151 R1 = C5H11, R2 = C3H7 152 R1 = C5H11, R2 = C5H11 153 R1 = C5H11, R2 = OC4H9 19a = R1CHO, PTSA, Na2SO4, DCM. 19b = Pd(PPh3)4, Na2CO3, DME, H2O. 10 R2 = C3H7 11 R2 = C5H11 25 R2 = OC4H9 60 Scheme 20 O 146 R1 = C3H7 147 R1 = C5H11 148 R1 = C7H15 R1 O Br F R2 20a F R 2 O B(OH)2 R1 O 154 R1 = C3H7, R2 = OC4H9 155 R1 = C3H7, R2 = OC6H13 156 R1 = C3H7, R2 = OC8H17 157 R1 = C5H11, R2 = OC4H9 158 R1 = C5H11, R2 = OC6H13 159 R1 = C5H11, R2 = OC8H17 160 R1 = C7H15, R2 = OC4H9 20a = Pd(PPh3)4, Na2CO3, DME, H2O. 31 R2 = OC4H9 32 R2 = OC6H13 33 R2 = OC8H17 61 Scheme 21 O Br R1 O 146 R1 = C3H7 147 R1 = C5H11 148 R1 = C7H15 F 21a F R 2 R2 F O F B(OH)2 R1 O 161 R1 = C3H7, R2 = C7H15 162 R1 = C3H7, R2 = OC4H9 163 R1 = C5H11, R2 = C7H15 164 R1 = C5H11, R2 = OC3H7 165 R1 = C5H11, R2 = OC4H9 166 R1 = C7H15, R2 = C5H11 21a = Pd(PPh3)4, Na2CO3, DME, H2O. 40 R2 = OC3H7 41 R2 = OC4H9 50 R2 = C5H11 51 R2 = C7H15 62 Scheme 22 OH Br 145 OH F 22a F C5H11 F C5H11 F B(OH)2 OH 167 OH 22b F F O R C5H11 O 168 R = C3H7 169 R = C5H11 22a = Pd(PPh3)4, KF, THF. 22b = RCHO, PTSA, Na2SO4, DCM. 50 63 Scheme 23 F R F 1 64 R1 = C3H7 65 R1 = C5H11 B(OH)2 O F R1 O Br 23a F O R2 R2 O 170 R1 = C3H7, R2 = C3H7 171 R1 = C3H7, R2 = C5H11 172 R1 = C3H7, R2 = C7H15 173 R1 = C5H11, R2 = C3H7 174 R1 = C5H11, R2 = C5H11 175 R1 = C5H11, R2 = C7H15 23a Pd(PPh3)4, Na2CO3, DME, H2O. 146 R1 = C3H7 147 R1 = C5H11 148 R1 = C7H15 64 Scheme 24 OH 145 OH Br O 24a OC2H5 H 176 O 177 OC2H5 Br O X C5H11 24b X X X B(OH)2 O OC2H5 C5H11 O 178 X = H 179 X = F 24a = 4-Ethoxybenzaldehyde. 24b = Pd(PPh3)4, Na2CO3, DME, H2O. 11 Y = H 50 Y = F 65 Scheme 25 F F 36 C2H5O 25a F F O 180 C2H5O H OH Br 25b F OH F O 181 OC2H5 Br 145 O X C5H11 25c F X X X B(OH)2 F O OC2H5 C5H11 O 182 X = H 183 X = F 25a = (i) nBuLi, THF; (ii) DMF; (iii) 10% HCl. 25b = Na2SO4, DCM. 25c = Pd(PPh3)4, Na2CO3, DME, H2O. 11 Y = H 50 Y = F 66 Scheme 26 O R1 OH 184 R1 = C3H7 185 R1 = C5H11 OH 186 R1 = C3H7 187 R1 = C5H11 26a R1 26b O R1 188 R1 = C3H7 189 R1 = C5H11 H OH 145 26c Br O Br OH 190 R1 = C3H7 191 R1 = C5H11 R1 O F R2 26d F R 2 F O F B(OH)2 40 R2 = OC3H7 50 R2 = C5H11 R1 O 192 R1 = C3H7, R2 = C5H11 193 R1 = C3H7, R2 = OC3H7 194 R1 = C5H11, R2 = C5H11 195 R1 = C5H11, R2 = OC3H7 26a =LiAlH4, THF. 26c = PCC, DCM. 26c = PTSA, Na2SO4, DCM. 26d = Pd(PPh3)4, Na2CO3, DME, H2O. 67 Scheme 27 O C3H7 190 O Br F 27a 31 R = OC3H7 34 R = OC8H17 B(OH)2 R O F C3H7 R O 196 R1 = OC3H7 197 R1 = OC8H17 27a = Pd(PPh3)4, Na2CO3, DME, H2O. Scheme 28 O C5H11 191 O Br C5H11 28a B(OH)2 O C5H11 O C5H11 198 28a = Pd(PPh3)4, Na2CO3, DME, H2O. 11 68 Scheme 29 F Br 199 OH 200 B(OH)2 29a F Br O B O 201 OH 202 29b F Br OH O 29c 188 C3H7 H F O Br 203 C3H7 O F 29d C3H7O F C3H7O B(OH)2 F O O C3H7 204 29a = C2H5COOH, (HCHO)n , toluene. 29b = H2O2, THF. 29c = PTSA, Na2SO4, DCM. 29d = Pd(PPh3)4, Na2CO3, DME, H2O. 31 69 Scheme 30 C7H15 115 B(OH)2 N 30a I Br N N C7H15 Br 206 N 30b N C7H15 N C5H11 207 30c N C7H15 N C7H15 208 30a Pd(PPh3)4, Na2CO3, DME, H2O. 30b (i) nBuLi, hept-1-yne, THF; (ii) ZnCl2; (iii) Pd(PPh3)4. 30c 10% PdC, ethanol, THF. 205 70 Scheme 31 F F 1 R 64 R1 = C3H7 65 R1 = C5H11 B(OH)2 HO 31a R2 HO F 209 R2 = C5H11 210 R2 = C7H15 F O B O R1 R2 211 R1 = C3H7, R2 = C7H15 212 R1 = C5H11, R2 = C5H11 31a Na2SO4, THF. Scheme 32 S I I 213 F R 32a F R F F F 40 R = OC4H9 B(OH)2 50 R = C H 5 11 F R S 214 R = C5H11 215 R = OC4H9 32a Pd(PPh3)4, Na2CO3, DME, H2O. 71 Scheme 33 S I I 213 C5H11 33a C5H11 S C5H11 216 33a Pd(PPh3)4, Na2CO3, DME, H2O. B(OH)2 11 72 Scheme 34 Br 19 OH 34a Br OCH3 O 217 OCH3 34b Br 218 O 34c Br 14 C2H5S C2H5S 219 O 34d C2H5S O B(OH)2 220 34e R C2H5S Br 6 R = C3H7 7 R = C5H11 8 R = C7H15 R O 221 R = C3H7 222 R = C5H11 223 R = C7H15 34a BrCH2CH(OMe)2, K2CO3, cyclohexanone. 34b PPA, chlorobenzene. 34c Pd(PPh3)4, Na2CO3, DME, H2O. 34d (i) nBuLi, THF, (ii) B(OMe)3, (iii) 10% HCl. 34e Pd(Ph3)4, Et3N, DMF. 73 Scheme 35 HO CN 224 CN 225 35a C8H17O 35b O C8H17O 226 OH O HO 35c O O C8H17O O OC2H5 228 35a C8H17Br, K2CO3, butanone. 35b cH2SO4, H2O, AcOH. 35c DCC, DMAP, DCM. OC2H5 227 74 Scheme 36 O C4H9 229 OH O HO 36a O O C4H9 O OC2H5 230 36c DCC, DMAP, DCM. OC2H5 227 75 Scheme 37 O C8H17O 226 OH O HO 37a OBn 231 O O C8H17O OBn 232 OH 233 O 37b O O C8H17O O HO 37c 234 OH O O C8H17O O O O O O O 235 37a DCC, DMAP, DCM. 37b 10% PdC, ethanol, ethyl acetate. 37c DCC, DMAP, DCM. OC8H17 76 Scheme 38 O C4H9 229 OH O HO 38a OBn 231 O O C4H9 OBn 236 OH 237 O 38b O O C4H9 O 38c 234 HO OH O O C4H9 O O O O O O 238 38a DCC, DMAP, DCM. 38b 10% PdC, ethanol, ethyl acetate. 38c DCC, DMAP, DCM. C4H9 77 Scheme 39 O 239 BnO OH O HO 39a OC2H5 227 O O BnO O OC2H5 240 OC2H5 241 39b O O HO O O 39c 226 C8H17O OH O C8H17O O O O O 242 39a DCC, DMAP, DCM. 39b 10% PdC, ethanol, THF. 39c DCC, DMAP, DCM. OC2H5 78 Scheme 40 O O HO O OC2H5 241 O 40a 229 C4H9 OH O C4H9 O O OC2H5 O O 243 40a DCC, DMAP, DCM. Scheme 41 O C8H17O 226 OH C8H17O 234 HO 41a OH O O O O 244 41a DCC, DMAP, DCM. OC8H17 79 Scheme 42 R B(OH)2 10 R = C3H7 42 R = OC2H5 OH 245 R = C3H7 246 R = OC2H5 42a R O O 42b C4H9 OH O O O C4H9 O R O 247 R = C3H7 248 R = OC2H5 42a H2O2, THF. 42b DCC, DMAP, DCM. 237 80 3.3: Experimental Procedures 3.3.1: Scheme 1 1-Bromo-4-propanoylbenzene (2) Propanoyl chloride (38.0 g, 0.40 mol) was added dropwise to a mixture of bromobenzene (1) (150 ml) and aluminium chloride (62.0 g, 0.46 mol). The mixture was stirred at 0 °C for one hour, then heated at 80°C for two hours, cooled and poured into 10 % hydrochloric acid and 100 g of crushed ice. The product was extracted into dichloromethane twice, and the combined organic extracts washed with water and dried (MgSO 4 ). The dichloromethane was removed in vacuo, and the excess of bromobenzene was removed by steam distillation. The residue was distilled to yield a colourless solid. Yield 41.69 g (49 %). Bp 130-133 °C at 20 mmHg. (Lit Bp 138 °C at 20 mmHg) [2]. Mp 47.1 °C. (Lit Mp 47-48 °C) [3]. 1 H NMR CDCl 3 /δ: 0.47 (3H, t), 1.17 (2H, q), 7.35 (2H, d), and 7.45 (2H, d). MS m/z: 214 (M+), 212 (M+) (100 %), 213, 196, and 183. 1-Bromo-4-pentanoylbenzene (3) Compound 3 was prepared and purified in a similar manner to that described for the preparation of compound 2 using the quantities stated. Pentanoyl chloride (50.0 g, 0.41 mol), aluminium chloride (62.0 g, 0.46 mol), and bromobenzene (1) (150 ml). The product was purified by distillation to yield a colourless liquid. Yield 37.86 g (39 %). Bp 156-158 °C at 20 mmHg. (Lit Bp 170 °C at 20 mmHg) [2]. Mp 37.0 °C. (Lit Mp 37 °C) [4]. 1 H NMR CDCl 3 /δ: 0.83 (3H, t), 1.29 (2H, sext), 1.58 (2H, sext), 2.80 (2H, t), 7.45 (2H, d), and 7.67 (2H, d). MS m/z: 242 (M+), 240 (M+) (100 %), 213, 198, and 185. 81 1-Bromo-4-heptanoylbenzene (4) Compound 4 was prepared and purified in a similar manner to that described for the preparation of compound 3 using the quantities stated. Heptanoyl chloride (60.0 g, 0.40 mol), aluminium chloride (62.0 g, 0.46 mol), and bromobenzene (1) (150 ml). The product was purified by distillation to yield a colourless liquid. Yield 37.86 g (39 %). Bp 133-135 °C at 0.2 mmHg. (Lit Bp 130-135 °C at 0.1 mmHg) [5]. Mp 70.3 °C. (Lit Mp 69-72 °C) [4]. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.28-1.38 (6H, m), 1.71 (2H, quin), 2.92 (2H, t), 7.58 (2H, d), and 7.81 (2H, d). MS m/z: 270 (M+), 268 (M+) (100 %), 213, 200, 183, 157, and 132. 1-Bromo-4-nonoylbenzene (5) Compound 5 was prepared and purified in a similar manner to that described for the preparation of compound 2 using the quantities stated. Nonanoyl Chloride (70.67 g, 0.40 mol), aluminium chloride (62.0 g, 0.46 mol), and bromobenzene (1) (200 ml). The product was purified by distillation to yield a colourless liquid. Yield 109.27 g (92 %). Bp 153 °C at 0.2 mmHg. (Lit Bp 138-140 °C at 0.1 mmHg) [4]. Mp 72.1 °C. (Lit Mp 68-69 °C) [4]. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.21-1.38 (10H, m), 1.63 (2H, quin), 2.35 (2H, t), 7.12 (2H, dd), and 7.62 (2H, dd). MS m/z: 298 (M+), 296 (M+), 200, 198, 185, 183, 157, and 155. 1-Bromo-4-propylbenzene (6) Compound 2 (41.69 g, 0.24 moles), hydrazine hydrate (36.0 g, 0.70 moles), potassium hydroxide (42.1 g, 0.75 moles) were added to diethylene glycol (250 ml) and heated at 130 °C for two hours. The excess of hydrazine hydrate was distilled off and the temperature 82 raised to 200 °C for two hours. After cooling, the mixture was poured into 18 % hydrochloric acid and the product extracted into ether (2 x 200 ml). The combined extracts were washed with water (100 ml) and dried (MgSO 4 ). The solvent was removed and the residue distilled to yield a colourless liquid. Yield 7.94 g (18 %). Bp 100-107 at 20 mmHg. (Lit Bp 108 °C at 20 mmHg) [2]. 1 H NMR CDCl 3 /δ: 0.93 (3H, t), 1.62 (2H, quin), 2.54 (2H, t), 7.05 (2H, d), and 7.40 (2H, d). MS m/z: 200 (M+), 198 (M+), 169 (100 %), 119, 103, and 90. 1-Bromo-4-pentylbenzene (7) Compound 7 was prepared and purified in a similar manner to that described for the preparation of compound 6 using the quantities stated. Compound 3 (33.86 g, 0.16 mol), hydrazine hydrate (23.3 g, 0.46 moles), potassium hydroxide (29.5 g, 0.53 mol), diethylene glycol (250 ml). The product was purified by distillation to yield a colourless liquid. Yield 21.94 g (61 %). Bp 125-127 °C at 20 mmHg. (Lit Bp 130 °C at 20 mmHg) [2]. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.28-1.40 (4H, m), 1.58 (2H, quin), 2.57 (2H, t), 7.05 (2H, d), and 7.40 (2H, d). MS m/z: 228 (M+), 226 (M+) (100 %), 195, 185, and 171. 1-Bromo-4-heptylbenzene (8) Compound 8 was prepared and purified in a similar manner to that described for the preparation of compound 6 using the quantities stated. Compound 4 (70.33 g, 0.26 mol), hydrazine hydrate (37.6 g, 0.77 mol), potassium hydroxide (49.3 g, 0.88 mol), diethylene glycol (250 ml). The product was purified by distillation to yield a colourless liquid. Yield 43.35 g (65 %). Bp 105-110 °C at 2.0 mmHg. (Lit Bp 105-115 °C at 2.0 mmHg) [5]. 83 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.25-1.37 (8H, m), 1.59 (2H, quin), 2.54 (2H, t), 7.05 (2H, d), and 7.39 (2H, d). MS m/z: 256 (M+), 254 (M+) (100 %), 169, 103, and 91. 1-Bromo-4-nonylbenzene (9) Compound 9 was prepared and purified in a similar manner to that described for the preparation of compound 6 using the quantities stated. Compound 5 (109.5 g, 0.37 mol), hydrazine hydrate (55.4 g, 1.11 mol), potassium hydroxide (68.3 g, 1.22 mol), and diethylene glycol (300 ml). The product was purified by distillation to yield a colourless liquid. Yield 43.35 g (65 %). Bp 134 °C at 0.2 mmHg. (Lit Bp 124-126 °C at 0.1 mmHg) [5]. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.30 (12H, m), 1.61 (2H, quin), 2.58 (2H, t), 7.05 (2H, d), and 7.39 (2H, d). MS m/z: 284 (M+), 282 (M+) (100 %), 169, 91, and 71. 4-Propylphenylboronic acid (10) A Grignard reagent was prepared by dissolving compound 6 (10 g, 0.0540 mol), in dry THF (200 ml) with magnesium (1.6 g, 0.0650 mol), and a crystal of iodine. The solution was heated to reflux for 1 hour under dry nitrogen. Complete reaction was indicated by GLC analysis. The mixture was cooled to (-78 °C) and trimethyl borate (11.4 g, 0.118 mol), added dropwise. The stirred mixture was allowed to warm to room temperature overnight and stirred with 10 % hydrochloric acid (250 ml) at room temperature for 1 hour. The product was extracted into ether (2 x 150 ml), and the combined ethereal extracts were washed with water (100 ml) and dried (MgSO 4 ). The solvent was removed to afford an off-white solid. Yield 7.14 g (quantitative). 84 4-Pentylphenylboronic acid (11) Compound 11 was prepared and purified in a similar manner to that described for the preparation of compound 10 using the quantities stated. Compound 7 (10 g, 0.0480 mol), magnesium (1.4 g, 0.0578 mol), trimethyl borate (10.4 g, 0.100 mol), and (THF 200 ml). Yield 6.80 g (89 %). 4-Heptylphenylboronic acid (12) Compound 12 was prepared and purified in a similar manner to that described for the preparation of compound 10 using the quantities stated. Compound 8 (20 g, 0.0780 mol), magnesium (2.3 g, 0.0940 mol), trimethyl borate (16.2 g, 0.156 mol), and (THF 200 ml). An off-white solid was obtained. Yield 14.48 g (quantitative). 3.3.2: Scheme 2 1-Bromo-4-ethylsulfanylbenzene (14) Bromoethane (70.13 g, 0.644 mol), 4-bromothio-phenol (13) (27.57 g, 0.146 mol) and potassium carbonate (60.53 g, 0.438 mol) were added to butanone (550 ml), and heated under reflux for 48 hrs, with stirring.. When the reaction was complete, the mixture was allowed to cool and decanted into water (300 ml), and ether (200 ml). The aqueous phase was saturated with salt, and washed with ether (2 x 300 ml). The combined organic layers are washed with 10% NaOH solution (100 ml), and dried (MgSO 4 ). After the solvent was removed in vacuo, the crude product was purified by distillation to afford a colourless oil. Yield 28.62 g (90 %). Bp 124 °C at 20 mmHg. (Lit Bp 136-137 °C at 20 mmHg) [6]. 1 H NMR CDCl 3 /δ: 1.29 (3H, t), 2.90 (2H, quin), 7.18 (2H, d), 7.37 (2H, d). MS m/z: 218 (M+), 216 (M+) (100 %), 122, 110, and 108. 85 1-Bromo-4-butylsulfanylbenzene (15) Compound 15 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromobutane (60.60 g, 0.42 mol), 4-bromothiophenol (13) (50.40 g, 0.21 mol), potassium carbonate (87.1 g, 0.63 mol), and butanone (550 ml). The product was purified by distillation to yield a colourless oil. Yield 45.39 g (86 %). Bp 157 °C at 20 mmHg. (Lit Bp 155-157 °C at 20 mmHg) [6]. 1 H NMR CDCl 3 /δ 0.92 (3H, t), 1.45 (2H, sext), 1.61 (2H, quin), 2.89 (2H, t), 7.16 (2H, d), 7.40 (2H, d). MS m/z: 246 (M+), 244 (M+) (100 %), 190, 188, 110, and 108. (S)-(+)-1-Bromo-4-(2-methyl-butylsulfanyl)benzene (16) Compound 16 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. (S)-(+)-1-Bromo-2-methylbutane (21.70 g, 0.144 mol), 4-bromothiophenol (13) (22.64 g, 0.120 mol), potassium carbonate (49.64 g, 0.359 mol), and butanone (400 ml). The product was purified by distillation to yield a colourless oil. Yield 28.13 g (93 %). Bp 126 °C (0.6 mmHg). 1 H NMR CDCl 3 /δ 0.90 (3H, t), 0.99 (3H, d), 1.16-1.29 (1H, m), 1.48-1.57 (1H, m), 1.60- 1.68 (1H, m), 2.72 (1H, dd), 2.91 (1H, dd), 7.17 (2H, d), 7.37 (2H, d). MS m/z: 260 (M+), 258 (M+), 203, 201, 192 (100 %), 190, 149, 122, 121, 109, 108, 82, 75, 71, 70, and 69. [α]D25° : +11.8° (0.183 g/ml). 4-Ethylsulfanylphenylboronic acid (17) Compound 17 was prepared and purified in a similar manner to that described for the preparation of compound 10 using the quantities stated. 86 Compound 14 (22.00 g, 0.103 mol), magnesium (2.95 g, 0.120 mol), trimethyl borate (20.78 g, 0.200 mol), and dry THF (200 ml). An off-white solid was obtained. Yield 16.14 g (89 %). 4-Butylsulfanylphenylboronic acid (18) Compound 18 was prepared and purified in a similar manner to that described for the preparation of compound 10 using the quantities stated. Compound 15 (10.00 g, 0.0410 mol), magnesium (1.15 g, 0.0492 mol), trimethyl borate (9.33 g, 0.0900 mol), and dry THF (200 ml). A colourless solid was obtained. Yield 5.64 g (40 %). 3.3.3: Scheme 3 1-Bromo-4-ethoxybenzene (20) Compound 20 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. Bromoethane (100.00 g, 0.918 mol), 4-bromophenol (19) (52.92 g, 0.0306 mol), potassium carbonate (126.80 g, 0.918 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 55.07 g (90 %). Bp 109°C at 20 mmHg. (Lit Bp 109 °C at 20 mmHg) [2]. 1 H NMR CDCl 3 /δ: 1.40 (3H, t), 3.97 (2H, q), 6.76 (2H, d), and 7.35 (2H, d). MS m/z: 202 (M+), 200 (M+), 174 (100 %), 172, 93, 75, and 65. 1-Bromo-4-butoxybenzene (21) Compound 21 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 87 1-Bromobutane (100.00 g, 0.729 mol), 4-bromophenol (19) (105.19 g, 0.608 mol), potassium carbonate (252.10 g, 1.824 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 98.83 g (70 %). Bp 134 °C at 20 mmHg. (Lit Bp 135 °C at 20 mmHg) [2]. 1 H NMR CDCl 3 /δ: 0.96 (3H, t), 1.48 (2H, quin), 1.74 (2H, q), 3.90 (2H, t), 6.76 (2H, d), and 7.35 (2H, d). MS m/z: 230 (M+), 228 (M+), 174 (100 %), 172, 93, 75, and 65. 1-Bromo-4-hexoxybenzene (22) Compound 22 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromohexane (33 g, 0.200 mol), 4-bromophenol (19) (28.82 g, 0.167 mol), potassium carbonate (69.07 g, 0.500 mol), and butanone (400 ml). The product was purified by distillation to yield a colourless liquid. Yield 41.5 g (97 %). Bp 117 °C at 0.5 mmHg. (Lit Bp 100-110 °C at 0.1 mmHg) [5]. 1 H NMR CDCl 3 /δ 0.92 (3H, t), 1.29-1.39 (4H, m), 1.46 (2H, quin), 1.77 (2H, quin), 3.92 (2H, t), 6.78 (2H, d), and 7.40 (2H, d). MS m/z: 258 (M+), 256 (M+) (100 %), 174, and 172. 1-Bromo-4-octylbenzene (23) Compound 23 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromooctane (19.31 g, 0.110 mol), 1-Bromophenol (19) (17.30 g, 0.100 mol), potassium carbonate (41.46 g, 0.300 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 23.88 g (84 %). Bp 150 °C at 0.2 mmHg. (Lit Bp 145 °C at 0.1 mmHg) [5]. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.22-1.36 (8H, m), 1.43 (2H, quin), 1.77 (2H, quin), 3.90 (2H, t), 6.76 (2H, d), and 7.35 (2H, d). 88 MS m/z: 286 (M+), 284 (M+), 174 (100 %), 172, 71, 57, 55, 43, 41. 4-Ethoxyphenylboronic acid (24) Compound 24 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated Compound 20 (15.00 g, 0.0746 moles), magnesium (2.18 g, 0.0898 moles), trimethyl borate (15.50 g, 0.149 moles), and THF (200 ml). A white solid was obtained. Yield 10.9 g (88 %). 4-Butoxyphenylboronic acid (25) Compound 25 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. Compound 21 (15.00 g, 0.065 moles), magnesium (1.75 g, 0.067 moles), trimethyl borate (14.96 g, 0.144 moles), and THF (200 ml). An off-white solid was obtained. Yield 10.5 g (83 %). 3.3.4: Scheme 4 1-Bromo-2-fluoro-4-propoxybenzene (27) Compound 27 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromopropane (58.00 g, 0.472 mol), 4-bromo-3-fluorophenol (26) (36.02 g, 0.189 mol), potassium carbonate (65.17 g, 0.471 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 40.38 g (92 %). Bp 105 °C (0.7 mmHg). 89 1 H NMR CDCl 3 /δ 1.02 (3H, t), 1.79 (2H, sext), 3.87 (2H, t), 6.59 (1H, ddd, J 12.9, 3.8, 1.1), 6.68 (1H, dd, J 12.9, 2.6), and 7.38 (1H, dd, J 17.0, 8.1). MS m/z: 234 (M+), 232, 190, 188, 149, 111, 94, 84, 63, 49 (100 %). 1-Bromo-4-butoxy-2-fluorobenzene (28) Compound 28 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromobutane (29.95 g, 0.219 mol), 4-bromo-3-fluorophenol (26) (20.00 g, 0.168 mol), potassium carbonate (69.72 g, 0.504 mol), and butanone (400 ml). The product was purified by distillation to yield a colourless oil. Yield 16.37 g (39 %). Bp 108 °C (0.4 mmHg). 1 H NMR CDCl 3 /δ: 0.98 (3H, t), 1.49 (2H, sext), 1.77 (2H, quin), 3.93 (2H, t), 6.60 (1H, ddd, J 12.8, 3.8, 1.1), 6.69 (1H, dd, J 13.2, 2.7), and 7.39 (1H, dd, J 17.0, 8.0). MS m/z: 248 (M+), 246 (M+), 192 (100 %), 190, 94, 83, and 63. 1-Bromo-2-fluoro-4-hexyloxybenzene (29) Compound 29 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromohexane (18.00 g, 0.109 mol), 4-bromo-3-fluorophenol (26) (10.00 g, 0.091 mol), potassium carbonate (34.8 g, 0.25 mol), and butanone (400 ml). The product was purified by distillation to yield a colourless oil. Yield 8.49 g (34 %). Bp 128 °C (0.6 mmHg). (Lit Bp 145 °C at 0.1 mmHg) [7]. 1 H NMR CDCl 3 /δ: 0.92 (3H, t), 1.29-1.39 (4H, m), 1.46 (2H, quin), 1.78 (2H, quin), 3.92 (2H, t), 6.61 (1H, ddd, J 12.9, 3.9, 1.0), 6.69 (1H, dd, J 13.2, 2.8), and 7.39 (1H, dd, J 17.1, 8.1). MS m/z: 276 (M+), 274 (M+), 192, 190, 83, 55, 53, 43 (100 %), 41. 90 1-Bromo-2-fluoro-4-octylbenzene (30) Compound 30 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromooctane (23.19 g, 0.120 mol), 4-bromo-3-fluorophenol (26) (12.00 g, 0.100 mol), potassium carbonate (41.46 g, 0.300 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 12.39 g (40 %). Bp 132 °C (0.9 mmHg). (Lit Bp 145 °C at 0.1 mmHg) [7]. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.20-1.40 (8H, m), 1.45 (2H, quin), 1.78 (2H, quin), 3.92 (2H, t), 6.59 (1H, ddd, J 12.9, 3.9, 1.0), 6.67 (1H, dd, J 13.2, 2.6), and 7.38 (1H, dd, J 0.72). MS m/z: 304 (M+), 302 (M+), 192 (100 %), 190, 83, 71, 69, 57, 55, 43, and 41. 2-Fluoro-4-propoxyphenylboronic acid (31) n-Butyllithium (2.5 M in hexanes, 28.32 ml, 0.0708 mol) was added dropwise to a solution of compound 27 (15.00 g, 0.064 mol) in dry THF (150 ml), at -78 °C under nitrogen. The mixture was stirred for 30 mins and trimethyl borate (14.71 g, 0.140 moles) added dropwise, maintaining the temperature below -70 °C. The mixture was left to return to room temperature overnight. Hydrochloric acid (10%, 200 ml) was added with stirring. The mixture was poured into water (100 ml) and ether was added (100 ml). The aqueous layer was extracted with ether (2 x 150 ml). The organic layers are washed with water and brine, then dried (MgSO 4 ) and the solvent removed in vacuo to give a colourless solid. Yield 7.19 g (56 %). 4-Butoxy-2-fluorophenylboronic acid (32) Compound 32 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 28 (5.00 g, 0.0220 mol), n-butyllithium (2.5 M in hexanes, 8.9 ml, 0.0222 mol), trimethyl borate (4.63 g, 0.0445 mol), and THF 200ml. 91 A colourless solid was obtained. Yield 2.62 g (62 %). 2-Fluoro-4-hexyloxyphenylboronic acid (33) Compound 33 was prepared and purified in a similar manner to that described for the preparation of compound 21 using the quantities stated Compound 29 (7.00 g, 0.0254 mol), n-butyllithium (2.5 M in hexanes, 11.2 ml, 0.0280 mol), trimethyl borate (6.40 g, 0.0616 moles), and THF 200ml. A colourless solid was obtained. Yield 4.38 g (63 %). 2-fluoro-4-octyloxyphenylboronic acid (34) Compound 34 was prepared and purified in a similar manner to that described for the preparation of compound 21 using the quantities stated Compound 30 (8.00 g, 0.0264 mol) n-butyllithium (2.5 M in hexanes, 11.6 ml, 0.0290 mol), trimethyl borate (6.03 g, 0.0580 mol), and THF (200ml). A colourless solid was obtained. Yield 6.60 g (93 %). 3.3.5: Scheme 5 1-Ethoxy-2,3-difluorobenzene (36) Compound 36 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. Bromoethane (120 g, 1.10 mol), 2,3-difluorophenol (13) (47.75 g, 0.367 mol), potassium carbonate (152.20 g, 1.10 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless liquid. Yield 49.06 g (85 %). Bp 76 °C at 20 mmHg. 92 1 H NMR CDCl 3 /δ 1.45 (3H, t), 4.11 (2H, q), 6.70-6.75 (2H, m), and 6.93-7.00 (1H, m). MS m/z: 158 (M+), 149, 130 (M+) (100 %), 102, 101, 82, and 63. 1,2-Difluoro-3-propoxybenzene (37) Compound 37 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromopropane (89.66 g, 0.729 mol), 2,3-difluorophenol (13) (80.00 g, 0.608 mol), potassium carbonate (252.10 g, 1.82 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless oil. Yield 94.80 g (91 %). Bp 190 °C (20 mmHg). 1 H NMR CDCl 3 /δ 1.03 (3H, t), 1.89 (2H, sext), 3.99 (2H, t), 6.68-6.78 (2H, m), and 6.94- 6.97 (1H, m). MS m/z: 246 (M+), 130 (100 %), 101, 84, 63, and 40. 1-Butoxy-2,3-difluorobenzene (38) Compound 38 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromobutane (100 g, 0.729 mol), 2,3-difluorophenol (79.10 g, 0.608 mol), potassium carbonate (252.20 g, 1.824 mol), and butanone (600 ml). The product was purified by distillation to yield a colourless liquid. Yield 82.79 g (73 %). Bp 101 °C at 20 mmHg. (Lit Bp 93-95 °C at 20 mmHg) [8]. 1 H NMR CDCl 3 /δ: 0.99 (3H, t), 1.51 (2H, sext), 1.08 (2H, quin), 4.02 (2H, t), 6.68-6.78 (2H, m), and 6.97-6.99 (1H, m). MS m/z: 186 (M+), 130 (100 %), 113, 101, 82, and 63. 4-Ethoxy-2,3-difluorophenylboronic acid (39) Compound 39 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated 93 Compound 36 (20.00 g, 0.126 mol), n-butyllithium (10 M) (15.18 ml, 0.152 mol), trimetyl borate (26.32 g, 0.253 mol), and THF (200 ml). A white solid was obtained. Yield 23.89 g (89 %). 2,3-Difluoro-4-propoxyphenylboronic acid (40) Compound 40 was prepared and purified in a similar manner to that described for the preparation of compound 21 using the quantities stated. Compound 37 (20.00 g, 0.116 mol), n-butyllithium (2.5 M in hexanes, 51.11 ml, 0.0128 mol), trimethyl borate (26.56 g, 0.26 mol), and THF (200 ml). A white solid was obtained. Yield 18.05 g (72 %). 4-Butoxy-2,3-difluorophenylboronic acid (41) Compound 41 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 38 (20.00 g, 0.107 mol), n-butyllithium (10 M) (11.82 ml, 0.118 mol), trimetyl borate (22.32 g, 0.215 mol ), and THF (200 ml). A white solid was obtained. Yield 23.35 g (95 %). 3.3.6: Scheme 6 1-(2,3-Difluorophenyl)propan-1-ol (43) n-Butyllithium (10M, 24.10 ml) was added dropwise to a stirred, cooled (-78 °C) of solution of 1,2-difluorobenzne (43) (25.00 g, 0.219 mol), in THF (400 ml), under nitrogen. The mixture was stirred under these conditions for one hour and propanal (12.73 g, 0.219 mol) was added dropwise, at -78 °C. The mixture was allowed to warm to room temperature slowly overnight. Ammonium chloride solution (100 ml) added and the 94 product was extracted into ether (2 x 250 ml). The combined etheral extracts were washed with water (200 ml) and dried (MgSO 4 ). The solvent was removed in vacuo and the residue distilled to yield a colourless liquid. Yield 25.54 g (68 %). Bp 78 °C at 0.6 mmHg. 1 H NMR CDCl 3 /δ 0.94 (3H, t), 1.73-1.88 (2H, m), 1.97 (1H, d), 4.97 (1H, t), 7.03-7.11 (2H, m), and 7.20-7.23 (2H, m). MS m/z: 172 (M+), 149, 143, 126, 115 (100 %), 114, 113, 95, 75, and 63. 1-(2,3-Difluorophenyl)pentan-1-ol (44) Compound 44 was prepared and purified in a similar manner to that described for the preparation of compound 43 using the quantities stated. 1,2-Difluorobenzne (43) (25.00 g, 0.219 mol), n-butyllithium (10 M) (24.10 ml, 0.241 mol), pentanal (18.87 g, 0.219 mol), and THF (200 ml). The product was purified by distillation to yield a colourless liquid. Yield 41.50 g (97 %). Bp 102 °C at 0.6 mmHg. (Lit Bp 82-86 °C at 0.5 mmHg) [8]. 1 H NMR CDCl 3 /δ 0.86 (3H, t), 1.21-1.48 (4H, m), 1.66-1.88 (2H, m), 2.80 (1H, s), 4.96 (1H, t), 6.98-7.13 (2H, m), and 7.19-7.23 (1H, m). MS m/z: 200 (M+) (100 %), 149, 143, 127, and 115. 1-(2,3-Difluorophenyl)heptan-1-ol (45) Compound 45 was prepared and purified in a similar manner to that described for the preparation of compound 43 using the quantities stated. 1,2-Difluorobenzne (43) (25.00 g, 0.219 mol), n-butyllithium (10 M) (24.10 ml, 0.241 mol), heptanal (24.96 g, 0.219 mol), and THF (200 ml). The product was purified by distillation to yield a colourless liquid. Yield 40.96 g (82 %). Bp 124 °C at 0.6 mmHg. (Lit Bp 106-108 °C at 0.1 mmHg) [5]. 1 H NMR CDCl 3 /δ 0.87 (3H, t), 1.18-1.51 (8H, m), 1.65-1.85 (2H, m), 2.80 (1H, s), 4.96 (1H, t), 6.99-7.11 (2H, m), and 7.14-7.24 (1H, m). 95 MS m/z: 228 (M+) (100 %), 149, 143, 127, 115, 75, and 63. 1,2-Difluoro-3-propylbenzene (46) Phosphorus pentoxide (63.17 g, 0.444 mol) was added to a stirred solution of compound 43 (25.50 g, 0.148 mol) in hexane (500 ml). The mixture was stirred at room temperature overnight (GLC analysis indicated a complete reaction); and the solid was filtered off. 5% Palladium-on-charcoal (4.00 g) was added to the filtrate and the stirred mixture was hydrogenated for six hours at room temperature and pressure. GLC analysis indicated a complete reaction, and the palladium-on-charcoal filtered off. The solvent was removed in vacuo and the residue distilled to yield a colourless liquid. Yield 8.83 g (38 %). Bp 105 °C at 20 mmHg. 1 H NMR CDCl 3 /δ: 0.95 (3H, t), 1.64 (2H, sext), 2.64 (2H, t), and 6.90-7.01 (3H, m). MS m/z: 156 (M+), 155(M+), 141, 139, 128, 127 (100 %), and 71. 1,2-Difluoro-3-pentylbenzene (47) Compound 47 was prepared and purified in a similar manner to that described for the preparation of compound 46 using the quantities stated. Phosphorus pentoxide (99.22 g, 0.699 mol), compound 44 (41.20 g, 0.233 mol), 5% Palladium-on-charcoal (4.00 g), and hexane (500 ml). The product was purified by distillation to yield a colourless liquid. Yield 18.26 g (32 %). Bp 116 °C at 20 mmHg. (Lit Bp 82-86 °C at 20 mmHg) [8]. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.26-1.42 (4H, m), 1.62 (2H, quin), 2.66 (2H, t), and 6.90- 7.25 (3H, m). MS m/z: 184 (M+) (100 %), 143, 127, 115 and 101. 1,2-Difluoro-3-heptylbenzene (48) Compound 48 was prepared and purified in a similar manner to that described for the preparation of compound 46 using the quantities stated 96 Phosphorus pentoxide (76.64 g, 0.540 mol), compound 44 (40.80 g, 0.180 mol), 5% Palladium-on-charcoal (4.00 g), and hexane (500 ml). The product was purified by distillation to yield a colourless liquid. Yield 13.35 g (35 %). Bp 126 °C at 20 mmHg. (Lit Bp 124-126 °C at 20 mmHg) [8]. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.16-1.40 (8H, m), 1.62 (2H, quin), 2.66 (2H, t), and 6.92- 7.25 (3H, m). MS m/z: 212 (M+) (100 %), 143, 127, and 71. 2,3-Difluoro-4-propylphenylboronic acid (49) Compound 49 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 46 (8.60 g, 0.0550 mol), n-butyllithium (10 M in hexanes, 6.06 ml, 0.0606 mol), trimethyl borate (13.85 g, 0.133 mol), and THF (200ml). A white solid was obtained. Yield 11.10 g (quantitative). 2,3-Difluoro-4-pentylphenylboronic acid (50) Compound 50 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 47 (10.00 g, 0.0543 mol), n-butyllithium (10 M) (5.98 ml, 0.0598 mol), trimethyl borate (12.42 g, 0.120 mol), and THF (200 ml). An off-white solid was obtained. Yield 12.00 g (97 %). 2,3-Difluoro-4-heptylphenylboronic acid (51) Compound 51 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 48 (10.00 g, 0.0472 mol), n-butyllithium (10 M) (5.19 ml, 0.0519 mol), trimethyl borate (10.70 g, 0.104 mol), and THF (200 ml). 97 An off-white solid was obtained. Yield 10.27 g (85 %). 3.3.7: Scheme 7 1-Ethylsulfanyl-2,3-difluorobenzene (52) n-Butyllithium (2.5 M in hexanes) (0.158 mol) was added dropwise to a solution of 1,2difluorobenzene (42) (15.00 g, 0.132 mol) in dry THF (200 ml), at -78°C under nitrogen. The mixture was stirred for 45 min and diethyl disulfide (19.29 g, 0.158 mol) added dropwise, maintaining the temperature below -70 °C. The mixture was left to return to room temperature overnight. The mixture was poured into water (100 ml) and dichloromethane was added (200 ml). The aqueous layer was extracted with dichloromethane (2 x 200 ml). The organic layers are washed with water and brine, then dried over MgSO 4 and the solvent removed. The residue was distilled to give a colourless liquid. Yield 17.0 g (74 %). Bp 186.0 °C at 20 mmHg. 1 H NMR CDCl 3 /δ: 1.30 (3H, t), 2.94 (2H, q), and 7.00-7.13 (3H, m). MS m/z: 244, 234 (100 %), 206, 188, 174 (M+), 159, 146, 126, 114, and 101. 1-Butylsulfanyl-2,3-difluorobenzene (53) Compound 53 was prepared and purified in a similar manner to that described for the preparation of compound 52 using the quantities stated. 1,2-Difluorobenzene (20) (10.71 g, 0.0938 mol), n-butyllithium (2.5 M in hexanes, 45.00 ml, 0.113 mol), butyl disulfide (20.28 g, 0.112 mol), and dry THF (200 ml). The product was purified by distillation to yield a colourless liquid. Yield 20.09 g (95 %). Bp 132 °C at 20 mmHg. 98 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.43 (2H, sext), 1.58 (2H, sext), 2.89 (2H, t), and 6.98- 7.11 (3H, m). MS m/z: 202 (M+), 178, 159, 146 (100 %), 126, 102, 101, 75, and 63. 4-Ethysulfanyl-2,3-difluorophenylboronic acid (54) Compound 54 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 52 (17.00 g, 0.0970 mol), n-butyllithium (2.5 M in hexanes, 46.84 ml, 0.117 mol), trimethyl borate (20.28 g, 0.200 mol), and dry THF (200 ml). An off-white solid was obtained. Yield 0.88 g (98 %). 4-Butylsulfanyl-2,3-difluorophenylboronic acid (55) Compound 55 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 50 (14.90 g, 0.0737 mol), n-butyllithium (2.5 M in hexanes, 35.36 ml, 0.0884 mol), trimethyl borate (15.32 g, 0.150 mol), and dry THF (200 ml). An off-white solid was obtained. Yield 17.69 g (98 %). 3.3.8: Scheme 8 2,3-Difluorophenylboronic acid (56) Compound 56 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated Compound 42 (15.00 g, 0.158 mol), n-butyllithium (2.5 M) (63.10 ml, 0.158 mol), trimethyl borate (27.81 g, 0.263 mol), and THF (200 ml). An off-white solid was obtained. Yield 23.05 g. 99 MS m/z: 158 (M+) (100 %), 140, 125, and 114. 2,3-Difluoro-4’-propylbiphenyl (57) Compound 6 (11.64 g, 0.0629 mol), sodium carbonate (2.00 g, 0.138 mol), 1,2-DME (150 ml), and water (120 ml) were stirred under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.00176 mol) was added, followed by compound 56 (9.51 g, 0.0755 mol). The solution was heated to reflux for 18 hours. Completion of the reaction was indicated by TLC and GLC analysis. The reaction mixture is allowed to cool and poured into water, and ether added. The separated aqueous layer is washed with ether twice and the combined extracts washed with water and brine, and dried (MgSO 4 ). After removal of the solvent in vacuo the residue is purified by column chromatography [silica gel/hexane] to give a colourless liquid. Yield 9.51 g (65 %). 1 H NMR CDCl 3 /δ 0.89 (3H, t), 1.72 (2H, sext), 2.68 (2H, quin), 7.12-7.16 (3H, m), 7.31 (2H, d, J 8.0), 7.49 (2H, d, J 8.4). MS m/z: 232 (M+), 204, 203 (100 %), 201, 188, 183, 149, and 101. 2,3-Difluoro-4’-pentylbiphenyl (58) Compound 58 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 56 (4.00 g, 0.0316 mol), compound 7 (5.49 g, 0.0242 mol), sodium carbonate (5.65 g, 0.0534 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (150 ml), and water (120 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1]. A colourless liquid was obtained. Yield 5.03 g (80 %). 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.29-1.43 (4H, m), 1.65 (2H, quin), 2.66 (2H, t), 7.14- 7.42 (3H, m), 7.28 (2H, d, J 8.1), and 7.46 (2H, d, J 8.4). MS m/z: 261 (M+), 260 (M+), 203 (100 %), 201, 183, and 101. 100 2,3-Difluoro-4’-heptylbiphenyl (59) Compound 23 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. compound 56 (4.00 g, 0.0316 mol), compound 8 (6.20 g, 0.0242 mol), sodium carbonate (5.65 g, 0.0534 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (150 ml), and water (120 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1]. A colourless liquid was obtained. Yield 5.77 g (82 %). 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.20-1.43 (8H, m), 1.64 (2H, quin), 2.66 (2H, t), 7.13- 7.42 (3H, m), 7.29 (2H, d, J 8.2), and 7.46 (2H, d, J 8.3). MS m/z: 289 (M+), 288 (M+), 203 (100 %), 201, and 183. 2,3-Difluoro-4’-nonylbiphenyl (60) Compound 60 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. compound 56 (4.00 g, 0.0316 mol), compound 9 (6.85 g, 0.0242 mol), sodium carbonate (5.65 g, 0.0534 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (150 ml), and water (120 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1]. A colourless liquid was obtained. Yield 5.89 g (77 %). 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.20-1.43 (12H, m), 1.65 (2H, quin), 2.66 (2H, t), 7.12- 7.42 (3H, m), 7.28 (2H, d, J 8.2), and 7.46 (2H, d, J 8.4). MS m/z: 316 (M+), 183, 204, 203 (100 %), 201, 183, and 101. 4’-Ethylsulfanyl-2,3-difluorobiphenyl (61) Compound 61 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 101 Compound 56 (4.07 g, 0.0323 mol), compound 14 (6.60 g, 0.0269 mol), sodium carbonate (6.28 g, 0.0592 mol), tetrakis(triphenylphosphine)palladium(0) (1.00 g, 0.00142 mol), DME (160 ml), and water (100 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 15:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 2.20 g (33 %). Mp 38.7 °C. 1 H NMR CDCl 3 /δ: 1.35 (3H, t), 2.98 (2H, q), 7.06-7.17 (3H, m), 7.36 (2H, d, J 8.6), and 7.45 (2H, d, J 8.6). MS m/z: 251 (M+), 250 (M+) (100 %), 235, 222, 221, 220, 202, 188, and 151. 4’-Butylsulfanyl-2,3-difluorobiphenyl (62) Compound 62 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 56 (7.00 g, 0.0556 mol), compound 15 (11.34 g, 0.0463 mol), sodium carbonate (10.80 g, 0.101 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000567 mol), 1,2-DME (140 ml), and water (100 ml). The product was purified by column chromatography [silica gel/hexane dichloromethane 20:1]. Colourless crystals were obtained. Yield 5.70 g (44 %). Mp 46.0 °C. 1 H NMR CDCl 3 /δ: 0.94 (3H, t), 1.48 (2H, sext), 1.67 (2H, quin), 2.96 (2H, t), 7.09-7.17 (3H, d), 7.36 (2H, d, J 8.2), 7.43 (2H, d, J 8.0). MS m/z: 278 (M+) (100 %), 222, 221, 202, 188, 177, and 151. (S)-(+)-2,3-Difluoro-4’-(2-methyl-butylsulfanyl)biphenyl (63) Compound 63 was prepared and purified in a similar manner to that described for the preparation of compound 20 using the quantities stated. Compound 56 (7.11 g, 0.0564 mol), compound 16 (12.00 g, 0.0470 mol), sodium carbonate (10.97 g, 0.103 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000567 mol), DME (160 ml), and water (100 ml). 102 The product was purified by column chromatography [silica gel/hexane-dichloromethane 15:1], followed by recrystallisation from ethanol. A colourless liquid was obtained. Yield 5.02 g (37 %). 1 H NMR CDCl 3 /δ: 0.95 (3H, t), 1.06 (3H, d), 1.27-1.33 (1H, m), 1.51-1.62 (1H, m), 1.68- 1.81 (1H, m), 2.81 (1H, dd), 3.00 (1H, dd), 7.09-7.21 (3H, m), 7.39 (2H, d, J 8.4), and 7.46 (2H, d, J 8.3). MS m/z: 293 (M+), 292 (M+), 223, 222 (100 %), 221, 202, 188, and 71. [α]D25° : +12.8° (0.168 g/ml). 2,3-Difluoro-4’-propylbiphenyl-4-ylboronic acid (64) Compound 64 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 57 (8.85 g, 0.0440 mol), n-butyllithium (2.5 M in hexanes, 19.37 ml, 0.0484 mol), trimethyl borate (0.833 g, 0.0968 mol), and dry THF (250 ml). An off-white solid was obtained. Yield 10.06 g (91 %). 2,3-Difluoro-4’-pentylbiphenyl-4-ylboronic acid (65) Compound 65 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 58 (10.00 g, 0.0384 mol), n-butyllithium (2.5 M in hexanes, 16.8 ml, 0.0423 mol), trimethyl borate (8.78 g, 0.0845 mol). A white solid was obtained. Yield 9.96 g (85 %). 2,3-Difluoro-4’-heptylbiphenyl-4-ylboronic acid (66) Compound 66 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 59 (5.77 g, 0.0242 mol), n-butyllithium (2.5 M in hexanes, 9.6 ml, 0.0266 mol), trimethyl borate (4.16 g, 0.0532 mol), and dry THF (250 ml). 103 An off-white solid was obtained. Yield 5.67 g (95 %). 2,3-Difluoro-4’-nonylbiphenyl-4-ylboronic acid (67) Compound 67 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 60 (5.00 g, 0.0158 mol), n-butyllithium (2.5 M in hexanes, 6.95 ml, 0.0174 mol), trimethyl borate (3.62 g, 0.0348 mol), and dry THF (250 ml). An off-white solid was obtained. Yield 4.98 g (89 %). 4’-Ethylsulfanylbiphenyl-2,3-difluoro-4’-biphenyl-4-ylboronic acid (68) Compound 68 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 61 (2.20 g, 0.00879 mol), n-butyllithium (2.5 M in hexanes, 4.3 ml, 0.0105 mol), trimethyl borate (2.01 g, 0.0193 mol), and dry THF (250 ml). An off-white solid was obtained. Yield 5.02 g (37 %). 4’-Butylsulfanylbiphenyl-2,3-difluoro-4’-biphenyl-4-ylboronic acid (69) Compound 69 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 62 (5.50 g, 0.0198 mol), n-butyllithium (2.5 M in hexanes, 9.2 ml, 0.0230 mol), trimethyl borate (4.16 g, 0.0400 mol), and dry THF (250 ml). An off-white solid was obtained. Yield 6.74 g (quantitative). (S)-(+)-2,3-Difluoro-4’-(2-methylbutylsulfanyl)biphenyl-4-boronic acid (70) Compound 70 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. 104 Compound 63 (4.59 g, 0.0158 mol) n-butyllithium (10 M) (1.73 ml, 0.0173 mol), trimethyl borate (3.27 g, 0.0.315 mol), and dry THF (250 ml). A white solid was obtained. Yield 4.76 g (90 %). 3.3.9: Scheme 9 2’,3’-Difluoro-4,4”-dipropyl-[1,1’:4’,1”]-terphenyl (71) Compound 71 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (2.00 g, 0.00724 mol), compound 6 (1.12 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.55 g (26 %). Transitions (°C) Cr 93.6 N 128.0 I. 1 H NMR CDCl 3 /δ: 0.99 (6H, t), 1.70 (4H, sext), 2.65 (4H, t), 7.24-7.25 (2H, m), 7.29 (4H, d, J 7.9), and 7.51 (4H, d, J 7.9). 13 C NMR CDCl 3 /δ: 13.90, 24.48, 37.80, 124.53, 124.57, 124.60, 128.71, 128.74, 132.04, and 142.82. MS m/z: 351(M+), 350 (M+) (100%), 322, 321, 292, and 146. Elemental Analysis: Calculated (Found): C 82.26 (82.33); H 6.90 (7.10). 2’,3’-Difluoro-4-pentyl-4-propyl-[1,1’:4’,1”]-terphenyl (72) Compound 72 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 105 Compound 64 (2.00 g, 0.00724 mol), compound 7 (1.37 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium (0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 0.93 g (41 %). Transitions (°C) Cr 53.9 N 123.4 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 0.99 (3H, t), 1.32-1.41 (4H, m), 1.63-1.72 (4H, m), 2.62- 2.67 (4H, m), 7.23-7.25 (2H, m), 7.28 (4H, d, J 8.0), and 7.51 (4H, d, J 7.9). 13 C NMR CDCl 3 /δ: 13.90, 14.05, 22.57, 24.49, 31.11, 31.57, 35.70, 37.80, 124.56, 124.60, 128.68, 128.71, 128.75, 142.82, 143.09, 147.17, 147.33, and 148.82. MS m/z: 379 (M+), 378 (M+) (100%), 349, 321, 292, and 146. Elemental Analysis: Calculated (Found): C 82.51 (82.23); H 7.46 (7.71). 2’,3’-Difluoro-4-nonyl-4”-propyl-[1,1’:4’,1”]-terphenyl (73) Compound 73 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (2.00 g, 0.00724 mol), compound 9 (1.71 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.04 g (39 %). Transitions (°C) Cr 40.0 N 110.5 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.99 (3H, t), 1.25-1.35 (12H, m), 1.62-1.73 (4H, m), 2.63- 2.66 (4H, m), 7.24-7.25 (2H, m), 7.29 (4H, d, J 8.4), and 7.51 (4H, d, J 7.9). 13 C NMR CDCl 3 /δ: 13.91, 24.49, 29.35, 29.40, 29.54, 29.56, 31.44, 31.91, 35.74, 37.81, 124.56, 128.69, 128.71, 128.76, 142.83, and 143.12. MS m/z: 435 (M+), 434 (M+) (100 %), 405, 321, 292, and 146. Elemental Analysis: Calculated (Found): C 82.91 (82.77); H 8.35 (8.55). 106 4-Ethoxy-2’,3’difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (74) Compound 74 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (2.00 g, 0.00724 mol), compound 20 (1.21 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 15:1], followed by recrystallisation from ethanol/ethyl acetate 10:1] .A colourless solid was obtained. Yield 1.22 g (57 %). Transitions (°C) Cr 108.0 N 185.8 I. 1 H NMR CDCl 3 /δ: 0.99 (3H, t), 1.46 (3H, t), 1.70 (2H, sext), 2.65 (2H, t), 4.10 (2H, q), 7.00 (2H, d, J 6.8), 7.22-7.24 (2H, m), 7.29 (2H, d, J 8.1), and 7.50-7.54 (4H, m). 13 C NMR CDCl 3 /δ: 13.89, 14.83, 24.48, 37.78, 63.52, 114.59, 124.33, 124.52, 128.66, 128.69, 128.72, 129.99, 130.02, 142.77, and 158.92. MS m/z: 353 (M+), 352 (M+) (100 %), 324, 323, 296, 295, 266, and 148. Elemental Analysis: Calculated (Found): C 78.39 (78.11); H 6.29 (6.36). 4-Butoxy-2’,3’difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (75) Compound 74 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (2.00 g, 0.00724 mol), compound 21 (1.38 g, 0.00604 mol) sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 15:1], followed by recrystallisation from ethanol and a few drops of ethyl acetate. A colourless solid was obtained. Yield 1.39 g (61 %). Transitions (°C) Cr 80.6 N 166.4 I. 107 1 H NMR CDCl 3 /δ: 0.99 (6H, 2 x t), 1.51 (2H, sext), 1.74 (2H, sext), 1.80 (2H, quin), 2.65 (2H, t), 4.02 (2H, t), 6.99 (2H, d, J 8.8), 7.20-723 (2H, m), 7.28 (2H, d, J 8.2), and 7.497.53 (4H, m). 13 C NMR CDCl 3 /δ: 13.85, 13.88, 19.25, 24.47, 31.29, 37.78, 67.74, 114.60, 128.96, 129.98, 142.76, and 159.14. MS m/z: 381 (M+), 380 (M+), 324, 295 (100 %), and 266. Elemental Analysis: Calculated (Found): C 78.92 (79.06); H 6.89 (7.85). 2’,3’-Difluoro-4-hexyloxy-4”-propyl-[1’,1’:4’,1”]-terphenyl (76) Compound 76 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (0.75 g, 0.00272 mol), compound 76 (0.77 g, 0.00299 mol), sodium carbonate (0.63 g, 0.005598 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.43 g (35 %). Transitions (°C) Cr 65.7 N 156.1 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 0.91 (3H, t), 1.24-1.33 (4H, m), 1.41 (2H, quin) 1.62 (2H, sext), 1.74 (2H, quin), 2.58 (2H, t), 3.94 (2H, t), 6.92 (2H, d, J 6.8), 7.14-7.17 (2H, m), 7.20 (2H, d, J 8.2), and 7.42-7.46 (4H, m). 13 C NMR CDCl 3 /δ: 13.90, 14.04, 22.62, 24.49, 25.73, 29.21, 31.58, 37.78, 68.06, 124.51, 124.33, 126.79, 128.65, 128.68, 128.72, 129.26, 129.28, 129.96, 132.06, 132.03, 142.77, and 159.13. MS m/z: 409 (M+), 408 (M+) (100 %), 323, 324, 294, 295, 266, 55, 43, and 41. Elemental Analysis: Calculated (Found): C 79.38 (78.86); H 7.40 (7.41). 2’,3’-Difluoro-4-octyloxy-4”-propyl-[1’,1’:4’,1”]-terphenyl (77) Compound 77 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 108 Compound 64 (0.75 g, 0.00272 mol), compound (23) (0.85 g, 0.00299 mol), sodium carbonate (0.63 g, 0.005598 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.60 g (46 %). Transitions (°C) Cr 45.1 SmC 62.6 N 130.2 I. 1 H NMR CDCl 3 /δ: 0.92 (3H, t), 1.00 (3H, t), 1.24-1.44 (8H, m), 1.50 (2H, quin) 1.71 (2H, sext), 1.83 (2H, quin), 2.66 (2H, t), 4.02 (2H, t), 7.01 (2H, d, J 8.5), 7.05-7.26 (2H, m), 7.30 (2H, d, J 8.2), and 7.49-7.58 (4H, m). 13 C NMR CDCl 3 /δ: 13.89, 14.11, 22.66, 24.48, 26.04, 29.25, 29.36, 31.82, 37.77, 68.05, 114.43, 114.58, 124.31, 124.35, 124.50, 126.76, 128.64, 128.67, 128.71, 129.37, 129.25, 129.15, 129.06, 129.95, 129.98, 132.04, 132.15, 142.74, and 159.13. MS m/z: 437 (M+), 436 (M+), 325, 324 (100 %), 295, 266, and 170. Elemental Analysis: Calculated (Found): C 79.78 (79.73); H 7.85 (7.81). 2’,3’-Difluoro-4-heptyl-4”-propyl-[1,1’:4’,1”]-terphenyl (78) Compound 78 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 66 (2.5 g, 0.00833 mol), compound 6 (1.38 g, 0.00694 mol), sodium carbonate (1.62 g, 0.0153 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 33:1], followed by recrystallisation from ethanol. Colourless needle-like crystals were obtained. Yield 0.44 g (16 %). Transitions (°C) Cr 48.5 N 116.1 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.99 (3H, t), 1.25-1.36 (8H, m), 1.68 (4H, quin), 2.65 (4H, t), 7.24-7.26 (2H, m), 7.28 (4H, d, J 8.0), and 7.50 (4H, d, J 7.8). 13 C NMR CDCl 3 /δ: 13.66, 14.46, 21.76, 22.55, 24.50, 29.20, 29.37, 31.56, 31.90, 35.66, 37.72, 35.66, 37.72, 124.82, 128.70, and 132.0 MS m/z: 406 (M+) (100 %), 377, 321, 292, 149, 105, 77, and 71. 109 Elemental Analysis: Calculated (Found): C 82.72 (82.96); H 7.93 (8.13). 2’,3’-Difluoro-4,4”-diheptyl-[1,1’:4’,1”]-terphenyl (79) Compound 79 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 66 (1.60 g, 0.00533 mol), compound 8 (1.13 g, 0.00444 mol), sodium carbonate (1.03 g, 0.00973 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 50:1], followed by recrystallisation from ethanol/ethyl acetate 10:1. Colourless needle-like crystals were obtained. Yield 0.60 g (30 %). Transitions (°C) Cr 60.7 SmC 69.6 N 110.2 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, t), 1.25-1.41 (16H, m), 1.66 (4H, quin), 2.66 (4H, t), 7.24- 7.25 (2H, m), 7.29 (4H, d, J 8.2), and 7.50 (4H, d, J 8.3). 13 C NMR CDCl 3 /δ: 14.11, 22.67, 29.19, 29.34, 31.42, 31.81, 35.72, 124.55, 128.66, 128.70, 131.97, and 143.09. MS m/z: 462(M+) (100 %), 463 (M+), 378, 377, and 292. Elemental Analysis: Calculated (Found): C 83.07 (82.94); H 8.71 (8.95). 4-Ethylsulfanyl-2’,3’-Difluoro-4”-heptyl-[1,1’:4’,1”]-terphenyl (80) Compound 80 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 66 (1.56 g, 0.00520 mol), compound 14 (0.94 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol/ethyl acetate 10:1. Colourless needle-like crystals were obtained. Yield 0.52 g (34 %). 110 Transitions (°C) Cr 77.1 N 125.1 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.25-1.39 (11H, m), 1.66 (2H, quin), 2.66 (2H, t), 3.01 (2H, q), 7.23-7.25 (2H, m), 7.40 (2H, d, J 8.4), 7.50-7.53 (4H, m). 13 C NMR CDCl 3 /δ: 14.13, 14.33, 22.69, 27.26, 29.21, 29.35, 31.44, 31.83, 35.74, 124.38, 128.47, 128.71, 129.22, 137.26, and 143.24. MS m/z: 425 (M+), 424 (M+) (100 %), 340, 339, and 310. Elemental Analysis: Calculated (Found): C 76.38 (76.34); H 7.12 (7.33); S 7.55 (7.47). 2’,3’-Difluoro-4,4”-dinonyl-[1,1’:4’,1”]-terphenyl (81) Compound 81 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 67 (2.10 g, 0.005829 mol), compound 12 (1.38 g, 0.004858 mol), sodium carbonate (1.13 g, 0.01068 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation [ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 0.68 g (27 %). Transitions (°C) Cr 69.8 SmC 79.8 SmA 103.3 N 108.0 I. 1 H NMR CDCl 3 /δ: 0.88 (6H, t), 1.27-1.36 (24H, m), 1.66 (4H, quin), 2.66 (4H, t), 7.23- 7.24 (2H, m), 7.28 (4H, d, J 8.2), and 7.50 (4H, d, J 7.9). 13 C NMR CDCl 3 /δ: 14.11, 22.68, 29.33, 29.38, 29.52, 29.54, 31.42, 31.89, 35.72, 124.55, 128.66, 128.70, 131.97, and 143.10. MS m/z: 519 (M+), 518 (M+) (100 %), 406, 405, 305, 293, and 292. Elemental Analysis: Calculated (Found): C 83.35 (83.45); H 9.33 (9.54). 2’,3’-Difluoro-4-nonyl –4”-octyloxy[1,1’:4’,1”]-terphenyl (82) Compound 82 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 67 (1.50 g, 0.00416 mol), compound 23 (0.99 g, 0.00347 mol), sodium carbonate (0.74 g, 0.00694 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). 111 The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. A colourless solid was obtained. Yield 1.05 g (58 %). Transitions (°C) Cr 65.7 SmC 116.5 SmA 119.3 N 135.2 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, 2 x t), 1.25-1.36 (20H, m), 1.49 (2H, quin), 1.66 (2H, quin), 1.82 (2H, quin), 2.66 (2H, t), 4.01 (2H, t), 6.99 (2H, d, J 8.9), 7.21-7.23 (2H, m), 7.29 (2H, d, J 8.0), and 7.49-7.53 (4H, m). 13 C NMR CDCl 3 /δ: 14.13, 22.69, 29.27, 29.37, 29.54, 29.56, 31.44, 31.83, 31.91, 68.11, 114.64, 124.35, 28.68, 130.01, 143.18, and 159.51. MS m/z: 522 (M+) (100 %), 408, 295, and 71. Elemental Analysis: Calculated (Found): C 80.73 (80.55); H 8.90 (9.10). 4-Ethylsulfanyl-2’,3’-difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (83) Compound 83 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 68 (0.75 g, 0.00255 mol), compound 6 (0.39 g, 0.00212 mol), sodium carbonate (0.50 g, 0.00467 mol), tetrakis(triphenylphosphine)palladium(0) (0.15 g, 0.000213 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.11 g (14 %). Transitions (°C) Cr 90.4 N 130.4 I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.37 (3H, t), 1.70 (2H, sext), 2.65 (2H, t), 3.01 (2H, q), 7.24 (2H, m), 7.29 (2H, d, J 8.2), 7.40 (2H, d, J 8.6), 7.50-7.53 (4H, m). 13 C NMR CDCl 3 /δ: 13.90, 14.33, 24.48, 27.26, 37.80, 124.37, 124.68, 128.48, 128.68, 128.71, 128.77, 129.11, 129.22, 142.93, 131.91, and 137.24. MS m/z: 369 (M+), 368 (M+) (100 %), 340, 339, 311, 310, 170, 155, and 146. Elemental Analysis: Calculated (Found): C 74.97 (74.99); H 6.02 (6.22); S 7.70 (7.70). 112 4-Ethylsulfanyl-2’,3’-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (84) Compound 84 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 84 (0.75 g, 0.00255 mol), compound 7 (0.48 g, 0.00212 mol), sodium carbonate (0.50 g, 0.00467 mol), tetrakis(triphenylphosphine)palladium(0) (0.15 g, 0.000213 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 11:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.27 g (32 %). Transitions (°C) Cr 76.5 N 126.4 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.32-1.41 (7H, m), 1.65 (2H, sext), 2.66 (2H, t), 3.01 (2H, q), 7.21-7.27 (2H, m), 7.29 (2H, d, J 8.3), 7.40 (2H, d, J 8.4), 7.49-7.53 (4H, m). 13 C NMR CDCl 3 /δ: 14.05, 14.33, 22.57, 27.26, 31.11, 31.56, 35.70, 124.37, 124.68, 128.48, 128.71, 129.19, 129.22, 131.89, 137.24, and 143.20. MS m/z: 397 (M+), 396 (M+) (100 %), 340, 339, 311, 310, 277, 170, and 155. Elemental Analysis: Calculated (Found): C 75.72 (75.44); H 6.61 (6.84); S 8.09 (8.08). 4-Ethylsulfanyl-2’,3’-difluoro-4”-nonyl-[1,1’:4’,1”]-terphenyl (85) Compound 85 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 68 (0.75 g, 0.00255 mol), compound 9 (0.62 g, 0.00212 mol), sodium carbonate (0.50 g, 0.00467 mol), tetrakis(triphenylphosphine)palladium(0) (0.15 g, 0.000213 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 11:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.11 g (11 %). Transitions (°C) Cr 72.0 N 120.8 I. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.28-1.40 (15H, m), 1.66 (2H, quin), 2.66 (2H, t), 3.01 (2H, q), 7.24 (2H, d, J 7.7), 7.29 (2H, d, J 8.2), 7.40 (2H, d, J 8.6), 7.49-7.54 (4H, m). 13 C NMR CDCl 3 /δ: 14.13, 14.33, 22.69, 27.26, 29.34, 29.39, 29.53, 29.56, 31.43, 31.90, 35.74, 124.22, 124.68, 128.48, 128.71, 129.19, 129.22, 131.82, 137.23, and 143.21. 113 MS m/z: 453 (M+), 452 (M+) (100 %), 340, 339, 311, 310, 277, 170, and 155. Elemental Analysis: Calculated (Found): C 76.95 (76.76); H 7.57 (7.56); S 7.08 (7.02). 4-Butylsulfanyl-2’,3’-difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (86) Compound 86 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 69 (1.50 g, 0.00517 mol), compound 6 (0.86 g, 0.00431 mol), sodium carbonate (0.91 g, 0.00862 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. Colourless needle-like crystals were obtained. Yield 0.55 g (32 %). Transitions (°C) Cr 91.8 N 115.3 I. 1 H NMR CDCl 3 /δ: 0.99 (6H, 2 x t), 1.50 (2H, quin), 1.69 (4H, quin), 2.65 (2H, t), 2.99 (2H, t), 7.23-7.25 (2H, m), 7.29 (2H, d, J 7.9), 7.39 (2H, d, J 8.4), and 7.49-7.52 (4H, m). 13 C NMR CDCl 3 /δ: 14.09, 14.11, 18.26, 22.65, 29.33, 29.40, 29.58, 29.60, 39.64, 68.05, 68.29, 100.19, 105.20, 111.24, 114.73, 127.58, 128.06, 128.18, 128.44, 132.94, 134.42, 138.25, 142.70, 150.11, 158.64, 161.65, 164.15, and 164.39. MS m/z: 397 (M+), 396 (M+) (100 %), 367, 340, 311, and 155. Elemental Analysis: Calculated (Found): C 75.72 (75.65); H 6.61 (6.65); S 8.09 (7.89). 4-Butylsulfanyl-2’,3’-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (87) Compound 87 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 69 (1.50 g, 0.00517 mol), compound 7 (0.98 g, 0.00431 mol), sodium carbonate (0.91 g, 0.00862 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 10:1]. 114 Colourless needle-like crystals were obtained. Yield 0.74 g (41 %). Transitions (°C) Cr 86.5 N 114.5 I. 1 H NMR CDCl 3 /δ: 0.93 (6H, 2 x t), 1.32-1.38 (4H, m), 1.49 (2H, sext), 1.69 (4H, quin), 2.66 (2H, t), 2.99 (2H, t), 7.23-7.25 (2H, m), 7.29 (2H, d, J 8.0), 7.64 (2H, d, J 6.9), and 7.49-7.52 (4H, m). 13 C NMR CDCl 3 /δ: 13.67, 14.06, 22.02, 22.57, 31.11, 31.16, 32.84, 35.70, 124.17, 124.73, 128.29, 128.71, 129.17, 132.33, 134.40, 137.85, and 143.24. MS m/z: 425 (M+), 424 (M+) (100 %), 368, 367, 311, 310, 277, 257, 201, 155, and 71. Elemental Analysis: Calculated (Found): C 76.38 (76.32); H 7.12 (7.03); S 7.55 (7.62). 4-Butylsulfanyl-2’,3’-difluoro-4”-heptyl-[1,1’:4’,1”]-terphenyl (88) Compound 88 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 69 (2.20 g, 0.00758 mol), compound 8 (1.61 g, 0.00632 mol), sodium carbonate (1.47 g, 0.0139 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. Colourless needle-like crystals were obtained. Yield 0.96 g (34 %). Transitions (°C) Cr 71.4 SmA 101.5 N 112.2 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.95 (3H, t), 1.25-1.36 (8H, m), 1.50 (2H, q), 1.64-1.73 (4H, m), 2.66 (2H, t), 2.99 (2H, t), 7.23-7.24 (2H, m), 7.29 (2H, d, J 8.3), 7.39 (2H, d, J 8.4), and 7.50-7.52 (4H, m). 13 C NMR CDCl 3 /δ: 13.26, 13.67, 21.77, 22.69, 29.20, 29.35, 31.44, 31.83, 35.74, 123.00, 124.49, 124.87, 128.29, 128.71, 128.94, 129.17, 129.75, 136.68, 137.05, 137.78, and 143.30. MS m/z: 452 (M+) (100 %), 396, 367, 311, 149, 105, 77, and 71. Elemental Analysis: Calculated (Found): C 76.95 (77.28); H 7.57 (7.87); S 7.08 (6.99). 115 4-Butylsulfanyl-2’,3’-difluoro-4”-nonyl-[1,1’:4’,1”]-terphenyl (89) Compound 89 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 89 (1.50 g, 0.00517 mol), compound 9 (1.22 g, 0.00431 mol), sodium carbonate (0.91 g, 0.00862 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. Colourless needle-like crystals were obtained. Yield 0.99 g (48 %). Transitions (°C) C 72.9 SmA 106.1 N 109.2 I. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 0.95 (3H, t), 1.27-1.36 (12H, m), 1.49 (2H, sext), 1.62- 1.71 (4H, m), 2.66 (2H, t), 2.99 (2H, t), 7.21-7.25 (2H, m), 7.29 (2H, d, J 8.2), 7.39 (2H, d, J 8.4), and 7.49-7.52 (4H, m). 13 C NMR CDCl 3 /δ: 13.67, 14.13, 22.02, 22.70, 29.35, 29.39, 29.54, 29.56, 31.15, 31.91, 32.84, 35.74, 124.35, 124.39, 124.67, 128.29, 129.81, 128.71, 129.17, 129.29, 131.87, 131.87, 131.76, 137.66, and 143.21. MS m/z: 453 (M+), 452 (M+) (100 %), 368, 367, 311, 310, 277, 257, and 165. Elemental Analysis: Calculated (Found): C 77.46 (77.43); H 7.97 (8.27); S 6.67 (6.48). (S)-(+)-2’,3’-Difluoro-4-(2-methylbutylsulfanyl)-4”-pentyl-[1,1’:4’,1”]-terphenyl (90) Compound 90 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 70 (1.20 g, 0.00366 mol), compound 7 (0.68 g, 0.00297 mol), sodium carbonate (0.69 g, 0.00654 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.69 g (53 %). Transitions (°C) Cr 88.6 (N* 73.1) I. 116 1 H NMR CDCl 3 /δ: 0.94 (6H, 2 x t), 1.05 (3H, d), 1.27-1.32 (1H, m), 1.34-1.39 (4H, m), 1.53-1.61 (1H, m), 1.66 (2H, quin), 1.74 (1H, m), 2.66 (2H, t), 2.81 (1H, dd), 3.97-3.03 (1H, m), 7.23-7.25 (2H, m), 7.29 (2H, d, J 8.1), 7.39 (2H, d, J 8.4), and 7.49-7.51 (4H, m). 13 C NMR CDCl 3 /δ: 11.27, 14.03, 18.96, 22.26, 22.55, 28.83, 31.09, 31.55, 34.46, 35.69, 37.89, 40.25, 128.70, 129.05, 124.65, 128.22, 128.69, 129.15, 131.61, 131.96, 138.13, and 143.17. MS m/z: 439 (M+), 438 (M+) (100 %), 368, 312, 311, 310, 279, and 71. [α]D21° : +4.9° (0.00244 g/ml). Elemental Analysis: Calculated (Found): C 77.69 (78.95); H 8.15 (8.20); S 6.48 (6.50). (S)-(+)-2’,3’-Difluoro-4-heptyl-4”-(2-methyl-butylsulfanyl)-[1,1’:4’,1”]-terphenyl (91) Compound 87 was prepared and purified in a similar manner to that described for the preparation of compound 20 using the quantities stated. Compound 70 (1.20 g, 0.00366 mol), compound 8 (0.76 g, 0.00297 mol), sodium carbonate (0.69 g, 0.00654 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.76 g (55 %). Transitions (°C) Cr 64.6 SmA* 72.1 N* 76.8 I. 1 H NMR CDCl 3 /δ: 0.93 (6H, 2 x t), 1.06 (3H, d), 1.23-1.40 (8H, m), 1.56 (1H, m), 1.56- 1.79 (4H, m), 2.66 (2H, t), 2.81 (1H, dd), 3.00 (1H, dd), 7.21-7.25 (2H, m), 7.29 (2H, d, J 8.1),7.39 (2H, d, J 8.1), and 7.49-7.51 (4H, m). 13 C NMR CDCl 3 /δ: 11.26, 14.10, 18.96, 22.26, 22.66, 27.52, 28.82, 29.18, 29.33, 31.17, 31.41, 31.81, 34.46, 35.72, 37.95, 40.25, 124.33, 124.65, 128.21, 128.68, 129.12, 129.15, 131.64, 131.87, 138.13, and 143.18. MS m/z: 467 (M+), 466 (M+) (100 %), 396, 381, 312, 311, 310, and 71. [α]D21° : +8.8° (0.00679 g/ml). Elemental Analysis: Calculated (Found): C 77.21 (77.11); H 7.78 (7.89); S 6.87 (6.87). 117 (S)-(+)-4”-Butoxy-2’,3’-difluoro-4”-(2-methyl-butylsulfanyl)-[1,1’:4’,1”]-terphenyl (92) Compound 92 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 82 (1.20 g, 0.00366 mol, compound 21 (0.68 g, 0.00297 mol), sodium carbonate (0.69 g, 0.00654 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.77 g (55 %). Transitions (°C) Cr 88.6 SmA* 109.8 N* 121.7 I. 1 H NMR CDCl 3 /δ: 0.94 (3H, t), 1.00 (3H, t), 1.05 (3H, d), 1.24-1.36 (1H, m), 1.48-1.62 (2H, m), 1.68-1.75 (1H, m), 1.80 (2H, quin), 2.58 (2H, dd), 2.98-3.03 (1H, m), 4.02 (2H, t), 6.99 (2H, d, J 8.8), 7.21 (2H, m), 7.39 (2H, d, J 8.2), and 7.47-7.52 (4H, m). 13 C NMR CDCl 3 /δ: 11.26, 13.84, 18.96, 19.24, 22.29, 27.52, 28.82, 31.19, 31.28, 34.46, 37.96, 40.26, 67.76, 114.63, 126.69, 124.29, 124.42, 128.23, 129.10, 129.13, 129.96, 129.99, 131.61, 138.06, and 159.21. MS m/z: 441 (M+), 440 (M+) (100 %), 384, 370, 314, 294, 282, and 71. [α]D22° : +11.0° (0.00983 g/ml). Elemental Analysis: Calculated (Found): C 73.60 (73.60); H 6.89 (6.90); S 7.28 (7.17). (S)-(+)-2’,3’-Difluoro-4”-hexyloxy-4”-(2-methylbutylsulfanyl)-[1,1’:4’,1”]-terphenyl (93) Compound 93 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 70 (1.2 g, 0.00366 mol), compound 22 (0.76 g, 0.00297 mol), sodium carbonate (0.69 g, 0.00654 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. 118 Yield 0.71 g (51 %). Transitions (°C) Cr 70.2 SmA* 113.2 N* 118.1 I. 1 H NMR CDCl 3 /δ: 0.93 (6H, 2 x t), 1.05 (3H, d), 1.25-1.40 (5H, m), 1.48 (2H, quin), 1.54-1.61 (1H, m), 1.73 (1H, sext), 1.81 (2H, quin), 2.81 (1H, dd), 3.00 (1H, m), 4.01 (2H, t), 6.99 (2H, d, J 9.1), 7.19-7.25 (2H, m), 7.39 (2H, d, J 8.2), and 7.51 (4H, m). 13 C NMR CDCl 3 /δ: 11.26, 14.04, 18.96, 22.61, 25.73, 28.83, 31.58, 34.47, 40.27, 68.09, 114.64, 128.24, 129.11, 129.96, 124.23, 126.86, and 159.51. MS m/z: 469 (M+), 468 (M+) (100 %), 398, 384, 314, 313, 294, and 71. [α]D22° : +11.1° (0.00970 g/ml). Elemental Analysis: Calculated (Found): C 74.32 (74.21); H 7.31 (7.30); S 6.84 (6.84). 3.3.10: Scheme 10 4-Bromo-4’-propylbiphenyl (95) Anhydrous aluminium chloride (15.73 g, 0.118 mol) was added to a solution of propanoyl chloride (11.91 g, 0.129 mol) in dry DCM (150 ml). A solution of 4-bromobiphenyl (94) (25.00 g, 0.107 mol) in 100 ml DCM was added dropwise, and the mixture was heated under reflux for 24 hours, under nitrogen. When GLC analysis indicated that the reaction was complete, the mixture was cooled in an ice/water bath. PHMS (18.08 g, 0.300 mol) was added dropwise with stirring and the mixture was heated under reflux for 24 hours. GLC analysis indicated complete conversion of the ketone. The solvent was removed in vacuo and 10 % sodium hydroxide solution (200 ml) added. The residue was extracted using diethyl ether (2 x 300 ml). The combined organic layers were washed with 10 % sodium hydroxide solution (200 ml), water (200 ml), brine (200 ml), and dried (MgSO 4 ). Removal of the solvent in vacuo gave a residue which was purified by column chromatography [silica gel/hexane]. A colourless solid was obtained. Yield 15.38 g (54 %). Mpt 105.3 °C. (Lit Mp 107 °C) [9]. 1 H NMR CDCl 3 /δ: 0.97 (3H, t), 1.67 (2H, sept), 2.62 (2H, t), 7.25 (2H, d), 7.36 (2H, d), and 7.43-7.48 (4H, m). MS m/z: 276 (M+), 274 (M+), 247 (100 %), 245, 165, and 82. 119 4-Bromo-4’-nonylbiphenyl (98) Compound 98 was prepared and purified in a similar manner to that described for the preparation of compound 95 using the quantities stated. Nonanoyl chloride (22.72 g, 0.129 mol), 4-bromobiphenyl (94) (25.00 g, 0.107 mol), aluminium chloride (15.73 g, 0.118 mol), PHMS (18.08 g, 0.300 mol), dichloromethane (200 ml). The product was purified by column chromatography [silica gel/hexane]. A colourless solid was obtained. Yield 16.61 g (43 %). Mp 68.8 °C. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.21-1.32 (12H, m), 1.63 (2H, quin), 2.34 (2H, t), 7.25 (2H, d), 7.46 (2H, d), 7.47 (2H, d), and 7.55 (2H, d). MS m/z: 361 (M+), 360 (M+) (100 %), 358, 248, 127, 246, 245, 167, 166, and 165. 4-Ethoxy-2,3-difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (99) Compound 99 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 95 (2.00 g, 0.00727 mol), compound 39 (1.76 g, 0.00872 mol), sodium carbonate (1.69 g, 0.0160 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 1.10 g (43 %). Transitions (°C) Cr 131.3 N 195.4 I. 1 H NMR CDCl 3 /δ: 0.98 (3H, t), 1.49 (3H, t), 1.69 (2H, quin), 2.64 (2H, t), 4.17 (2H, q), 6.79-6.82 (1H, m), 7.14 (1H, td, J 19.2, 2.4), 7.27 (2H, d, J 8.2), 6.79-6.83 (4H, m), 7.66 (2H, d, J 10.5). 13 C NMR CDCl 3 /δ: 13.91, 14.78, 24.57, 37.72, 65.39, 109.50, 123.47, 123.55, 123.51, 126.89, 127.09, 128.97, 129.03, 129.06, 137.91, 140.42, and 142.11. MS m/z: 353 (M+), 352 (M+) (100 %), 324, 323, 296, 295, 266, and 148. Elemental Analysis: Calculated (Found): C 78.39 (78.33); H 6.29 (6.12). 120 4-Propyl-2,3-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (100) Compound 100 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 4-Bromo-4’-pentylbiphenyl (96) (1.00 g, 0.00330 mol), compound 49 (0.73 g, 0.00363 mol), sodium carbonate (0.75 g, 0.0290 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 0.27 g (22 %). Transitions (°C) Cr 94.4 N 134.5 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.00 (3H, t), 1.35-1.37 (4H, m), 1.68 (4H, quin), 2.63- 2.70 (4H, m), 6.98-7.02 (1H, m), 7.15 (1H, td, J 19.0, 2.3), 7.27 (2H, d, J 8.2), 7.56 (2H, d, J 8.2), 7.60 (2H, d, J 8.1), and 7.67 (2H, dd, J 8.6, 1.5). 13 C NMR CDCl 3 /δ: 13.80, 14.06, 22.57, 23.25, 30.78, 31.19, 31.57, 35.61, 124.13, 124.88, 124.83, 126.93, 127.06, 128.91, 129.15, 129.18, 130.57, 130.71, 133.60, 140.67, 137.86, and 142.40. MS m/z: 379 (M+), 378 (M+) (100 %), 349, 322, 321, 292, 293, 165, and 146. Elemental Analysis: Calculated (Found): C 82.50 (82.59); H 7.46 (7.42). 4-Butoxy-2,3-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (101) Compound 101 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 4-Bromo-4’-pentylbiphenyl (96) (2.00 g, 0.00660 mol), compound 41 (1.82 g, 0.00791 mol), sodium carbonate (1.54 g, 0.0145 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. A colourless solid was obtained. Yield 1.40 g (52 %). Transitions (°C) Cr 104.4 SmC 143.4 N 172.9 I. 121 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.00 (3H, t), 1.30-1.40 (4H, m), 1.52 (2H, sext), 1.66 (2H, quin), 1.83 (2H, quin), 2.65 (2H, t), 4.08 (2H, t), 6.77-6.82 (1H, m), 7.12 (1H, td, J 19.0, 2.4), 7.26 (2H, d, J 8.1), 7.53-7.57 (4H, m), and 7.65 (2H, d, 8.4). 13 C NMR CDCl 3 /δ: 13.82, 14.06, 19.13, 22.58, 31.20, 31.58, 35.61, 69.55, 109.55, 122.53, 122.63, 123.44, 123.47, 123.51, 126.90, 127.07, 128.91, 129.01, 129.04, 133.56, 137.87, 140.39, and 142.36. MS m/z: 409 (M+), 408 (M+), 352, 296, 295 (100 %), 266, and 165. Elemental Analysis: Calculated (Found): C 79.38; (79.29); H 7.40 (7.42). 4-Ethylsulfanyl-2,3-difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (102) Compound 102 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 54 (1.92 g, 0.00872 mol), compound 95 (2.00 g, 0.00727 mol), sodium carbonate (1.69 g, 0.0160 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 1.41 g (53 %). Transitions (°C) Cr 106.2 SmA 139.2 N 144.3 I. 1 H NMR CDCl 3 /δ: 0.98 (3H, t), 1.35 (3H, t), 1.69 (2H, sext), 2.64 (2H, t), 3.00 (2H, t), 7.15-7.22 (2H, m), 7.28 (2H, d, J 8.4), 7.56 (2H, d, J 8.2), 7.61 (2H, dd, J 10.2, 1.5), and 7.67 (2H, d, J 8.6). 13 C NMR CDCl 3 /δ: 13.90, 14.50, 25.55, 27.56, 27.59, 27.72, 124.48, 124.50, 124.61, 125.80, 125.82, 126.92, 127.16, 129.01, 129.10, 129.13, 133.05, 137.78, 141.01, and 142.26. MS m/z: 369 (M+), 368 (M+) (100 %), 340, 339, 311, 310, 277, 266, 184, 170, and 155. Elemental Analysis: Calculated (Found): C 74.97 (74.68); H 6.02 (6.10); S 8.70 (8.75). 122 4-Butylsulfanyl-2,3-difluoro-4”-propyl-[1,1’:4’,1”]-terphenyl (103) Compound 103 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 55 (2.15 g, 0.00872 mol), compound 95 (2.00 g, 0.00727 mol), sodium carbonate (1.69 g, 0.0160 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.70 g (24 %). Transitions (°C) Cr 72.4 SmA 129.9 I. 1 H NMR CDCl 3 /δ: 0.96 (6H, 2 x t), 1.48 (2H, sext), 1.61-1.72 (4H, m), 2.64 (2H, t), 2.97 (2H, t), 7.15-7.21 (2H, m), 7.28 (2H, d, J 8.4), 7.56 (2H, d, J 8.2), 7.60 (2H, dd, J 10.2, 1.5), and 7.67 (2H, d, J 8.6). 13 C NMR CDCl 3 /δ: 13.60, 13.88, 21.83, 24.53, 31.28, 33.08, 33.10, 37.70, 124.86, 125.03, 125.58, 128.73, 128.65, 124.46, 126.89, 127.13, 128.98, 129.08, 129.11, 137.76, 142.23, and 140.96. MS m/z: 397 (M+), 396 (M+) (100 %), 368, 367, 340, 312, 311, 310, 277, 165, and 145. Elemental Analysis: Calculated (Found): C 75.72 (76.11); H 6.61 (6.49); S 8.09 (7.99). 4-Ethylsulfanyl-2,3-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (104) Compound 104 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 54 (1.73 g, 0.00791 mol), compound 96 (2.00 g, 0.00660 mol), sodium carbonate (1.54 g, 0.01451 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.76 g (29 %). Transitions (°C) C 79.0 SmA 140.7 I. 123 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.33-1.39 (7H, m), 1.67 (2H, sext), 2.66 (2H, t), 3.00 (2H, t), 7.15-7.23 (2H, m), 7.28 (2H, d, J 8.2), 7.56 (2H, d, J 8.2), 7.60 (2H, dd, J 10.1, 1.6), and 7.68 (2H, d, J 8.6). 13 C NMR CDCl 3 /δ: 14.06, 14.51, 22.57, 27.57, 27.59, 31.18, 31.57, 35.61, 124.49, 125.81, 126.93, 127.16, 128.94, 129.10, 129.13, 137.74, 141.01, and 142.53. MS m/z: 397 (M+), 396 (M+) (100 %), 340, 339, 311, 310, and 155. Elemental Analysis: Calculated (Found): C 75.72 (75.89); H 6.61 (6.80); S 8.09 (7.85). 4-Butylsulfanyl-2,3-difluoro-4”-pentyl-[1,1’:4’,1”]-terphenyl (105) Compound 105 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 55 (1.95 g, 0.00791 mol), 4-Bromo-4’-pentylbiphenyl (96) (2.00 g, 0.00660 mol), sodium carbonate (1.54 g, 0.01451 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.17 g (42 %). Transitions (°C) Cr 65.9 (E 58.2) SmA 126.9 I. 1 H NMR CDCl 3 /δ: 0.94 (6H, 2 x t), 1.34-1.1.41 (4H, m), 1.48 (2H, sext), 1.66 (4H, quin), 2.66 (2H, t), 2.97 (2H, t), 7.02-7.14 (2H, m), 7.28 (2H, d, J 8.1), 7.56 (2H, d, J 8.1), 7.60 (2H, dd, J 9.9, 1.5), and 7.67 (2H, d, J 8.2). 13 C NMR CDCl 3 /δ: 13.62, 14.06, 21.85, 22.57, 31.30, 31.57, 35.61, 33.10, 33.12, 124.47, 124.90, 125.59, 125.05, 125.62, 126.93, 127.15, 128.94, 129.10, 129.13, 137.74, 140.98, and 142.52. MS m/z: 425 (M+), 424 (M+) (100 %), 368, 367, 312, 311, and 310. Elemental Analysis: Calculated (Found): C 76.38 (76.40); H 7.12 (7.19); S 7.55 (7.47). 4-Ethylsulfanyl-2,3-difluoro-4”-heptyl-[1,1’:4’,1”]-terphenyl (106) Compound 106 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 124 Compound 54 (1.58 g, 0.00724 mol), compound 97 (2.00 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 9:1], followed by recrystallisation from ethanol/ethyl acetate 10:1] .A colourless solid was obtained. Yield 0.96 g (38 %). Transitions (°C) Cr 71.3 E 72.2 SmA 140.5 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.28-1.37 (11H, m), 1.66 (2H, quin), 2.66 (2H, t), 3.00 (2H, q), 7.15-7.22 (2H, m), 7.28 (2H, d, J 8.2), 7.59 (2H, d, J 8.2), 7.60 (2H, dd, J 10.1, 1.5), and 7.68 (2H, d, J 8.8). 13 C NMR CDCl 3 /δ: 14.13, 14.51, 22.69, 27.56, 29.21, 29.36, 31.52, 31.83, 35.65, 124.45, 124.49, 125.79, 126.93, 127.16, 128.84, 129.14, 129.10, 133.03, 137.72, 141.01, and 142.54. MS m/z: 425 (M+), 424 (M+) (100 %), 340, 339, 311, 310, and 155. Elemental Analysis: Calculated (Found): C 76.38 (76.47); H 7.12 (7.24); S 7.55 (7.44). 4-Butylsulfanyl-2,3-difluoro-4”-heptyl-[1,1’:4’,1”]-terphenyl (107) Compound 107 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 55 (1.78 g, 0.00724 mol), compound 97 (2.00 g, 0.00604 mol), sodium carbonate (1.41 g, 0.01328 mol), tetrakis(triphenylphosphine)palladium (0) (0.30 g, 0.000426 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol/ethyl acetate 10:1] .A colourless solid was obtained. Yield 0.96 g (38 %). Transitions (°C) C 68.5 SmA 129.2 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.94 (3H, t), 1.24-1.60 (8H, m), 1.48 (2H, sext), 1.66 (4H, quin), 2.65 (2H, t), 2.97 (2H, t), 7.14-7.21 (2H, m), 7.27 (2H, d, J 8.2), 7.53 (2H, d, J 8.2), 7.60 (2H, dd, J 9.7, 1.4), and 7.68 (2H, d, 8.6). 125 13 C NMR CDCl 3 /δ: 13.61, 14.11, 21.84, 22.67, 29.19, 29.34, 31.26, 31.50, 31.82, 33.08, 35.63, 124.46, 124.87, 125.02, 125.57, 126.90, 127.12, 128.92, 129.08, 129.11, 137.70, 140.96, and 142.51. MS m/z: 453 (M+), 452 (M+) (100 %), 368, 367, 311, 310, 277, 257, and 165. Elemental Analysis: Calculated (Found): C 76.95 (77.18); H 7.57 (7.57); S 7.08 (6.89). 4-Ethylsulfanyl-2,3-difluoro-4”-nonyl-[1,1’:4’,1”]-terphenyl (108) Compound 108 was prepared and purified in a similar manner to that described for the preparation of compound 20 using the quantities stated. Compound 54 (1.56 g, 0.00668 mol), compound 98 (2.00 g, 0.00557 mol), sodium carbonate (1.30 g, 0.0122 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 11:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.68 g (27 %). Transitions (°C) Cr 137.9 SmA 139.6 I. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.27-1.38 (15H, m), 1.64 (2H, quin), 2.65 (2H, t), 3.00 (2H, q), 7.15-7.22 (2H, m), 7.28 (2H, d, J 10.6), 7.56 (2H, d, J 8.2), 7.60 (2H, dd, J 9.9, 1.4), and 7.68 (2H, d, J 8.1). 13 C NMR CDCl 3 /δ: 14.13, 14.51, 22.69, 29.35, 29.39, 29.55, 29.57, 31.50, 31.91, 35.65, 124.48, 125.81, 126.93, 127.16, 128.94, 129.10, 129.13, 137.73, 141.02, and 142.55. MS m/z: 453 (M+), 452 (M+) (100 %), 340, 339, 311, 310, and 155. Elemental Analysis: Calculated (Found): C 76.95 (76.71); H 7.57 (7.74); S 7.08 (7.09). 4-Butylsulfanyl-2,3-difluoro-4”-nonyl-[1,1’:4’,1”]-terphenyl (109) Compound 109 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 55 (1.64 g, 0.00668 mol), compound 98 (2.00 g, 0.00557 mol), sodium carbonate (1.30 g, 0.0122 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). 126 The product was purified by column chromatography [silica gel/hexane-dichloromethane 14:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.64 g (16 %). Transitions (°C) Cr 64.6 E 69.6 SmA 125.4 I. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 0.94 (3H, t), 1.27-1.34 (12H, m), 1.48 (2H, sext), 1.66 (4H, quin), 2.65 (2H, t), 2.97 (2H, t), 7.14-7.21 (2H, m), 7.28 (2H, d, J 8.1), 7.56 (2H, d, J 8.0), 7.60 (2H, dd, J 9.7, 1.3), and 7.68 (2H, d, J 8.2). 13 C NMR CDCl 3 /δ: 21.85, 13.62, 14.13, 22.69, 29.34, 29.39, 29.54, 29.56, 31.29, 31.50, 33.10, 35.65, 31.90, 124.47, 125.59, 126.92, 127.15, 128.94, 129.09, 129.12, 137.73, 140.98, and 142.53. MS m/z: 481 (M+), 480 (M+) (100 %), 368, 367, 311, and 310. Elemental Analysis: Calculated (Found): C 77.46 (77.33); H 7.97 (8.00); S 6.67 (6.64). 3.3.11: Scheme 11 4-Bromo-4’-butylsulfanylbiphenyl (111) Compound 111 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 1-Bromo-4-iodobenzene (110) (5.01 g, 0.0177 mol), compound 18 (5.00 g, 0.0177 mol), sodium carbonate (4.13 g, 0.0390 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 3.92 g (69 %). Mp 73.0 °C. 1 H NMR CDCl 3 /δ: 0.95 (3H, t), 1.25-1.39 (2H, m), 1.52 (2H, sext), 1.69 (2H, quin) 2.98 (2H, t), 7.38 (2H, d), 7.46 (4H, q), and 7.56 (2H, d). MS m/z: 321 (M+), 320 (M+) (100 %), 266, 265, 185, 167, 152, 149, 51, and 49. 127 4”-Butylsulphanyl-2,3-difluoro-4-propyl-[1,1’:4’,1”]-terphenyl (112) Compound 112 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 111 (1.55 g, 0.00482 mol), compound 49 (1.06 g, 0.00530 mol), sodium carbonate (1.12 g, 0.0107 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.13 g (72 %). Transitions (°C) Cr 78.1 SmA 134.3 I. 1 H NMR CDCl 3 /δ: 0.97 (6H, 2 x t), 1.48 (2H, sext), 1.68 (4H, quin), 2.68 (2H, t) 2.97 (2H, t), 7.12-7.67 (1H, m), 7.14 (1H, td, J 16.9, 2.4), 7.39 (2H, d, J 8.6), 7.56 (2H, d, J 8.6), 7.60 (2H, dd, J 10.0, 1.5), and 7.66 (2H, d, J 8.6). 13 C NMR CDCl 3 /δ: 13.65, 13.78, 21.99, 23.23, 30.76, 31.19, 33.12, 124.09, 124.85, 126.92, 127.38, 128.93, 129.26, 130.80, 131.88, 133.87, 136.57, 137.78, and 139.96. MS m/z: 397 (M+), 396 (M+) (100 %), 340, 311, 57, and 41. Elemental Analysis: Calculated (Found): C 75.72 (75.73); H 6.61 (6.71); S 8.09 (8.12). 4”-Butylsulphanyl-2,3-difluoro-4-pentyl-[1,1’:4’,1”]-terphenyl (113) Compound 113 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 112 (1.00 g, 0.00311 mol), compound 50 (0.78 g, 0.00342 mol), sodium carbonate (0.73 g, 0.00684 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.99 g (75 %). Transitions (°C) Cr 66.6 SmA 139.6 I. 1 H NMR CDCl 3 /δ: 0.94 (3H, t), 0.96 (3H, t), 1.34-1.42 (4H, m), 1.49 (2H, sext) 1.62-1.72 (4H, m), 2.70 (2H, t), 2.99 (2H, t), 7.01 (1H, td, J 16.5, 2.3), 7.16 (1H, td, J 16.9, 2.4), 7.41 (2H, d, J 8.6), 7.57 (2H, d, J 8.4), 7.62 (2H, dd, J 9.9, 1.5), and 7.67 (2H, d, J 8.6). 128 13 C NMR CDCl 3 /δ: 13.69, 14.03, 22.05, 22.53, 28.82, 29.80, 31.26, 31.49, 33.20, 124.18, 124.26, 124.78, 124.87, 126.96, 127.43, 127.82, 128.69, 128.92, 129.31, 131.04, 133.87, 133.97, 136.66, 137.74, 137.86, 140.00, and 149.26. MS m/z: 425 (M+), 424 (M+), 368, 311, 279, 186, 152, 57, and 41. Elemental Analysis: Calculated (Found): C 76.38 (76.42); H 7.12 (7.13); S 7.55 (7.61). 4”-Butylsulphanyl-2,3-difluoro-4”-heptyl-[1,1’:4’,1”]-terphenyl (114) Compound 114 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 111 (1.00 g, 0.00311 mol), compound 51 (0.88 g, 0.00342 mol), sodium carbonate (0.73 g, 0.00684 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.62 g (44 %). Transitions (°C) Cr 61.6 E 784 SmA 137.1 I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 0.96 (3H, t), 1.25-1.42 (8H, m), 1.51 (2H, sext) 1.60-1.72 (4H, m), 2.70 (2H, t), 2.99 (2H, t), 6.96 (1H, td, J 16.5, 2.4), 7.14 (1H, td, J 16.6, 2.4), 7.41 (2H, d, J 8.5), 7.57 (2H, d, J 8.4), 7.62 (2H, dd, J 9.9, 1.5), and 7.67 (2H, d, J 8.4). 13 C NMR CDCl 3 /δ: 13.69, 14.17, 22.10, 22.75, 28.89, 29.19, 30.00, 31.26, 31.86, 33.10, 33.23, 124.12, 124.78, 126.45, 126.93, 127.44, 127.88, 128.80, 128.97, 129.26, 131.79, 133.84, 134.04, 136.30, 137.82, 139.86, 140.05, and 149.25. MS m/z: 453 (M+), 452 (M+), 396, 367, 311 (100 %), 291, 279, 184, 127, and 57. Elemental Analysis: Calculated (Found): C 76.95 (76.99); H 7.57 (7.55); S 7.08 (7.10). 3.3.12: Scheme 12 4’-Heptylbiphenyl-4yl-boronic acid (115) Compound 115 was prepared and purified in a similar manner to that described for the preparation of compound 10 using the quantities stated. 129 Compound 97 (20.00 g, 0.0600 mol), magnesium (1.76 g, 0.0724 mol), trimethyl borate (12.54 g, 0.1207 mol), and dry THF (250 ml). An off-white solid was obtained. Yield 16.45 g (64 %). MS m/z: 429 (M+), 428 (M+) (100 %), 343, 314, 105, 77, 71. 4-Heptyl-4”-pentyl-[1,1’:4’,1”]-terphenyl (116) Compound 116 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 115 (3.00 g, 0.114 mol), compound 7 (1.92 g, 0.00946 mol), sodium carbonate (2.20 g, 0.0208 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000567 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation [ethanol/ethyl acetate 5:1]. Colourless crystals were obtained. Yield 0.59 g (16 %). Transitions (°C) C 196.5 SmA 210.2 I. 1 H NMR CDCl 3 /δ: 0.88 (6H, 2 x t), 1.23-1.35 (12H, m), 1.63 (4H, q), 2.63 (4H, t), 7.24 (2H, d), 7.53 (4H, d), and 7.63 (4H, s). 13 C NMR CDCl 3 /δ: 14.05, 22.67, 29.20, 29.34, 31.56, 31.82, 126.82, 127.24, 128.8, 133.8, 135.5, and 138.3. MS m/z: 398 (M+) (100 %), 313, 256, 149, 105, 77, and 71. Elemental Analysis: Calculated (Found): C 90.39 (90.39); H 9.61 (9.46). 4-Butylsulfanyl -4”-heptyl-[1,1’:4’,1”]-terphenyl (117) Compound 117 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 15 (1.55 g, 0.00631 mol), compound 115 (2.00 g, 0.00757 mol), sodium carbonate (1.47 g, 0.01329 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), DME (110 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from toluene. A colourless solid was obtained. 130 Yield 1.11 g (42 %). Transitions (°C) C 196.7 SmA 212.1 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.94 (3H, t), 1.29-1.35 (8H, m), 1.48 (2H, sext), 1.66 (2H, sext), 2.65 (2H, t), 2.97 (2H, t), 7.27 (2H, d), 7.39 (2H, d), 7.55 (2H, d), 7.57 (4H, d), and 7.65 (4H, d). 13 C NMR CDCl 3 /δ: 13.66, 14.11, 21.99, 22.68, 29.20, 29.35, 31.22, 31.62, 32.82, 33.23, 35.63, 126.82, 127.11, 127.30, 127.33, 128.87, 129.05, 136.20, 137.90, 138.06, 139.039, 140.55, and 142.26. MS m/z: 417 (M+), 416 (M+) (100 %), 331, 275, 274, 241, and 137. Elemental Analysis: Calculated (Found): C 76.95 (77.22); H 7.57 (7.51); S 7.08 (7.02). 3.3.13: Scheme 13 4-Ethoxy-4”-propyl-[1,1’:4’,1”]-terphenyl (118) Compound 118 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 17 (1.45 g, 0.00872 mol), compound 95 (2.00 g, 0.00727 mol), sodium carbonate (1.69 g, 0.0160 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol and a few drops of toluene. A colourless solid was obtained. Yield 0.44 g (19 %). Transitions (°C) Cr 243.8 N 255.3 I. 1 H NMR CDCl 3 /δ: 0.98 (3H, t), 1.44 (3H, t), 1.69 (2H, sext), 2.63 (2H, t), 4.08 (2H, q), 6.98 (2H, d), 7.26 (2H, d), 7.54-7.57 (4H, m), and 7.60-7.07 (4H, m). 13 C NMR CDCl 3 /δ: 13.91, 14.88, 24.58, 37.72, 63.52, 114.80, 126.80, 26.96, 127.26, 128.00, 128.92, 133.12, 138.13, 139.41, 139.46, 141.84, and 158.55. MS m/z: 317 (M+), 316 (M+) (100 %), 287, 259, 230, and 130. Elemental Analysis: Calculated (Found): C 87.30 (87.34); H 7.64 (7.94). 131 4”-Ethylsulfanyl-4-heptyl-[1,1’,4’,1”]terphenyl (119) Compound 119 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 97 (2.00 g, 0.00604 mol), compound 17 (1.57 g, 0.00724 moles), sodium carbonate (1.28 g, 0.0121 moles), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.0002835 moles), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from toluene. A colourless solid was obtained. Yield 0.26 g (11 %). Transitions (°C) C 227.1 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.23-1.38 (9H, m), 1.63 (4H, q), 2.65 (2H, t), 3.00 (2H, q), 7.26 (2H, s), 7.40 (2H, dd), 7.54-7.58 (4H, m), and 7.65 (4H, d). 13 C NMR CDCl 3 /δ: 14.12, 14.42, 22.69, 27.68, 29.21, 29.36, 31.53, 31.84, 35.65, 127.15, 127.35, 128.89, 135.73, 138.01, 139.21, 140.05, and 142.33. MS m/z: 388 (M+) (100 %), 303, 274, and 137. Elemental Analysis: Calculated (Found): C 83.45 (83.25); H 8.30 (8.40); S 8.25 (8.23). 3.3.14: Scheme 14 2-Bromo-6-ethoxynaphthalene (121) Compound 121 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. Bromoethane (36.54 g, 0.336 mol), 6-bromo-2-napthol (120) (25.00 g, 0.112 mol), potassium carbonate (46.47 g, 0.336 mol), and butanone (500 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 13.42 g (48 %). Mp 80.0 °C. 1 H NMR CDCl 3 /δ 1.48 (3H, t), 4.13 (2H, quin), 7.08 (1H, d), 7.16 (1H, dd), 7.49 (1H, dd), 7.58 (1H, d), 7.63 (1H, d), and 7.91 (1H, d). 132 MS m/z: 252 (M+), 250 (M+), 224, 222 (100 %), 195, 193, 143, 126, 115, 113, 89, 88, and 63. 2-Bromo-6-butoxynaphthalene (122) Compound 122 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 1-Bromobutane (18.43 g, 0.134 mol), 6-bromo-2-napthol (120) (25.00 g, 0.112 mol), potassium carbonate (46.47 g, 0.336 mol), and butanone (500 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 24.4 g (78 %). Mp 57.0 °C. (Lit Mp 56-57 °C) [10]. 1 H NMR CDCl 3 /δ 0.99 (3H, t), 1.52 (2H, quin), 4.05 (2H, t), 7.08 (1H, d), 7.15 (1H, dd), 7.47 (1H, dd), 7.57 (1H, d) 7.62 (1H, d), and 7.40 (1H, d). MS m/z: 280 (M+), 278 (M+), 224, 222 (100 %), 195, 193, 143, 126, 115, 113, 89, 88, and 63. 2-Ethoxynaphthalene-6-(2,3-difluoro-4-propylphenyl)-2-naphthalene (123) Compound 123 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.09 g, 0.00833 mol), compound 49 (2.00 g, 0.001 mol), sodium carbonate (1.94 g, 0.0183 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.57 g (63 %). Transitions (°C) Cr 101 (N 86.5) I. 1 H NMR CDCl 3 /δ: 0.10 (3H, t), 1.49 (3H, t), 1.69 (2H, sext), 2.67 (2H, t), 4.17 (2H, q), 6.99-7.03 (1H, m), 7.14-7.20 (3H, m), 7.61 (1H, dt, J 8.6, 3.8), 7.78 (2H, dd, J 8.6, 1.5), 7.92 (1H, s). 133 13 C NMR CDCl 3 /δ: 13.80, 14.81, 23.28, 30.79, 63.52, 106.29, 119.51, 124.35, 124.39, 124.42, 124.78, 124.83, 124.87, 126.88, 127.13, 127.16, 127.76, 127.78, 128.76, 129.73, 130.11, 130.35, 130.48, 134.00, and 157.39. MS m/z: 327 (M+), 326 (M+) (100 %), 298, 297, 270, 269, 240, 149, and 134. Elemental Analysis: Calculated (Found): C 77.28 (77.18); H 6.18 (6.13). 2-Ethoxynaphthalene-6-(2,3-Difluoro-4-pentylphenyl)-2-naphthalene (124) Compound 124 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.00 g, 0.00796 mol), compound 50 (2.18 g, 0.00956 mol), sodium carbonate (1.86 g, 0.0175 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.36 g (49 %). Transitions (°C) Cr 60.8 N 93.2 I. 1 H NMR CDCl 3 /δ: 0.92 (3H, t), 1.32-1.41 (4H, m), 1.49 (3H, t), 1.66 (2H, quin), 2.70 (2H, t), 4.17 (2H, q), 6.99-7.03 (1H, m), 7.14-7.22 (3H, m), 7.61 (1H, dt, J 8.6, 2.3), 7.78 (2H, d, J 8.4), and 7.92 (1H, s). 13 C NMR CDCl 3 /δ: 13.99, 14.79, 22.46, 28.74, 29.74, 31.44, 63.51, 106.30, 119.49, 124.39, 124.42, 124.68, 124.73, 124.77, 126.85, 127.11, 127.14, 127.73, 127.76, 128.76, 129.70, 133.99 and 157.38. MS m/z: 355 (M+), 354 (M+) (100 %), 326, 297, 270, 269, 240, and 135. Elemental Analysis: Calculated (Found): C 77.94 (77.90); H 6.83 (6.80). 2-Ethoxy-6-(4-ethoxy-2,3-difluorophenyl)naphthalene (125) Compound 125 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.00 g, 0.00796 mol), compound 39 (2.20 g, 0.00956 mol), sodium carbonate (1.86 g, 0.0175 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). 134 The product was purified by column chromatography [silica gel/hexane-dichloromethane 8:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.9 g (34 %). Transitions (°C) Cr 125.3 N 142.2 I. 1 H NMR CDCl 3 /δ: 1.57 (6H, t), 1.85 (2H, quin), 4.10 (2H, t), 4.17 (2H, q), 6.80-6.84 (1H, m), 7.15-7.21 (3H, m), 7.58 (1H, dt, J 8.4, 2.4), 7.77 (2H, dd, J 9.0, 1.5), and 7.89 (1H, s). 13 C NMR CDCl 3 /δ: 14.76, 14.78, 63.49, 65.40, 106.30, 109.54, 109.57, 119.47, 123.11, 123.22, 123.123.68, 123.72, 123.77, 126.87, 127.10, 127.12, 127.50, 127.53, 129.62, and 157.30. MS m/z: 329 (M+), 328 (M+) (100 %), 301, 300, 272, 271, 243, and 136. Elemental Analysis: Calculated (Found): C 73.16 (73.03); H 5.53 (5.60). 2-(4-Butoxy-2,3-difluorophenyl)-6-ethoxy-naphthalene (126) Compound 126 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.00 g, 0.00796 mol), compound 41 (2.20 g, 0.00956 mol), sodium carbonate (1.86 g, 0.0175 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 8:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.73 g (61 %). Transitions (°C) Cr 102.1 N 129.2 I. 1 H NMR CDCl 3 /δ: 1.01 (3H, t), 1.50 (3H, t), 1.46-1.58 (2H, m), 1.84 (2H, quin), 4.10 (2H, t), 4.17 (2H, q), 6.80-6.85 (1H, m), 7.14-7.21 (3H, m), 7.58 (1H, dt, J 8.6, 2.4), 7.77 (2H, dd, J 8.6, 1.6), and 7.89 (1H, s). 13 C NMR CDCl 3 /δ: 13.80, 14.79, 19.11, 31.19, 63.50, 69.60, 106.30, 109.60, 119.47, 123.16, 123.04, 123.65, 123.69, 123.77, 126.87, 127.11, 127.14, 127.50, 128.80, 129.63, 130.03, 133.84, and 157.29. MS m/z: 358 (M+), 356 (M+), 301, 300, 273, 272 (100 %), 271, 243, 225, and 194. Elemental Analysis: Calculated (Found): C 74.13 (73.95); H 6.22 (6.30). 135 2-Butoxy-6-(2,3-Difluoro-4-propylphenyl)-2-naphthalene (127) Compound 127 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 122 (2.33 g, 0.00833 mol), compound 49 (2.00 g, 0.00100 mol), sodium carbonate (1.94 g, 0.0183 mol), tetrakis(triphenylphosphine)palladium (0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.87 g (91 %). Transitions (°C) Cr 60.8 N 80.4 I. 1 H NMR CDCl 3 /δ: 0.10 (6H, 2 x t), 1.56 (2H, sext), 1.69 (2H, sext), 1.84 (2H, quin), 2.68 (2H, t), 4.09 (2H, t), 6.99-7.02 (1H, m), 7.14-7.25 (3H, m), 7.61 (1H, dt, J 8.6, 2.3), 7.77 (2H, dd, J 8.5, 1.6), 7.92 (1H, s). 13 C NMR CDCl 3 /δ: 13.80, 13.92, 19.33, 23.28, 30.79, 31.30, 67.77, 106.29, 119.56, 124.39, 124.42, 124.82, 124.78, 124.86, 126.87, 127.11, 127.14, 127.75, 127.78, 128.56, 128.45, 128.75, 128.79, 128.74, 129.68, 130.04, 130.33, 130.46, 134.02, and 157.61. MS m/z: 355 (M+), 354 (M+), 299, 298, 270, 269 (100 %), 240, 251, 239, and 220. Elemental Analysis: Calculated (Found): C 77.94 (78.03); H 6.83 (6.88). 2-Butoxy-6-(2,3-Difluoro-4-pentylphenyl)-2-naphthalene (128) Compound 128 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 122 (2.00 g, 0.00716 mol), compound 50 (1.96 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0157 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.17 g (43 %). Transitions (°C) Cr 50.8 N 83.3 I. 136 1 H NMR CDCl 3 /δ: 0.94 (3H, t), 1.04 (3H, t), 1.33-1.46 (4H, m), 1.56 (2H, quin), 1.87 (2H, quin), 1.69 (2H, quin), 2.73 (2H, t), 4.12 (2H, t), 7.01-7.05 (1H, m), 7.17-7.24 (3H, m), 7.64 (1H, dt, J 8.6, 2.3), 7.80 (2H, dd, J 8.8, 1.6), and 7.95 (1H, s). 13 C NMR CDCl 3 /δ: 13.88, 14.00, 19.31, 22.46, 28.75, 29.75, 31.28, 31.44, 67.76, 106.31, 119.53, 126.85, 127.10, 127.13, 127.13, 127.73, 127.76, 129.67, 157.59, 124.39, 124.68, 124.72, 124.77, 128.39, 128.50, 128.73, 130.06, 130.59, 130.59, 130.72, and 134.00. MS m/z: 383 (M+), 382 (M+), 327, 326, 270, 269 (100 %), 240, 149, and 251. Elemental Analysis: Calculated (Found): C 78.50 (78.38); H 7.38 (7.40). 2-Butoxy-6-(4-ethoxy-2,3-difluorophenyl)naphthalene (129) Compound 129 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 122 (2.00 g, 0.00716 mol), compound 39 (1.74 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0157 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 8:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.54 g (60 %). Transitions (°C) Cr 92.6 N 127.1 I. 1 H NMR CDCl 3 /δ: 1.02 (3H, t), 1.45-1.58 (5H, m), 1.85 (2H, quin), 4.10 (2H, t), 4.18 (2H, q), 6.80-6.85 (1H, m), 7.15-7.21 (3H, m), 7.58 (1H, dt, J 8.6, 2.3), 7.77 (2H, dd, J 8.9, 1.6), and 7.89 (1H, s). 13 C NMR CDCl 3 /δ: 13.88, 14.77, 19.31, 31.28, 65.40, 67.76, 106.30, 109.55, 119.52, 123.14, 123.25, 123.72, 123.77, 126.85, 127.08, 127.11, 127.50, 127.53, 128.68, 128.77, 129.59, 133.86, 129.96, and 157.51. MS m/z: 357 (M+), 356 (M+), 301, 300, 273, 272 (100 %), 271, 243, and 225. Elemental Analysis: Calculated (Found): C 74.14 (73.92); H 6.22 (6.30). 2-Butoxy-6-(4-butoxy-2,3-difluorophenyl)naphthalene (130) Compound 130 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 137 Compound 122 (2.00 g, 0.00716 mol), compound 41 (1.98 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0158 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 8:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.16 g (42 %). Transitions (°C) Cr 99.9 N 117.8 I. 1 H NMR CDCl 3 /δ: 1.01 (6H, 2 x t), 1.54 (4H, hept), 1.80-1.88 (4H, m), 4.10 (4H, t), 6.80- 6.84 (1H, m), 7.14-7.21 (3H, m), 7.58 (1H, dt, J 8.4, 2.3), 7.76 (2H, dd, J 9.0, 1.4), and 7.88 (1H, s). 13 C NMR CDCl 3 /δ: 13.80, 13.88, 19.12, 19.31, 31.20, 31.28, 67.76, 67.60, 106.31, 109.60, 119.51, 123.69, 123.74, 123.65, 123.17, 123.06, 128.77, 126.85, 127.10, 127.12, 127.49, 127.52, 129.59, and 157.50. MS m/z: 385 (M+), 384 (M+), 324, 273, 272 (100 %), 271, 243, and 225. Elemental Analysis: Calculated (Found): C 74.98 (74.84); H 6.82 (7.02). 3.3.15: Scheme 15 2-Bromo-6-phenoxynaphthalene (131) Compound 131 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 6-Bromo-2-naphthol (120) (50.00 g, 0.224 mol), benzylbromide (46.00 g, 0.269 mol), potassium carbonate (92.93 g, 0.672 mol), and butanone (600 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 44.46 g (63 %). Mp 108.7 °C. (Lit Mp 110 °C) [11]. 1 H NMR CDCl 3 /δ: 5.72 (2H, s), 7.19 (1H, d), 7.25 (1H, q), 7.41 (1H, t), 7.40-7.44 (2H, m), 7.48-7.51 (3H, m), 7.59 (1H, d) 7.67 (1H, d), and 7.92 (1H, d). MS m/z: 314 (M+), 312 (M+), 195, 193, 149, 114, 113, 92, 91 (100 %), and 65. 138 2-Benzyloxy-6-pent-1-ynylnaphthalene (132) A solution of n-butyllithium (2.5 M in hexanes, 38.28 ml, 0.0958 mol) was added dropwise to a stirred solution of pent-1-yne (6.53 g, 0.0958 mol), in dry THF (100 ml) at below 0 °C, under dry nitrogen. The mixture is stirred for 10 min and zinc chloride (17.41 g, 0.128 mol) was added with stirring. The mixture was allowed to reach room temperature and stirred for 15 min and a solution of compound 131 (15.20 g, 0.0639 mol) in dry THF (120 ml) followed by a solution of tetrakis(triphenylphosphine)palladium(0) (6.00 g, 0.00852 mol) in dry THF (30 ml). The mixture was heated to reflux for 24 hours, cooled and poured into 10 % hydrochloric acid (200 ml). The product was extracted into ether (2 x 200 ml), and the combined extracts washed with aqueous sodium hydrogen carbonate and water. After drying (MgSO 4 ), the ether was removed in vacuo. The product was purified by column chromatography [silica gel/hexane-dichloromethane 1:1], affording colourless crystals. Yield 14.26 g (75 %). Mp 78.0 °C. 1 H NMR CDCl 3 /δ: 1.08 (3H, t), 1.66 (2H, sext), 2.43 (2H, t), 5.16 (2H, s), 7.16- 7.47 (6H, m), 7.62 (1H, d), 7.68 (1H, d), 7.48 (2H, d), and 7.84 (1H, s). MS m/z: 301 (M+), 300 (M+) (100 %), 209, 165, 152, 139, 91 and 65. 6-Pentylnapth-2-ol (133) A stirred mixture of compound 132 (14.09 g, 0.0472 mol) and palladium-on-charcoal (4.00 g) in ethanol (300 ml) and ethyl acetate (300 ml) was hydrogenated at 1.0 mmHg pressure for 24 hours. (GC analysis indicated absence of starting material). The catalyst was filtered off and the solvent was removed in vacuo. No further purification was necessary. A colourless solid was obtained. Yield 9.21 g (91 %). Mp 74.2 °C. (Lit Mp 110 °C) [12]. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.32-1.36 (4H, m), 1.68 (2H, quin), 2.72 (2H, t), 7.06 (1H, dd), 7.11 (1H, d), 7.28 (1H, dd), 7.53 (1H, s), 7.59 (1H, d), and 7.67 (1H, d). Hydroxy proton not seen. 139 MS m/z: 215 (M+), 214 (M+), 158, 157 (100 %), 128, 127, and 115. 6-Pentylnaphth-2-yl triflate (134) Trifluoromethanesulphonic anhydride (11.85 g, 0.0420 mol) was added dropwise to a stirred, cooled (0 °C) solution of compound 133 (9.0 g, 0.0420 mol) in dry pyridine (100 ml) under dry nitrogen. The mixture was stirred at room temperature overnight. The solution was then poured into water (100 ml) and ether added (100 ml). The separated aqueous layer was washed with ether (2 x 100 ml). The combined organic layers were washed with water (100 ml), 10 % HCl (2 x 100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The residue was purified by column chromatography [silica gel/hexane-dichloromethane 7:3]. A colourless liquid was obtained. Yield 9.50 g (65 %). Mp 74.2 °C. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.26-1.41 (4H, m), 1.70 (2H, quin), 2.77 (2H, t), 7.33 (1H, dd), 7.43 (1H, dd), 7.65 (1H, s), 7.70 (1H, d), 7.78 (1H, d), and 7.84 (1H, d). MS m/z: 346 (M+), 289, 276, 214, 213 (100 %), 185, 157, 156, 143, 141, 129, 128, 115, and 69. 62-(4-Propyl-2,3-difluorophenyl)- 2-pentylnapthalene (135) Compound 134 (1.50 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium carbonate (0.55 g, 0.0130 mol, DME (80 ml), and water (40 ml) were stirred under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.00176 mol) was added, followed by compound 49 (1.05 g, 0.0519 mol). The solution was heated to reflux for 18 hours. Completion of the reaction was indicated by TLC and GLC analysis. The reaction mixture was allowed to cool and poured into water (100 ml), and ether (100 ml) added. The separated aqueous layer was washed with ether (2 x 100 ml) and the combined ethereal extracts washed with water (100 ml) and brine (100 ml). The solvent was dried over magnesium sulphate and removed in vacuo. The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.54 g (38 %). 140 Transitions (°C) Cr 37.6 N 42.4 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.00 (3H, t), 1.34-1.37 (4H, m), 1.70 (4H, quin), 2.69 (2H, t), 2.78 (2H, t), 6.99-7.03 (1H, m), 7.20 (1H, td, J 10.0, 2.4), 7.36 (1H, dd, J 10.0, 1.5), 7.62-7.63 (2H, m), 7.77 (1H, d, J 8.4), 7.83 (1H, d, J 8.6), and 7.96 (1H, s). 13 C NMR CDCl 3 /δ: 13.80, 14.06, 22.59, 23.27, 30.79, 31.05, 31.50, 36.12, 126.07, 127.58, 127.76, 127.99, 128.08, 141.15, 124.47, 124.83, 131.79, 132.93, 126.70, 126.68, 127.73, and 126.70. MS m/z: 353 (M+), 312 (M+), 296, 295 (100 %), 267, 266, 251, and 149. Elemental Analysis: Calculated (Found): C 81.78 (81.72); H 7.44 (7.39). 2-Pentyl-6-(4-pentyl-2,3-difluorophenyl)napthalene (136) Compound 136 was prepared and purified in a similar manner to that described for the preparation of compound 135 using the quantities stated. Compound 50 (1.18 g, 0.00519 mol), compound 134 (1.5 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium chloride (0.55 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.71 g (43 %). Transitions (°C) Cr 29.1 N 37.2 I. 1 H NMR CDCl 3 /δ: 0.91 (6H, 2 x t), 1.37 (8H, m), 1.64-1.75 (4H, m), 2.68 (2H, d), 2.78 (2H, t), 6.99-7.03 (1H, m), 7.19 (1H, td, J 10.2, 2.4), 7.36 (1H, dd, J 10.0, 1.5), 7.58-7.63 (2H, m), 7.79 (1H, d, J 8.6), 7.83 (1H, d, J 8.6), and 7.96 (1H, s). 13 C NMR CDCl 3 /δ: 14.03, 14.06, 22.49, 22.60, 28.78, 29.78, 31.05, 31.47, 31.52, 36.13, 126.07, 127.58, 127.76, 127.99, 128.09, 141.15, 124.58, 124.77, 124.81, 126.68, 126.71, 127.73, 131.80, and 132.94. MS m/z: 381 (M+), 380 (M+) (100 %), 324, 323, 267, 266, 253, and 251. Elemental Analysis: Calculated (Found): C 82.07 (82.00); H 7.95 (8.02). 141 2-(4-Ethoxy-2,3-difluorophenyl)-6-pentylnapthalene (137) Compound 137 was prepared and purified in a similar manner to that described for the preparation of compound 135 using the quantities stated. Compound 39 (1.18 g, 0.00519 mol), compound 134 (1.5 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium chloride (0.55 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.50 g (33 %). Transitions (°C) Cr 68.5 N 88.4 I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.35-1.37 (4H, m), 1.49 (3H, t), 1.71 (2H, quin), 2.78 (2H, t), 4.17 (2H, q), 6.82-6.85 (1H, m), 7.20 (1H, td, J 10.4, 2.3), 7.36 (1H, dd, J 10.0, 1.5), 7.59 (1H, dt, J 10.2, 3.6), 7.63 (1H, s), 7.79 (1H, d, J 8.4), 7.83 (1H, d, J 8.6), and 7.92 (1H, s). 13 C NMR CDCl 3 /δ: 14.06, 14.79, 22.59, 31.05, 31.50, 36.11, 65.41, 109.52, 123.85, 123.89, 126.06, 126.67, 126.70, 127.49, 127.52, 127.59, 127.98, 128.00, 131.84, 132.80, 141.04, 131.45, 123.25, and 123.12. MS m/z: 355 (M+), 355 (M+) (100 %), 298, 297, 270, 269, 256, 240, 239, 220, 207, 149, and 135. Elemental Analysis: Calculated (Found): C 77.94 (77.89); H 6.83 (6.79). 2-(4-Butoxy-2,3-difluorophenyl)- 6-pentylnapthalene (138) Compound 138 was prepared and purified in a similar manner to that described for the preparation of compound 135 using the quantities stated. Compound 41 (1.20 g, 0.00520 mol), compound 158 (1.50 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium chloride (0.55 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.42 g (25 %). Transitions (°C) Cr 62.3 N 72.6 I. 142 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.01 (3H, t), 1.38-1.39 (4H, m), 1.54 (2H, sext), 1.72 (2H, quin), 1.84 (2H, quin), 2.78 (2H, t), 4.10 (2H, t), 6.83 (1H, m), 7.20 (1H, td, J 8.4, 2.4), 7.37 (1H, dd, J 10.1, 1.6), 7.60 (1H, dt, J 8.4, 3.8), 7.63 (1H, s), 7.80 (1H, d), 7.83 (1H, d), and 7.92 (1H, s). 13 C NMR CDCl 3 /δ: 13.83, 14.06, 19.14, 22.59, 31.05, 31.21, 31.51, 36.11, 69.60, 109.61, 123.06, 123.18, 123.82, 126.06, 126.68, 127.48, 127.51, 127.58, 127.98, 128.00, 131.51, 131.84, 132.80, and 141.03. MS m/z: 383 (M+), 382 (M+), 326, 270, 269 (100 %), 258, 240, 220, 149, 256, and 238. Elemental Analysis: Calculated (Found): C 78.50 (78.49); H 7.38 (7.38). 2-(4-Ethylsulfanyl-2,3-difluorophenyl)- 6-pentylnapthalene (139) Compound 139 was prepared and purified in a similar manner to that described for the preparation of compound 135 using the quantities stated. Compound 54 (1.28 g, 0.00520 mol), compound 134 (1.50 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium chloride (0.55 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.68 g (42 %). Transitions (°C) Cr 50.3 (N 35.6) I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.34-1.44 (7H, m), 1.72 (2H, quin), 2.78 (2H, t), 3.00 (2H, q), 7.19-7.28 (2H, m), 7.38 (1H, dd, J 10.1, 1.5), 7.61 (2H, dt, J 8.4, 3.9), 7.81 (1H, d, J 8.4), 7.85 (1H, d, J 8.4), and 7.97 (1H, s). 13 C NMR CDCl 3 /δ: 14.06, 14.51, 22.58, 27.59, 31.03, 31.50, 36.13, 124.83, 125.87, 126.09, 126.43, 126.46, 127.72, 127.81, 127.84, 128.12, 129.39, 129.50, 130.98, 131.75, 133.05, and 141.40. MS m/z: 371 (M+), 370 (M+) (100 %), 314, 313, 300, 285, 284, 271, 251, 238, and 225. Elemental Analysis: Calculated (Found): C 74.56 (74.51); H 6.53 (6.52); S 8.65 (8.66) 143 2-(4-Butylsulfanyl-2,3-difluorophenyl)- 6-pentylnapthalene (140) Compound 140 was prepared and purified in a similar manner to that described for the preparation of compound 135 using the quantities stated. Compound 55 (1.07 g, 0.00433 mol), compound 158 (1.5 g, 0.00433 mol), sodium carbonate (1.01 g, 0.00953 mol), lithium chloride (0.55 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.27 g (74 %). Transitions (°C) Cr 34.5 I. 1 H NMR CDCl 3 /δ: 0.93 (6H, 2 x t), 1.34-1.37 (4H, m), 1.48 (2H, sext), 1.66 (2H, quin), 1.72 (2H, quin), 2.78 (2H, t), 2.97 (2H, t), 7.23 (2H, m), 7.38 (1H, dd, J 9.9, 1.4), 7.61 (1H, dt, J 8.6, 3.6), 7.64 (1H, s), 7.81 (1H, d, J 8.4), 7.85 (1H, d, J 8.6), and 7.97 (1H, s). 13 C NMR CDCl 3 /δ: 13.64, 14.06, 21.87, 22.60, 31.05, 31.31, 31.53, 33.14, 36.14, 124.86, 125.73, 126.11, 126.45, 126.48, 127.74, 127.85, 128.14, 129.23, 129.34, 131.03, 131.79, 133.08, and 141.42. MS m/z: 399 (M+), 398 (M+) (100 %), 341, 328, 285, 284, 271, 251, 238, 149, and 69. Elemental Analysis: Calculated (Found): C 74.34 (74.31); H 7.08 (7.08); S 8.05 (8.00). 3.3.16: Scheme 16 2-Butoxy-6-(4-pentylphenyl)naphthalene (141) Compound 141 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.00 g, 0.00716 mol), compound 10 (1.37 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0157 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 14:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.45 g (18 %). 144 Transitions (°C) Cr 137.1 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.01 (3H, t), 1.22-1.41 (4H, m), 1.55 (2H, sext), 1.67 (2H, quin), 1.85 (2H, quin), 2.66 (2H, t), 4.10 (2H, t), 7.15 (1H, s), 7.17 (1H, d), 7.28 (2H, d), 7.62 (2H, dt), 7.70 (1H, dd), 7.77 (2H, d), and 7.95 (1H, d). 13 C NMR CDCl 3 /δ: 13.89, 14.04, 19.32, 22.57, 31.21, 31.31, 31.55, 35.58, 67.73, 106.33, 119.38, 125.26, 125.93, 127.01, 127.08, 128.87, 129.10, 129.55, 136.20, 138.52, 141.87, and 157.15. MS m/z: 347 (M+), 348 (M+) (100 %), 291, 290, 289, 234, 233, 215, 204, and 189. Elemental Analysis: Calculated (Found): C 86.66 (86.41); H 8.73 (8.80). 2-Butoxy-6-(4-butoxyphenyl)naphthalene (142) Compound 142 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2 g, 0.00716 mol), compound 25 (1.67 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0157 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from toluene. A colourless solid was obtained. Yield 0.73 g (29 %). Transitions (°C) Cr 165.2 N 169.3 I. 1 H NMR CDCl 3 /δ: 0.98 (6H, 2 x t), 1.52 (4H, sept), 1.81 (4H, sept), 4.01 (2H, t), 4.08 (2H, t), 6.99 (2H, d), 7.13 (1H, s), 7.15 (1H, d), 7.60 (2H, d), 7.65 (1H, dd), 7.74 (2H, d), and 7.89 (1H, s). 13 C NMR CDCl 3 /δ: 13.87, 13.89, 19.26, 19.32, 31.31, 31.36, 67.73, 67.79, 106.34, 114.83, 119.37, 124.81, 125.80, 127.09, 128.13, 129.14, 129.44, 129.44, 133.42, 133.55, 135.93, 157.04, and 158.57. MS m/z: 349 (M+), 348 (M+) (100 %), 292, 235, 236, 237, 207, 189, 178, and 57. Elemental Analysis: Calculated (Found): C 82.72 (82.67); H 8.10 (8.12). 145 3.3.17: Scheme 17 2-Butoxy-6-(2-fluoro-4-propoxyphenyl)naphthalene (143) Compound 143 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 121 (2.00 g, 0.00716 mol), compound 31 (1.70 g, 0.00859 mol), sodium carbonate (1.67 g, 0.0158 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.92 g (37 %). Transitions (°C) Cr 75.6 N 111.0 I. 1 H NMR CDCl 3 /δ: 1.07 (6H, 2 x t), 1.50-1.60 (2H, m), 1.78-1.88 (4H, m), 3.96 (2H, t), 4.10 (2H, t), 6.74 (1H, dd), 6.80 (1H, dd), 7.13-7.18 (2H, m), 7.41-7.46 (1H, m), 7.61 (1H, dt, J 8.6, 3.6), 7.76 (2H, d, J 8.4), and 7.89 (1H, s). 13 C NMR CDCl 3 /δ: 10.49, 13.90, 19.32, 22.47, 31.29, 67.72, 69.90, 102.52, 106.28, 110.84, 119.32, 126.65, 127.32, 127.42, 128.84, 129.52, 130.90, 131.07, 133.58, 157.27, 159.67, and 161.64. MS m/z: 353 (M+), 352 (M+), 296, 254 (100 %), 225, 207, and 91. Elemental Analysis: Calculated (Found): C 78.38 (78.32); H 7.15 (7.11). 3.3.18: Scheme 18 2-Butoxy-6-(2,3-difluoro-4’-propylbiphenyl-4-yl)napthalene (144) Compound 144 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 64 (0.50 g, 0.00181 mol), compound 121 (0.46 g, 0.00164 mol), sodium carbonate (0.39 g, 0.00362 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). 146 The product was purified by column chromatography [silica gel/hexane], followed by recrystallisation from ethanol .A colourless solid was obtained. Yield 0.31 g (44 %). Transitions (°C) Cr 115.8 N 241.3 I. 1 H NMR CDCl 3 /δ: 1.01 (6H, 2 x t), 1.57 (2H, sext), 1.70 (2H, sext), 1.86 (2H, quin), 2.65 (2H, t), 4.10 (2H, t), 7.17-7.21 (2H, m), 7.30 (2H, d), 7.35-7.36 (1H, m), 7.53 (2H, dd, J 8.0, 1.4), 7.67 (1H, dt, J 8.4, 3.6), 7.80 (2H, dd, J 8.4, 1.5), and 7.99 (1H, s). 13 C NMR CDCl 3 /δ: 13.90, 19.31, 24.49, 31.26, 37.79, 67.76, 106.28, 119.63, 124.64, 124.75, 126.95, 127.91, 128.71, 128.75, 129.73, 134.14, 142.89, and 157.7 MS m/z: 431 (M+), 430 (M+), 375, 374 (100 %), 346, 345, 316, and 166. Elemental Analysis: Calculated (Found): C 80.90 (80.91); H 6.56 (6.50). 3.3.19: Scheme 19 6-Bromo-2-propyl-benzo-[1,3]-dioxinane (146) A mixture of 5-bromo-2-hydroxybenzyl alcohol (145) (20.00 g, 0.0985 mol), butanal (8.52 g, 0.118 mol), anhydrous sodium sulphate (27.98 g, 0.197 mol), and toluene-4-sulphonic acid (1.08 g, 0.00985 mol) in dichloromethane (200 ml) was heated to reflux overnight. The cooled solution was washed with 10% sodium hydrogen carbonate solution (100 ml), and water (100 ml). Followed by drying (MgSO 4 ). The solvent was removed in vacuo and the residue purified by column chromatography [silica gel/hexane-dichloromethane 12:1] to give a colourless oil. Yield 19.4 g (81 %). 1 H NMR CDCl 3 /δ 0.91 (3H, t), 1.48 (2H, sext), 1.66-1.80 (2H, m), 4.86 (2H, dd), 4.98 (1H, t), 6.66 (1H, d), 7.01-7.02 (1H, m), and 7.17 (1H, ddt). MS m/z: 258 (M+), 256 (M+), 184 (100 %), 183, 156, 78 and 77. 6-Bromo-2-pentylbenzo-[1,3]-dioxinane (147) Compound 147 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. 147 5-bromo-2-hydroxybenzyl alcohol (145) (20.00 g, 0.0985 mol), hexanal (11.84 g, 0.118 mol), anhydrous sodium sulphate (27.98 g, 0.197 mol), and toluene-4-sulphonic acid (1.08 g, 0.00985 mol) in dichloromethane (200 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 20.52 g (73 %). Mp 31.2 °C. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 1.25-1.39 (4H, m), 1.49 (2H, quin), 1.73-1.83 (2H, m), 4.84 (2H, dd), 4.95 (1H, t), 6.71 (1H, d), 7.06-7.07 (1H, m), and 7.22 (1H, ddt). MS m/z: 286 (M+), 284 (M+), 187, 186 (100 %), 185, 184, 158, 156, 78, and 77. 6-Bromo-2-heptylbenzo-[1,3]-dioxinane (148) Compound 148 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. 5-bromo-2-hydroxybenzyl alcohol (145) (20.00 g, 0.0985 mol), octanal (15.13 g, 0.118 mol), anhydrous sodium sulphate (27.98 g, 0.197 mol), and toluene-4-sulphonic acid (1.08 g, 0.00985 mol) in dichloromethane (200 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 25.92 g (84 %). Mp 39.7 °C. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.23-1.40 (8H, m), 1.51 (2H, quin), 1.76-1.89 (2H, m), 4.87 (2H, dd), 4.98 (1H, t), 6.74 (1H, d), 7.09 (1H, d), and 7.25 (1H, ddt). MS m/z: 314 (M+), 312 (M+), 181, 182, 183, 184 (100 %), 158, 156, 78, and 77. 2-Propyl-6-(4-propylphenyl)benzo-[1,3]-dioxinane (149) Compound 149 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (1.68 g, 0.00658 mol), compound 10 (1.00 g, 0.00757 mol, sodium carbonate (1.61 g, 0.00151 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. 148 Yield 0.23 g (11 %). Transitions (°C) Cr 87.6 I. 1 H NMR CDCl 3 /δ: 0.98 (6H, 2 x t), 1.57 (2H, sext), 1.67 (2H, sext), 1.78-1.92 (2H, m), 2.61 (2H, t), 4.97 (2H, dd), 5.06 (1H, t), 6.91 (1H, d), 7.16-1.17 (1H, m), 7.22 (2H, d), 7.38 (1H, dd), and 7.43 (2H, d). 13 C NMR CDCl 3 /δ: 13.87, 13.94, 17.00, 24.56, 36.45, 37.64, 66.61, 99.93, 116.93, 121.09, 123.28, 126.53, 126.55, 128.85, 135.11, 38.01, 141.40, and 152.41. MS m/z: 296 (M+), 225, 224 (100 %), 195, 181, 167, 165, 152, 149, 128, 115, 83, and 43. Elemental Analysis: Calculated (Found): C 81.04 (81.01); H 8.16 (8.18). 6-(4-Butoxyphenyl)-2-propylbenzo-[1,3]-dioxinane (150) Compound 150 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (1.14 g, 0.00469 mol), compound 25 (1.00 g, 0.00515 mol), sodium carbonate (1.20 g, 0.0113 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.82 g (54 %). Transitions (°C) Cr 132.2 I. 1 H NMR CDCl 3 /δ: 0.92 (6H, 2 x t), 1.43 (2H, sext), 1.50 (2H, sext), 1.71 (4H, quin), 3.92 (2H, t), 4.89 (2H, dd), 4.98 (1H, t), 6.82 (1H, d), 6.86 (2H, d), 7.05-7.06 (1H, m), 7.27 (1H, dd), and 7.36 (2H, d). 13 C NMR CDCl 3 /δ: 13.86, 13.94, 17.00, 19.25, 31.34, 36.45, 66.60, 67.76, 99.91, 114.74, 116.92, 121.09, 122.99, 126.30, 127.67, 133.04, 133.90, 152.14, and 158.39. MS m/z: 326 (M+), 298, 254 (100 %), 198, 186, 170, 141, and 115. Elemental Analysis: Calculated (Found): C 77.27 (77.31); H 8.03 (8.01). 2-Pentyl-6-(4-propylphenyl)benzo-[1,3]-dioxinane (151) Compound 151 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 149 Compound 151 (1.96 g, 0.00688 mol), compound 10 (1.00 g, 0.00757 mol), sodium carbonate (1.61 g, 0.0151 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.67 g (30 %). Transitions (°C) Cr 64.1 E 66.4 SmA 74.5 I. 1 H NMR CDCl 3 /δ: 0.88 (6H, 2 x t), 1.29 (4H, quin), 1.47 (2H, quin), 1.60 (2H, sext), 1.72-1.85 (2H, m), 2.54 (2H, t), 4.90 (2H, dd), 4.98 (1H, t), 6.84 (1H, d), 7.10 (1H, d), 7.15 (2H, d), 7.31 (1H, dd), and 7.36 (2H, d). C NMR CDCl 3 δ: 13.87, 14.01, 22.56, 23.30, 24.56, 31.62, 34.42, 37.63, 66.63, 100.13, 13 116.92, 121.08, 123.27, 126.52, 126.55, 128.85, 134.10, 138.00, 141.40, and 152.42. MS m/z: 324 (M+), 225, 224 (100 %), 195, 181, 167, 165, and 152. Elemental Analysis: Calculated (Found): C 81.44 (81.45); H 8.70 (8.66). 2-Pentyl-6-(4-pentylphenyl)benzo-[1,3]-dioxinane (152) Compound 152 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 11 (0.62 g, 0.00386 mol), compound 147 (1.00 g, 0.00351 mol), sodium carbonate (0.82 g, 0.00772 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.34 g (27 %). Transitions (°C) Cr 72.0 I. 1 H NMR CDCl 3 /δ: 0.84 (6H, 2 x t), 1.21-1.35 (8H, m), 1.48 (2H, quin), 1.57 (2H, quin), 1.71-1.86 (2H, m), 2.55 (2H, t), 4.89 (2H, dd), 4.97 (1H, t), 6.84 (1H, d), 7.12 (1H, d), 7.17 (2H, d), 7.31 (1H, dd), and 7.36 (2H, d). 13 C NMR CDCl 3 /δ: 14.01, 22.56, 23.30, 31.19, 31.53, 31.63, 34.42, 35.53, 66.63, 100.13, 116.92, 121.08, 123.27, 126.53, 128.79, 134.11, 137.97, 141.66, and 152.41. MS m/z: 342 (M+), 253, 252 (100%), 195, 181, 167, 165, and 152. Elemental Analysis: Calculated (Found): C 81.77 (81.77); H 9.15 (9.16). 150 6-(4-Butoxyphenyl)-2-pentylbenzo-[1,3]-dioxinane (153) Compound 153 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (1.34 g, 0.00469 mol), compound 25 (1.00 g, 0.00515 mol), sodium carbonate (1.20 g, 0.0113 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.74 g (44 %). Transitions (°C) Cr 99.0 E 109.4 SmA 124.3 I. 1 H NMR CDCl 3 /δ: 0.85 (3H, t), 0.91 (3H, t), 1.28 (4H, sext), 1.39-1.51 (4H, m), 1.71 (2H, quin), 1.74-1.80 (2H, m), 3.91 (2H, t), 4.89 (2H, dd), 4.97 (2H, t), 6.82-6.86 (2H, m), 7.06 (1H, d), 7.26 (1H, dd), and 7.36 (2H, d). 13 C NMR CDCl 3 /δ: 13.85, 14.01, 19.25, 12.56, 23.30, 31.33, 31.62, 34.42, 66.61, 67.74, 100.12, 114.73, 116.91, 121.09, 122.98, 126.29, 127.66, 133.03, 133.88, 152.14, and 158.38. MS m/z: 354 (M+), 255, 254 (100 %), 198, 197, 170, 169, 141, and 115. Elemental Analysis: Calculated (Found): C 77.93 (78.01); H 8.53 (8.53). 3.3.20: Scheme 20 6-(4-Butoxy-2-fluorophenyl)-2-propylbenzo-[1,3]-dioxinane (154) Compound 154 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 31 (1.00 g, 0.00471 mol), compound 146 (1.05 g, 0.00428 mol), sodium carbonate (0.91 g, 0.00857 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. 151 Yield 0.51 g (35 %). Transitions (°C) Cr 66.3 (N 48.1) I. 1 H NMR CDCl 3 /δ: 0.91 (6H, 2 x t), 1.42 (2H, sext), 1.50 (2H, sext), 1.70 (2H, quin), 1.74- 1.76 (2H, m), 3.89 (2H, t), 4.87 (2H, dd), 5.00 (1H, t), 6.60 (1H, dd, J 15.0, 1.5), 6.65 (1H, dd, J 11.0, 2.0), 6.82 (1H, d, J 8.3), 7.03 (1H, s), and 7.13-7.24 (2H, m). 13 C NMR CDCl 3 /δ: 13.80, 13.92, 16.97, 19.19, 31.15, 36.42, 66.54, 68.06, 99.91, 102.56, 110.76, 116.66, 125.20, 128.37, 130.65, 152.32, 158.89, 159.41, and 161.34. MS m/z: 344 (M+), 273, 272 (100 %), 216, 188, 159, and 133. Elemental Analysis: Calculated (Found): C 73.23 (73.20); H 7.32 (7.31). 6-(2-Fluoro-4-hexyloxyphenyl)-2-propylbenzo-[1,3]-dioxinane (155) Compound 155 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (0.85 g, 0.00347 mol), compound 32 (1.00 g, 0.00417 mol), sodium carbonate (0.81 g, 0.00764 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.35 g (27 %). Transitions (°C) Cr 28.0 N 52.9 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.00 (3H, t), 1.28-1.38 (4H, m), 1.46 (2H, quin), 1.57 (2H, sext), 1.78 (2H, quin), 1.80-1.87 (2H, m), 3.96 (2H, t), 4.95 (2H, dd), 5.06 (1H, t), 6.67 (1H, dd, J 15.0, 2.1), 6.73 (1H, dd, J 11.0, 2.0), 6.90 (1H, d, J 8.4), 7.11 (1H, s), and 7.26-7.29 (2H, m). 13 C NMR CDCl 3 /δ: 13.93, 14.02, 16.98, 22.59, 25.66, 29.09, 31.54, 36.43, 66.56, 68.41, 99.93, 102.31, 110.74, 116.67, 120.67, 125.21, 128.38, 130.66, 152.32, 159.53, and 161.35. MS m/z: 372 (M+), 301, 300 (100 %), 216, 188, 169, 159, 133, 55, 43, and 41. Elemental Analysis: Calculated (Found): C 74.17 (74.15); H 7.85 (7.85). 152 6-(2-Fluoro-4-octylphenyl)-2-propylbenzo-[1,3]-dioxinane (156) Compound 156 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (1.24 g, 0.00508 mol), compound 33 (1.50 g, 0.00559 mol), sodium carbonate (1.30 g, 0.0123 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.48 g (23 %). Transitions (°C) Cr 45.9 N 58.9 I. 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 0.93 (3H, t), 1.18-1.32 (8H, m), 1.39 (2H, quin), 1.49 (2H, quin), 1.75 (2H, quin), 1.75-1.81 (4H, m), 4.88 (2H, dd), 4.99 (1H, t), 6.60 (1H, dd, J 15.0, 2.2), 6.66 (1H, dd, J 11.4, 2.2), 6.83 (1H, d, J 11.0), 7.04 (1H, s), and 7.18-7.22 (2H, m). 13 C NMR CDCl 3 /δ: 13.93, 14.10, 16.98, 22.65, 25.98, 29.10, 29.22, 29.32, 31.79, 36.41, 66.55, 68.39, 99.90, 102.55, 110.76, 116.66, 120.64, 120.84, 125.20, 128.37, 128.53, 130.65, 152.30, 159.50, 161.32. MS m/z: 401 (M+), 400 (M+), 328, 217, 216 (100 %), 188, and 150. Elemental Analysis: Calculated (Found): C 74.97 (74.97); H 8.30 (8.31). 6-(4-Butoxy-2-fluorophenyl)-2-pentylbenzo-[1,3]-dioxinane (157) Compound 157 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (1.22 g, 0.00428 mol), compound 31 (1.00 g, 0.00471 mol), sodium carbonate (0.91 g, 0.00857 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.49 g (30 %). Transitions (°C) Cr 45.4 N 56.8 I. 153 1 H NMR CDCl 3 /δ: 0.92 (3H, t), 0.98 (3H, t), 1.31-1.40 (4H, m), 1.50 (2H, sext), 1.54 (2H, quin), 1.78 (2H, quin), 1.80-1.90 (2H, m), 3.97 (2H, t), 4.95 (2H, dd), 5.05 (1H, t), 6.67 (1H, dd, J 15.0, 2.4), 6.73 (1H, d, J 11.0), 6.90 (1H, d, J 8.4), 7.11 (1H, s), and 7.28-7.30 (2H, m). 13 C NMR CDCl 3 /δ: 13.82, 14.02, 19.19, 22.56, 23.28, 31.16, 31.63, 34.40, 66.56, 68.08, 100.13, 102.31, 102.57, 110.74, 110.77, 116.67, 120.84, 125.18, 128.38, 130.61, 130.66, and 152.33. MS m/z: 372 (M+), 273, 272 (100 %), 216, 188, 159, and 133. Elemental Analysis: Calculated (Found): C 74.17 (74.13); H 7.85 (7.80). 6-(2-Fluoro-4-hexyloxyphenyl)-2-pentylbenzo-[1,3]-dioxinane (158) Compound 158 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (0.99 g, 0.00347 mol), compound 32 (1.00 g, 0.00417 mol), sodium carbonate (0.81 g, 0.00764 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.42 g (31 %). Transitions (°C) Cr 34.4 SmA 41.3 N 58.0 I. 1 H NMR CDCl 3 /δ: 0.91 (6H, 2 x t), 1.30-1.40 (8H, m), 1.46 (2H, quin), 1.53 (2H, quin), 1.9 (2H, quin), 1.80-1.87 (2H, quin), 3.96 (2H, t), 4.95 (2H, dd), 5.05 (1H, t), 6.67 (1H, dd, J 15.0, 2.4), 6.72 (1H, dd, J 11.0, 2.2), 6.90 (1H, d), 7.11 (1H, s), and 7.19-7.30 (2H, m). 13 C NMR CDCl 3 /δ: 14.02, 22.56, 22.59, 23.29, 25.67, 29.09, 31.55, 31.62, 34.41, 66.57, 68.41, 100.14, 102.32, 110.78, 116.67, 120.85, 125.18, 128.36, 130.61, 152.33, 159.60, and 161.64. MS m/z: 400 (M+), 301, 300 (100 %), 216, 188, 159, 149, 57, 55, 43, and 41. Elemental Analysis: Calculated (Found): C 74.97 (74.96); H 8.30 (8.30). 6-(2-Fluoro-4-octyloxy-phenyl)-2-pentylbenzo-[1,3]-dioxinane (159) 154 Compound 159 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (1.45 g, 0.00509 mol), compound 33 (1.50 g, 0.00559 mol), sodium carbonate (1.30 g, 0.0123 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.66 g (30 %). Transitions (°C) Cr 36.3 SmA 57.5 I. 1 H NMR CDCl 3 /δ: 0.90 (6H, 2 x t), 1.22-1.40 (12H, m), 1.45 (2H, quin), 1.54 (2H, quin), 1.79 (2H, quin), 1.80-1.87 (2H, m), 3.95 (2H, t), 4.95 (2H, dd), 5.05 (1H, t), 6.67 (1H, dd, J 15.0, 2.4), 6.72 (1H, dd, J 10.8, 2.2), 6.89 (1H, d, J 8.4), 7.11 (1H, s), 7.24-7.31 (2H, m). 13 C NMR CDCl 3 /δ: 14.01, 14.10, 22.52, 22.65, 23.28, 25.98, 29.11, 29.22, 29.32, 31.62, 31.79, 34.40, 66.56, 68.40, 100.12, 102.55, 110.77, 116.66, 120.83, 125.20, 128.37, 128.53, 130.65, 152.32, 159.51, and 161.34. MS m/z: 428 (M+), 329, 328 (100 %), 216, 188, 159, 69, 57, and 43. Elemental Analysis: Calculated (Found): C 75.67 (75.65); H 8.70 (8.70). 6-(4-Butoxy-2-fluorophenyl)-2-heptyl-benzo-[1,3]-dioxinane (160) Compound 160 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 148 (0.47 g, 0.00150 mol), compound 33 (0.35 g, 0.00165 mol), sodium carbonate (0.38 g, 0.00363 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.31 g (52 %). Transitions (°C) Cr 42.4 SmA 53.4 N 58.0 I. 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 0.91 (3H, t), 1.27-1.34 (8H, m), 1.44-1.48 (4H, quin), 1.71 (2H, quin), 1.74-1.81 (2H, m), 3.90 (3H, t), 4.88 (2H, dd), 4.98 (1H, t), 6.61 (1H, dd), 6.66 (1H, dd, J 15.0, 2.2), 6.83 (1H, d, J 10.8, 2.2), 7.04 (1H, s), and 7.17-7.23 (2H, m). 155 13 C NMR CDCl 3 /δ: 13.82, 14.09, 19.19, 22.64, 23.60, 29.18, 29.38, 31.16, 31.76, 34.43, 66.56, 68.08, 100.13, 102, 30, 110.74, 116.67, 120.85, 125.18, 128.38, 130.61, 152.33, 158.89, 159.52, and 161.35. MS m/z: 401 (M+), 400 (M+), 273, 272 (100 %), 216, 188, 159, 57, and 41. Elemental Analysis: Calculated (Found): C 74.97 (75.00); H 8.30 (8.27). 3.3.21: Scheme 21 6-(2,3-Difluoro-4-heptylphenyl)-2-propylbenzo-[1,3]-dioxinane (161) Compound 161 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (1.30 g, 0.00532 mol), compound 51 (1.50 g, 0.00585 mol), sodium carbonate (1.24 g, 0.0117 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.0 g (48 %). Transitions (°C) Cr 33.2 (N 2.9) I. 1 H NMR CDCl 3 /δ: 0.81 (3H, t), 0.93 (3H, t), 1.15-1.32 (8H, m), 1.51-1.55 (4H, m), 1.70- 1.84 (2H, m), 2.59 (2H, t), 4.88 (2H, dd), 5.00 (1H, t), 6.84-6.90 (2H, m), 6.96 (1H, td, J 15.0, 1.6), 7.07 (1H, s), and 7.25 (1H, d, J 8.4). 13 C NMR CDCl 3 /δ: 13.92, 14.08, 16.96, 22.64, 28.73, 29.06, 29.22, 29.05, 30.05, 31.77, 36.40, 66.51, 100.00, 116.83, 120.99, 123.94, 124.64, 125.37, 127.67, 128.44, 130.57, 152.93, 147.43, and 149.89. MS m/z: 388 (M+), 317, 316 (100 %), 231, 217, 203, 183, 57, 43, and 41. Elemental Analysis: Calculated (Found): C 74.20 (74.21); H 7.78 (7.77). 6-(4-Butoxy-2,3-difluorophenyl)-2-propylbenzo-[1,3]-dioxinane (162) 156 Compound 162 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (0.72 g, 0.00296 mol), compound 41 (0.75 g, 0.00326 mol), sodium carbonate (0.68 g, 0.00652 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.12 g (11 %). Transitions (°C) Cr 59.1 I. 1 H NMR CDCl 3 /δ: 0.93 (6H, 2 x t), 1.47 (4H, sext), 1.71-1.81 (4H, m), 4.00 (2H, t), 4.88 (2H, dd), 5.00 (1H, t), 6.68-6.72 (1H, m), 6.84 (1H, d, J 8.6), 6.95 (1H, td, J 19.2, 2.4), 7.04 (1H, s), and 7.21 (1H, d, J 8.5). 13 C NMR CDCl 3 /δ: 13.85, 14.01, 19.25, 12.56, 23.30, 31.33, 31.62, 34.42, 66.61, 67.74, 100.12, 114.73, 116.91, 121.09, 122.98, 126.29, 127.66, 133.03, 133.88, 152.14, and 158.38. MS m/z: 362 (M+), 290, 279, 234, 206, 167, 149 (100 %), and 71. Elemental Analysis: Calculated (Found): C 69.60 (69.64); H 6.67 (6.66). 6-(2,3-Difluoro-4-heptylphenyl)-2-pentylbenzo-[1,3]-dioxinane (163) Compound 163 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (1.52 g, 0.00532 mol), compound 51 (1.50 g, 0.00586 mol), sodium carbonate (0.38 g, 0.00363 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.91 g (41 %). Transitions (°C) Cr 19.1 I. 1 H NMR CDCl 3 /δ: 0.85 (6H, 2 x t), 1.14-1.34 (12H, m), 1.45 (2H, quin), 1.55 (2H, quin), 1.71-1.83 (2H, m), 2.59 (2H, t), 4.88 (2H, dd), 4.98 (1H, t), 6.85 (1H, d, J 8.4), 6.84-6.87 (2H, m), 7.07 (1H, s), and 7.18-7.22 (1H, m). 157 13 C NMR CDCl 3 /δ: 14.01, 14.08, 22.56, 22.64, 23.26, 28.73, 29.07, 29.22, 30.05, 31.61, 31.77, 34.38, 66.52, 100.21, 116.83, 120.99, 123.94, 124.64, 125.36, 127.73, 128.46, 130.50, 147.43, 149.89, and 152.93. MS m/z: 417 (M+), 416 (M+), 317, 316 (100 %), 231, 217, 203, 183, 57, 43, and 41. Elemental Analysis: Calculated (Found): C 74.97 (74.92); H 8.23 (8.21). 6-(2,3-Difluoro-4-propoxyphenyl)-2-pentylbenzo-[1,3]-dioxinane (164) Compound 164 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (2.50 g, 0.00877 mol), compound 40 (2.08 g, 0.00964 mol), sodium carbonate (2.04 g, 0.0193 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.68 g (51 %). Transitions (°C) Cr 65.4 I. 1 H NMR CDCl 3 /δ: 0.85 (3H, t), 0.99 (3H, t), 1.24-1.36 (4H, m), 1.45 (2H, quin), 1.72- 1.84 (4H, m), 3.96 (2H, t), 4.88 (2H, dd), 4.98 (1H, t), 6.67-6.72 (1H, m), 6.84 (1H, d, J 8.4), 6.96 (1H, td, J 19.4, 2.4), 7.05 (1H, s), and 7.18-7.22 (1H, m). 13 C NMR CDCl 3 /δ: 10.30, 13.95, 22.44, 22.51, 23.22, 31.55, 34.32, 66.47, 71.27, 100.15, 109.51, 116.79, 120.94, 123.22, 125.20, 127.56, 128.31, 141.72, 147.48, 148.67, and 152.66. MS m/z: 376 (M+), 277, 276 (100 %), 234, 206, and 43. Elemental Analysis: Calculated (Found): C 70.19 (70.20); H 9.96 (9.96). 6-(4-Butoxy-2,3-difluorophenyl)-2-pentylbenzo-[1,3]-dioxinane (165) Compound 165 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (1.82 g, 0.00790 mol), compound 41 (2.00 g, 0.00896 mol), sodium carbonate (1.84 g, 0.0174 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). 158 The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 2.28 g (74 %). Transitions (°C) Cr 75.2 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 0.91 (3H, t), 1.25-1.33 (4H, m), 1.43-1.47 (4H, m), 1.69- 1.84 (4H, m), 4.00 (2H, t), 4.87 (2H, dd), 4.98 (2H, t), 6.65-6.71 (1H, m), 6.84 (1H, d), 6.94 (1H, td, J 19.4, 2.2), 7.03 (1H, s), and 7.20 (1H, d). 13 C NMR CDCl 3 /δ: 13.78, 14.00, 19.09, 22.55, 23.26, 31.16, 31.61, 34.37, 66.50, 69.49, 69.55, 100.19, 109.49, 116.82, 120.99, 125.20, 125.23, 128.34, 140.63, 147.42, 147.56, 149.99, and 152.73. MS m/z: 390 (M+), 291, 290, 235, 234 (100 %), 206, 177, 157, and 151. Elemental Analysis: Calculated (Found): C 70.75 (70.75); H 7.23 (7.23). 6-(2,3-Difluoro-4-pentyl-phenyl)-2-heptylbenzo-[1,3]-dioxinane (166) Compound 166 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 148 (1.87 g, 0.00598 mol), compound 50 (1.50 g, 0.00658 mol), sodium carbonate (1.39 g, 0.00132 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.68 g (27 %). Transitions (°C) Cr 37.7 (SmA 17.6) I. 1 H NMR CDCl 3 /δ: 0.82 (6H, 2 x t), 1.18-1.34 (12H, m), 1.46 (2H, quin), 1.56 (2H, quin), 1.71-1.83 (2H, m), 2.59 (2H, t), 4.88 (2H, dd), 4.99 (1H, t), 6.83-6.89 (2H, m), 6.96 (1H, td, J 16.8, 1.6), 7.07 (1H, s), and 7.25 (1H, d, J 8.6). 13 C NMR CDCl 3 /δ: 13.98, 14.08, 22.44, 22.64, 23.57, 28.69, 29.18, 29.38, 29.72, 31.42, 31.76, 34.41, 66.52, 100.21, 116.83, 120.99, 123.97, 124.65, 125.37, 127.74, 128.47, 130.56, 147.43, 149.95, and 152.93. MS m/z: 417 (M+), 416 (M+), 289, 288 (100 %), 231, 217, 203, 183, 43, and 41. Elemental Analysis: Calculated (Found): C 74.97 (74.98); H 8.23 (8.22). 159 3.3.22: Scheme 22 2,3-Difluoro-4’-hydroxy-3’-(hydroxymethyl)-4-pentylbiphenyl (167) 5-bromo-2-hydroxybenzyl alcohol (167) (2.43 g, 0.0120 mol), potassium fluoride (1.53 g, 0.0263 mol), compound 50 (3.00 g, 0.0133 mol) were dissolved in 200 ml of THF, and stirred under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.00176 mol) was then added, and the solution was heated to reflux for 18 hours. Completion of the reaction was indicated by TLC and GLC analysis. The reaction mixture is allowed to cool and poured into water (100 ml), and ether (100 ml) added. The separated aqueous layer is washed with ether (2 x 100 ml) and the combined extracts washed with water (100 ml), and dried (MgSO 4 ). After removal of the solvent in vacuo the product was purified by column chromatography [silica gel/hexane-ethyl acetate 16:1] to give a colourless solid. Yield 2.94 g (84 %). Mp 57.6 °C. 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 1.15-1.27 (6H, m), 1.54 (1H, d), 2.81 (2H, t), 4.00-4.01 (2H, m), 4.80 (1H, s), 6.84-6.96 (3H, m), and 7.06-7.28 (2H, m). MS m/z: 307 (M+), 306 (M+), 289, 288 (100 %), 231, 217, 203, 183, 151, 57, 55, 43, and 41. 6-(2,3-Difluoro-4-pentylphenyl)-2-propylbenzo-[1,3]-dioxinane (168) Compound 168 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. Compound 167 (0.60 g, 0.00205 mol), butanal (0.28 g, 0.00385 mol), anhydrous sodium sulphate (0.81 g, 0.00569 mol), and toluene-4-sulphonic acid (0.22 g, 0.00205 mol) in dichloromethane (200 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.29 g (40 %). 160 Transitions (°C) Cr 61.0 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 0.93 (3H, t), 1.22-1.31 (4H, m), 1.50-1.55 (4H, m), 1.70- 1.82 (2H, m), 2.60 (2H, t), 4.89 (2H, dd), 5.00 (1H, t), 6.85 (1H, d, J 8.4), 6.87-6.90 (1H, m), 6.97 (1H, td, J 16.7, 1.6), 7.08 (1H, s), and 7.25 (1H, d, J 8.4). 13 C NMR CDCl 3 /δ: 13.93, 13.99, 16.96, 22.44, 28.70, 29.73, 31.42, 36.41, 66.52, 100.01, 116.84, 121.00, 123.95, 124.65, 125.35, 128.45, and 152.93. MS m/z: 360 (M+), 289, 288 (100 %), 260, 231, 217, 203, 183, 41, and 39. Elemental Analysis: Calculated (Found): C 73.31 (73.32); H 7.27 (7.31). 6-(2,3-Difluoro-4-pentylphenyl)-2-pentylbenzo-[1,3]-dioxinane (169) Compound 256 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. Compound 167 (0.75 g, 0.00259 mol), hexanal (0.39 g, 0.00385 mol), anhydrous sodium sulphate (0.81 g, 0.00569 mol), and toluene-4-sulphonic acid (0.28 g, 0.00259 mol) in dichloromethane (200 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.34 g (34 %). Transitions (°C) Cr 32.6 (SmA 9.3 N 14.0) I. 1 H NMR CDCl 3 /δ: 0.84 (6H, 2 x t), 1.21-1.30 (8H, m), 1.47 (2H, quin), 1.56 (2H, quin), 1.71-1.83 (2H, m), 2.60 (2H, t), 4.89 (2H, dd), 4.99 (1H, t), 6.85 (1H, d, J 8.4), 6.87-6.90 (1H, m), 6.97 (1H, td, J 16.6, 1.6), 7.07 (1H, s), and 7.25 (1H, d, J 8.1). 13 C NMR CDCl 3 /δ: 13.99, 14.01, 22.44, 22.56, 23.27, 28.70, 29.73, 31.42, 31.61, 34.39, 66.53, 100.22, 116.84, 120.99, 123.95, 124.65, 125.35, 128.45, 128.48, 130.44, 130.57, and 152.94. MS m/z: 388 (M+), 288 (100 %), 260, 231, 203, 183, and 41. Elemental Analysis: Calculated (Found): C 74.20 (74.21); H 7.78 (7.78). 161 3.3.23: Scheme 23 6-(2,3-Difluoro-4-propylbiphenyl-4-yl)-2-propylbenzo-[1,3]-dioxinane (170) Compound 170 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (2.45 g, 0.00988 mol), compound 64 (3.00 g, 0.0109 mol), sodium carbonate (2.53 g, 0.0239 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.50 g (37 %). Transitions (°C) Cr 80.91 N 185.8 I. 1 H NMR CDCl 3 /δ: 1.00 (6H, 2 x t), 1.58 (2H, sext), 1.69 (2H, sext), 1.78-1.82 (2H, m), 2.64 (2H, t), 4.97 (2H, dd), 5.08 (1H, t), 6.95 (1H, d, J 8.6), 7.16-7.24 (3H, m), 7.28 (2H, d, J 8.4), 7.38 (1H, d, J 8.6), and 7.49 (2H, dd, J 9.7, 1.6). 13 C NMR CDCl 3 /δ: 13.88, 13.93, 16.96, 24.47, 36.40, 37.78, 66.52, 100.05, 116.95, 121.10, 124.31, 124.57, 125.44, 128.52, 128.65, 128.68, 128.73, 128.79, 142.85, and 153.16. MS m/z: 409 (M+), 408 (M+), 337, 336 (100 %), 308, 307, 279, and 139. Elemental Analysis: Calculated (Found): C 76.45 (76.45); H 6.42 (6.49). 6-(2,3-Difluoro-4’-propylbiphenyl-4-yl)-2-pentylbenzo-[1,3]-dioxinane (171) Compound 171 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (2.82 g, 0.00988 mol), compound 35 (3.00 g, 0.0109 mol), sodium carbonate (2.53 g, 0.0239 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation [ethanol/ethyl acetate 20:1]. A colourless solid was obtained. 162 Yield 2.09 g (49 %). Transitions (°C) Cr 76.1 SmA 126.1 N 174.6 I. 1 H NMR CDCl 3 /δ: 0.85 (3H, t), 0.91 (3H, t), 1.24-1.34 (4H, m), 1.48 (2H, quin), 1.62 (2H, sext), 1.72-1.86 (2H, m), 2.56 (2H, t), 4.90 (2H, dd), 5.00 (1H, t), 6.88 (1H, d, J 8.4), 7.09-7.17 (3H, m), 7.20 (2H, d, J 8.3), 7.31 (1H, d, J 8.6), and 7.43 (2H, dd, J 9.9, 1.6). 13 C NMR CDCl 3 /δ: 13.87, 14.01, 22.56, 23.26, 24.46, 31.61, 34.39, 37.77, 66.53, 100.25, 116.94, 121.09, 125.43, 128.49, 128.64, 128.67, 128.73, 142.54, 153.16, 131.95, 129.46, 124.60, 124.30, and 127.33. MS m/z: 436 (M+), 337, 336 (100 %), 307, 279, 139, and 154. Elemental Analysis: Calculated (Found): C 77.04 (77.04); H 6.93 (6.93). 6-(2,3-Difluoro-4’-propylbiphenyl-4-yl)-2-heptylbenzo-[1,3]-dioxinane (172) Compound 172 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 148 (0.83 g, 0.00263 mol), compound 64 (0.80 g, 0.00289 mol), sodium carbonate (0.61 g, 0.00579 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.74 g (61 %). Transitions (°C) Cr 63.7 SmA 133.0 N 164.3 I. 1 H NMR CDCl 3 /δ: 0.83 (3H, t), 0.91 (3H, t), 1.19-1.35 (8H, m), 1.48 (2H, quin), 1.62 (2H, sext), 1.74-1.86 (2H, m), 2.56 (2H, t), 4.91 (2H, dd), 5.00 (1H, t), 6.88 (1H, d, J 8.6), 7.10-7.43 (5H, m), 7.31 (1H, d, J 8.5), and 7.43 (2H, dd, J 10.0, 1.6). 13 C NMR CDCl 3 /δ: 13.88, 14.09, 22.65, 23.58, 24.47, 29.18, 29.38, 31.77, 34.42, 37.79, 66.53, 100.27, 116.94, 121.10, 124.31, 124.57, 125.41, 125.44, 128.50, 128.53, 128.66, 128.69, 128.74, 142.85, and 153.17. MS m/z: 464 (M+) (100 %), 337, 336, 307, 279, 154, and 139. Elemental Analysis: Calculated (Found): C 77.56 (77.60); H 7.38 (7.40). 163 6-(2,3-Difluoro-4’-pentylbiphenyl-4-yl)-2-propylbenzo-[1,3]-dioxinane (173) Compound 173 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 146 (2.19 g, 0.0897 mol), compound 64 (3.00 g, 0.00986 mol), sodium carbonate (2.09 g, 0.0197 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation [ethanol/ethyl acetate 10:1] A colourless solid was obtained. Yield 1.93 g (45 %). Transitions (°C) Cr 75.8 SmA 126.1 N 172.5 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 0.96 (3H, t), 1.25-1.32 (4H, m), 1.51 (2H, sext), 1.59 (2H, quin), 1.72-1.82 (2H, m), 2.59 (2H, t), 4.91 (2H, dd), 5.02 (1H, t), 6.88 (2H, d, J 8.4), 7.117.22 (6H, m), 7.31 (1H, d, J 8.5), and 7.43 (2H, dd, J 10.1, 1.5). 13 C NMR CDCl 3 /δ: 13.93, 14.03, 16.96, 22.55, 31.09, 31.55, 35.68, 36.40, 66.52, 116.95, 100.05, 121.10, 124.30, 124.57, 125.44, 128.52, 128.67, 143.12, and 153.16. MS m/z: 436 (M+), 365, 364 (100 %), 307, 279, and 140. Elemental Analysis: Calculated (Found): C 77.04 (77.05); H 6.93 (6.92). 6-(2,3-Difluoro-4’-pentylbiphenyl-4-yl)-2-pentylbenzo-[1,3]-dioxinane (174) Compound 174 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 147 (2.56 g, 0.0897 mol), compound 65 (3.00 g, 0.00986 mol), sodium carbonate (2.09 g, 0.0197 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation [ethanol/ethyl acetate 10:1]. A colourless solid was obtained. Yield 2.00 g (48 %). Transitions (°C) Cr 55.9 SmA 145.3 N 165.2 I. 164 1 H NMR CDCl 3 /δ: 0.92 (6H, 2 x t), 1.30-1.41 (8H, m), 1.53 (2H, quin), 1.66 (2H, quin), 1.80-1.90 (2H, m), 2.65 (2H, t), 4.97 (2H, dd), 5.07 (1H, t), 6.95 (1H, d, J 8.6), 7.16-7.24 (4H, m), 7.28 (2H, d, J 8.6), and 7.49 (2H, dd, J 9.7, 1.6). 13 C NMR CDCl 3 /δ: 14.01, 22.55, 22.56, 23.26, 31.09, 31.54, 31.61, 34.38, 35.68, 66.53, 100.25, 116.94, 121.09, 124.57, 124.30, 125.40, 128.50, 128.67, 143.12, and 153.16. MS m/z: 465 (M+), 464 (M+), 365, 364 (100 %), 308, 307, 279, 257, 154, and 139. Elemental Analysis: Calculated (Found): C 77.56 (77.55); H 7.38 (7.40). 6-(2,3-Difluoro-4’-pentylbiphenyl-4-yl)-2-heptylbenzo-[1,3]-dioxinane (175) Compound 175 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 148 (2.80 g, 0.0897 mol), compound 65 (3.00 g, 0.00986 mol), sodium carbonate (2.09 g, 0.0197 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.83 g (37 %). Transitions (°C) Cr 64.7 SmA 144.3 N 156.4 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, 2 x t), 1.30-1.37 (12H, m), 1.54 (4H, quin), 1.66 (2H, quin), 1.80-1.90 (2H, m), 2.65 (2H, t), 4.97 (2H, dd), 5.07 (1H, t), 6.95 (1H, d, J 8.6), 7.18-7.29 (2H, m), 7.38 (2H, d, J 8.6), and 7.49 (2H, dd, J 9.8, 1.6). 13 C NMR CDCl 3 /δ: 14.02, 22.55, 22.65, 23.56, 29.19, 29.38, 31.10, 31.55, 31.76, 35.68, 34.38, 66.47, 100.25, 116.95, 121.08, 124.35, 124.61, 125.52, 128.68, 143.21, and 153.16. MS m/z: 492 (M+), 365, 364 (100 %), 302, 279, 257, 201, 77 and 69. Elemental Analysis: Calculated (Found): C 78.02 (78.02); H 7.77 (7.77). 165 3.3.24: Scheme 24 6-Bromo-2-(4-ethoxyphenyl)benzo-[1,3]-dioxinane (177) 5-bromo-2-hydroxybenzyl alcohol (145) (10.00 g, 0.0492 mol), and 4-ethoxybenzaldehyde (176) (8.86 g, 0.0590 mol) were mixed together and heated to 50 °C. This temperature was maintained for 20 minutes and the resultant solid was taken up into ether (200 ml). The ether was then washed with water (100 ml), dried over magnesium sulphate, and removed in vacuo. The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 9.96 g (61 %). Mp 94.5 °C. 1 H NMR CDCl 3 /δ: 1.44 (3H, t), 4.06 (2H, q), 5.04 (2H, dd), 5.91 (1H, s), 7.73 (1H, d), 6.94 (2H, d), 7.15-7.16 (1H, m), 7.29 (1H, dd), and 7.49 (2H, d). MS m/z: 336 (M+), 334 (M+), 150 (100 %), 149, 120, 121, 91, 72, 65, and 51. 2-(4-Ethoxyphenyl)-6-(4-pentylphenyl)benzo-[1,3]-dioxinane (178) Compound 178 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 177 (1.50 g, 0.00449 mol), compound 11 (0.79 g, 0.00493 mol), sodium carbonate (1.05 g, 0.00988 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.73 g (40 %). Transitions (°C) Cr 142.4 N 170.3 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 1.22-1.31 (4H, m), 1.37 (3H, t), 1.57 (2H, quin), 2.56 (2H, t), 3.99 (2H, q), 5.07 (2H, dd), 5.91 (1H, s), 6.88 (2H, d), 6.93 (1H, d), 7.15-7.17 (3H, m), 7.34 (1H, dd), 7.38 (2H, d), and 7.46 (2H, d). 13 C NMR CDCl 3 /δ: 14.04, 14.78, 22.55, 31.20, 31.54, 35.53, 63.50, 66.96, 99.24, 114.43, 117.27, 120.96, 123.27, 126.57, 126.66, 127.74, 128.83, 129.25, 131.99, 134.46, 137.90, 141.75, 152.55, and 159.77. 166 MS m/z: 402 (M+), 253, 252, 195, 181, 150, 121 (100 %), 93, 77, 65, and 51. Elemental Analysis: Calculated (Found): C 80.56 (80.55); H 7.51 (7.51). 6-(2,3-Difluoro-4-pentylphenyl)-2-(4-ethoxyphenyl)benzo-[1,3]-dioxinane (179) Compound 357 was prepared and purified in a similar manner to that described for the preparation of compound 20 using the quantities stated. Compound 177 (1.50 g, 0.00449 mol), compound 50 (0.79 g, 0.00493 mol), sodium carbonate (1.05 g, 0.00988 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.67 g (34 %). Transitions (°C) Cr 113.0 N 162.4 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.32-1.38 (4H, m), 1.43 (3H, t), 1.64 (2H, quin), 2.68 (2H, t), 4.07 (2H, q), 5.13 (2H, dd), 5.99 (1H, s), 6.94-7.08 (2H, d, J 8.7), 7.01 (2H, d, J 8.6), 7.04-7.06 (1H, m), 7.21 (1H, s), 7.37 (1H, d, J 8.4), and 7.53 (2H, d, J 8.6). 13 C NMR CDCl 3 /δ: 14.00, 14.78, 22.45, 28.68, 29.73, 31.42, 63.52, 66.86, 99.31, 114.44, 117.18, 120.88, 123.95, 124.69, 125.36, 127.75, 128.02, 128.58, 129.11, 130.51, 153.05, and 159.79. MS m/z: 439 (M+), 438 (M+), 289, 288 (100 %), 231, 217, 203, 150, and 121. Elemental Analysis: Calculated (Found): C 73.95 (73.90); H 6.44 (6.50). 3.3.25: Scheme 25 4-Ethoxy-2,3-difluorobenzaldehyde (180) n-Butyllithium (2.5 M in hexanes, 33.38 ml, 0.083 mol) was added dropwise to a solution of compound 36 (12.00 g, 0.0759 mol) in dry THF (200 ml), at -78 °C under nitrogen. The mixture was stirred for 30 mins and DMF (12.87 g, 0.167 mol) added dropwise, maintaining the temperature below -70 °C. The mixture was left to return to room temperature overnight. Hydrochloric acid (10 %, 200 ml) was added with stirring. The 167 mixture is poured into water (100 ml) and ether is added (100 ml). The aqueous layer was extracted with ether (2 x 200 ml). The organic layers are washed with water and brine; dried (MgSO 4 ), and the solvent removed in vacuo to give a white solid. The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 12.30 g (87 %). Mp 68.1 °C. 1 H NMR CDCl 3 /δ: 1.50 (3H, t), 4.21 (2H, q), 6.81-6.85 (1H, m), 7.58-7.62 (1H, m), and 10.19 (1H, s). MS m/z: 187 (M+), 186 (M+), 157, 149 (100 %), 149, 104, 84, 71, and 57. 6-Bromo-2-(4-ethoxy-2,3-difluorophenyl)benzo-[1,3]-dioxinane (181) A mixture of 5-bromo-2-hydroxybenzyl alcohol (145) (10.00 g, 0.0491 mol), compound 180 (10.98 g, 0.00590 mol), and anhydrous sodium sulphate (15.34 g, 0.108 mol) in dichloromethane (200 ml) was heated to reflux overnight. The cooled solution was washed with 10% sodium hydrogen carbonate solution (100 ml), and water (100 ml). Followed by drying (MgSO 4 ). The solvent was removed in vacuo and the residue purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 13.64 g (74 %). Mp 141.4 °C. 1 H NMR CDCl 3 /δ: 1.48 (3H, t), 4.16 (2H, q), 5.07 (2H, dd), 6.17 (1H, s), 6.82 (1H, d, J 8.8), 7.18 (1H, m), 7.17-7.18 (1H, m), 7.31 (1H, dd, J 11.1, 2.4), and 7.35-7.37 (1H, m). MS m/z: 372 (M+), 370 (M+), 186 (100 %), 184, 158, 157, 156, 101, 77 and 51. 2-(4-Ethoxy-2,3-difluorophenyl)-6-(4-pentylphenyl)benzo-[1,3]-dioxinane (182) Compound 182 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 181 (2.00 g, 0.00539 mol), compound 11 (0.95 g, 0.00593 mol), sodium carbonate (1.26 g, 0.0119 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). 168 The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.92 g (39 %). Transitions (°C) Cr 102.3 N 147.8 I. 1 H NMR CDCl 3 /δ: 0.84 (3H, t), 1.28 (4H, m), 1.40 (3H, t), 1.58 (2H, quin), 2.56 (2H, t), 4.08 (2H, q), 5.09 (2H, dd), 6.17 (1H, s), 6.72-6.76 (1H, m), 6.92 (1H, d, J 8.4), 7.15-7.19 (3H, m), and 7.32-7.39 (3H, m). 13 C NMR CDCl 3 /δ: 14.04, 14.65, 22.55, 31.19, 31.53, 35.53, 65.35, 67.21, 93.70, 109.34, 117.27, 120.76, 121.33, 123.32, 126.59, 126.77, 128.84, 134.83, 137.79, 141.87, and 152.32. MS m/z: 438 (M+), 253, 252 (100 %), 195, 182, 157, 152, 101, and 57. Elemental Analysis: Calculated (Found): C 73.95 (73.99); H 6.44 (6.44). 6-(2,3-Difluoro-4-pentylphenyl)-2-(4-ethoxy-2,3-difluorophenyl)benzo-[1,3]-dioxinane (183) Compound 183 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 181 (2.00 g, 0.00539 mol), compound 50 (1.35 g, 0.00593 mol), sodium carbonate (1.26 g, 0.0119 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 moles), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.96 g (38 %). Transitions (°C) Cr 99.1 N 113.7 I. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.30-1.40 (4H, m), 1.48 (3H, t), 1.64 (2H, quin), 2.68 (2H, t), 4.16 (2H, q), 5.15 (2H, dd), 6.25 (1H, s), 6.80-6.85 (1H, m), 6.96-6.98 (1H, m), 7.01 (1H, d, J 8.4), 7.06 (1H, td, J 16.5, 1.6), 7.22 (1H, s), 7.36-7.43 (2H, m). 13 C NMR CDCl 3 /δ: 13.99, 14.65, 22.44, 28.70, 29.72, 31.41, 65.35, 67.11, 93.73, 109.34, 117.18, 117.98, 120.67, 121.32, 123.94, 124.72, 125.45, 127.50, 128.38, 128.66, 130.67, 130.79, and 152.83. MS m/z: 474 (M+), 289, 288 (100 %), 231, 217, 203, 183, 157, and 91. Elemental Analysis: Calculated (Found): C 68.35 (68.36); H 5.52 (5.51). 169 3.3.26: Scheme 26 trans-4-Propylcyclohexylmethanol (186) A solution of trans-4-propylcyclohexylcarboxylic acid (184) (40.00 g, 0.234 mol) in dry THF (80 ml) was added drop wise to a stirred mixture of lithium aluminium hydride (10.00 g, 0.264 moles) in dry THF (200 ml) at room temperature under dry nitrogen. The mixture was heated under reflux for one hour and stirred at room temperature. The mixture was cooled and a mixture of THF (70 ml) and 10% HCl (30 ml) was added dropwise and the product was extracted into ether (2 x 300 ml). The combined ethereal extracts were washed with water, and dried (MgSO 4 ). The solvent was removed in vacuo and the residue distilled to give a colourless oil. Yield 36.25 g (79 %). Bp 105 °C at 1.0 mmHg. (Lit Bp 155 °C at 3.0 mmHg) [13]. 1 H NMR CDCl 3 /δ: 0.82-0.98 (7H, m), 1.12-1.21 (3H, m), 1.31 (2H, sext), 1.43 (2H, s), 1.77 (4H, d), and 3.44 (2H, d). MS m/z: 156 (M+), 138, 109, 95, 83, 69 (100 %), and 55. trans-4-Pentylcyclohexylmethanol (187) Compound 187 was prepared and purified in a similar manner to that described for the preparation of compound 186 using the quantities stated. trans-4-Pentylcyclohexylcarboxylic acid (185) (45.00 g, 0.227 mol), lithium aluminium hydride (10.00 g, 0.264 mol) and THF (200 ml). Yield 32.64 g (79 %). Bp 120.3 °C at 1.0 mmHg. (Lit Bp 99 °C at 0.1 mmHg) [13]. 1 H NMR CDCl 3 /δ: 0.81-0.95 (7H, m), 1.10-1.41 (10H, m), 1.75 (4H, d), 2.00 (1H, s), 3.40 (2H, d). MS m/z: 184 (M+), 138, 137, 110, 97, 95 (100 %), 69, 55, and 41. 170 trans-4-Propylcyclohexylmethanal (188) To a suspension of pyridium chlorochromate (37.36 g, 0.173 mol), in dry dichloromethane (200 ml) compound 186 (18.00 g, 0.1156 mol) was added all at once and the resultant mixture was stirred for three hours at room temperature. It was then diluted with ether (200 ml), and the insoluble black gum washed with ether (2 x 150 ml). The solvent was then removed, and the residue was purified by column chromatography [silica gel/hexane-ethyl acetate 10:1]. A colourless solid was obtained. Yield 13.99 g (79 %). Mp 44.8 °C 1 H NMR CDCl 3 /δ: 0.80-0.91 (3H, t), 1.10-1.20 (4H, m), 1.20-1.34 (4H, m), 1.48-1.58 (1H, m), 1.72 (2H, d), 1.85 (2H, d), 1.98 (1H, tt), and 9.61 (1H, d). MS m/z: 155 (M+), 137, 107, 95, 81, 69 (100 %), and 55. trans-4-Pentylcyclohexylmethanal (189) Compound 189 was prepared and purified in a similar manner to that described for the preparation of compound 188 using the quantities stated. Pyridium chlorochromate (21.17 g, 0.0982 mol), compound 187 (12.00 g, 0.0654 mol), and dichloromethane (200 ml). The product was purified by column chromatography [silica gel/hexane-ethyl acetate 10:1]. A colourless liquid was obtained. Yield 6.77 g (56 %). Mp 51.3 °C. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.28 (12H, m), 1.48-1.64 (1H, m), 1.82 (2H, d), 2.00 (2H, d), 2.36 (1H, tt), and 9.60 (1H, d). MS m/z: 337, 279, 181 (M+), 180 (M+), 169 (100 %), 124, 109, 97, 83, 81, 67, 55, and 39. trans-6-Bromo-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (190) Compound 190 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. 5-bromo-2-hydroxybenzyl alcohol (145) (11.98 g, 0.0589 mol), compound 188 (10.7 g, 0.0648 mol), anhydrous sodium sulphate (4.67 g, 0.0329 mol), and toluene-4-sulphonic 171 acid (0.64 g, 0.00589 mol) in dichloromethane (200 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 14.23 g (72 %). Mp 78.6 °C. 1 H NMR CDCl 3 /δ: 0.85-0.95 (5H, m), 1.14-1.24 (5H, m), 1.31 (2H, quin), 1.64-1.73 (1H, m), 1.81 (2H, d), 1.92 (2H, tt), 4.72 (1H, d), 4.85 (2H, dd), 6.73 (1H, d), 7.08 (1H, dd), and 7.23 (1H, dd). MS m/z: 340 (M+), 338 (M+), 186 (100 %), 184, 156, and 154, 125, 77, 69, and 55. trans-6-Bromo-2-(4-pentylcyclohexyl)benzo-[1,3]-dioxinane (191) Compound 191 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. 5-bromo-2-hydroxybenzyl alcohol (145) (4.52 g, 0.0985 mol), compound 189 (3.00 g, 0.0164 mol), anhydrous sodium sulphate (4.67 g, 0.00985mol), and toluene-4-sulphonic acid (1.07 g, 0.00985 mol) in dichloromethane (200 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 2.75 g (50 %). Mp 83.2 °C. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.13-1.34 (16H, m), 1.81 (2H, d), 1.91 (2H, tt), 4.71 (1H, d), 4.85 (2H, dd), 6.73 (1H, d), 7.07-7.08 (1H, m), and 7.23 (1H, dd). MS m/z: 367 (M+), 366 (M+) (100 %), 213, 182, 164, 108, 97, 78, and 52. trans-6-(2,3-Difluoro-4-pentylphenyl)-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (192) Compound 192 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 190 (2.00 g, 0.00590 mol), compound 50 (1.62 g, 0.00708 mol), sodium carbonate (1.37 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. 172 Yield 1.68 g (64 %). Transitions (°C) Cr 40.2 SmA 121.1 N 148.1 I. 1 H NMR CDCl 3 /δ: 0.88-0.98 (8H, m), 1.15-1.41 (12H, m), 1.64 (2H, quin), 1.69-1.79 (1H, m), 1.84 (2H, d), 1.96 (2H, tt), 2.67 (2H, t), 4.81 (1H, d), 4.95 (2H, dd), 6.91-6.97 (2H, m), 7.04 (1H, td, J 19.1, 2.4), 7.14 (1H, s), and 7.32 (1H, d, J 8.4). 13 C NMR CDCl 3 /δ: 13.99, 14.38, 19.99, 22.44, 26.66, 26.66, 26.88, 28.69, 29.73, 31.42, 32.44, 37.25, 39.65, 42.00, 66.63, 102.94, 116.84, 121.10, 123.93, 124.59, 125.30, 127.50, 127.87, 128.41, 130.51, 147.80, 149.87, and 153.10. MS m/z: 443 (M+), 442 (M+), 287, 288 (100 %), 231, and 203. Elemental Analysis: Calculated (Found): C 75.99 (75.99); H 8.20 (8.20). trans-6-(2,3-Difluoro-4-propoxyphenyl)-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (193) Compound 193 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 190 (2.00 g, 0.00590 mol), compound 40 (1.53 g, 0.00708 mol), sodium carbonate (1.37 g, 0.0130 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.70 g (28 %). Transitions (°C) Cr 107.6 SmA 123.7 N 180.6 I 1 H NMR CDCl 3 /δ: 0.86-0.97 (5H, m), 1.06 (3H, t), 1.15-1.24 (5H, m), 1.32 (2H, quin), 1.69-1.78 (1H, m), 1.69-1.78 (4H, m), 1.98 (2H, tt), 4.02 (2H, d), 4.80 (1H, d), 4.94 (2H, dd), 6.74-6.78 (1H, m), 6.91 (1H, d, J 8.4), 7.02 (1H, td, J 19.2, 2.4), 7.10 (1H, s), and 7.27 (1H, d, J 8.4). 13 C NMR CDCl 3 /δ: 10.37, 14.38, 19.99, 22.50, 26.66, 26.89, 32.46, 37.25, 39.68, 42.00, 66.65, 71.32, 102.94, 109.50, 116.85, 121.12, 122.49, 123.22, 125.22, 127.49, 128.30, 147.41, 147.55, 150.02, and 152.90. MS m/z: 431(M+), 430 (M+), 277, 276 (100 %), 234, 206, 177, 69, and 55. Elemental Analysis: Calculated (Found): C 72.53 (72.55); H 7.49 (7.45). 173 trans-6-(2,3-Difluoro-4-pentylphenyl)-2-(4-pentylcyclohexyl)benzo-[1,3]-dioxinane (194) Compound 194 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 191 (0.75 g, 0.00205 mol), compound 50 (0.51 g, 0.00225 mol), sodium carbonate (0.48 g, 0.00450 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.29 g (31 %). Transitions (°C) Cr 49.9 SmA 130.3 N 143.4 I. 1 H NMR CDCl 3 /δ: 0.90 (8H, m), 1.15-1.38 (16H, m), 1.62 (2H, quin), 1.68-1.78 (1H, m), 1.82 (2H, d), 1.95 (2H, tt), 2.66 (2H, t), 4.80 (2H, d), 4.94 (2H, dd), 6.91 (1H, d, J 8.4), 6.95-6.97 (1H, m), 7.03 (1H, td, J 16.7, 1.5), 7.13 (1H, s), and 7.31 (1H, d, J 8.4). 13 C NMR CDCl 3 /δ: 13.99, 14.12, 22.44, 22.70, 26.63, 26.67, 26.89, 28.70, 29.73, 31.41, 32.19, 32.49, 37.33, 37.56, 42.01, 66.65, 102.96, 116.85, 121.10, 123.94, 124.64, 125.32, 127.51, 127.82, 128.35, 130.38, 148.18, and 153.10. MS m/z: 451 (M+), 289, 288 (100 %), 231, 203, 182, 55, and 43. Elemental Analysis: Calculated (Found): C 76.56 (76.55); H 8.57 (8.61). trans-6-(2,3-Difluoro-4-propoxyphenyl)-2-(4-pentylcyclohexyl)benzo-[1,3]-dioxinane (195) Compound 195 was prepared and purified in a similar manner to that described for the preparation of compound 20 using the quantities stated. Compound 191 (0.75 g, 0.00205 mol), compound 40 (0.49 g, 0.00225 mol), sodium carbonate (0.48 g, 0.00456 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.22 g (23 %). Transitions (°C) Cr 107.7 SmA 149.3 N 184.4 I. 174 1 H NMR CDCl 3 /δ: 0.91 (5H, t), 1.07 (3H, t), 1.17-1.35 (12H, m), 1.69-1.79 (1H, m), 1.81- 1.90 (4H, m), 1.96 (2H, tt), 4.04 (2H, t), 4.81 (1H, d), 4.95 (2H, dd), 6.76-6.77 (1H, m), 6.92 (1H, d, J 8.6), 7.03 (1H, td, J 19.4, 2.4), 7.11 (1H, s), and 7.28 (1H, d, J 8.6). 13 C NMR CDCl 3 /δ: 10.38, 14.12, 22.50, 22.70, 26.63, 26.67, 26.90, 32.19, 32.49, 37.33, 37.55, 42.00, 66.65, 71.32, 103.00, 109.51, 116.88, 121.12, 122.59, 123.27, 125.25, 127.47, 128.31, 147.43, 147.53, and 152.91. MS m/z: 458 (M+), 275, 276 (100 %), 234, 206, 55, and 43. Elemental Analysis: Calculated (Found): C 73.33 (73.30); H 7.91 (7.96). 3.3.27: Scheme 27 trans-6-(2-Fluoro-4-propoxyphenyl)-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (196) Compound 196 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 190 (2.00 g, 0.00590 mol), compound 31 (1.29 g, 0.00649 mol), sodium carbonate (1.51 g, 0.0143 mol), tetrakis(triphenylphosphine)palladium (0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.75 g (31 %). Transitions (°C) Cr 75.4 N 182.6 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.90-0.96 (2H, m), 1.04 (3H, t), 1.15-1.26 (5H, m), 1.34 (2H, sept), 1.68-1.76 (1H, m), 1.78-1.87 (4H, m), 1.95 (2H, tt), 3.93 (2H, t), 4.80 (1H, d), 4.94 (2H, q), 6.68 (1H, dd, J 15.0, 2.4), 6.73 (1H, dd, J 11.0, 2.4), 6.90 (1H, d, J 8.6), 7.10 (1H, s), and 7.22-7.29 (2H, m). 13 C NMR CDCl 3 /δ: 10.47, 14.38, 19.99, 22.56, 26.69, 26.92, 32.47, 37.26, 39.66, 42.03, 66.69, 69.87, 102.45, 102.89, 110.74, 116.69, 120.96, 125.17, 128.33, 130.63, 152.51, 158.89, 159.19, and 161.35. MS m/z: 412 (M+), 258 (100 %), 257, 216, 188, 159, 69, and 55. Elemental Analysis: Calculated (Found): C 75.16 (75.17); H 8.07 (8.07). 175 trans-6-(2-Fluoro-4-octyloxyphenyl)-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (197) Compound 197 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 190 (2.27 g, 0.00848 mol), compound 34 (2.50 g, 0.00932 mol), sodium carbonate (1.98 g, 0.0187 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.24 g (30 %). Transitions (°C) Cr 62.7 SmC 64.8 SmA 120.0 N 163.6 I. 1 H NMR CDCl 3 /δ: 0.87-0.97 (8H, m), 1.16-1.40 (15H, m), 1.46 (2H, quin), 1.68-1.87 (5H, m), 1.95 (2H, tt), 3.96 (2H, t), 4.80 (1H, d), 4.94 (2H, dd), 6.67 (1H, dd, J 15.0, 2.4), 6.73 (1H, dd, J 11.0, 2.4), 6.90 (1H, d, 8.6), 7.10 (1H, s), and 7.24-7.30 (2H, m). 13 C NMR CDCl 3 /δ: 14.11, 14.39, 20.00, 22.65, 25.99, 26.92, 29.12, 29.22, 29.32, 31.30, 32.46, 37.26, 39.66, 42.02, 66.69, 68.40, 102.29, 102.55, 102.89, 110.76, 116.69, 120.96, 125.16, 128.40, 130.66, 152.50, 152.20, and 161.34. MS m/z: 483 (M+), 482 (M+), 329, 328 (100 %), 216, 188, 69, and 55. Elemental Analysis: Calculated (Found): C 76.72 (76.72); H 9.01 (9.05). 3.3.28: Scheme 28 trans-2-(4-Pentyl-cyclohexyl)-6-(4-pentylphenyl)benzo-[1,3]-dioxinane (198) Compound 198 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 191 (0.75 g, 0.00204 mol), compound 11 (0.36 g, 0.00225 mol), sodium carbonate (0.477 g, 0.00456 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 20:1], followed by recrystallisation from ethanol. A colourless solid was obtained. 176 Yield 0.20 g (22 %). Transitions (°C) Cr 143.2 SmA 185.9 I. 1 H NMR CDCl 3 /δ: 0.92 (8H, t), 1.16-1.41 (15H, m), 1.65 (2H, quin), 1.75 (1H, td), 1.85 (2H, d), 1.98 (2H, tt), 2.64 (2H, t), 4.81 (1H, d), 4.97 (2H, dd), 6.92 (1H, d, J 8.4), 7.18 (1H, d, J 2.2), 7.23 (2H, d, J 8.1), 7.39 (1H, dd, J 10.6, 2.2), and 7.44 (2H, d, J 8.2). 13 C NMR CDCl 3 /δ: 14.10, 22.55, 22.70, 26.63, 26.92, 31.20, 31.53, 32.19, 32.50, 35.43, 37.34, 37.56, 42.03, 66.73, 102.81, 116.88, 121.19, 123.17, 126.45, 128.83, 133.96, 137.98, 141.61, and 152.58. MS m/z: 434 (M+), 253, 252 (100 %), 195, 181, 163, 152, 51, and 43. Elemental Analysis: Calculated (Found): C 82.61 (82.58); H 9.80 (9.82). 3.3.29: Scheme 29 6-Bromo-8-fluoro-2-phenylbenzo-[1,3,2]-dioxaborinane (201) 4-Bromo-2-fluorophenol (199) (10.00 g, 0.0524 mol), benzene boronic acid (7.66 g, 0.0628 mol), propanoic acid (1.88 g, 0.0628 mol), and toluene (100 ml), were mixed in a 250 ml three necked flask fitted with a Dean-Stark trap and heated to reflux. Paraformaldehyde (9.43 g, 0.314 mol), was added in small portions over a period of two hours. Heating was continued overnight, the solution was then cooled and the solvent removed in vacuo. The residue was dissolved in ether (100 ml), and water (100 ml) added. The aqueous layer was washed with ether (2 x 100 ml), and the combined ethereal layers washed with 10 % sodium hydrogen carbonate solution (100 ml). The ether was removed in vacuo, and the residue washed with hexane and filtered off. A colourless solid was obtained. Yield 3.50 g (22 %). Mp 135.7 °C. 1 H NMR CDCl 3 /δ: 5.22 (2H, s), 6.96 (1H, sext), 7.21-7.24 (1H, m), 7.41-7.45 (2H, m), 7.50-7.54 (1H, m), and 7.96-7.99 (2H, m). MS m/z: 307 (M+), 306 (M+), 227, 202, 200, 174, 173, 153, 113, 95 (100 %), 75, and 51. 177 4-Bromo-2-fluoro-6-(hydroxymethyl)phenol (202) Compound 201 (3.45 g, 0.01124 mol) was dissolved in THF (80 ml), and 30% hydrogen peroxide solution (20 ml) added. The solution was stirred at room temperature for two hours. Ether (100 ml) and water (100 ml) were then added and the aqueous layer washed with ether (2 x 100 ml). The combined ethereal layers were washed with 10 % ammonium ferrosulphate sulphate solution (100 ml), and removed in vacuo. The residue was recrystallised from [hexane-toluene 3:1]. A colourless solid was obtained. Yield 1.50 g (60 %). Mp 103.1 °C. 1 H NMR CDCl 3 /δ: 2.52 (1H, s), 4.82 (2H, s), 6.61 (1H, s), 7.10 (1H, s), and 7.19 (1H, dd, J 12.4, 2.2). MS m/z: 222 (M+), 220 (M+), 202 (100 %), 200, 174, 173, 112, 95, 75, 70, and 57. trans-6-Bromo-8-fluoro-2-(4-propylcyclohexyl)benzo-[1,3]-dioxinane (203) Compound 203 was prepared and purified in a similar manner to that described for the preparation of compound 146 using the quantities stated. Compound 202 (1.47 g, 0.00672 mol), compound 188 (1.14 g, 0.00739 mol), anhydrous sodium sulphate (2.10 g, 0.0148 mol), and toluene-4-sulphonic acid (0.07 g, 0.000672 mol) in dichloromethane (200 ml). The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.95 g (40 %). Mp 66.5 °C. 1 H NMR CDCl 3 /δ: 0.88 (3H, m), 0.89-0.95 (1H, m), 1.16-1.34 (8H, m), 1.74-1.93 (3H, m), 1.89-1.97 (2H, m), 4.76 (1H, d), 4.86 (2H, dd), 6.88-6.89 (1H, m), and 7.10 (1H, dd, J 12.3, 2.2). MS m/z: 358 (M+), 356 (M+), 202 (100 %), 200, 154, 136, 95, 83, 69, and 55. 178 trans-8-Fluoro-6-(2-fluoro-4-propoxyphenyl)-2-(4-propylcyclohexyl)-4Hbenzo[1,3]dioxinane (204) Compound 204 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 203 (0.90 g, 0.00253 mol), compound 31 (0.55 g, 0.00278 mol), sodium carbonate (0.59 g, 0.00556 mol), tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.000142 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 10:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.60 g (54 %). Transitions (°C) Cr 102.4 N 171.0 I. 1 H NMR CDCl 3 /δ: 0.86 (5H, m), 1.04 (3H, t), 1.14-1.26 (5H, m), 1.31 (2H, sept), 1.71- 1.86 (5H, m), 1.93-2.00 (2H, m), 3.92 (2H, t), 4.83 (1H, d), 4.94 (2H, dd), 6.65 (1H, dd, J 15.2, 2.4), 6.72 (1H, dd, J 10.8, 2.4), 6.88 (1H, s), 7.11 (1H, d, J 11.8), and 7.22-7.26 (1H, m). 13 C NMR CDCl 3 /δ: 10.47, 14.38, 20.00, 22.44, 25.51, 26.94, 32.38, 32.42, 37.21, 39.64, 41.90, 66.53, 69.92, 102.29, 120.02, 130.48, 149.44, 151.98, 159.79, and 161.46. MS m/z: 430 (M+), 277, 276 (100 %), 234, 205, 177, and 51. Elemental Analysis: Calculated (Found): C 71.92 (71.88); H 7.48 (7.50). 3.3.30: Scheme 30 5-Bromo-2-(4’-heptylbiphenyl-4-yl)pyrimidine (206) Compound 206 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 115 (10.00 g, 0.0379 mol), 5-bromo-2-iodopyrimidine (205) (9.80 g, 0.0344 mol), sodium carbonate (7.29 g, 0.0688 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000709 mol), DME (180 ml), and water (100 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 5:1]. Colourless crystals were obtained. 179 Yield 9.89 g (68 %). Mp 131.2 °C. 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 1.25-1.29 (8H, m), 1.56 (2H, q), 2.59 (2H, t), 7.20 (2H, d), 7.52 (2H, d), 7.65 (2H, d), 8.39 (2H, d), and 8.76 (2H, s). MS m/z: 410 (M+), 408, 326, 325, 324, 323 (100 %), 302, 192, and 165. 2-(4’-Heptylbiphenyl-4-yl)-5-hept-1-ynylpyrimidine (207) Compound 207 was prepared and purified in a similar manner to that described for the preparation of compound 132 using the quantities stated Compound 206 (2.00 g, 0.00489 mol), n-butyllithium (2.5 M in hexanes, 2.9 ml, 0.00733 mol), zinc chloride (1.30 g, 0.00977 mol), hept-1-yne (0.70 g, 0.00733 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000426 mol), and THF 300 ml. The product was purified by column chromatography [silica gel/hexane-dichloromethane 1:1]. A colourless solid was obtained. Yield 0.28 g (13 %). Transitions (°C) C 95.6 N 172.8 I. 1 H NMR CDCl 3 /δ: 0.88 (3H, t), 0.94 (3H, t), 1.25-1.46 (12H, m), 1.66 (2H, quin), 2.48 (2H, t), 2.66 (2H, t), 7.26 (2H, d), 7.60 (2H, d), 7.72 (2H, d), 8.47 (2H, d), and 8.78 (2H, d). MS m/z: 424 (M+) (100 %), 340, 339, 282, 192, 155, and 63. 5-Heptyl-2-(4’-heptylbiphenyl-4-yl)pyrimidine (208) Compound 207 was prepared and purified in a similar manner to that described for the preparation of compound 133 using the quantities stated Compound 207 (0.20 g, 0.000471 mol), 10% palladium-on-charcoal (2.00 g), ethanol (100 ml), THF (100 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 2:3], followed by recrystallisation from ethanol and a few drops of toluene. A colourless solid was obtained. Yield 0.078 g (39 %). Transitions (°C) C 55.8 SmC 113.2 SmA 137.1 N 161.8 I. 180 1 H NMR CDCl 3 /δ: 0.89 (6H, t), 1.22-1.36 (16H, m), 1.65 (4H, sext), 2.64 (4H, q), 7.28 (2H, d), 7.60 (2H, d), 7.73 (2H, d), 8.46 (2H, d) and 8.64 (2H, s). 13 C NMR CDCl 3 /δ: 14.08, 14.18, 22.68, 29.02, 29.21, 29.33, 30.22, 30.81, 31.52, 31.74, 31.83, 35.65, 126.97, 127.07, 128.26, 128.90, 132.89, 136.48, 137.85, 142.60, 157.06, and 162.54. MS m/z: 429 (M+), 428 (M+) (100 %), 344, 343, 271, 258, and 192. Elemental Analysis: Calculated (Found): C 84.06 (84.12); H 9.41 (9.32); N 6.54 (6.60). 3.3.31: Scheme 31 2-(2,3-Difluoro-4’-propylbiphenyl-4-yl)-5-heptyl-[1,3,2]-dioxaborinane (211) A mixture of compound 64 (0.75 g, 0.00271 mol), compound 210 (0.52 g, 0.00299 mol), anhydrous sodium sulphate (0.85 g, 0.00597 mol), was stirred at room temperature in THF (100 ml) for 12 hours. The product was extracted into ether (2 x 100 ml), and the combined ethereal extracts were washed with water (100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo and the residue purified by column chromatography [silica gel/hexane-ethyl acetate 20:1], followed by recrystallisation from hexane. A colourless solid was obtained. Yield 0.37 g (30 %). Transitions (°C) Cr 53.4 N 96.1 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 0.96 (3H, t), 1.22-1.40 (12H, m), 1.67 (2H, sext), 2.09- 2.14 (1H, m), 2.62 (2H, t), 3.79 (2H, dd), 4.20 (2H, dd), 7.13-7.17 (1H, m), 7.25 (2H, d, J 8.4), and 7.42-7.49 (3H, m). 13 C NMR CDCl 3 /δ: 13.86, 14.08, 22.62, 24.46, 26.74, 28.18, 29.09, 29.67, 31.78, 36.37, 37.77, 67.02, 124.38, 128.63, 128.74, 128.77, 128.71, 129.76, 129.84, 132.11, 132.16, 132.91, and 133.03. MS m/z: 415 (M+), 414 (M+) (100 %), 386, 385, 229, 57, 55, 39, and 41. Elemental Analysis: Calculated (Found): C 72.47 (72.50); H 8.03 (8.01). 181 2-(2,3-Difluoro-4’-pentylbiphenyl-4-yl)-5-pentyl-[1,3,2]-dioxaborinane (212) Compound 212 was prepared and purified in a similar manner to that described for the preparation of compound 266 using the quantities stated. Compound 65 (1.00 g, 0.00329 mol), compound 209 (0.53 g, 0.00329 mol), anhydrous sodium sulphate (1.03 g, 0.00723 mol), and THF (150 ml). The product was purified by column chromatography [silica gel/hexane-ethyl acetate 20:1], followed by recrystallisation from hexane. A colourless solid was obtained. Yield 0.38 g (28 %). Transitions (°C) Cr 42.1 N 83.1 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, 2 x t), 1.22-1.40 (12H, m), 1.64 (2H, quin), 2.09-2.14 (1H, m), 2.64 (2H, t), 3.79 (2H, t), 4.20 (2H, dd), 7.13-7.17 (1H, m), 7.24 (2H, d, J 8.4), and 7.42-7.48 (3H, m). 13 C NMR CDCl 3 /δ: 13.99, 14.01, 22.46, 22.53, 26.40, 28.14, 31.07, 31.52, 31.87, 35.66, 36.37, 67.01, 124.36, 128.57, 128.75, 128.78, 129.71, 129.76, 129.79, 132.06, 132.92, 133.02, and 143.17. MS m/z: 415 (M+), 414 (M+), 357 (100 %), 229, 183, 149, 69, 57, 55, 39, 41. Elemental Analysis: Calculated (Found): C 72.47 (72.48); H 8.03 (8.06). 3.3.32: Scheme 32 2,5-Bis-(4-pentyl-2,3-difluorophenyl)thiophene (214) Compound 214 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 2,5-Diiodothiopene (213) (1.00 g, 0.00298 mol), compound 50 (1.49 g, 0.00655 mol), sodium carbonate (0.69 g, 0.00655 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.29 g (22 %). Transitions (°C) Cr 66.1 N 85.6 I. 182 1 H NMR CDCl 3 /δ: 0.93 (6H, t), 1.35-1.38 (8H, m), 1.64 (4H, quin), 2.69 (4H, t), 6.96- 7.00 (2H, m), 7.30-7.35 (2H, m), and 7.48 (2H, s). 13 C NMR CDCl 3 /δ: 13.98, 22.43, 28.72, 29.64, 31.39, 121.18, 121.29, 122.19, 124.92, 127.06, 127.13, 130.93, and 131.06. MS m/z: 449 (M+), 448 (M+), 392, 391, 347, 335, 334 (100 %), and 151. Elemental Analysis: Calculated (Found): C 69.62 (69.60); H 6.29 (6.22); S 7.15 (7.23). 2,5-Bis-(4-butoxy-2,3-difluorophenyl)thiophene (215) Compound 215 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 2,5-Diiodothiopene (213) (1.00 g, 0.00298 mol), compound 41 (1.51 g, 0.00655 mol), sodium carbonate (0.69 g, 0.00655 mol), tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation [ethanol/ethyl acetate 10:1] A colourless solid was obtained. Yield 0.24 g (18 %). Transitions (°C) Cr 135.4 N 138.5 I. 1 H NMR CDCl 3 /δ: 1.01 (3H, t), 1.54 (4H, sext), 1.83 (4H, quin), 4.04 (4H, t), 6.76-6.80 (2H, m), 7.29-7.32 (2H, m), and 7.38 (2H, t, J 2). 13 C NMR CDCl 3 /δ: 13.75, 19.06, 31.11, 69.64, 109.54, 115.98, 116.09, 121.65, 121.69, 121.73, 126.27, 126.33, 135.94, and 147.84. MS m/z: 453 (M+), 452 (M+), 396, 340 (100 %), 339, and 311. Elemental Analysis: Calculated (Found): C 63.70 (63.70); H 5.35 (5.33); S 7.09 (7.01). 3.3.33: Scheme 33 2,5-Bis-(4-pentylphenyl)thiophene (216) Compound 216 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. 183 2,5-Diiodothiopene (213) (6.00 g, 0.0179 mol), compound 11 (2.86 g, 0.0129 mol), sodium carbonate (4.16 g, 0.0393 mol), tetrakis(triphenylphosphine)palladium(0) (0.40 g, 0.000568 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 12:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 4.24 g (63 %). Transitions (°C) Cr 136.7 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, t), 1.32-1.36 (8H, m), 1.64 (4H, quin), 2.62 (4H, t), 7.20 (4H, d), 7.24 (2H, d), and 7.54 (4H, d). 13 C NMR CDCl 3 /δ: 14.03, 22.55, 31.10, 31.48, 35.62, 123.40, 125.47, 128.91, 131.83, 132.38, and 143.26. MS m/z: 377 (M+), 376 (M+) (100 %), 320, 319, and 262. Elemental Analysis: Calculated (Found): C 82.92 (82.90); H 8.56 (8.61); S 8.51 (8.57). 3.3.34: Scheme 34 1-Bromo-4-(2,2-dimethoxyethoxy)benzene (217) Compound 23 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 4-Bromophenol (19) (87.2 g, 0.504 mol), bromoacetaldehyde dimethyl acetal (85.2 g, 0.520 mol) and potassium carbonate (71.9 g, 1.500 mol), and hexanone (600 ml). The product was purified by distillation to yield a colourless liquid. Yield 103.9 g (79 %). Bp 108.0 °C at 20 mmHg. (Lit Bp 105 °C at 25 mmHg) [14]. 1 H NMR CDCl 3 /δ: 3.45 (6H, s), 3.97 (2H, d), 4.70 (1H, t), 6.81 (2H, d), and 7.38 (2H, d). MS m/z: 262 (M+), 260 (M+) (100 %), 231, 199, 173, and 75. 5-Bromobenzofuran (218) Compound (219) (103.9 g, 0.400 mol) was added dropwise to polyphosphoric acid (170 g) in 600 ml of chlorobenzene under reflux with stirring. The reaction was left for 24 hours 184 then, allowed to cool. The solvent was removed and 10% NaOH solution (50 ml), added. The aqueous layer was washed with ether (3 x 100 ml). The combined organic layers were washed with water (100 ml) and brine (100 ml), and dried using MgSO 4 . The solvent was removed in vacuo, followed by distillation to give a colourless liquid. Yield 60.1 g (77 %). Bp 77.0 °C at 0.4 mmHg. (Lit Bp 80 °C at 0.01 mmHg) [14]. 1 H NMR CDCl 3 /δ: 6.71 (1H, d), 7.38-7.39 (2H, m), 7.61 (1H, d), and 7.72 (1H, dd). MS m/z: 198 (M+), 196 (M+) (100 %), 168, 155, 117, and 89. 5-(4-Ethylsulfanylphenyl)benzofuran (219) Compound 219 was prepared and purified in a similar manner to that described for the preparation of compound 57 using the quantities stated. Compound 14 (13.00 g, 0.660 mol), sodium carbonate (15.4 g, 0.145 mol), compound 218 (14.24 g, 0.796 mol), tetrakis(triphenylphosphine)palladium(0) (1.70 g, mol), (0.2 g, 0.000284 mol), DME (90 ml), and water (50 ml). The product was purified by column chromatography [silica gel/hexane/dichloromethane 10:1]. A colourless solid was obtained. Yield 8.04 g (48 %). Mp 101.5 °C. 1 H NMR CDCl 3 /δ: 1.35 (3H, t), 2.99 (2H, q), 6.84 (1H, dd), 7.40 (2H, d), 7.47-7.57 (4H, m), 7.66 (1H, d), and 7.77 (1H, d). MS m/z: 256 (M+), 254 (M+) (100 %), 225, 197, 165, 152, 105, and 77. 5-(4-Ethylsulfanylphenyl)benzofuran-2-boronic acid (220) Compound 220 was prepared and purified in a similar manner to that described for the preparation of compound 31 using the quantities stated. Compound 219 (8.00 g, 0.0312 mol), n-butyllithium (2.5 M in hexanes, 15.20 ml, 0.038 mol), trimethyl borate (6.48 g, 0.0624 mol), and dry THF (300 ml). An off-white solid was obtained. Yield 9.06 g (quantitative). MS m/z: 255, 254, 225, 197, 165, 152, 105, and 77. 185 5-(4-Ethylsulfanylphenyl)-2-(4-propylphenyl)benzofuran (221) Compound 6 (1.63 g, 0.00880 mol), triethylamine (1.78 g, 0.0176 mol), in dry DMF (40 ml) were stirred under nitrogen. tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.000176 mol) were added, followed by compound 220 (3.00 g, 0.0106 mol). The solution was heated to reflux for 48 hours. Completion of the reaction was indicated by TLC and GLC analysis. The reaction mixture was allowed to cool and ether (100 ml) and water (100 ml) added. The separated aqueous layer was washed with ether (2 x 100 ml) and the combined extracts washed with water (100 ml) and brine (100 ml), and dried (MgSO 4 ). After removal of the solvent the residue was purified by column chromatography [silica gel/hexane-dichloromethane 5:1] followed by recrystallisation from toluene to give colourless crystals. Yield 0.96 g (21 %). Transitions (°C) C 170.1 I. 1 H NMR CDCl 3 /δ: 0.97 (3H, t), 1.36 (3H, t), 1.69 (2H, quin), 2.64 (2H, t), 3.00 (2H, q), 7.01 (1H, s), 7.26 (1H, s), 7.29 (1H, s), 7.41 (2H, d), 7.47 (1H, dd), 7.55 (2H, s), 7.57 (1H, s), 7.74 (1H, d), and 7.80 (2H, d). 13 C NMR CDCl 3 /δ: 14.48, 24.46, 27.75, 29.69, 37.98, 100.73, 111.31, 119.03, 123.47, 124.94, 127.78, 128.96, 129.47, 135.86, and 143.70. MS m/z: 372 (M+) (100 %), 343, 314, 254, 225, 172, and 157. Elemental Analysis: Calculated (Found): C 80.60 (80.70); H 6.49 (6.61) S 8.61 (8.57). 5-(4-Ethylsulfanylphenyl)-2-(4-pentylphenyl)benzofuran (222) Compound 222 was prepared and purified in a similar manner to that described for the preparation of compound 221 using the quantities stated. Compound 220 (2.00 g, 0.00704 mol), compound 7 (1.33 g, 0.00587 mol), triethylamine (1.18 g, 0.0117 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000213 mol), and DMF (40 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 5:1], followed by recrystallisation from toluene. A colourless solid was obtained. 186 Yield 0.88 g (38 %). Transitions (°C) C 158.8 N 183.0 I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.34-1.38 (7H, m), 1.65 (2H, quin), 2.64 (2H, t), 3.00 (2H, q), 7.00 (1H, s), 7.26 (1H, s), 7.28 (1H, s), 7.40 (2H, d), 7.47 (1H, dd), 7.54 (1H, s), 7.55 (2H, s), 7.74 (1H, d), and 7.79 (2H, d). 13 C NMR CDCl 3 /δ: 14.04, 14.44, 22.55, 27.81, 30.85, 31.37, 35.74, 100.59, 101.43, 111.33, 119.11, 124.94, 124.97, 127.78, 128.83, 128.89, and 129.46. MS m/z: 401 (M+), 400 (M+) (100 %), 343, 314, 254, 225, 172, and 157 Elemental Analysis: Calculated (Found): C 80.96 (80.65); H 7.05 (7.10) S 8.00 (8.12). 5-(4-Ethylsulfanylphenyl)-2-(4-heptylphenyl)benzofuran (223) Compound 223 was prepared and purified in a similar manner to that described for the preparation of compound 221 using the quantities stated. Compound 220 (2.00 g, 0.00704 mol), compound 8 (2.00 g, 0.00704 mol), triethylamine (1.18 g, 0.0117 mol), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.000213 mol), and DMF (40 ml). The product was purified by column chromatography [silica gel/hexane-dichloromethane 4:1], followed by recrystallisation from toluene. A colourless solid was obtained. Yield 1.01 g (41 %). Transitions (°C) C 155.9 SmA 199.4 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.25-1.36 (11H, m), 1.65 (2H, quin), 2.65 (2H, t), 2.99 (2H, q), 7.01 (1H, s), 7.28 (2H, d), 7.43 (2H, d), 7.47 (1H, dd), 7.55 (3H, d), 7.73 (1H, d), and 7.79 (2H, d). 13 C NMR CDCl 3 /δ: 14.01, 14.43, 22.61, 27.68, 29.18, 29.27, 31.38, 31.82, 35.99, 100.65, 111.21, 118.96, 123.33, 124.94, 127.77, 128.89, 129.46, 135.01, 135.73, 137.00, 143.89, 154.32, and 157.00. MS m/z: 429 (M+), 428 (M+) (100 %), 343, 314, 105, 77, and 71. Elemental Analysis: Calculated (Found): C 81.26 (80.78); H 7.52 (7.71); S 7.48 (6.88). 187 3.3.35: Scheme 35 4’-Octyloxybiphenyl-4-carbonitrile (225) Compound 225 was prepared and purified in a similar manner to that described for the preparation of compound 14 using the quantities stated. 4’-Hydroxybiphenyl-4-carbonitrile (224) (50.00 g, 0.256 mol), 1-bromooctane (59.36 g, 0.307 mol), potassium carbonate (106.20 g, 0.768 mol), and butanone (600 ml). The crude product was recrystallised from ethanol. A colourless solid was obtained. Yield 71.40 g (91 %). Transitions (°C) Cr 53.3 SmA 67.3 N 76.2 I. (Lit. Cr 54.5 SmA 67 N 80 I [15]). 1 H NMR CDCl 3 /δ: 0.87 (3H, t), 1.20-1.52 (10H, m), 1.79 (2H, quin), 3.99 (2H, t), 6.97 (2H, d), 7.50 (2H, d), and 7.64 (4H, q). MS m/z: 308 (M+), 307 (M+), 196, 195 (100 %), 166, 151, 140, and 71. 4’-Octyloxybiphenyl-4-carboxylic acid (226) A stirred mixture of compound 225 (65.30 g, 0.212 mol), glacial acetic acid (500 ml), concentrated sulphuric acid (80 ml), and water (80 ml) was heated under reflux for 24 hours. The hot solution was poured onto ice and the crude product was filtered off, and washed well with water to afford a colourless solid. Yield 67.69 g (97 %). Transitions (°C) Cr 182.4 SmA 254.7 N 264.1 I. (Lit. Cr 183 SmA 255 N 264.5 I [16]). 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 1.18-1.27 (8H, m), 1.39-1.51 (2H, m), 1.75 (2H, quin), 3.94 (2H, t), 6.92 (2H, d), 7.51 (2H, d), 7.59 (2H, d), and 8.07 (2H, d). The carboxylic acid proton was not observed. MS m/z: 326 (M+), 215, 214 (100 %), 197, 152, 139, 115, and 69. S-(+)-1-Ethyloxycarbonyl-1-ethyl-4’-octyloxybiphenyl-4-carboxylate (228) Compound 226 (2.00 g, 0.00613 mol), (S)-(-)-ethyl lactate (227) (10.66 g, 0.00557 mol), and DMAP (0.34 g, 0.00278 mol) were dissolved in dichloromethane (150 ml) and the mixture stirred under nitrogen. DCC (1.38 g, 0.00668 mol) was then added and stirring was 188 continued for 24 hours. TLC analysis indicated a complete reaction. The precipitate of N,N’-dicyclohexylurea was then filtered off. The filtrate was washed successively with 10 % potassium hydroxide solution (2 x 100 ml), water (100 ml), 10 % acetic acid (100 ml), water (100 ml), and dried over magnesium sulphate. The solvent was removed in vacuo and the crude product was purified by column chromatography [silica gel/hexane-ethyl acetate 15:1], followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.75 g (32 %). Transitions (°C) Cr 46.3 (SmA 41.7) I. 1 H NMR CDCl 3 /δ: 0.87 (3H, t), 1.23-1.39 (11H, m), 1.40 (2H, quin), 1.57 (3H, d), 1.74 (2H, quin), 3.93 (2H, t), 4.17 (2H, q), 5.25 (1H, q), 6.91 (2H, d), 7.49 (2H, d), 7.56 (2H, d), and 8.05 (2H, d). 13 C NMR CDCl 3 /δ: 14.09, 14.11, 17.10, 22.64, 26.03, 29.23, 29.35, 31.80, 61.38, 68.13, 69.12, 114.92, 126.43, 127.47, 128.33, 130.36, 132.09, 145.65, 159.47, 165.91, and 170.89. MS m/z: 425 (M+), 426 (M+) (100 %), 314, 309, 198, 197, 196, 169, 168, 141, 139, 115, and 69. [α]D22° : +31.9° (0.00749 g/ml). Elemental Analysis: Calculated (Found): C 73.21 (73.26); H 8.03 (8.03). 3.3.36: Scheme 36 trans-S-(+)-1-Ethyloxycarbonyl-1-ethyl-4-butylcyclohexylbenzoate (230) Compound 230 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. trans-4-(4-Butylcyclohexyl)benzoic acid (229) (2.00 g, 0.00774 mol), (S)-(-)-ethyl lactate (0.83 g, 0.00704 mol), DMAP (0.43 g, 0.00352 mol), DCC (1.69 g, 0.00844 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 12:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.17 g (46 %). Transitions (°C) Cr 142.7 I. 189 1 H NMR CDCl 3 /δ: 0.83 (3H, t), 0.94-1.04 (2H, m), 1.32-1.53 (11H, m), 1.54 (3H, d), 1.81 (4H, d), 2.45 (1H, tt), 4.15 (2H, q), 5.22 (1H, q), 7.21 (2H, d), and 7.93 (2H, d). 13 C NMR CDCl 3 /δ: 14.08, 14.11, 17.06, 22.96, 26.18, 29.11, 30.68, 33.39, 34.00, 34.14, 37.01, 37.18, 44.76, 61.29, 69.00, 126.88, 127.06, 129.93, 153.73, 65.98, and 170.89. MS m/z: 360 (M+), 244, 243 (100%), 131, 149, 131, 129, 115, 91, and 71. [α]D22° : +22.7° (0.00947 g/ml). Elemental Analysis: Calculated (Found): C 73.76 (73.80); H 9.15 (9.16). 3.3.37: Scheme 37 S-(+)-1-Benzyloxycarbonyl-1-ethyl-4’-octyloxybiphenyl-4-carboxylate (232) Compound 232 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 226 (30.00 g, 0.0919 mol), (S)-(-)-benzyl lactate (231) (16.56 g, 0.0919 mol), DMAP (5.61 g, 0.0460 mol), DCC (22.72 g, 0.110 mol), and dichloromethane 800 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 12:1]. A colourless solid was obtained. Yield 24.71 g (55 %). Mp 195.5 °C. 1 H NMR CDCl 3 /δ: 0.82 (3H, t), 1.22-1.34 (9H, m), 1.51 (3H, d), 3.94 (2H, t), 4.23-4.26 (2H, m), 5.15 (2H, d), 5.20 (2H, s), 6.92 (2H, d), 7.24-7.31 (5H, m), 7.49 (2H, d), 7.56 (2H, d), and 8.05 (2H, d). MS m/z: 489 (M+), 488 (M+) (100 %), 376, 309, 214, 198, 197, 169, 141, 139, 115, 110, and 91. [α]D22° : +20.6° (0.0104 g/ml). (S)-(+)-1-Hydroxycarbonyl-1-ethyl-4’-octyloxybiphenyl-4-carboxylate (233) Compound 233 was prepared and purified in a similar manner to that described for the preparation of compound 132 using the quantities stated. 190 Compound 232 (24.46 g, 0.0501 mol), ethyl acetate (400 ml), and ethanol (100 ml). The charcoal was filtered off and the solvent removed in vacuo. No further purification was necessary. A colourless solid was obtained. Yield 20.1 g (99 %). Mp 92.7 °C. 1 H NMR CDCl 3 /δ: 0.87 (3H, t), 1.15-1.33 (9H, m), 1.45 (2H, quin), 3.33 (3H, d), 3.93 (2H, t), 5.34 (2H, q), 6.96 (2H, d), 7.54 (2H, d), 7.60 (2H, d), and 8.10 (2H, d). Hydroxy proton not seen. MS m/z: 399 (M+), 398 (M+) (100 %), 309, 287, 286, 214, 197, 168, 139, and 91. ° [α]19 D : +43.4° (0.02290 g/ml). 2R,3R,S-(+)-2,3-Bis(4-octyloxybiphenyl-4-ylcarbonyloxy-(1methyl)methylcarbonyloxy)butane (235) Compound 235 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 114 (2.00 g, 0.00503 mol), 2R,3R-(+)-butanediol (234) (0.22 g, 0.00240 mol), DMAP (0.29 g, 0.00240 mol), DCC (1.09 g, 0.00527 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 14:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.38 g (19 %). Transitions (°C) Cr 122.8 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, t), 1.24-1.33 (22H, m), 1.47 (4H, quin), 1.61 (6H, d), 1.80 (4H, quin), 3.99 (4H, t), 5.07-5.08 (2H, m), 5.34 (2H, quin), 6.97 (4H, d), 7.54 (4H, d), 7.60 (4H,d), and 8.12 (4H, d). 13 C NMR CDCl 3 /δ: 14.08, 16.03, 16.96, 22.64, 26.03, 29.22, 29.35, 31.80, 68.12, 69.03, 72.33, 76.68, 114.90, 126.40, 127.47, 128.31, 130.35, 132.06, 145.59, 159.44, 165.79, and 70.31. MS m/z: 851 (M+), 850 (M+), 310, 309 (100 %), 214, 197, 196, 169, 141, 119, 105, 70, and 69. ° [α]19 D : +41.3° (0.0104 g/ml). Elemental Analysis: Calculated (Found): C 73.38 (72.48); H 7.82 (7.80). 191 3.3.38: Scheme 38 trans-(S)-(-)-1-Benzyloxycarbonyl-1-ethyl-4-butylcyclohexylbenzoate (236) Compound 236 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. trans-4-(4-Butylcyclohexyl)benzoic acid (229) (14.23 g, 0.0546 mol), S-(-)-benzyl lactate (231) (10.93 g, 0.0607 mol), DMAP (3.71 g, 0.0304 mol), DCC (15.01 g, 0.0729 mol), and dichloromethane 150 ml. The product was purified by recrystallisation from ethanol. A colourless solid was obtained. Yield 17.69 g (76 %). Mp 91.3 °C. 1 H NMR CDCl 3 /δ: 0.91 (3H, t), 1.05 (2H, q), 1.31-1.25 (6H, m), 1.42-1.50 (2H, m), 1.62 (3H, d), 1.88 (4H, d), 2.53 (1H, tt), 5.21 (2H, d), 5.37 (1H, q), 7.23 (2H, d), 7.29-7.34 (5H, m), and 8.00 (2H, d). MS m/z: 244, 243 (100 %), 162, 149, 131, 105, and 91. ° [α]19 D : -50.5° (0.00995 g/ml). trans-S-(+)-1-Hydroxycarbonyl-1-ethyl-4-butylcyclohexylbenzoate (237) Compound 237 was prepared and purified in a similar manner to that described for the preparation of compound 132 using the quantities stated. Compound 236 (17.58 g, 0.0416 mol), ethyl acetate (300 ml), and ethanol (300 ml). The charcoal was filtered off and the solvent removed in vacuo. No further purification was necessary. A colourless solid was obtained. Yield 11.7 g (84 %). Mp 70.8 °C. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.04 (2H, m), 1.20-1.33 (6H, m), 1.40-1.53 (2H, m), 1.65 (3H, d), 1.88 (4H, d), 2.52 (1H, tt), 5.33 (1H, q), 7.27 (2H, d), 7.99 (2H, d). Hydroxy proton not seen. MS m/z: 332 (M+), 288, 244, 243 (100 %), 242, 150, 144, 131, 105, and 91. 192 ° [α]19 D : +29.2° (0.0998 g/ml). trans-2R,3R,(S)-(+)-2,3-Bis(4-butylcyclohexylphenylcarbonyl-(1methyl)methylcarbonyloxy)butane (238) Compound 238 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 237 (1.63 g, 0.00488 mol), (2R,3R)-(+)-butane-2,3-diol (234) (0.2 g, 0.00222 mol), DMAP (0.27 g, 0.00222 mol), DCC (1.01 g, 0.0488 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 20:1]. Followed by recrystallisation from ethanol. A colourless liquid was obtained. Yield 0.20 g (23 %). 1 H NMR CDCl 3 /δ: 0.90 (6H, t), 1.07 (4H, q), 1.24-1.32 (20H, m), 1.41-1.50 (4H, m), 1.61 (6H, d), 1.88 (8H, d), 2.53 (2H, tt), 4.22 (2H, q), 5.29 (2H, q), 7.28 (4H, d), and 8.00 (2H, q). 13 C NMR CDCl 3 /δ: 14.08, 14.13, 17.06, 22.97, 29.17, 33.39, 33.98, 37.02, 37.17, 44.75, 61.30, 68.95, 126.88, 127.04, 129.93, 153.74, 165.98, and 170.90. MS m/z: 388 (M+), 360, 242, 243 (100%), 131, and 91. [α]D23° : +19.6° (0.02318 g/ml). Elemental Analysis: Calculated (Found): C 73.74 (73.77); H 8.80 (8.84). 3.3.39: Scheme 39 S-(+)-1-Ethyloxycarbonyl-1-ethyl-4-benzyloxybenzoate (240) Compound 240 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. 4-Phenoxybenzoic acid (239) (20.00 g, 0.0925 mol), (S)-(-)-ethyl lactate (227) (13.11 g, 0.111 mol), DMAP (5.65 g, 0.0462 mol), DCC (22.86 g, 0.111 moles), and dichloromethane 500 ml. 193 The product was purified by column chromatography [silica gel/hexane-ethyl acetate 15:1]. A colourless solid was obtained. Yield 28.38 g (93 %). Mp 212.0 °C. 1 H NMR CDCl 3 /δ: 1.24 (3H, t), 1.57 (3H, d), 4.19 (2H, q), 5.10 (2H, s), 5.23 (1H, q), 6.93 (2H, d), 7.41-7.75 (5H, m), and 8.00 (2H, d). MS m/z: 328 (M+) (100 %), 211, 120, 92, 91, and 65. [α]D22° : +20.6° (0.01043 g/ml). S-(+)-1-Ethoxycarbonylethyl 4-hydroxy benzoate (241) Compound 241 was prepared and purified in a similar manner to that described for the preparation of compound 132 using the quantities stated. Compound 240 (28.18 g, 0.0856 mol), THF (400 ml), and ethanol (100 ml). The charcoal was filtered off and the solvent removed in vacuo. No further purification was necessary. A colourless solid was obtained. Yield 10.46 g (51 %). Mp 79.9 °C. 1 H NMR CDCl 3 /δ: 1.29 (3H, t), 1.62 (3H, d), 3.49 (1H, s), 4.24 (2H, q), 5.25 (1H, q), 6.85 (2H, q), and 7.93 (2H, d). MS m/z: 238 (M+), 193, 165, 120, 121 (M+) (100 %), 93, and 65. [α]D22° : +22.0° (0.04459 g/ml). S-(+)-1-Ethoxycarbonylethyl-4-(4’-octyloxybiphenyl-4-ylcarbonyloxy)benzoate (242) Compound 242 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 226 (2.00 g, 0.00503 mol), compound 241 (1.09 g, 0.00457 mol), DMAP (0.28 g, 0.00229 mol), DCC (1.13 g, 0.00549 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 12:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 1.07 g (38 %). 194 Transitions (°C) Cr 93.8 I. 1 H NMR CDCl 3 /δ: 0.89 (3H, t), 1.24-1.39 (7 H, m), 1.47 (2H, quin), 1.62 (3H, d), 1.80 (2H, quin), 1.85-1.87 (5H, m), 4.01 (2H, t), 5.30 (1H, q), 5.39 (1 H, q), 6.99 (2H, d), 7.24 (2H, d), 7.56 (2H, d), 7.64 (2H, d), 8.12 (2H, d), and 8.15 (2H, d). 13 C NMR CDCl 3 /δ: 14.10, 16.99, 17.05, 22.65, 26.03, 29.23, 29.35, 31.80, 61.44, 68.13, 69.31, 114.94, 121.45, 126.53, 127.02, 127.38, 128.35, 130.44, 131.50, and 131.96. MS m/z: 618 (M+), 382, 381, 310, 309 (100 %), 197, 196, 121, and 69. [α]D24° : +60.3° (0.00913 g/ml). Elemental Analysis: Calculated (Found): C 69.88 (69.90); H 6.84 (7.08). 3.3.40: Scheme 40 trans-S-(+)-1-Ethoxycarbonylethyl-4-(4-butylcyclohexylphenylcarbonyloxy)benzoate (243) Compound 243 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. trans-4-(4-Butylcyclohexyl)benzoic acid (229) (2.00 g, 0.00774 mol), compound 241 (1.68 g, 0.00704 mol), DMAP (0.43 g, 0.00352 mol), DCC (1.69 g, 0.00845 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 20:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.89 g (25 %). Transitions (°C) Cr 158.8 I. 1 H NMR CDCl 3 /δ: 0.92 (3H, t), 1.08 (2H, q), 1.23-1.31 (11H, m), 1.62 (3H, d), 2.23 (4H, q), 2.57 (1H, t), 3.72 (2H, q), 5.33 (1H, q), 7.31 (2H, d), 7.36 (2H, d), 8.12 (2H, d), and 8.17 (2H, d). 13 C NMR CDCl 3 /δ: 14.11, 14.15, 17.08, 18.42, 22.98, 29.19, 33.39, 34.01, 37.02, 37.21, 44.86, 58.48, 61.44, 69.28, 121.87, 126.58, 126.99, 127.21, 130.40, 131.48, 154.58, 155.03, 164.65, 165.22, and 170.76. MS m/z: 511 (M+), 510 (M+), 435, 242, 243 (100 %), 131, 125, 121, 105, 91, and 77. 195 [α]D24° : +12.3° (0.00776 g/ml). Elemental Analysis: Calculated (Found): C 72.48 (72.50); H 7.55 (7.49). 3.3.41: Scheme 41 (2R, 3R)-(-)-2,3-Bis-4’-octyloxybiphenyl-4-ylcarbonyloxybutane (244) Compound 244 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 226 (2.00 g, 0.0063 mol), (2R,3R)-(+)-butanediol (234) (0.52 g, 0.00557 mol), DMAP (0.68 g, 0.00557 mol), DCC (2.52 g, 0.0123 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 16:1]. Followed by recrystallisation [ethanol/ethyl acetate 20:1]. A colourless solid was obtained. Yield 0.40 g (10 %). Transitions (°C) Cr 136.4 I. 1 H NMR CDCl 3 /δ: 0.89 (6H, t), 1.28-1.58 (26H, m), 1.80 (4H, quin), 4.00 (4H, q), 5.38- 5.39 (2H, m), 6.00 (4H, d), 7.53 (4H, d), and 7.60 (4H, d). 13 C NMR CDCl 3 /δ: 14.11, 16.46, 22.67, 26.05, 29.25, 29.37, 31.88, 68.14, 72.25, 114.91, 126.45, 128.20, 128.32, 130.16, 132.13, 145.39, 159.43, and 165.95. MS m/z: 708 (M+), 707 (M+), 693, 310, 309 (100 %), 214, 197, 168, 141, 120, 122, 105, 84, 69, and 71. ° [α]19 D : -50.5° (0.00995 g/ml). Elemental Analysis: Calculated (Found): C 78.15 (78.22); H 8.27 (8.25). 196 3.3.42: Scheme 42 4-Propylphenol (245) Hydrogen peroxide (10%) (41.20 ml, 0.121 mol) was added dropwise to a stirred solution of compound 10 in ether (50 ml). The mixture was then stirred at reflux temperature for three hours and allowed to cool. Water (50 ml) was then added and the aqueous layer was washed with ether (2 x 100 ml). The combined ethereal extracts were washed with 10 % sodium hydroxide solution (100 ml) and the separated aqueous layer was acidified with 37 % hydrochloric acid (20 ml). The product was then extracted into ether (2 x 100 ml) and all the combined ethereal extracts were washed with water and dried (MgSO 4 ). The solvent was removed in vacuo and the residue distilled to give a colourless liquid. Yield 3.23 g (78 %). Bp 132.0 °C at 20 mmHg. (Lit Bp 232.4 °C) [17]. 1 H NMR CDCl 3 /δ 0.90 (3H, t), 1.57 (2H, sext), 2.48 (2H, t), 6.17 (1H, s), 6.74 (2H, d), 6.99 (2H, d). MS m/z: 147, 136 (M+), 108, 107 (100 %), 91, 78, 77, 63, and 61. 4-Ethoxyphenol (246) Compound 246 was prepared in a similar manner to that described for the preparation of compound 245 using the quantities stated. Compound 42 (4.00 g, 0.0267 mol), hydrogen peroxide (10 %) (36.29 ml, 0.107 mol), diethyl ether 50 ml. The product was purified by distillation. A colourless solid was obtained. Yield 2.79 g (86 %). Bp 124.2 °C at 20 mmHg. (Lit Bp 232.3-232.5 °C) [18]. Mp 66.5 °C. (Lit Mp 66.0 °C) [18]. 1 H NMR CDCl 3 /δ 1.38 (3H, t), 3.95 (2H, q), 6.17 (1H, s), and 6.74 (4H, d). MS m/z: 293, 274, 217, 169, 149 (100 %), 138, 122 (M+), 110, 94, 81, 71, and 69. 197 trans-(S)-(+)-1-(4-Propylphenoxycarbonyl)ethyl-4-(4-butylcyclohexyl)benzoate (247) Compound 247 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 237 (2.00 g, 0.00599 mol), compound 247 (0.74 g, 0.00545 mol), DMAP (0.33 g, 0.00273 mol), DCC (1.35 g, 0.0654 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 20:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.58 g (24 %). Transitions (°C) Cr 48.3 I. 1 H NMR CDCl 3 /δ: 0.91 (6H, 2 x t), 1.06 (2H, q), 1.22-1.31 (6H, m), 1.45 (2H, m), 1.61 (2H, sext), 1.77 (3H, d), 1.88 (4H, d), 2.48-2.60 (3H, m), 5.48 (1H, q), 7.02 (2H, d), 7.16 (2H, d), 7.28 (2H, d), and 8.03 (2H, d). 13 C NMR CDCl 3 /δ: 14.16, 13.75, 17.07, 23.00, 24.54, 29.21, 33.41, 34.01, 37.04, 37.20, 37.40, 44.80, 69.04, 120.92, 126.89, 126.97, 129.33, 130.02, 140.50, 148.26, 153.92, 166.07, and 169.73. MS m/z: 316, 315, 242, 243 (100 %), 131, 107, and 91. [α]D23° : +22.22° (0.09258 g/ml). Elemental Analysis: Calculated (Found): C 77.30 (77.35); H 8.50 (8.50). trans-(S)-(+)-1-(4-Ethoxyphenoxycarbonyl)ethyl-4-(4-butylcyclohexyl)benzoate (248) Compound 248 was prepared and purified in a similar manner to that described for the preparation of compound 228 using the quantities stated. Compound 237 (2.00 g, 0.00599 mol), compound 246 (0.67 g, 0.00545 mol), DMAP (0.33 g, 0.00273 mol), DCC (1.35 g, 0.0654 mol), and dichloromethane 150 ml. The product was purified by column chromatography [silica gel/hexane-ethyl acetate 20:1]. Followed by recrystallisation from ethanol. A colourless solid was obtained. Yield 0.97 g (40 %). Transitions (°C) Cr 65.8 I. 1 H NMR CDCl 3 /δ: 0.90 (3H, t), 1.05 (2H, q), 1.20-1.32 (6H, m), 1.40 (3H, t), 1.44-1.46 (2H, m), 1.76 (3H, d), 1.88 (4H, d), 2.53 (1H, tt), 4.00 (2H, q), 5.47 (1H, q), 6.86 (2H, d), 7.02 (2H, d), 7.29 (2H, d), and 8.00 (2H, d). 198 13 C NMR CDCl 3 /δ: 14.17, 14.81, 17.09, 23.00, 29.21, 33.42, 34.02, 37.05, 37.21, 44.81, 63.82, 69.04, 115.00, 122.06, 126.88, 126.99, 130.29, 143.70, 153.95, 156.79, 166.09, and 169.94. MS m/z: 450 (M+), 316, 315, 244, 243 (100 %), and 131. [α]D23° : +23.19° (0.01444 g/ml). Elemental Analysis: Calculated (Found): C 74.31 (74.41); H 8.02 (8.08). 199 3.4: Discussion of Synthetic Routes and Methods Employed This section of the thesis involves a discussion of the synthetic routes and methods employed in the preparation of the desired target materials. 3.4.1: Convergent Synthesis Methodology Boronic acids and Coupling Reactions To achieve the desired properties of high negative dielectric anisotropy and moderate to high birefringence most of the target materials possess multi-aryl cores with one or two fluoro substituents. The general preparation of multi-aryl core compounds with two terminal chains and several fluoro substituents cannot be accomplished from the core unit directly. The introduction of structural units into a phenyl ring is usually achieved using electrophillic substituents reactions. The type and positions of substituents already present direct the point of substitution, and may, due to steric hindrance, activating/deactivating properties prevent the desired substitution from taking place. In biphenyls and terphenyls, substitution in the bay regions of the core (i.e., the 2- and 2’-positions) is particularly unlikely due to steric hindrance from the ring structure itself. Clearly, alternative methods are required, in which the individual aryl units are first prepared and the subsequent, systematic linking of these units provide the desired multiaryl final product materials. Fortunately, many methods of generating carbon-carbon bonds between aryl units have been developed and are now in widespread use in synthetic chemistry. All such methods involve coupling an aryl unit with an organometallic unit to another aryl unit possessing a good leaving group. The presence of a suitable transition metal catalyst is also required to facilitate the reaction. The leaving group is normally a halogen, such as iodo, bromo, or an activated chloro (not fluorine), or a peusdohalogen, i.e., triflate or exceptionally tosylate groups. The most 200 widely used organometallic units are boronic acids and their ester analogues. This is because of their ease of preparation, lack of significant homocoupling, compatibility with other functional groups, and low toxicity. The use of arylboronic acids was pioneered by Suzuki and co-workers [19]. Since then the methodology has been developed successfully for use with a wide range of substrates, including the synthesis of mesogenic materials [5, 20, 21]. This methodology has been developed further in order to synthesise most of the materials contained in this thesis. The Suzuki Reaction ArX Ar-Ar' PdL4 A 2L 2L ArPdX•L2 ArPdAr'•L2 D B HONa HOB(OH)2 NaX ArPdOH•L2 C Ar'B(OH)2 Na2CO3 + H2O ⇔ NaOH + NaHCO3 Figure 3.4.1.1: The suggested mechanism of the Suzuki reaction. The coupling reaction starts with oxidative addition of an organic halide to palladium(0) complex. This is followed by the substitution of the halide ion from ArPdX•L2 (B), to 201 give a hydroxopalladium (II) complex (C). The intermediate palladium complex then reacts with an arylboronic acid to produce the organopalladium complex (D). Finally, reductive elimination of intermediate C yields the corresponding cross-coupled product and regenerates the catalyst. Two molar equivalents of a suitable base is required to carry out a successful coupling. Under aqueous conditions this is usually sodium carbonate. Tetrakis(triphenylphosphine)palladium(0), is most commonly used as the catalyst, and is used exclusively in this work. Esterification Reactions Ester groups are widely used in liquid crystal synthesis, both to link core units together, and as a spacer group between the core unit and terminal chains. They are primarily used to introduce a chiral group from readily available chiral alcohol and carboxylic acid precursors in the synthesis of ferroelectric materials. The two esterification reactions most commonly used are the Mitsunobu (DEAD) reaction, and the DCC-DMAP method [22-24]. The most significant difference between the two is that the chiral centre at the site of the reaction is unaltered (retained stereochemistry) in the DCC-DMAP method, whereas the configuration at the reaction site of the alcoholic hydroxyl group is inverted in the Mitsunobu reaction. In the synthesis of the chiral dopants contained in this work the DCC-DMAP method was used exclusively to introduce the required chiral centre into the desired material. 202 a N C N N C N H A 1 B O H R1 R O O O b c H N C N O H R1 H H N C N O R1 O C O D d H N C N O H R1 O e E O R2 H N H O C N H F + H O R1 R2 O f -H O R1 O R2 G Figure 3.4.1.2: Mechanism for esterification using the DCC-DMAP method. The carboxylic acid is effectively activated to nucleophillic attack by the formation of a mixed acid anhydride, which has a better leaving group (E). This process eliminates the protonated ester, and forms dicyclohexylurea (DCU) as a byproduct. In the final step the ester is deprotonated by the added base (DMAP). 203 3.4.2: Preparation of Aryl Intermediates (Schemes 1-7) The main focus in the development of valid synthetic routes was the need to synthesise aryl intermediates with a bromo substituent, and others with a boronic acid moiety, these two units can be coupled together to form intermediates or the desired target materials. The 1-alkyl-4-bromobenzene intermediates (scheme 1) were prepared by the overall alkylation of bromobenzene, which was achieved by the conventional two-step methodology of acylation followed by Wolff-Kishner reduction [25]. Overall yields of around 40 % were obtained, except in the synthesis of 1-bromo-4-propanoylbezene (6), which has a low boiling point, and hence significant losses occurred during steam distillation. The aryl bromides were converted into boronic acids, via the Grignard reagent; the organometallic species was quenched using trimethyl borate at -78 °C. This gave the borate ester which was hydrolysed in situ with 10 % hydrochloric acid to yield the boronic acid [26]. Intermediates with alkylsulphanyl and alkoxy chains (schemes 2-5) were prepared by removing the acidic proton using potassium carbonate, then reacting the resultant anion with the appropriate alkyl bromide. For the preparation of the ethoxy and propoxy homologues (compounds 14, 20, 27, 36, and 37), a triple excess of the alkyl bromide was used, allowing for the high volatility or the reagent. To make the alkoxyfluorophenylboronic acids (scheme 4) the Grignard method could not be used as the high temperatures required to form the Grignard reagent would result in the elimination of the ortho fluoro substituent, and a highly reactive benzyne species would result [27]. Instead, the bromide group was removed in a metal-halogen exchange using n- butyllithium at -78 °C, producing the organolithium derivative. Low temperatures (ca. -65 °C) are required in order to stabilise the ortho-fluoroaryllithium species as at higher temperatures the ortho-fluoroaryllithium intermediates will decompose to form the benzyene [28]. Quenching of the organolithium species with trimethyl borate, maintaining the temperature at -78 °C, gave the boronic acid, after hydrolysis with 10 % hydrochloric acid. 204 Since the bromo-alkoxyfluorophenyl compounds have an acidic proton ortho to the fluoro substituent it was feared that in lithiating the bromo substituent a small degree of lithiation would occur at the reactive acidic proton site. Careful monitoring by GLC analysis for the removal of the bromo substituent and immediate quenching with trimethyl borate ensured that this did not occur. The difluoroalkoxyphenylboronic acids shown in scheme 5, (39-40), were prepared by removing the acidic proton ortho to the fluoro substituents using n-butyllithium at -78 °C. The organolithium species was then quenched with trimethyl borate to produce the required boronic acid. This method of exploiting the acidic proton ortho to fluoro substituents to introduce a useful functional group has been used extensively in the synthesis of multiaryl liquid crystals, including this work [27, 29-31]. The procedure for the preparation of the alkyl-2,3-difluorophenylboronic acids (49-51) is illustrated in scheme 6. Difluorobenzene was lithiated using n-butyllithium, producing the lithium salt of the difluorophenyl anion. The anion is a good nucleophillic reagent and attacks the carbon of the aldehyde added to the solution. This forms the difluorophenylalkoxide ion, which was protonated using aqueous ammonium chloride to the secondary alcohol (43-45). Dehydration of the alcohol was accomplished by adding a solution of the alcohol in hexane dropwise to a suspension of phosphorus pentoxide in hexane. Caution was needed as the reaction is strongly exothermic. When the reaction was complete the solids were filtered off, and palladium-on-charcoal added directly to the reaction mixture, which was then hydrogenated at room temperature and pressure to produce the desired 1-alkyl-2,3-difluorobenzenes (46-48). The boronic acids (49-51) were then prepared by exploiting the remaining acidic proton in the same way described above (scheme 5). Unlike the other substituted aryl intermediates considered in this thesis, 1-alkylsulphanyl2,3-difluorobenzenes are not known literature materials and hence their synthesis is one of the main achievements of this work. 1-Alkoxy-2,3-difluorobenzenes were prepared by o-alkylation of the phenol (scheme 5). As difluorothiophenol is unavailable as a starting material, this method could not be used 205 for the alkylsulphanyl analogues. An experimental method based on the preparation of 1,4bis(methylthio)benzene was developed [32]. 2,3-Difluorobenzene (42) was ortho-lithiated as achieved many times previously, and the appropiate alkyldisulfide was added. The nucleophillic lithiated difluorophenyl anion attacks the one of the sulphur atoms of the alkyldisulfide producing the 1-alkylsulphanyl-2,3-difluorobenzene (52-53), and the lithium forms a salt with the resultant alkylsulfanyl anion. Only minimal purification (distillation) of the product was needed, and excellent yields were achieved (74 % and 79 %). The desired boronic acids (54 and 55) were then made prepared in the manner described above. 3.4.3: Preparation of Terphenyls (Schemes 8-13) The methodogy used to prepare the ortho-difluoroterphenyls was based on a general method of synthesising terphenyls and biphenyls presented in the literature [5]. The terphenyls with the fluoro substituents in the centre ring were prepared by starting from the difluorophenyl centre ring, and adding the aryl rings with the desired terminal chains via two consecutive Suzuki coupling reactions. As shown in scheme 8, the boronic acid of 1,2-difluorobenzene (42) was prepared via lithiation ortho to one of the two identical fluoro substituents. The boronic acid was then coupled with an aryl bromide using tetrakis(triphenylphosphine)palladium(0) as the catalyst and a DME-water mix as the solvent to give several biphenyl intermediates (5763). Subsequent lithiation ortho to the other fluoro substituents gave a biphenyl-4ylboronic acid (64-70). This was subsequently, coupled to another aryl bromide, producing the required terphenyl compound (scheme 9, 71-93). A 20 % excess of the boronic acid is generally used, to allow for any hydrodeboronation that always occurs to some extent with ortho-fluoro boronic acids. The target compounds were all produced in acceptable yields after column chromatography and recrystallisation (at least 40 %). The terphenyls with the difluoro substituents on the end phenyl ring, and an akyl chain attached to the opposite end of the core were prepared by alkylating 1-bromobiphenyl (see below) and then utilising the bromine in a final coupling reaction with the appropriate arylboronic acids (scheme 10). 206 The pentyl- and heptyl-1-bromo-4’-alkylbiphenyls (96 and 97) are commercially available, the propyl and nonyl homologues (95 and 98) prepared by a convenient one-pot FriedelCrafts acylation and reduction procedure [33]. The reducing agent, poly(methylhydrosiloxane) (PMHS), is inexpensive and the reaction takes place under mild conditions, avoiding the hazards of the use of anhydrous hydrazine. Yields of 50 % were obtained; similar to the overall yield obtained by the conventional two-step acylation and Wolff-Kishner reduction procedure [25]. The isomeric target compounds shown in scheme 11 were realized by a selective coupling with 1-bromo-4-iodobenzene (110) and the butylsulphanylboronic acid (18). The iodo is the better leaving group, and only the required bromobiphenyl, 111 was isolated after column chromatographic purification in a 69 % yield. Compound 111 was then successfully coupled to the appropriate alkyl-2,3-difluorophenylboronic acids (49-51) to generate the desired terphenyls (112-114). The terphenyl compounds with no fluoro substituents (parent materials for comparison) were synthesised by coupling of 4’-heptylbiphenyl-4-ylboronic acid to an appropriate aryl bromide (7 and 15). Only three synthectic steps were needed, as there were no complications arising from lateral substituents. Both possible synthetic pathways were evaluated, converting a bromobiphenyl to the boronic acid and coupling to a bromophenyl, (scheme 12) and vice versa (scheme 13). Both routes were equally effective, and the final compounds (116-119) were produced in good overall yields. 3.4.4: Preparation of 2,6-Disubstituted Naphthalene Materials (Schemes 14-18) One difficulty in the synthesis of a general range of 2,6-disubstituted naphthalene compounds is the lack of starting materials with useful functional groups in the required 2,6-positions. However, 6-bromonaphth-2-ol (120) is available and so was used as the starting point for the synthesis of all the naphthalene materials in this research. Compounds with a naphthalene unit substituted with either an alkoxy or alkyl chain were desired. 207 As compounds with a similar structure to the required alkoxy substituted compounds materials are easiest to prepare and have been made previously, these were prepared first [34]. O-alkylation of compound 120 gave the required naphthyl bromides 121 and 122. These intermediates were then coupled to the appropriate boronic acid (39, 41, 49, and 50) to give the required final materials (123-130). After purification by column chromatography and recrystallisation the final yield averaged 65 %. OMe A a O C4H9 OMe B OMe C b C5H11 c C5H11 133 OH a = AlCl3, pentanoyl chloride, nitrobenzene. b = NH2NH2 / KOH, DCM. c = HBr, hydrobromic acid, acetic acid. Figure 3.4.4.1: Literature preparation of compound 133 [12]. 208 Coates and Gray developed a good method of introducing an alkyl chain to a naphthalene core unit [12], and this is reproduced in figure 3.4.4.1. Starting from 2methoxynaphthalene (A), the pentyl chain was introduced via the usual two step process of Friedel-Crafts acylation followed by reduction. 6-pentylnaphth-2-ol (133) was then obtained by removing the methoxy group of B using 45 % hydrogen bromide in acetic acid and boiling hydrobromic acid. However, while this synthetic route gave reasonable results, it was thought that it could be improved by more modern synthetic techniques. The new route was successfully followed and is shown in scheme 15. This route represents a major improvement as the triple bond of 132 is reduced in the same step as the deprotection. Additionally, the benzyl protecting group is much easier to remove than a methoxy group, avoiding the use of hydrobromic acid. First, protection of the hydroxy group of 6-bromonaphth-2-ol (120) was effected with benzyl bromide generating compound 131. Such protection was required to enable the use of a zinc organometallic reagent in the next step. Pentynylzinc chloride was prepared in situ and a palladium-catalysed cross-coupling to 131 introduced the terminal chain. The alkynylzinc chloride coupling method (step 15b) involves lithiation with n-butyllithium at the acidic proton site of the terminal alkyne, followed by treatment with zinc chloride [35]. Subsequent addition of the bromide and catalyst and heating the mixture to reflux facilitates the coupling. Reduction of the triple bond under high pressure of hydrogen also effectively removed the protecting group in one efficient step in near-quantitative yields. The phenol group of 133 facilitated the introduction of a trifluoromethanesulfonyl (triflate) group, which is an excellent leaving group in palladium-catalysed cross-coupling reactions [36]. The usual conditions for boronic acid (Suzuki) couplings were used, expect that lithium chloride was added to the reaction mixture, and good yields (60-65 %) for the final materials (135-140) were obtained. 209 The parent systems shown in scheme 16 (141 and 142), and the monofluoro phenyl naphthalene shown in scheme 17 (143) were made by simply coupling the bromide (121) with the appropriate phenylboronic acid (10, 25, and 31). In a similar manner, the difluorobiphenylnaphthalene, 144 was prepared by coupling the biphenylboronic acid (64) with 2-butoxy-6-bromonapthalene as shown in scheme 18 (121). 3.4.5: Preparation of Benzodioxinane Materials (Schemes 19-28) The key step in the synthesis of the benzodioxinane materials was the formation of the benzodioxinane ring from 5-bromo-2-hydroxybenzyl alcohol (145) and the appropriate aldehyde. The method used was an acetal formation, and the mechanism is shown in figure 3.4.1.5. First, the oxygen of the aldehyde (A) is protonated, this is followed by nucleophillic attack of the carbon by one of the oxygens of the diol (B) to give C. Elimination of a proton gives a hemiacetal (D). Protonation of the hemiacetal hydroxyl group allows it to ionise in an S N 1 reaction to give the carbonium ion, which is stabilised by the electrons on the adjacent oxygen atom (F). This stabilisation of the carbonium ion ensures a rapid rate for the ionisation by a proton, and therefore formation of the acetal (H) [37]. As acetal formation is reversible, the position of equilibrium is influenced by the relative proportions of alcohol and water present. As the reactant is a diol, this ensures an initial excess of alcohol, relative to the aldehyde. 0.1 molar equivents of para-toluenesulfonic acid was used as a catalyst, to convert H 2 O into the non-nucleophilic H 3 O+ ion. In addition, sodium sulphate was added to the reaction mixture in order to remove any water present. A literature preparation for 1,3-dioxadecalins was followed, with dichloromethane was used as the solvent [38]. The alternative conditions, using toluene as the solvent, and a Dean-Stark apparatus to remove the water by azeotropic distillation, as used for the preparation of dioxinanes, were found to cause decomposition of the product [39]. In all cases the resultant dioxinane 210 products were recrystalised from ethanol, except the propyl homologue, 146 which is a liquid, and so was purified by column chromatography. H O OH O R Br H OH H+ Br H B A H O O Br R H H O H O R OH - H+ H H R OH C O O Br E H H R D OH + H - H2O O Br R H F R G R H OH O Br O H - H+ O Br O Figure 3.4.5.1: Mechanism of the formation of the benzodioxinane ring. The first final products containing a benzodioxinane ring were those with an attached phenyl ring, compounds 149-166 (schemes 19-21). These compounds were prepared by the 211 utilisation of the bromo substituent of the alkyl-substituted benzodioxinanes 146-148 in a coupling reaction with the appropriate phenylboronic acid (10, 11, 25, 31-33, 40, 41, 50, and 51). After purification by column chromatography and recrystalisation the yields of this coupling reaction were comparable to the terphenyls (35-45 %). In scheme 22, an alternative synthetic strategy was used. 5-Bromo-2-hydroxybenzyl alcohol (145) was coupled directly to a boronic acid. Potassium fluoride was used as the base instead of sodium carbonate, as it has been shown to give better yields when used in the coupling of hydroxyl, or carboxylic acid substituted systems [40]. As potassium fluoride is insoluble in aqueous systems, an alternative solvent, THF had to be used. Cyclisation of the diol (167) using butanal and hexanal gave the final compounds, 168 and 169. It was found that the overall yield for this scheme was significantly lower than that for the alternative route. This is likely to be because of the extra purification needed, as column chromatography was used in both steps in scheme 22, as opposed to only the final one, scheme 19. The main reason for trying this route is because it was desirable to synthesise final products containing a benzodioxaborinane ring (249 and 250) (see figure 3.4.5.2). Compound 167 was reacted with propyl- and pentyl-boronic acids, under the same conditions used to prepare compounds 146-148. The benzodioxaborinane products were purified successfully by column chromatography and recrystalisation from hexane. However, they were found to be very thermally unstable, and decomposed to the diol, when dried using phosphorus pentoxide, and hence no physical information was obtained. F F C5H11 OH F OH a F C5H11 249 R = C3H7 250 R = C5H11 167 a = RB(OH)2, PTSA, Na2SO4, DCM. Figure 3.4.5.2: Synthesis of benzodioxaborinanes. O B R O 212 The 2,3-difluorobiphenyl-4-ylbenzodioxinanes (170-175) shown in scheme 23 were prepared in a similar way to the analogous phenyl-substituted materials. The propyl- and pentyl-substituted difluorophenyboronic acids, 64 and 65 were coupled to compounds 146148, producing the target materials 170-175 in similar yields to the phenyl-substituted equivalents. Compounds with a phenyl ring on both sides of the benzodioxine group were also targeted. Once again, a stepwise methodology was employed: beginning with a condensation reaction with 5-bromo-2-hydroxybenzyl alcohol (145) and a phenylaldehyde. There is a lack of examples in the literature of the preparation of 2-phenyl-1,3benzodioxines, but a general method was discovered [41]. As shown in scheme 24 the diol (145) was mixed with an excess of the commercially available aldehyde, 176, and heated to 50 °C, until a homogeneous liquid (the product) resulted. The presence of a catalyst was not necessary. As the phenylaldehyde is a liquid it functioned as the solvent and after purification by recrystallisation a good yield of compound 177 (61 %) was achieved. The 2,3-difluorobenzaldehyde (180) shown in scheme 25 is not available from commercial sources, however, a synthetic route from 1-ethoxy-2,3-difluorobenzene (36) was devised. n-Butyllithium was used to remove the acidic proton of compound 36; and the organolithium species was quenched by anhydrous DMF [39]. This produced an amide in situ, which was hydrolysed using dilute hydrochloric acid to the aldehyde. Recrystallisation from hexane gave the purified product (180) in an excellent yield (87 %). As compound 180 has a high melting point it was thought that the method employed to produce compound 177 would not be suitable to generate compound 181, so the reaction was attempted using the conditions required for the preparation of the alkyl substituted materials (146-148). This method gave unsatisfactory results, the reaction mixture turned black upon adding the PTSA catalyst, indicating a decomposition. So, the experiment was repeated without the addition of the acid catalyst, which was successful. Given the experimental results obtained, it appears that 2-hydroxybenzyl alcohols are more reactive, in condensation reactions, than the alkyldiols used to prepare dixoxanes. In 213 addition, phenylaldehydes are more reactive than their alkyl counterparts. This can be explained by the delocalising effect of the phenyl rings. The protons of the hydroxyl groups are more acidic, and the carbonyl group of the aldehyde is more susceptible to nucleophillic attack. Also, the carbonium ion will be stabilised, and so more likely to form the acetal. The target materials (178, 179, 182, and 183) of schemes 24 and 25 were then made by coupling the bromides (177 and 181) with the boronic acids 11 or 50. Target compounds with a trans-cyclohexyl ring attached to the oxygenated ring of benzodioxinane, and a phenyl on the aromatic side were prepared. The trans-cyclohexyl ring was introduced, like the phenyl equivalent in schemes 23 and 24, via the aldehyde (scheme 26). Both propyl- and pentyl-substituted aldehydes were prepared (188 and 189). First, the commercially available acids (184 and 185) were reduced to the alcohols (186 and 187) using lithium aluminium hydride (LiAlH 4 ) in THF [42, 43]. The alcohols (186 and 187) were then oxidised to the aldehydes using pyridium chlorochromate (PCC, Corey’s reagent), using DCM as the solvent [42, 44]. The reduction of an acid to an aldehyde can be accomplished in one step by the use of LiAlH(OBut) 3 , however due to the expense of the reagent and possible complications due to disproportionation, (which may cause LiAlH 4 to be the active species) it was thought that on a large scale, the two-step method was preferable [45]. Having prepared the aldehyde, the desired 6-bromo-2-(4-alkylcyclohexyl)benzodioxinanes (190 and 191) were easily made by the condensation of the diol (145) with the aldehydes under the same conditions as for compounds 146-147 (scheme 19). The coupling reaction final step of schemes 26-28, was carried out in the same manner as analogous preparations. Yields were quite low (~ 30 %) as a large volume of solvent was needed to successfully purify the product. 214 3.4.6: Preparation of 8-Fluoro-6-(2-fluoro-4-propoxyphenyl)-2-(4- propylcyclohexyl)benzodioxinane (Scheme 29) To produce a final compound with a fluoro substituent attached to the benzodioxinane ring a new synthetic strategy had to be devised. Casiraghi has shown that it is possible to prepare 2-hydromethylphenol by direct ortho-monohydroxymethylation of phenol with formaldehyde [46]. A 10 molar equivalent excess of paraformaldehyde is needed as the presence of a 1 molar equivalent of an ether additive, such as DME, xylene is the solvent. The experiment was attempted using 4-bromo-2-fluorophenol (199) as the substrate, however a GLC taken after 24 hours showed no trace of the desired product was detected in the reaction mixture. It is likely that the strongly electron-withdrawing effect of the fluorine of the phenol inhibited the reaction. The desired diol (202) was produced by using benzeneboronic acid to form an intermediate boronate ester [47, 48]. Chelation of formaldehyde with the ester strongly promotes orthoalkylation, and the generation of the alkylation product as a boronate ester minimised further alkylation. The benzodioxaborinane (201) is then produced by a [3,3] sigmatrophic rearrangement. The reaction requires propanoic acid as a catalyst, and toluene was the solvent. A Dean-Stark trap was used, and given the complexity of the reaction an acceptable yield (22 %) achieved. The dioxaborinane (201) was then subjected to oxidation with hydrogen peroxide in THF, and the free diol (202) resulted in a 60 % yield [47]. Having obtained the free diol, the final product, 204, was synthesised by the same method used in scheme 26: a condensation reaction with the aldehyde 188 to generate intermediate 203; followed by the usual Suzuki coupling to generate compound 204. 3.4.7: Preparation of 5-Heptyl-2-(4’-heptylbiphenyl-4-yl)pyrimidine (Scheme 30) The preparation of compound 208 was achieved via a selective coupling of 5-bromo-2iodo-pyrimidine (205) to the biphenyl boronic acid 115. The intermediate (206) bromide 215 was then used to introduce the heptyl chain via alkynylation using an organozinc reagent in the same manner as the preparation of compound 132 (scheme 15). The final step was the reduction of the alkyne to the required alkane (208). This was accomplished by hydrogenation using hydrogen gas and palladium-on-charcoal as the catalyst. 3.4.8: Preparation of 2-(2,3-Difluorobiphenyl-4-yl)-[1,3,2]-dioxaborinane Materials (Scheme 31) Unlike the benzodioxinane materials, the formation of the heterocyclic ring system had to be the last step in the preparation of compounds 211 and 212. This is because the dioxaborinane ring is a type of boronic ester, and will hydrolyse to the boronic acid and react with the aryl bromide in a cross-coupling reaction. Dioxaborinanes have been previously made by a condensation reaction between a propan-1,3-diol and an arylboronic acid under a variety of conditions [48-50]. The 2,3-difluorobiphenyl-4-ylboronic acids (64 and 65) were successfully reacted with the 2-alkylpropan-1,3-diols (209 and 210) using THF as the solvent and sodium sulphate as a drying agent to generate final compounds 211 and 212. The presence of an acid catalyst was not required. In contrast to dioxinanes, the dioxaborinane ring structure shows no cisand trans-isomersism, because the boron atom is sp2 hybridised, so no isomer separation was required. 3.4.9: Preparation of 2,5-Bis-(4-phenyl)thiophene Materials (Schemes 32 and 33) Compounds 214, 215 and 216 are mesogenic compounds containing a thiophene group appended by two phenyl units, as they are symmetrical the synthesis was relatively facile. Thiophene derivatives have been used extensively in cross-coupling reactions, and the synthetic methodology used is similar to other heteroaromatic units. [52]. Accordingly, the target compounds (214-216) were prepared in one step by the coupling of 2,5- 216 diidothiophene (213) with 2.2 molar equivalents of the appropriate boronic acid (11, 40, and 50) under the usual conditions. 3.4.10: Preparation of 2,5-Diphenylbenzofuran Materials (Scheme 34) As the benzofuran ring is a fused heterocycle, a synthetic strategy towards the final compounds 211, 222 and 223 needed to begin with a starting material containing suitable functional groups, to give the desired substitution patterns. 4-Bromophenol (19) was chosen as the starting material, and the formation of the 5bromobenzo[b]furan unit (218) was achieved by etherification with bromoacetaldehyde dimethyl acetal [53, 54]. The acetal moiety of 217 acts as a masked acylium ion in an electrophillic substitution reaction with the phenyl ring, and cyclisation occurs rapidly with the addition of an acid catalyst. However, the acetal was found to be particularly susceptible to hydrolysis under slightly acidic conditions and was therefore used in the subsequent step as soon as it was isolated. In the removal of the acidic proton at the 2-position and subsequent formation of the boronic acid a relatively large volume of dry THF (300 ml) was needed to dissolve the starting material (219) at the low temperature required. The final coupling reactions in this scheme were done under anhydrous conditions because benzofuranboronic acids, such as 220, are particularly prone to hydrodeboronation in aqueous conditions [14]. 3.4.11: Preparation of Chiral Dopants (Schemes 35-42) All the chiral dopants synthesised in this work have a common structural unit, either an ester derivative of 4-(4-butylcyclohexyl)benzoic acid or 4’-octyloxybiphenyl-4-carboxylic acid. The former was commercially available, but the later was prepared using a literature procedure [55]. 217 O-alkylation of 4-cyano-4’-hydroxybiphenyl (224) with 1-bromooctane afforded compound 225, which was then hydrolysed to the acid (226) using a refluxing mixture of acetic acid, concentrated sulphuric acid, and water. The amide intermediate was not isolated. The final compound of scheme 35, 228, was obtained by esterification of the acid 226, with ethyl (S)-(-)-lactate (227), using the DCC-DMAP method, and DCM as the solvent. This experiment was repeated as shown in scheme 36, with 4-(4-butyl-cyclohexyl)benzoic acid (229) to give the target compound 230. The dimeric compound 235 has four ester groups, and was prepared from compound 226 by a stepwise approach (scheme 37). First, the lactate group was introduced by esterification with (S)-(-)-benzyl lactate (231), producing compound 232. The benzyl group was then removed, exposing the carboxylic acid group, this was used in a subsequent reaction with (2R,3R)-(+)-butanediol (234). 2.1 molar equivalents of the acid relative to the diol was used, and compound 235 was successfully purified in a yield of 19 %. This synthetic strategy was repeated in scheme 38, using 4-(4-butylcyclohexyl)benzoic acid (229) as the starting material. The final compound, 238, was prepared in a similar yield (23 %) to compound 235. Two compounds with a phenyl centre ring were synthesised (242 and 243), starting from 4-phenoxybenzoic acid (239). The synthetic strategy was similar to schemes 37 and 38, the chiral lactate group was introduced by the formation of an ester linkage, producing compound 240. The phenolic hydroxyl group was then deprotected, and a second esterification with the acid, 226, afforded the final product. In scheme 40, the intermediate 241 was reacted with 229, producing the analogous compound to 242, 243. Compound 244 is the same as 235, but without the lactate groups. As, such it was made by simply reacting 2.1 molar equivalents of 226, with (2R,3R)-(+)-butanediol (234). The low 218 yield obtained (10 %) was likely due to steric hinderance, the biphenyl ring of the monoester intermediate blocking the hydroxyl active site. The products of scheme 42, 247 and 248 have a lactate group in the centre, linking the 4(4-butyl-cyclohexyl)benzene unit and a phenyl group. They were prepared by ester formation of the intermediate acid, 237, and the substituted phenol, 245 and 248. The phenols were, in turn synthesised by hydrolysis of the boronic acids, 10 and 14, by hydrogen peroxide in THF. 219 3.5: Experimental References 1. D. R. Coulson, Inorg. Synth., 1972, 13, 121. 2. L. K. M. Chan, G. W. Gray, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1988, 158, 209. 3. K. LeRoi Nelson, J. C. Robertson, J. J. Duvall, J. Am. Chem. Soc., 1964, 86, 684. 4. J. Malthete, Mol. Cryst. Liq. Cryst., 1973, 23, 233. 5. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, J. Chem. Soc. Perkin 2, 1989, 2041 6. M. Hird, A. J. Seed, K. J. Toyne, J. W. Goodby. G. W. Gray, J. Mater. Chem., 1993, 3, 851. 7. G. W. Gray, M. Hird, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1991, 195, 221. 8. M. Glenndenning, PhD Thesis, The University of Hull, England, 1998. 9. G. W. Gray, A. Mosley, J. Chem. Soc., Perkin 2, 1976, 97. 10. M. Hird, K. J. Toyne, G. W. Gray, Liq. Cryst., 1993, 14, 741. 11. H.-J. Deussen, E. Hendrick, C. Boutton, D. Krog, K. Clays, J. Am. Chem. Soc., 1996, 118, 6841. 12. D. Coates, G. W. Gray, Mol. Cryst. Liq. Cryst., 1977, 119, 122. 13. N. Carr, G. W. Gray, Liq. Cryst., 1989, 6, 467. 14. M. R. Friedman, Ph.D. Thesis, The University of Hull, England, 2001. 15. S. C. Jain, S. A. Agnihotry, V. G. Bhide, Mol. Cryst. Liq. Cryst., 1982, 88, 281. 16. L. Jullien, J. Canceill, B. Valeur, E. Bardez, J-P. Lefevre, J-M. L, V. MarchiArtzner, R. Pansu, J. Am. Chem. Soc. 1996, 118, 5432. 17. E. Berliner, F. Berliner, I. Nelidow, J. Am. Chem. Soc., 1954, 76, 507. 18. D. J. Byron, D. Lacey, R. C. Wilson, Mol. Cryst. Liq. Cryst., 1979, 51, 265. 19. N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commum., 1981, 11, 513. 20. R. B. Millar, S. Dugar, Organometallics, 1984, 3, 1261. 21. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1989, 172, 165. 22. O. Mitsunobu, Synthesis, 1981, 1. 23. A. Hassner, V. Alexanian, Tet. Lett., 1978, 4475. 24. B. Neises, W. Steglich, Angew. Chem. Int. Ed., 1978, 17, 522. 25. Huang-Minlon, J. Am. Chem. Soc., 1949, 71, 3301. 220 26. R. M. Washburn, E. Levens, C. F. Albright, F. A. Billig and E. S. Cernak, Adv. Chem. Ser., 1959, 23, 102. 27. B. J. Wakefield ‘The Chemistry of Organometallic Compounds’, Pergamon Press, Oxford, 1974, p39. 28. G. Wittig, G. Pieper and G. Fufrman, Chem Ber., 1940, 73, 1193. 29. C. Tamborsaki, E. J. Soloski, J. Org. Chem., 1966, 31, 746. 30. A. M. Roe, R. A. Burton, G. L. Willey, M. W. Barnes, A. C. Rasmussen, J. Med. Chem., 1968, 11, 814. 31. D. L. Ladd, J. Weinstock, J. Org. Chem., 1981, 46, 203. 32. K. Kobayashi, E. Koyama, K. Namatame, T. Kitaura, C. Kono, M. Goto, T. Obinata, N. Furukawa, J. Org. Chem., 1999, 64, 3190. 33. A. Jaxa-Chamiec, V. P. Shah, and L. I. Kruse, J. Chem. Soc., Perkin Trans. 1, 1989, 1705. 34. M. Hird, K. J. Toyne, G. W. Gray, S. E. Day, D. G. McDonnel, Liq. Cryst., 1993, 15, 123. 35. A. O. King, E. Neishi, J. Org. Chem., 1978, 43, 358. 36. K. Ritter, Synthesis, 1993, 735. 37. J. B. Henduckson, D. J. Cram, G. S. Hammond, Organic Chemistry, 3rd edition, McGraw-Hill Book Company, New York, 1970, p.233. 38. D. Dietrich, Z. Horst, T. Carsten, H. Maike, German Patent, DD 227720 A1, 1986. 39. G-X. Sun, B. Chen, H. Tang, S-Y. X, J. Mater. Chem., 2003, 13, 742. 40. S. W. Wright, D. L. Hageeman, L. D. McClure, J. Org. Chem., 1994, 59, 6095. 41. R. Adams, A. W. Sloan, B. S. Taylor, J. Am. Chem. Soc., 1923, 45, 2417. 42. S. M. Kelly, H. Scad, Helv. Chim. Acta., 1985, 68, 1444. 43. N. G. Gaylord, Reduction with Complex Metal Hydrides, Wiley, New York, 1956, p322. 44. C. J. Corey, J. W. Suggs, Tet. Lett., 1975, 2647. 45. J. Malek, M. Cerny, Synthesis, 1972, 217. 46. G. Casiraghi, G. Casnati, G. Puglia, G. Sartori, Synthesis, 1980, 124. 47. W. Nagata, K. Okada, T. Aoki, Synthesis, 1979, 365. 48. P. J. Duggan, E. M. Tyndall, J. Chem. Soc., Perkin Trans. 1, 2002, 1325. 49. V. S. Bezborodov, V. I. Lapanik, Liq. Cryst., 1991, 10, 803. 50. C. C. Dong, P. Styring, L. K. M. Chan, J. W. Goodby, Mol. Cryst. Liq. Cryst., 1997, 302, 289. 221 51. M. E. Glendenning, J. W. Goodby, M. Hird, K. J. Toyne, J. Chem. Soc. Perkin Trans. 2, 2000, 27. 52. S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron, 2002, 58, 9633. 53. P. Spagnolo, M. Tiecco, A. Tundo, G. Martelli, J. Chem. Soc., Perkin 1, 1972, 556. 54. M. R. Friedman, K. J. Toyne, J. W. Goodby, and M. Hird., J. Mater. Chem., 2001, 11, 2759. 55. B. Heinrich, D. Guillon, Mol. Cryst. Liq. Cryst. Sci. Technol. Sect. A., 1995, 268, 21. 222 Chapter Four: Materials Evaluation 223 4.1: Terphenyls 4.1.1: Introduction The vast majority of liquid crystalline compounds exhibiting nematic or other mesophases contain one or more phenyl rings, often with the rings connected by polarisable linkages such as ester or alkynyl spacers, or directly linked to other aromatic and heteroaromatic units. Biphenyls and terphenyls in particular, are excellent core systems for generating liquid crystals, as the intermolecular attractions between the near-planar, conjugated aromatic systems are very large. Because of this terphenyls with alkyl or alkoxy substituents at the terminal 4-, and 4”positions are characterised by extremely high clearing points, however, melting points are also very high, and so the temperature ranges of the liquid crystal phases are short. The temperature and therefore, energy required to sever the side-to-side intermolecular attractions is high such that the nematic phase is not produced and hence the phase morphology is solely smectogenic. C7H15 C7H15 C5H11 OC8H17 36 37 Cr 181 SmA 205 I Cr 195 B 211 SmA 222 I Figure 4.1.1.1: Terphenyls with no lateral substituents [1, 2]. A reduction in the melting point and smectic tendency can be achieved by introducing a lateral fluoro substituent to the terphenyl core [2-5]. Generally, the protrusion of the fluoro substituent from the terphenyl core tends to disrupt the intermolecular forces necessary for lamellar packing, therefore reducing the melting point and smectic phase thermal stability [2, 6-9]. However, experimental evidence shows that while a lateral fluoro substituent on a 224 terphenyl core does not reduce smectic phases significantly as originally predicted, because the fluoro substituent is small, and the lateral dipole aids molecular tilting, and this is most cases results in the generation of tilted smectic phases, particularly the smectic C phase. In figure 4.1.1.2 compounds 38, 40-43 illustrate this. In some cases, the only smectic phase generated is smectic C, as the steric effect of the lateral fluoro substituents reduces the intermolecular attraction enough for the full tilting effect of the lateral dipole is able to operate [10]. This is most often observed when more than one fluoro substituent is present. The introduction of a lateral fluoro substituent to an alkyl- and alkoxy-terminally substituent terphenyl system causes many changes to other physical properties: a) The polar fluoro group reduces the positive dielectric anisotropy possessed by the unsubstituted core system. b) The lateral fluoro substituent causes a reduces the optical anisotropy (birefringence). c) As the length-to-width ratio increases, the ratio of elastic constants (k 33 / k 11 ) is reduced. d) Viscosity is increased, but because of the small size of the fluoro substituent, the increases are minimal, when compared to other systems [2]. A fluoro substituent at an inner-core position also significantly increases interannular twisting compared to the parent system, this reduces the longitudinal polarisability, which also contributes to reducing melting point and liquid crystal phase stability. Therefore, a fluoro substituent in the centre ring causes the most severe reduction in melting points (see figure 4.1.1.2) A fluoro substituent on the outer edge of the terphenyl core fills vacant space on the edge of the core with a polar substituent, resulting in a greater potential for side-to-side intermolecular associations due to the increased molecular contact area. In addition, there is no increase in interannular twisting, the basic core is retained more successfully than for systems where the fluoro substituent is within the core. A combination of these two factors means that compounds with a fluoro substituent at an outer-edge position have a higher 225 melting point, higher clearing point, greater smectic tendency compared to the analogous, inner core materials. F F C5H11 OC8H17 C5H11 OC8H17 38 39 G 171 SmC 177 SmA 203 I G 146 B 158 SmA 195 I F C5H11 F OC8H17 C5H11 OC8H17 40 41 Cr 69 (K 25 J 44) SmC 119 N 158 I Cr 102 (SmI 100) SmC 138 N 160 I F C5H11 OC8H17 42 Cr 69 G 83 B 101 SmC 124 SmA 158 N 161 I F C5H11 OC8H17 43 Cr 47 (J 40) SmI 54 SmC 117 SmA 130 N 155 I Figure 4.1.1.2: Terphenyls with one lateral fluoro substituent [4, 11]. The very high mesophase stability of materials with a terphenyl core allows scope for the introduction of a second fluoro substituent to enable further tailoring of the physical properties of materials for applications. For terphenyls with non-identical terminal chains, there are six different vacant positions on the core, for a fluoro substituent (see figure 4.1.1.2), but with two fluoro substituents twenty-four difluoroterphenyl combinations are possible. In order to evaluate the effect of the fluoro substituents in different positions on 226 mesogenic stability different isomeric compounds have been made (see figure 4.1.1.3) [1115]. Except where one of the fluoro substituents is at an outer position and they are not next to each other on the same ring, difluorophenyls are generally nematogenic (46, 47, and 51). The elimination of all smectic phases in such systems is due to the large increase in molecule breadth due to the addition fluoro which is either fixed on the opposite side of the core (46, 47), or can be on the other side of the core through rotation (51). Compound 50 has a 2,2’-difluoro substitution pattern and it has been shown by dielectric anisotropy measurements that the two fluoro substituents attract each other minimising the possible increase in molecular breath [16]. Compounds 44 and 45 have a fluoro substituent fixed on each side of the molecule, but because only one interannular twist is created and the outer edge fluoro substituent fills space thereby enhancing intermolecular forces of attraction, smectic phases are favoured. When one fluoro substituent is at an outer position and one is in an inner-core position (48, 49) smectic phases are favoured. The space created by the two fluoro substituents in compound 48 limits the smectic phase stability in comparison with compound 49. Ortho-difluoroterphenyls (e.g., 52-54) where the fluoro substituents are fixed on the same side of the molecule have the most useful physical properties. When the difluoro unit is in the middle, the interannular twisting caused by the fluoro substituents eliminates all ordered smectic phases, but the smectic phase is not significantly affected as the increased lateral dipole enhances the tendency of the molecules to tilt (52). When the two fluoro substituents are in the end ring of a terphenyl system, very large smectic C temperature ranges are achieved. The unsubstituted biphenyl section, one interannular twisting and the space filling effect of the outer-edge fluoro substituent all increase liquid crystal phase stability, and the large lateral dipole induced by the fluorines provide the driving force for molecule tilting (53, 54). 227 F C5H11 F OC6H13 C5H11 OC6H13 F 44 F 45 Cr 77 SmC 88 SmA 136 N 142 I Cr 90 SmC 92 N 131 I F F C5H11 OC6H13 F C5H11 OC6H13 F 46 Cr 50 N 82 I F 47 Cr 51 N 117 I F C5H11 F OC6H13 F C5H11 OC6H13 48 49 Cr 90 SmC 106 N 139 I Cr 41 SmC 72 SmA 131 N 140 I F F F F OC6H13 C5H11 C5H11 OC6H13 50 51 Cr 52 (SmC 42) N 122 I Cr 45 N 131 I F F F C5H11 OC6H13 F C5H11 OC6H13 53 52 Cr 54 SmC 67 N 149 I Cr 101 SmC 157 SmA 167 N 172 I F F C5H11 OC6H13 54 Cr 98 SmC 146 N 166 I Figure 4.1.1.3: Terphenyls with two lateral fluoro substituents [11-15]. 228 4.1.2: Mesomorphism of 2’,3’-Difluoroterphenyls A large number of materials possessing a terphenyl core with ortho-difluoro substituents on the centre ring have been prepared. They should possess the highly desirable properties of a strong nematic character, low viscosity, moderately high negative dielectric anisotropy, and high birefringence. Of particular interest are the novel materials with a terminal alkylsulphanyl chain, and the effect such a substituent has on transition temperatures compared with alkoxy- and alkyl-substituted materials. The melting points and transition temperatures of these novel materials and homologues from the literature are tabulated in tables 4.1.2.1 and 4.1.2.2. 229 F F R2 R1 Cpd. Ref. R1 R2 Cr SmC SmA N I 71 - C 3 H7 C 3 H7 * 93.6 - --------- - --------- * 128.0 * 72 - C 3 H 7 C 5 H 11 * 53.9 - --------- - --------- * 123.4 * 78 - C 3 H 7 C 7 H 15 * 48.5 - --------- - --------- * 116.1 * 72 - C 3 H 7 C 9 H 19 * 40.0 - --------- - --------- * 110.5 * 74 - C 3 H 7 C 2 H 5 O * 108.0 - --------- - --------- * 185.8 * 75 - C 3 H 7 C 4 H 9 O * 80.6 - --------- - --------- * 166.4 * 76 - C 3 H 7 C 6 H 13 O * 60.5 - --------- - --------- * 161.5 * 77 - C 3 H 7 C 8 H 17 O * 45.1 * 62.6 - --------- * 130.2 * 83 - C 3 H 7 C 2 H 5 S * 90.4 - --------- - --------- * 130.4 * 86 - C 3 H 7 C 4 H 9 S * 91.8 - --------- - --------- * 115.3 * 55 [12] C 5 H 11 C 5 H 11 * 60.0 - --------- - --------- * 120.0 * 56 [12] C 5 H 11 C 7 H 15 * 36.5 * (24.0) - --------- * 111.5 * 57 [12] C 5 H 11 C 9 H 19 * 42.5 * 66.0 - --------- * 110.0 * 52 [12] C 5 H 11 C 6 H 13 O * 54.0 * 67.0 * --------- * 149.0 * 58 [12] C 5 H 11 C 8 H 7 O * 48.0 * 95.0 * --------- * 141.5 * 84 - C 5 H 11 C 2 H 5 S * 90.8 - --------- - --------- * 126.4 * 87 - C 5 H 11 C 4 H 9 S * 85.5 - --------- - --------- * 114.5 * 79 - C 7 H 15 C 7 H 15 * 58.0 * 69.0 - --------- * 110.0 * 59 [12] C 7 H 15 C 9 H 19 * 49.0 * 77.0 * 93.0 * 108.5 * 60 [12] C 7 H 15 C 6 H 13 O * 54.7 * 79.0 - --------- * 139.7 * 61 [12] C 7 H 15 C 8 H 7 O * 48.0 * 108.2 - --------- * 136.6 * 80 - C 7 H 15 C 2 H 5 S * 77.1 - --------- - --------- * 125.1 * 88 - C 7 H 15 C 4 H 9 S * 71.4 - --------- * 101.5 * 112.2 * 81 - C 9 H 19 C 9 H 19 * 69.8 * 79.8 * 103.3 * 108.0 * 82 - C 9 H 19 C 8 H 17 O * 65.8 * 116.5 * 119.3 * 135.2 * 85 - C 9 H 19 C 2 H 5 S * 72.0 - --------- * 106.1 * 120.8 * 89 - C 9 H 19 C 4 H 9 S * 72.9 - --------- * 106.1 * 109.2 * Table 4.1.2.1: Transition temperatures of 2’,3’-difluoroterphenyl compounds. 230 F F R S Cpd. R Cr SmA* N* I --------- * (73.1) * 90 C 5 H 11 * 87.2 * 91 C 7 H 15 * 64.6 * 72.1 92 C 4 H 9 O * 88.3 * 109.0 * 121.5 * 93 C 6 H 13 O * 70.2 * 113.2 * 118.1 * * 76.8 * Table 4.1.2.2: Transition temperatures of chiral 2’,3’-difluoroterphenyl compounds. The novel 1,2-difluoroterphenyl systems with the two ortho-fluorines in the centre ring display mesogenic behaviour in accordance with the homologues in the literature (see section 4.1.1) [12]. Generally, for the alkyl-alkyl, and alkyl-alkoxy systems the nematic phase is favoured when the terminal chains are short (3-5), medium length terminal chains show a high smectic C phase range, with the smectic A phase appearing when the terminal chains are long. The alkyl-alkylsulphanyl systems behave differently, the compounds with short chains are nematogenic, however, when the total chain length is long a short smectic A phases is seen, and the smectic C phase is not observed. The effect that changing the atom in one terminal chain, while keeping the total chain length constant on mesogenic properties is shown in figure 4.1.2.3. If the chains are short, as in figure 4.1.2.3, then the melting points of compounds dialkyl compounds (71 and 72) are similar to that of the alkyl-alkylsulphanyl compounds (83 and 86), while the melting points of the alkoxy-alkyl material, 74 is much higher. The very short chains of compounds 71, 74, and 83 mean that the molecular structure is very compact, so the faceto-face interactions of the core units are maximised, affording high melting points, compared to compounds with longer chains. Terminal groups also tend to coil with increasing length; this generally hinders the parallel alignment of the molecules, therefore reducing melting points, and T N-I values. This effect is illustrated in figure 4.1.2.4. The short C-O bond (see figure 4.1.2.5) allows the lone pairs on the oxygen in alkoxy chains, to interact with the aromatic rings, effectively expending the core, therefore 231 increasing the intermolecular attractions. This accounts for the particularly high melting point of compound 71, and explains why clearing points of the alkyl-alkoxy compounds are generally higher. The effect on chain length on molecular packing also explains why materials with terminal chains of very different lengths (e.g. 72) have low melting points compared to more symmetric homologues (e.g. 55), but low T N-I values. Compounds with an even number of atoms in the terminal chain were not prepared, but it is expected that the nematic clearing points would show a distinct odd-even effect. The trend in nematic to isotropic clearing point is alkyl-alkoxy> dialkyl>alkylsulphanyl. This can be explained by considering the relative bond lengths of the terminal chains (see figure 4.1.2.5). Due to the relatively large size of the sulphur atom, the bond lengths of the carbon-sulphur bond are on average longer than carbon-carbon and carbon-oxygen bonds [17]. In addition, the carbon-sulphur-carbon bond angle for a sulphanyl unit is slightly smaller than the analogous angle for an alkyl or alkoxy chain. The net effect of these features is that the alkylsulphanyl chain protrudes further away from the side of the mesogenic core than an alkyl or alkoxy chain. So the electrons shared between the sulphur atom and core are spread over a larger distance than when an alkyl or alkoxy chain is present, effectively increasing the length of the core to a greater extent. The electronegativity (2.5 on the Pauling scale) of the sulphur atom and the long bond length of the C-S bond should give rise to a large molecular tilt, and hence facilitate the generation of the smectic C phase. However, the large Van-der-Waals volume of the sulphur atom means that the electron cloud is diffuse, reducing the dipole. The alkysulphanyl compounds of longer chain lengths have much higher melting points than the alkyl-alkoxy analogues because they do not have a smectic C phase. Other examples of lowering of melting point with increasing smectic tendency are in the literature [12]. It is well known that a branched terminal chain causes a reduction in clearing temperature, relative to a homologue with an unbranched terminal chain [18-20], an effect exemplified by comparing the transition temperatures of 90 with those of 87. The melting points are similar (87.2 °C and 85.5 °C respectively), however, the T N-I value of 87 is 114.5 °C, 232 whereas compound 90 is monotropic (T N-I value is 73.1 °C). The alkoxy-alkylsulphanyl species (92 and 93) were developed as it was thought that the alkoxy chain would increase the clearing point, and possibly induce a ferroelectric (chiral smectic C) phase. The clearing points of 92 and 93 are quite high, but only the stability of the smectic A phase has increased. F F C3H7 R Temperature / oC R = C3H7, C5H11, C2H5O, C4H9O, C2H5S, C4H9S respectively. 200 180 160 140 120 100 80 60 40 20 0 Nematic Crystal 71 72 74 75 83 86 Compound Figure 4.1.2.3: Effect on transition temperatures of alkyl, alkoxy, and alkylsulphanyl terminal groups. 233 F F C2H5S R R = C3H7, C5H11, C7H15, C9H19, respectively. Temperature / oC 140 120 100 80 Nematic Smectic A Crystal 60 40 20 0 83 84 80 85 Compound Figure 4.1.2.4: Effect on transition temperatures of increasing the length of the terminal alkyl group. 234 Compound 71 (Two propyl chains) O Bond Length: C(phenyl)-C(chain) = 1.550 A Bond Angle: C(phenyl)-C(chain)-C(chain) = 110.622° Compound 74 (Propyl and ethoxy chains) O Bond Length: C(phenyl)-O(chain) = 1.420 A Bond Angle: C(phenyl)-O(chain)-C(chain) = 112.838° Compound 83 (Propyl and ethylsulphanyl chains) O Bond Length: C(phenyl)-S(chain) = 2.000 A Bond Angle: C(phenyl)-S(chain)-C(chain) = 108.989° Figure 4.1.2.5: Molecular models of compounds 71, 74 and 83. The lone pairs on the oxygen of 74 are shown. The bond length and bond angles are calculated using the energy minimization routine (MM2 force field) in Chem3D version 8.0. 235 4.1.3: Mesomorphism of 2,3-Difluoroterphenyls 2,3-Difluoroterphenyls were prepared because an oxygen atom on the same ring as a difluorophenyl unit will increase the overall negative dielectric anisotropy of the system. A sulphur atom should have a similar, but reduced effect, and the alkylsulphanyl terminal chain is likely to increase the birefringence, relative to a dialkyl system. The melting points and transition temperatures of the 2,3-difluoroterphenyls and homologues from the literature are tabulated in table 4.1.3.1. As expected, the compounds with the ortho-difluorophenyl unit as the end ring show much greater smectic tendencies, and smaller nematic ranges than those compounds with fluorines in the centre ring. This is because the molecules with fluoro substituents on the end ring have only one interannular twist in the core (as opposed to two for the compounds with the fluoro substituents in the middle ring) and the outer edge fluoro substituent fills space. These structural features allow the core units to come closer together, thereby enhancing lamellar interactions, and so favouring smectic phases (see section 4.1.1.1), and this also explains why the meting points of the 2,3-disubstituted terphenyls are higher than those with substituents in the centre ring. 236 F R1 Cpd. Ref. R1 62 [12] C 3 H 7 R2 Cr F R2 E SmC SmA N I C 9 H 19 * 63.0 - --------- * 84.5 * 117.0 * 131.5 * 99 - C 3 H 7 C 2 H 5 O * 131.3 - --------- - --------- - --------- * 195.4 * 102 - C 3 H7 C 2 H 5 S * 106.2 - --------- - --------- * 139.2 * 144.3 * 103 - C 3 H7 C 4 H 9 S * 72.4 - --------- - --------- * 129.9 - --------- * 100 - C 5 H 11 * 94.4 - --------- - --------- - --------- * 134.5 * 63 [12] C 5 H 11 C 5 H 11 * 81.0 - --------- * 115.5 * 131.5 * 142.0 * 64 [12] C 5 H 11 C 7 H 15 * 81.0 * --------- * 105.5 * 131.0 * 136.0 * C 5 H 11 C 4 H 9 O * 104.4 - --------- * 143.4 - --------- * 172.9 * 54 [12] C 5 H 11 C 6 H 13 O * 97.5 - --------- * 145.5 - --------- * 166.0 * 64 [12] C 5 H 11 C 8 H 17 O * 93.5 - --------- * 144.0 * 148.0 * 159.0 * 101 - C 3 H7 104 - C 5 H 11 C 2 H 5 S * 79.0 - --------- - --------- * 140.7 - --------- * 105 - C 5 H 11 C 4 H 9 S * 65.9 * (58.2) - --------- * 126.9 - --------- * 66 [12] C 7 H 15 C 8 H 17 O * 89.5 - --------- * 148.0 * 151.5 * 154.0 * 106 - C 7 H 15 C 2 H 5 S * 71.3 * 72.2 - --------- * 140.5 - --------- * 107 - C 7 H 15 C 4 H 9 S * 68.5 * 71.3 - --------- * 129.2 - --------- * 108 - C 9 H 19 C 2 H 5 S * 135.2 - --------- - --------- * 139.6 - --------- * 109 - C 9 H 19 C 4 H 9 S * 64.6 * 69.6 - --------- * 125.4 - --------- * 53 [12] C 6 H 13 O C 5 H 11 * 101.5 - --------- * 156.5 * 167.0 * 171.5 * 67 [12] C 8 H 17 O C 5 H 11 * 89.0 - --------- * 155.5 * 165.0 * 166.0 * 112 - C 4 H9 S * 78.1 - --------- - --------- * 134.2 - --------- * 113 - C 4 H 9 S C 5 H 11 * 66.6 - --------- - --------- * 139.6 - --------- * 114 - C 4 H 9 S C 7 H 15 * 61.6 * 78.4 - --------- * 137.1 - --------- * C 3 H7 Table 4.1.3.1: Transition temperatures of 2,3-difluoroterphenyl compounds. 237 F F C2H5S R R = C3H7, C5H11, C7H15, C9H19, respectively. 160 Temperature / oC 140 120 100 80 Nematic 60 Smectic A 40 Crystal 20 0 102 104 106 108 Compound Figure 4.1.3.2: Effect on transition temperatures of increasing the length of the terminal alkyl group. Because of the tilting effect of the ortho-difluorophenyl group, all the dialkyl, and alkylalkoxy materials (except those with very short chains, 99 and 100) exhibit the smectic C phase. In sharp contrast to such materials is the mesogenic behaviour of the alkylsulphanyl analogues, all exhibit the smectic A phase, but none show the smectic C phase. In addition, only the compound with the shortest chains, 102, has a nematic phase. The longer chain homologues (106, 107, 109, 114) differ from other terphenyls made previously in that they additionally show an E (disordered crystalline) phase. This mesogenic behaviour is due to the completely unfluorinated biphenyl section allowing for lamellar packing of the molecules, increasing the tendency for a smectic A phase [21]. The smectic A phase is formed rather than smectic C, because of the diffuse nature of the sulphur atom (see section 4.1.2). However, the difluoro group might be expected to give the molecular structure a large enough dipole to tilt. The trend in mesogenic properties by increasing the length of one of the terminal chains is represented graphically in figure 4.1.3.2. All four compounds have very similar clearing 238 points, and the melting point drops from going from a three atom chain to a seven atom chain. However, compound 108, with ethylsulphanyl and nonyl chains has an extremely high melting point (125.4 °C). This is very unusual for such a highly unsymmetric molecule, especially as compound 109, with butylsulphanyl and nonyl chains has a much lower melting point (69.6 °C). The structural isomers (103, 105, 107, and 112-114) have similar phase morphologies, however, the compounds with the butylsulphanyl group attached to the laterally unsubstituted biphenyl section of the core (112-114) display higher clearing points than 103, 105, and 107. This trend is also observed in the isomeric literature compounds 53 and 54. This effect is due alkoxybiphenyl and alkylsulphanylbiphenyl units having greater molecular polarisation than an alkylbiphenyl unit [12]. 4.1.4: Mesomorphism of Terphenyls With No Lateral Groups To compare with their laterally substituted counterparts four terphenyl materials with no lateral substituents were also prepared, see table 4.1.4.1. The mesogenic properties of compound 116 are very similar to those of the literature compounds, 36 and 69. As, stated in the introduction to this section, the parent terphenyl core strongly promotes orthogonal smectic phases. Compound 118 is a nematogen, but only because the terminal chains are too short to promote a smectic phase, at high termperature. Additionally, the melting point of compound 118 is very high, thus masking a smectic phase; which is in accordance with the observed melting points of the laterally substituted terphenyls with short chains (see tables 4.1.2.1 and 4.1.3.1). The compound with an alkylsulphanyl chain 117, exhibits a similar smectic range to the dialkyl compounds (36, 68, 116); however, 119 is non-mesogenic as the smectic phase is masked by the elevated melting point. The very short ethylsulphanyl chain destabilises both smectic and nematic phases. 239 R2 R1 Cpd. Ref. R2 Cr SmB SmA N I C 3 H 7 C 2 H 5 O * 243.8 - --------- - --------- * 255.3 * 51 [11] C 5 H 11 C 5 H 11 * 192.0 - --------- * 213.0 - --------- * - C 5 H 11 C 7 H 15 * 196.4 - --------- * 210.2 - --------- * 52 [11] C 5 H 11 C 6 H 13 O * 205.0 * 216.0 * 221.5 - --------- * 20 [11] C 5 H 11 C 8 H 17 O * 194.5 * 211.0 * 221.5 - --------- * 19 [1] C 7 H 15 C 7 H 15 * 181.0 - --------- * 205.0 - --------- * 119 - C 7 H 15 C 2 H 5 S * 227.1 - --------- - --------- - --------- * 117 - C 7 H 15 C 4 H 9 S * 194.4 - --------- * 207.5 - --------- * 118 116 - R1 Table 4.1.4.1: Transition temperatures for terphenyls without lateral groups. 4.1.5: Mesomorphism of Terphenyl Mixtures It was expected that the dipole moment of the sulphur atom should be significant enough to stabilise the smectic C phase, particularly in conjuction with outer-edge fluoro substituents, even though the pure compounds do not generate any tilted phases. To investigate this situation, the alkylsulphanyl compounds with fluorines on the end ring were mixed with a weakly smectic C commercially available host, 56. The transition temperatures of the mixtures are presented in table 4.1.5.1. In addition, a number of the new terphenyls with difluoro substituents in the middle ring were also used in binary mixtures with compound 56 (see table 4.1.5.2). 240 F F R2 R1 No. Ref. R1 R2 56 [12] C 7 H 15 C 5 H 11 % Host Cr E SmC SmA N I 100 * 36.5 - ------- * (24.0) * ------- * 111.5 * - C 3 H7 C 2 H5 S 0 * 106.2 - ------- - ------- * 139.2 * 144.3 * 102A - C 3 H7 C 2 H5 S 50 * 80.9 - ------- - ------- - ------- * 126.3 * 102B - C 3 H7 C 2 H5 S 80 * 35.2 - ------- * 42.0 - ------- * 119.1 * 102C - C 3 H7 C 2 H5 S 90 * 32.2 - ------- * 40.3 - ------- * 116.4 * - C 3 H7 C 4 H9 S 0 * 72.4 - ------- - ------- * 129.9 - --------- * 103A - C 3 H7 C 4 H9 S 80 * 28.9 - ------- * 46.0 - ------- * 115.0 * 103B - C 3 H7 C 4 H9 S 90 * 29.0 - ------- * 40.1 - ------- * 114.2 * - C 5 H 11 C 2 H 5 S 0 * 79.0 - ------- - ------- * 140.7 - --------- * 104A - C 5 H 11 C 2 H 5 S 80 * 18.0 - ------- * 51.3 - ------- * 117.2 * 104B - C 5 H 11 C 2 H 5 S 90 * 17.8 - ------- * 28.1 - ------- * 115.2 * - C 5 H 11 C 4 H 9 S 0 * 65.9 * (58.2) - ------- * 126.9 - --------- * 105A - C 5 H 11 C 4 H 9 S 80 * 24.1 - ------- * 54.8 - ------- * 114.4 * 105B - C 5 H 11 C 4 H 9 S 90 * 21.4 - ------- * 44.7 - ------- * 113.0 * - C 7 H 15 C 2 H 5 S 0 * 71.3 * 72.2 - ------- * 140.5 - --------- * 106A - C 7 H 15 C 2 H 5 S 80 * 16.7 - ------- * 67.4 * ------- * 117.2 * 106B - C 7 H 15 C 2 H 5 S 90 * 26.3 - ------- * 50.1 * ------- * 115.0 * - C 7 H 15 C 4 H 9 S 0 * 68.5 * 71.3 - ------- * 129.2 - --------- * 107A - C 7 H 15 C 4 H 9 S 50 * 41.2 - ------- * 65.2 * 109.0 * 116.5 * 107B - C 7 H 15 C 4 H 9 S 80 * 26.6 - ------- * 51.7 - ------- * 113.9 * 107C - C 7 H 15 C 4 H 9 S 90 * 26.7 - ------- * 72.9 - ------- * 115.4 * - C 9 H 19 C 2 H 5 S 0 * 135.2 - ------- - ------- * 139.6 - --------- * 108A - C 9 H 19 C 2 H 5 S 80 * 28.7 - ------- * 84.7 * ------- * 116.4 * 108B - C 9 H 19 C 2 H 5 S 90 * 28.8 - ------- * 55.9 * ------- * 115.5 * - C 9 H 19 C 4 H 9 S 0 * 64.6 * 69.6 - ------- * 125.4 - --------- * 109A - C 9 H 19 C 4 H 9 S 80 * 27.6 - ------- * 80.2 - ------- * 113.1 * 109B - C 9 H 19 C 4 H 9 S 90 * 28.0 - ------- * 55.6 - ------- * 113.6 * 102 103 104 105 106 107 108 109 Table 4.1.5.1: Transition temperatures for mixtures of 4-alkylsulfanyl-4”-alkyl-2,3difluoroterphenyls. 241 F F R2 R1 No. Ref. R1 R2 % Host Cr 56 [12] C 7 H 15 C 5 H 11 SmC SmA N 100 * 36.5 * (24.0) - --------- * 111.5 * - C 3 H 7 C 9 H 19 0 * 40.0 - --------- - --------- * 110.5 * 72A 72B - C 3 H 7 C 9 H 19 50 * 22.0 * 27.3 - --------- * 113.3 * C 3 H 7 C 9 H 19 80 * 26.2 * 26.7 - --------- * 112.2 * - C 3 H 7 C 8 H 17 O 0 * 45.1 * 62.6 - --------- * 130.2 * 77A 77B - C 3 H 7 C 8 H 17 O 50 * 11.9 * (36.0) - --------- * 115.0 * C 3 H 7 C 8 H 17 O 80 * 11.0 - --------- - --------- * 120.5 * - C 9 H 19 C 4 H 9 S 89A - C 9 H 19 C 4 H 9 S 0 * 72.9 - --------- * 106.1 * 109.2 * 50 * 39.1 * 51.8 * 85.3 * 110.4 * 89B - C 9 H 19 C 4 H 9 S 80 * 25.8 * 46.2 - --------- * 113.0 * 72 77 89 Temperature / C Table 4.1.5.2: Transition temperatures for mixtures of 2’,3’-difluoroterphenyls. o I 160 140 120 100 80 60 40 20 0 Crystal Smectic C Smectic A Nematic 0 20 40 60 80 100 Wt % of Compound 56 Figure 4.1.5.3: Phase diagram for the binary system of components 56 and 102. 242 140 o Temperature / C 120 Crystal 100 Crystal E Smectic C 80 60 Smectic A Nematic 40 20 0 0 20 40 60 80 100 Wt % of Compound 56 Figure 4.1.5.4: Phase diagram for the binary system of components 56 and 107. As can be seen from table 4.1.5.1, the mixtures with compound 56 as the majority component show an enhanced smectic C phase stability (especially 108A and 109A); this is clearly illustrated in the phase diagrams, figures 4.1.5.3 and 4.1.5.4. Such behaviour has been previously observed in binary mixtures of two monofluoro terphenyls [4]. This behaviour shows that the alkylsulphanyl terminal group promotes a molecular dipole of sufficient magnitude for the molecules to tilt; however, in the pure compound the tendency for the molecules to pack in a lamellar arrangement (promoted by the high molecular polarisability) is so great that a smectic C phase is unable to form. Interestingly, only the 50-50 mixture 107A exhibits both the smectic A and smectic C phases, here there is a balance of both physical factors. For 102A, however, only the nematic phase is observed, this is due to the short chains and high melting point. In all cases, the melting points of the mixtures are lower than the pure major component, this is because the dopant disrupts the crystal packing with the solid phase. This also explains why no E phase was observed in any of the mixtures. The transition temperatures for the mixtures of 2’,3’-difluoroterphenyls, 89A and 89B (table 4.1.5.2) also show that smectic C stability is enhanced, confirming the experimental results obtained from the 2,3-difluoroterphenyls. 243 It is surprising that the mixtures of the alkyloxy terphenyl 77 with 56 do not manifest an enantiotropic smectic C phase, as the alkoxy group should greatly enhance tilted phases. 4.1.6: Photomicrographs As stated in the experimental chapter of this work, the liquid crystalline phases exhibited by the synthesised materials were identified by optical microscopy. Plates 4.1.5.1 to 4.1.5.6 are photomicrographs of the different phases exhibited by the difluoroterphenyl based materials. Plate 4.1.6.1: Photomicrograph of the smectic C phase of compound 77 (55.0 °C), showing schlieren texture. 244 Plate 4.1.6.2: Photomicrograph of the nematic phase of compound 77 (70.0 °C), showing schlieren and homeotropic (black) texture. Plate 4.1.6.3: Photomicrograph of the smectic A phase of compound 93 (105.0 °C), showing homeotropic (black) texture. 245 Plate 4.1.6.4: Photomicrograph of the cholesteric phase of compound 93 (145.0 °C), showing spherulitic small focal-conic texture. Plate 4.1.6.5: Photomicrograph of the crystal E phase of compound 107 (40.0 °C), showing focal-conic fan texture. 246 Plate 4.1.6.6: Photomicrograph of the smectic A phase of compound 109 (85.0 °C), showing focal-conic fan texture. 247 4.2: 2,6-Phenylnaphthalenes 4.2.1: Introduction In addition to biphenyls and terphenyls, fused benzene rings have been used successfully as core units. Naphthalene has been shown to provide mostly linear molecules by disubstitution in three different combinations, (70-72). In order of decreasing tendency to form mesogens, these are 2,6-, 1,5-, and 1,4-disubstituted naphthalenes [22, 23]. MeO N N OMe 70 71 72 73 74 75 2,6- Cr 188.5 SmA 355 I 1,5- Cr 196 SmA 282.5 I 1,4- Cr 183 SmA 263 I 1,7- Cr 143 I 2,7- Cr 205 I 2,5- Cr 134 I Figure 4.2.1.1: The effect of different substitution patterns of the naphthalene core unit on mesogenic properties. Given the success of the terphenyl core system in generating liquid crystalline mesophases, compounds based on the analogous phenyl naphthalene core unit have been prepared; in each case a 2,6-disubsitution pattern was chosen so as to provide optimum liquid crystal phases stability (figure 4.2.1.2) [24-29]. The broad naphthalene unit prevents efficient molecular packing, and so mesogens based on the phenylnaphthalene core have lower melting points and smectic ranges than the equivalent terphenyls. If the terminal chains are relatively short, then the compound is likely to be nematogenic, (76 and 77) [24-27]. Like the terphenyls, phenylnaphthalenes with lateral fluoro substituents on the end (phenyl) ring have been synthesied, (e.g. 78). A lateral fluoro substituent on the phenyl group will broaden the molecule, therefore increasing nematic tendencies. An inner fluoro 248 substituent will also increase the interannular twist between the rings, which will further reduce smectic tendency and decrease the melting point further. Difluorophenylnaphthalenes were prepared in order to combine the negative dielectric anisotropy of the difluorophenyl unit with the high birefringence of the naphthalene unit. Like the 2,3-difluoroterphenyls the inclusion of a ether oxygen next to the lateral fluoro substituents is expected to increase the negative dielectric anisotropy; an alkylsulphanyl terminal chain should increase the birefringence. Different combinations of alkyl and alkoxy chains are desirable in order to evaluate the effect of the terminal chains on the physical properties of the system. C5H11 C5H11 CN CN 76 77 Cr 86 N 128 I Cr 85.5 N 128 I C4H9O CN F 79 Cr 65 N 130 I Figure 4.2.1.2: Some known phenylnaphthalnes [24-27]. 249 4.2.2: Mesomorphism of 2,3-Difluorophenylnaphthalenes Fourteen novel compounds containing the 2,3-difluorophenylnaphthalene core were prepared and the transistion temperatures are recorded in table 4.2.2.1. The effect of different terminal chains on transition temperatures is shown graphically in figure 4.2.2.2. F R1 Cpd. Ref. R1 R2 F R2 Cr SmC SmA N I 135 - C 5 H 11 C 3 H 7 * 37.6 - --------- - --------- * 42.4 * 136 - C 5 H 11 C 5 H 11 * 29.1 - --------- - --------- * 37.2 * 137 - C 5 H 11 C 2 H 5 O * 68.5 - --------- - --------- * 88.4 * 138 - C 5 H 11 C 4 H 9 O * 62.3 - --------- - --------- * 72.6 * 139 - C 5 H 11 C 2 H 5 S * 50.3 - --------- - --------- * (35.6) * 140 - C 5 H 11 C 4 H 9 S * 34.2 - --------- - --------- - --------- * 123 - C 2 H 5 O C 3 H 7 * 101.1 - --------- - --------- * (86.5) * 124 - C 2 H 5 O C 5 H 11 * 60.8 - --------- - --------- * 93.2 * 125 - C 2 H 5 O C 2 H 5 O * 125.3 - --------- - --------- * 142.2 * 126 - C 2 H 5 O C 4 H 9 O * 102.1 - --------- - --------- * 129.2 * 127 - C 4 H 9 O C 3 H 7 * 60.8 - --------- - --------- * 80.4 * 128 - C 4 H 9 O C 5 H 11 * 50.8 - --------- - --------- * 83.3 * 129 - C 4 H 9 O C 2 H 5 O * 92.6 - --------- - --------- * 127.1 * 130 - C 4 H 9 O C 4 H 9 O * 99.9 - --------- - --------- * 117.8 * 79 [28] C 8 H 17 O C 5 H 11 * 36.0 * 44.5 * 75.0 * 83.5 * Table 4.2.2.1: Transition temperatures for 2,3-difluorophenylnaphthalenes. 250 F F C5H11 R R = C3H7, C5H11, C2H5O, C4H9O, C2H5S, C4H9S, respectively. 90 o Temperature / C 80 70 60 50 Nematic Crystal 40 30 20 10 0 135 136 137 138 139 140 Figure 4.2.2.2: Effect on transition temperatures of alkyl, alkoxy, and alkylsulphanyl terminal groups. Only enantiotropic phases are shown. The most notable property of the novel 2,3-difluorophenylnaphthalenes is that the only phase exhibited is the nematic phase. This is not surprising as all of the compounds reported here have relatively short terminal chains of three or five atoms in length and the broad naphthalene core will promote the nematic phase. A comparison of the transition temperatures of the 2,3-difluorophenylnaphthalenes with the 2,3-difluoroterphenyls shows that replacing an laterally unsubstituted biphenyl core with a naphthalene unit dramatically reduces the smectic tendency of the system as well as reducing the melting and clearing points (e.g., compare 63 with 136 and 101 with 138). The literature compound, 79 shows that semctic phases do appear when longer terminal chains are present, but compared to compound 67 the mesogenic range is poor. Figure 4.2.2.2 shows a very similar trend to that shown in figure 4.1.2.3, again, the compounds with an ethoxy, or propyl terminal chain have higher melting points than the pentyl, or butoxy homologues. In addition, the compounds with the pentyl chain attached to the naphthalene core have lower melting points and T N-I values than those with an 251 alkoxy chain in that position. This trend is seen for most core systems and is due to the oxygen being in conjugation with the aromatic core, which, in addition to extending the length of the rigid core, enhances the polarisability anisotropy. Compound 123 exhibits a monotropic nematic phase, this is due to the high melting point (101.1 °C), and the inability of the propyl and ethoxy terminal chains to support a nematic phase above that temperature. Whereas 125, containing two ethoxy chains has a clearing point of 142.2 °C and a melting point of 125.3 °C. The two alkylsulphanyl materials are very poor mesogens, 139 displays a monotropic nematic phase, and 140 is non-mesogenic. This is in sharp contrast to the terphenyl anologues, (104 and 105) which despite having higher melting points they possess quite a large smectic A range. This reflects the inability of an alkylsulphanyl chain, when directly attached to a difluorophenyl unit to support a nematic phase. This is likely to be due to the lateral fluorines disrupting the delocalisation of the large electron cloud formed by the interaction of the highly polarisable sulphur with the aromatic system. 252 4.2.3: Mesomorphism of 2-Fluorophenylnaphthalene and Phenylnaphthalene Compounds Two phenylnaphthalene compounds without lateral substituents and a monofluorophenylnaphthalene material were prepared for comparison with the difluorophenylnaphthalenes. Table 4.2.3.1 reveals the transition temperatures of these compounds, as well as those of two analogous difluorophenylnaphthalenes. X R1 Cpd. R1 Y R2 R2 X Y Cr N I 141 C 4 H 9 O C 5 H 11 H H * 137.1 * --------- * 142 C 4 H 9 O C 4 H 9 O H H * 165.8 * 169.3 * 143 C 4 H 9 O C 3 H 7 O F H * 75.6 * 111.0 * 128 C 4 H 9 O C 5 H 11 F F * 50.8 * 83.3 * 130 C 4 H 9 O C 4 H 9 O F F * 99.9 * 117.8 * Table 4.2.3.1: Transition temperatures for a 2-fluorophenylnaphthalene and two parent phenylnaphthalene compounds. The melting points of 141 and 142 are, as expected, much higher than those materials with lateral fluoro substituents. Compound 141 does not show any mesogenic behaviour at all, again, this is because of a high melting point masking any possible mesophases. The introduction of one fluoro unit (143) greatly depresses the melting and clearing points, adding a second one actually increases them (130), but 130 does possess two identical terminal chains, a situation known to cause high meting points. Compounds 130 and 143 have similar T N-I values, this is surprising as the space filling effect of the outer-edge fluoro substituent would be expected to increase the mesogenic range. 253 4.2.4: Mesomorphism of a 2,3-Difluorobiphenylnaphthalene Compound One 2,3-difluorobiphenylnaphthalene compound was prepared, 144. If a comparison with 127 (table 4.2.2.1) is made, the extra phenyl ring significantly increases the melting point, but the clearing point is enhanced to an even greater extent. This observation demonstrates that the difluorobiphenyl unit is much better at stabilising liquid crystal phases than the difluorophenyl component. F R1 Cpd. R1 F R2 R2 Cr N I 144 C 4 H 9 O C 3 H 7 * 115.8 * 241.3 * Table 4.2.4.1: Transition temperatures for a 2,3-Difluorobiphenylnaphthalene. 254 4.3: Benzodioxinanes 4.3.1: Introduction The dioxane ring, in conjunction with one or two phenyl rings have been used successfully in ferroelectric applications [30, 31]. The introduction of a saturated ring into an aromatic system breaks the electronic conjugation, reducing birefringence and often the viscosity of the system. O C6H13O O O C6H13 C6H13O O C6H13 80 81 Cr 20 B 64 I Cr 34 SmA 45 N 53 I F F O C7H15O O C9H19 82 Cr 47 (SmA 37) I Figure 4.3.1.1: Compounds containing a phenyl and a dioxane ring [32-34]. As shown in figure 4.3.1.1, the 4,6-dioxinane ring (80) affords a larger mesogenic range than the 1,3-dioxane module (81). The difluoro system, 82 shows that lateral groups can be accommodated without destroying all mesogenic behaviour. The benzodioxinane ring, where a dioxane ring is fused to a phenyl ring is a related core system to the 4,6-dioxinane ring, with an attached phenyl unit. No mesomorphic compounds with a phenyl group attached to the benzodioxine ring have been reported, however, 83 and homologous compounds have been used in mixtures [35]. Many trans1,3-dioxadecalin materials (e.g. 67) are known, and almost all are show mesomorphic behaviour [36]. 255 O O C3H7 O 83 Cr 20 I C5H11 C5H11 O 84 Cr 77 (N 74) I Figure 4.3.1.2: Compounds containing a fused dioxinane ring [35, 36]. OC4H11 256 4.3.2: Mesomorphism of 2,3-Difluorophenylbenzodioxinanes As the 2,3-difluorophenylnaphthalenes showed promise as commercial materials a number of the structurally equivalent 2,3-difluorophenylbenzodioxinanes were synthesised. It was thought that the use of the benzodioxinane unit could possibly produce compounds of low viscosity. The compounds would also have a low birefringence, as opposed to the high birefringence of the phenylnaphthalenes and terphenyls. Again, the orthodifluorophenyl unit was to be incorporated into the target materials in order to afford high negative dielectric anisotropy. The transition temperatures of these compounds are shown in table 4.3.2.1. F R Cpd. Ref. R1 F 1 O R2 O R2 Cr SmA N I 168 - C 5 H 11 C 3 H 7 * 61.0 - --------- - --------- * 169 - C 5 H 11 C 5 H 11 * 32.6 * (9.3) * (14.0) * 166 - C 5 H 11 C 7 H 15 * 37.7 * (17.6) * --------- * 161 - C 7 H 15 C 3 H 7 * 33.2 * (-12.7) * (2.9) * 163 - C 7 H 15 C 5 H 11 * 19.1 - --------- - --------- * 164 - C 3 H 7 O C 5 H 11 * 65.4 - --------- - --------- * 162 - C 4 H 9 O C 3 H 7 * 59.1 - --------- - --------- * 165 - C 4 H 9 O C 5 H 11 * 75.2 - --------- - --------- * 83 [37] C 5 H 11 O C 5 H 11 * 76.4 - --------- - --------- * 84 [37] C 5 H 11 O C 7 H 15 * 72.3 * (68.9) * --------- * 85 [37] C 7 H 15 O C 5 H 11 * 70.5 * 71.0 * --------- * 86 [37] C 7 H 15 O C 7 H 15 * 70.0 * 77.3 * --------- * Table 4.3.2.1: Transition temperatures for 2,3-Difluorophenylbenzodioxinanes. 257 It is immediately noticeable from table 4.2.3.1 that the 2,3-difluorophenylbenzodioxinane ring system is a very poor mesogenic core, but it is as good as the difluorophenyldioxinane core (82, see figure 4.2.2.1). Only 85 and 86 show an enantiotropic smectic A phase, 84, and 166 exhibit a monotropic smectic A phase, whereas 161 and 169 display the smectic A phase and the nematic phase; however both are monotropic. Compounds 83, 168 and 163165 contain chains that are too short to stabilise any liquid crystal phase. As usual, the dialkyl compounds have a lower melting point than the alkyl-alkoxy compounds, particularly 163, which melts at a usefully low 19.1 °C. The very low clearing points of these compounds is because, unlike naphthalene, in the partially reduced ring systems electric charge cannot be effectively delocalised, reducing edge-to-edge attractive forces. The benzodioxinane ring is likely to be worse than the equivalent tetrahydronaphthalene system, as the electronegative oxygens in the aliphatic ring will reduce charge distribution further. The benzodioxinane systems would be expected to favour orthogonal smectic phases over the nematic phase, because there will be strong intermolecular interactions between the oxygens on one molecule and the oxgens on another molecule, increasing lammellar packing. In addition, the core is geometrically constrained by steric and electron repulsions with the benzodioxinane core being slightly more planar than a tetrahydronaphthalene core, due to the two sp3 hybridised oxygen heteroatoms. 258 4.3.3: Mesomorphism of 2-Fluorophenylbenzodioxinanes and Phenylbenzodioxinane Compounds Five phenylbenzodioxinane compounds without lateral substituents and seven 2fluorophenylbenzodioxinane were also prepared. Table 4.3.3.1 reveals the transition temperatures of these compounds, as well as those of two analogous 2,3-difluoro phenylbenzodioxinane, for comparison. X R Cpd. R1 R2 Y O 1 X F Cr R2 O E SmA N I 149 C 3 H 7 C 3 H 7 H H * 87.6 - --------- - --------- - --------- * 151 C 3 H 7 C 5 H 11 H H * 64.1 * 66.4 * 74.1 * --------- * 152 C 5 H 11 C 5 H 11 H H * 72.0 - --------- - --------- - --------- * 150 C 4 H 9 O C 3 H 7 H H * 132.2 - --------- - --------- - --------- * 153 C 4 H 9 O C 5 H 11 H H * 99.0 * 109.4 * 124.3 * --------- * 154 C 4 H 9 O C 3 H 7 H F * 66.3 - --------- - --------- * (48.1) * 157 C 4 H 9 O C 5 H 11 H F * 45.4 - --------- - --------- * 56.8 * 160 C 4 H 9 O C 7 H 15 H F * 42.4 - --------- * 53.36 * 58.0 * 155 C 6 H 11 O C 3 H 7 H F * 28.0 - --------- * (27.3) * 52.9 * 158 C 6 H 11 O C 5 H 11 H F * 34.4 - --------- * 41.3 * 58.0 * 156 C 8 H 17 O C 3 H 7 H F * 45.9 - --------- - --------- * 54.4 * 159 C 8 H 17 O C 5 H 11 H F * 36.3 - --------- * 57.5 * --------- * 162 C 4 H 9 O C 3 H 7 F F * 59.1 - --------- - --------- - --------- * 165 C 4 H 9 O C 5 H 11 F F * 75.2 - --------- - --------- - --------- * Table 4.3.3.1: Transition temperatures for seven 2-fluorophenylbenzodioxinane and five phenylbenzodioxinane compounds. 259 Only two of the five phenylbenzodioxinane compounds prepared are mesomorphic, the compounds that are (151 and 153) show enantiotropic smectic A and crystal E phases. All the 2-fluorophenylbenzodioxinanes display mesomorphic behaviour, with clearing points increasing with terminal chain length. Generally, the melting points of the laterally unsubstituted materials are higher than the 2- fluorophenylbenzodioxinanes, compound 154 (66.3 °C) appears to have a higher melting point than 151 (64.1 °C), but 151 exhibits the crystal E phase, so the real melting point is 66.4 °C, where the smectic A phase is formed. The difluorophenylbenzodioxinane, 165, has a higher melting point than all the monofluorophenylbenzodioxinanes, however, the homologue 162, has a lower melting point (59.1 °C) than 154. It is reasonable to expect the unsubstituted compounds to have the highest melting points, introducing a fluoro unit at the inner-core position will increase interannular twisting, reducing the longitudinal polarisability and therefore lowering the melting point (see section 4.1.1). Adding a second fluoro substituent on the outer edge of the core fills vacant space within the core system, resulting in a larger area for possible side-to-side intermolecular associations. Also, no increase in innterannular twisting occurs. This argument also explains the fact that all of the monofluoro compounds display nematic behaviour (except 159, which has the longest chains) while the difluorophenylbenzodioxinanes and phenylbenzodioxinane are primarily smectogenic, if a liquid crystalline phase is exihibited at all. As expected, the dialkyl phenylbenzodioxinanes have a lower melting points than the alkyl-alkoxy variants. No dialkyl monofluorophenylbenzodioxinanes were made as the melting and clearing points of the alkyl-alkoxy materials are so low it was thought that the dialkyl homologues would be just isotropic liquids. 260 4.3.4: Mesomorphism of 2,3-Difluorobiphenylbenzodioxinanes As the 2,3-difluorophenylbenzodioxinanes had such poor mesogenic stability a number 2,3-difluorobiphenylbenzodioxinanes were prepared as, like the 2,3- difluorobiphenylnaphthalene material, the extra phenyl ring should increase the clearing point dramatically. In addition, fluoro substituents on a centre ring should produce materials with a large nematic range, and shorter smectic range. Transition temperatures are shown in table 4.3.4.1 and shown graphically in figure 4.3.4.2. F F O 1 R Cpd. Ref. R2 O R1 R2 Cr SmA N I 170 - C 3 H 7 C 3 H 7 * 80.9 - --------- * 185.8 * 171 - C 3 H 7 C 5 H 11 * 76.1 * 126.1 * 174.6 * 172 - C 3 H 7 C 7 H 15 * 63.7 * 133.0 * 161.4 * 173 - C 5 H 11 C 3 H 7 * 75.8 * 126.1 * 172.5 * 174 - C 5 H 11 C 5 H 11 * 55.9 * 145.3 * 165.2 * - C 5 H 11 C 7 H 15 * 64.7 87 [37] C 5 H 11 O C 5 H 11 * 72.4 * 144.3 * 156.4 * * 177.2 * 190.1 * 88 [37] C 5 H 11 O C 7 H 15 * 60.4 89 [37] C 7 H 15 O C 5 H 11 * 71.7 * 178.6 * 184.5 * * 179.6 * 183.9 * 90 [37] C 7 H 15 O C 7 H 15 * 72.4 * 177.2 * 190.1 * 175 Table 4.3.4.1: Transition temperatures for 2,3-difluorobiphenylbenzodioxinanes. 261 F F O 1 R R2 O o Temperature / C R1 = C3H7, R2 = C3H7, C5H11, C7H15, and R1 = C5H11, R2 = C3H7, C5H11, C7H15, respectively. 200 180 160 140 120 100 80 60 40 20 0 Nematic Smectic A Crystal 170 171 172 173 174 175 Figure 4.3.4.2: Effect on transition temperatures of increasing terminal chain length in a dialkyl series. As can be seen from figure 4.3.4.2, the trend in transition temperatures with increasing chain length is similar to that observed for the 2’,3’-difluoroterphenyl compounds (see table 4.1.2.1). Clearing points fall with increasing chain length, and the smectic A phase range increases, reducing the nematic phase range. Unlike the terphenyls, however, the melting points of the alkyl-alkoxy 2,3-difluorobiphenylbenzodioxinanes are similar to the dialkyl homologues. The clearing points of the alkyl-alkoxy 2,3- difluorobiphenylbenzodioxinanes are higher than their dialkyl equivalents, as expected.The 2,3-difluorobiphenylbenzodioxinanes show much higher clearing points than the 2,3difluorophenyl variants, due to the extended, conjugated core. There is very little difference between the melting points of the literature alkoxy-alkyl 2,3difluorophenylbenzodioxinanes and the 2,3-difluorobiphenylbenzodioxinanes with same terminal chains. The melting point of 87 (72.4 °C) is actually lower than that of 83 (76.4 °C). However, the melting points of the dialkyl 2,3-difluorobiphenylbenzodioxinanes are higher than those of the dialkyl 2,3-difluorophenylbenzodioxinanes. 262 In the case of the dialkyl 2,3-difluorobiphenylbenzodioxinanes the extra phenyl group increases the molecular polarisability of the core, hence increasing both melting and clearing points; however both the phenyl-phenyl bonds are more twisted than an unsubstituted biphenyl moiety, due to the two fluorines and so the increase in melting point is not dramatic. It is possible that there is an intermolecular attraction between the oxygen atoms in the benzodioxinane ring and the oxygen in the alkoxy terminal chain of the alkyl-alkoxy terminal chains of the compact 2,3-difluorophenylbenzodioxinanes. This would increase the melting point, but not the clearing point relative to the dialkyl 2,3difluorophenylbenzodioxinanes. In the larger, less compact 2,3- difluorobiphenylbenzodioxinanes, this attraction does not occur, and so the melting points of the alkyl-alkoxy 2,3-difluorobiphenylbenzodioxinanes are similar to the dialkyl variants. 4.3.5: Mesomorphism of Laterally Substituted and Unsubstituted 2,6- Bis(phenyl)benzodioxinanes Two isomeric molecules to the 2,3-difluorobiphenylbenzodioxinanes were synthesised, with the second phenyl unit attached to the other side of the benzodioxinane ring, these are compounds 179 and 182. In addition, a parent molecule 178, and a compound with four lateral fluorines were prepared, 183. Y X X O R1 Cpd. Y R2 O R1 R2 X Y Cr N I 178 C 5 H 11 C 2 H 5 O H H * 142.4 * 170.3 * 179 C 5 H 11 C 2 H 5 O F H * 113.0 * 162.4 * 182 C 5 H 11 C 2 H 5 O H F * 102.3 * 147.8 * 183 C 5 H 11 C 2 H 5 O F F * 99.1 * 113.7 * Table 4.3.5.1: Transition temperatures for 2,6-Bisphenylbenzodioxinanes. 263 All of the 2,6-bisphenylbenzodioxinanes are high melting nematogens. The lack of any smectic phases is likely to be because the aromatic-aliphatic-aromatic core system gives a poor charge distribution. As usual, the melting and clearing points of the series decrease with adding the lateral fluoro groups, the difference is not great, however, due the molecular structure being broad and compact, so the introduction of the fluoro groups does not alter the molecule shape as much as the fluoro units in the difluorophenyl compounds, for example. This also explains why the melting points of 179 and 182 are greater than the 2,3- difluorobiphenylbenzodioxinanes. The melting and clearing points of compound 179 are higher than those of 182. Considering interannular twisting alone, the opposite result would be expected. A likely explanation is that the fluoro groups in 182 are on a phenyl ring which is adjacent to another phenyl ring, and the electronic conjugation of the two rings means that they can support the electron withdrawing fluoro substituents better than the unconjugated phenyl ring on the other side of the molecule. 264 4.3.6: Mesomorphism of Laterally Substituted and Unsubstituted 6-Phenyl-2cyclohexylbenzodioxinanes A number of compounds with a phenyl ring attached to the left hand side of the benzodioxinane core and a trans-cyclohexyl ring appended to the right hand side were prepared. Lateral fluoro substituents were introduced both on the phenyl ring and onto the benzodioxinane core; it was thought that the fluorine on the benzodioxinane core may also interact with the lone pair on the nearby heterocyclic oxygen. The transition temperatures of these materials are recorded in table 4.3.6.1. X R Y O 1 R2 O Z Cpd. R 1 R 2 X Y Z Cr SmC SmA N I 198 C 5 H 11 C 5 H 11 H H H * 143.2 - --------- * 185.9 - --------- * 196 C 3 H 7 O C 3 H 7 H F H * 75.4 - --------- - --------- * 182.6 * 197 C 8 H 17 O C 3 H 7 H F H * 62.7 * 64.8 * 120.0 * 162.3 * 193 C 3 H 7 O C 3 H 7 F F H * 107.6 - --------- * 123.7 * 180.6 * 195 C 3 H 7 O C 5 H 11 F F H * 107.7 - --------- * 149.3 * 184.4 * 192 C 5 H 11 C 3 H 7 F F H * 40.2 - --------- * 121.1 * 148.1 * 194 C 5 H 11 C 5 H 11 F F H * 49.9 - --------- * 130.3 * 143.4 * 204 C 3 H 7 O C 3 H 7 H F F * 102.4 - --------- - --------- * 171.0 * Table 4.3.6.1: Transition temperatures for 6-phenyl-2-cyclohexylbenzodioxinanes. Unlike the 2,6-bisphenylbenzodioxinanes, the 6-phenyl-2-cyclohexylbenzodioxinanes show the smectic A phase, this is because the replacement of the phenyl ring with a saturated cyclohexyl moiety gives the molecular structure a good charge distribution, which is vital for the formation of smectic phases. Compound 198, without any lateral substituents, has the highest melting point, with a smectic to isotropic clearing point of 185.9 °C. No nematic phase was observed as the terminal chains are too short to stabilise a nematic phase at that high temperature. 265 Compound 196 and 204 are, like the 2-fluorophenylbenzodioxinanes with very short chains (154 and 157), nematogenic. The melting point of 196 is lower than those of compound 204, however the clearing point is higher. This is likely to be because the extra lateral fluorine on the benzodioxinane core decreases the electron delocalisation of the system, decreasing the clearing point, but fills the vacant space in between the other fluorine and the dioxane part of the core, thereby increasing intermolecular attractions, and therefore the melting point. In compound 196, the fluorine on the phenyl ring is shielded by both the benzodioxinane core and the other fluoro substituent, so the detrimental effect of adding the second fluoro substituent on the clearing point is less than expected. Compound 197 exhibits both the smectic A and C phases, because the long alkoxy chain generates enough molecular tilt to allow the formation of the smectic C phase. All the compounds with a difluorophenyl unit (192-195) all display the smectic A and nematic phases. Like the 2,3-difluorophenylbenzodioxinanes the dialkyl materials are very low melting, demonstrating that the extra aliphatic ring has, relative to the 2,3difluorophenylbenzodioxinanes, greatly increased the clearing point, without raising the melting point. 266 4.4: Biphenylpyrimidines 4.4.1: Introduction Phenyl-pyrimidines were first invented by Zasche [38]. Terashima at Hoffmann-La Roche synthesised many more phenyl-pyrimidines and some biphenyl-pyrimidines (e.g. 91, 92) [39, 40]. Later Kelly developed homologues with unsaturated bonds in various positions within the terminal chains [40]. N N C6H13 N OC7H15 C5H11 N 91 92 Cr 33 SmC 51 SmA 77 I Cr 58 SmC 81 N 164 I C6H13 Figure 4.4.1.1: Pyrimidine based liquid crystals [39]. Comparisons have been made between the mesogenic properties of bi-, and ter-phenyls and their pyrimidine analogues [42, 43]. Usually, a higher clearing point and melting point is observed. It is suggested that the dominant effect of the heteroatom is to produce changes in the conjugate interactions within the molecule, thus affecting factors such as polarisability and dipolarity. The smectic tendency of such molecules is greatly increased. 267 4.4.2: Mesomorphism of Biphenylpyrimidine Compounds Only one final biphenylpyrimidine compound was prepared, for comparisons with the terphenyls, and the transition temperatures of it and the unsaturated precursor material are recorded in table 4.4.2.1. N R1 R2 N Cpd. Ref. 207 R1 - C 7 H 15 R2 Cr C5H11 * 95.6 SmC SmA N I - --------- - --------- * 172.8 * 92 [39] C 5 H 11 C 6 H 13 * 58.0 * 81.0 - --------- * 164.0 * 93 [39] C 6 H 13 C 7 H 15 * 72.0 * 107.6 * 134.1 * 160.7 * 94 [39] C 6 H 13 C 7 H 15 * 65.6 * 98.0 * 141.2 * 156.0 * - C 7 H 15 C 7 H 15 * 62.3 * 113.2 * 137.0 * 161.4 * 208 Table 4.4.2.1: Transition temperatures of biphenylpyrimidine compounds. The sole pyrimidine compound made, 208 has a low melting point relative to the parent terphenyl system (see 36 in table 4.1.3.1). The nitrogens of the hetroaromatic pyrimidine produce a dipole within the core structure, reducing intermolecular attractions. The lateral dipole parallel to the molecular axis due to the heterocyclic ring is sufficient to generate a tilted smectic C phase, which is exhibited 92-94 and 208. The smectic range C also increases with terminal chain length, and the higher homologues, (93, 94, and 208) show a smectic A phase, as the biphenyl group promotes stacking of the molecules. The overall mesogenic stability is high, with a nematic phase generated at high temperatures. The precursor compound, 208 is a nematogen. The acetylene terminal bridging group effectively extends the core unit, leading to a higher melting point than compound 208. 268 4.5: Difluorobiphenyldioxaborinanes 4.5.1: Introduction In 1985, Seto reported the synthesis of the first boron containing liquid crystalline material [44]. Since then, further molecules containing the dioxaborinane unit have been prepared, including a number of difluorobiphenyldioxaborinanes [45, 46]. Compared to analogous dioxane compounds with the same aliphatic chain lengths the dioxaborinanes are nematogenic in character, and less semectogenic [46]. This is because, when bonded to an aromatic ring, the p orbital of the boron, which is perpendicular to the plane of sp2 hybrid orbitals can interact with the p-π conjugated system of the aromatic ring. However, because, the p orbital is empty, and the delocalised electrons of the aromatic ring can be donated to it, reducing the electron density of the whole rigid mesogenic core. Consequently, intermolecular attraction is reduced, reducing the chance of the formation of a lamellar structure. F F F O B O C9H19O F O C7H15 C9H19O O 95 96 Cr 49 N 114 I Cr 86 N 120 I C7H15 Figure 4.5.1.1: A difluorobiphenyldioxaborinane and a difluorobiphenyldioxane [46]. Previously, difluorobiphenyldioxaborinanes have only been targeted as smectic C host materials, not as components in nematic mixtures [45, 46]. As they possess the useful properties of high nematic character and high negative dielectric anisotropy, they might have potential as nematic hosts for VAN devices. 269 4.5.2: Mesomorphism of Difluorobiphenyldioxaborinanes Due to the reactivity of the boronic ester group, and hence poor chemical stability of the system, only two difluorobiphenyldioxaborinane materials were synthesised. F F O B O R1 R1 Cpd. Ref. R2 Cr R2 N I 211 - C 5 H 11 C 5 H 11 * 42.1 * 83.1 * 212 - C 3 H 7 C 7 H 15 * 53.4 * 96.1 * 95 [46] C 9 H 19 O C 7 H 15 * 49.0 * 113.7 * Table 4.5.2.1: Transition temperatures of difluorobiphenyldioxaborinane compounds. All the materials in table 4.5.2.1 are nematogens, even 95, which has long terminal chains. Melting points are quite low and are similar to the 2’,3’-difluoroterphenyls (see table 4.1.2.1). The dipentyl homologue has the lowest melting point of the series, which is surprising, usually compounds with identical terminal chains have higher melting points than those with asymmetric chains. 270 4.6: Bis-(4-phenyl)thiophenes 4.6.1: Introduction The 2,5-disubstituted thiophene ring is a useful core unit for the production of new nematic liquid crystals due to a number of factors [47, 48]. It is aromatic and therefore has a flat, rigid structure, the sulphur atom in the thiophene ring imparts an internal dipole perpendicular to the long molecular axis of the molecule. In addition, the large angle between the thiophene ring and the bonds to the substituents at the 2- and 5- positions should result in a low melting point. Very few compounds with a thiophene ring in the centre of directly linked phenyl units (e.g., 97) have been previously reported [49, 50]. C4H9 S 97 Cr 142 I Figure 4.6.1.1: A bis-(4-phenyl)thiophene [49]. C4H9 271 4.6.2: Mesomorphism of Bis-(4-phenyl)thiophenes In order to enhance the lateral dipole conferred by the thiophene unit, two molecules with difluorophenyl groups attached to the central heteroaromatic ring were produced. Additionally, a parent compound, 216, was synthesised, this material has been reported previously and the observed transition temperatures are almost identical [50]. For ease of synthesis only symmetrical compounds were prepared. X R Cpd. Ref. R X X S X Cr 97 [49] C 4 H 9 H * 142.0 SmC X R N I - --------- - --------- * 216 - C 5 H 11 H * 140.0 * 141.4 * 146.0 * 214 - C 5 H 11 F * 66.1 - --------- * 85.6 * 215 - OC 4 H 9 F * 135.4 - --------- * 138.5 * Table 4.6.2.1: Transition temperatures for 2,6-Bis-(4-phenyl)thiophenes. As expected the fluorinated materials have lower melting points than the parent compounds; the high melting point of 215 is due to the two alkoxy chains. All the compounds expect 97 exhibit a nematic phase over a small temperature range, and compound 216 also shows smectic behaviour. Like the phenylnaphthalenes, the highly conjugated core and low length-to-breadth ratio of the bis-(4-phenyl)thiophenes explains the low clearing points and nematic tendency. The clearing points of 215 and 216 are similar, and the nematic range of 214 is actually greater than that of the parent compound, 216. The three rings of 216 all lie in the same plane, due to the interaction between the electron rich sulphur atom and the hydrogen atoms ortho to the bonds attaching the thiophene unit to the phenyl rings. This dipole attraction results in a relatively small intermolecular distance between adjacent molecules, and a resultant stabilisation of mesophase behaviour [50]. The fluoro substituents of 214 272 will interact with the sulphur atom to a greater extent than the hydrogen atoms, hence increasing the clearing point relative to the melting point. If, as seems likely, all four fluoro substituents do align with the sulphur atom, then 214 and 215 should display a very large negative dielectric anisotropy. 273 4.7: Diarylbenzo[b]furans 4.7.1: Introduction Benzo[b]furans are formally related to naphthalene and benzene, however, like thiophene based materials, a benzo[b]furan unit with substituents at the 2- and 5- positions will afford a bent molecular core. Several such materials have recently been studied, and it was found that directly linked phenyl groups are coplanar with the benzo[b]furan moiety, extending orbital conjugation and reducing the effect of the bent core on mesophase stability [51-53]. C5H11 C5H11 O C7H11 O 99 98 Cr 134 SmA 187 N 191 I C7H15 Cr 146 SmA 185 I Figure 4.7.1.1: Benzo[b]furan based materials [53]. Of the two isomers shown in figure 4.6.1.1 82 has the lower mesogenic range, despite the large bond angle between the two phenyl rings in 81. The additional twisted ring junction between the phenyl rings in 82 is likely to be responsible for the lower clearing point. As 81 exhibits a nematic phase, materials based on this isomer are preferable for commercial applications. 274 4.7.2: Mesomorphism of Diarylbenzo[b]furan Compounds Just three diarylbenzo[b]furan compounds were prepared, as recent studies have shown that compounds based on the benzo[b]furan core are unstable when exposed to UV light. R1 R2 O Cpd. Ref. R1 R2 Cr SmA N I 221 - SC 2 H 5 C 3 H 7 * 170.1 - --------- - --------- * 222 - SC 2 H 5 C 5 H 11 * 158.8 - --------- * 183.0 * 223 - SC 2 H 5 C 7 H 15 * 160.9 * 205.0 - --------- * 98 [53] C 5 H 11 C 7 H 15 * 134.0 * 186.8 * 191.4 * Table 4.7.2.1: Transition temperatures of 5-(4-ethylsulfanyl-phenyl)-2-(4-alkyl-phenyl)benzofurans. The series of benzo[b]furan compounds prepared are a striking example of the effect of altering the length of a terminal chain has on the mesogenic properities of a basic structure. Compound 221 is not mesomorphic, this is not surprising as the ratio of core unit length to the terminal chain length is very low. As observed for the terphenyl compounds with a sulphanyl group (see sections 4.1.2 and 4.1.3), the melting points are higher than the dialkyl analogues. The melting point of compound 223 is notably lower than that of the terphenyl homologue, 119 (see table 4.1.3.1). This is due to the effect of a bent structure and the presence of a heteroatom. 275 4.8: Chiral Dopants 4.8.1: Introduction Many chiral dopants based on the chiral ethyl lactate, or butandiol units have been made previously (for examples, see figure 4.8.1.1) [54-56]. The most common type of chiral nematic liquid chiral (type I) is when the chiral centre is located within the terminal chain [57]. These are most frequently encountered because of their relative ease of synthesis and their structural similarity to host nematic compounds, simplifying formulation into suitable eutectic mixtures. O C10H21O O O C O O O O S OC10H21 99 Cr 116 I C5H11 O C O O C O C5H11 100 Cr 212 (SmX* 197) N* 255 I Figure 4.8.1.1: Chiral dopants with lactate or chiral butandiol groups [54, 56]. When the chiral centre is trapped between two mesogeic units (type II), as in 99 and 100 the resultant molecule rarely shows liquid crystalline properties as the aromatic (sp2), polarisable, core units are separated by an aliphatic (sp3) region, this prevents conjugation of the cores, which usually leads to destablisation of any mesomorphic characteristics. However, the advantage of such materials is that it is possible to modulate the physical properties by variation of the length of the flexible spacer, and the spacer restricts 276 molecular rotation about the central axis, producing a high helical twisting power (HTP) when used as a dopant (see section 1.4.2). 4.8.2: Mesomorphism of Chiral Dopants Only one of the nine chiral dopants prepared is mesomorphic, compound 228, but only a monotropic smectic A phase is exhibited. The high melting point (142.7 °C), of the other type I compound synthesised (230) masks any mesophase that might be present. All the materials are solid at room temperature, except compound 238, which, despite having a high molecular weight, is an isotropic liquid. Interestingly, 230, containing a cyclohexyl ring directly linked to a phenyl group has a much higher (a difference of 96.4 °C) melting point than 228, with a biphenyl core, yet comparing the melting points of 235 and 238 the opposite is true. Also, 242, with the biphenyl core has a very similar melting point to 243. Ordinarily, compounds containing a cyclohexyl ring have a lower melting point than those with a fully aromatic core, as the cyclohexyl moiety is more bulky and flexible than benzene [57]. The seemingly erroneous trend observed here is entirely due to the effect of the chiral group on the overall structure, and hence packing order of the materials prepared. The melting point of 248 is higher than that of 247 because as observed previously, the highly polarisiable oxygen of the ethoxy chain increases the ability of the molecules to pack effectively. 277 O O R1 = C8H17O R2 = C4H9 O Cpd. Structure Transition Temperatures (°C) O 228 1 R O Cr 46.3 (SmA 41.7) I O Cr 142.7 I O 2 230 R 242 R1 243 R2 O O O Cr 160.4 I O Cr 158.8 I O O O O R2 247 O Cr 48.3 I O R2 248 O O Cr 65.8 I O R1 Cr 136.4 I 244 R1 O 235 R1 O O R1 Cr 122.8 I R2 Liquid O O 238 R 2 O O O O Table 4.8.2.1: Transition temperatures of chiral dopants. 278 4.9: References 1. H. Schubert, H. J. Lorenz, R. Hoffmann, F. Franke, Z. Chem., 1966, 6, 337. 2. G. W. Gray, M. Hird, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1991, 195, 221. 3. L. K. M. Chan, G. W. Gray, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1988, 158B, 209. 4. L. K. M. Chan, G. W. Gray, D. Lacey, T. Srithanratana, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1987, 150B, 335. 5. L. K. M. Chan, G. W. Gray, D. Lacey, Mol. Cryst. Liq. Cryst., 1985, 123, 185. 6. P. Balkwill, D. Bishop, A. Pearson, I. C. Sage, Mol. Cryst. Liq. Cryst., 1985, 123, 1. 7. M. Sasaki, K. Takeuchi, H. Sato, H. Takatsu, Mol. Cryst. Liq. Cryst., 1984, 109, 169. 8. S. M. Kelly, Helv. Chim. Acta, 1984, 67, 1572. 9. V. Reiffenrath, J. Krause, H. J. Plach, G. Weber, Liq. Cryst., 1989, 5, 159. 10. W. L. McMillian, Phys. Rev .A, 1973, 8, 1921. 11. M. Hird, Ph.D. Thesis, University of Hull, England, 1990. 12. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, J. Chem. Soc., Perkin. Trans. 2, 1989, 2041. 13. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1990, 191, 1. 14. G. W. Gray, M. Hird, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1991, 204, 43. 15. M. Hird, K. J. Toyne, G. W. Gray, D. G. McDonnell, I. C. Sage, Liq. Cryst., 1995, 18, 1. 16. C. Vauchier, F. Vinet, N. Maiser, Liq. Cryst., 1989, 5, 141. 17. M. Goulding, S. Greenfield, O. Parri, D. Coates, Mol. Cryst. Liq. Cryst., 1995, 265, 27. 18. H. Matsuzaki, Y. Matsunaga, Bull. Chem. Soc. Jpn., 1990, 63, 2300. 19. Y. Matsunaga, H. Matsuzaki, N. Miyajima, Bull. Chem. Soc. Jpn., 1990, 63, 886. 20. Y. Matsunaga, N. Miyajima, Mol. Cryst. Liq. Cryst., 1990, 178, 157. 21. M. Hird, K. J. Toyne, G. W. Gray, Liq. Cryst., 1995, 18, 1. 22. D. Volander, A. Apel, Ber. 1932, 65, 1101. 23. C. Wiegand, Z. Naturforsh, 1956, C.A. 50, 13543e. 24. G. W. Gray, D. Lacey, Mol. Cryst. Liq. Cryst., 1983, 99, 123. 279 25. U. Lauk, P. Strabal, H. Zollinger, 1981, Helv. Chim. Acta, 64, 1847. 26. U. Lauk, P. Strabal, H. Zollinger, 1983, Helv. Chim. Acta, 66, 1547. 27. M. Hird, K. J. Toyne, G. W. Gray, S. E. Day, D. G. McDonnell, Liq. Cryst., 1993, 15, 123. 28. G. W. Gray, K. J. Toyne, D. Lacey, M. Hird, European Patent 90902655.1, 1990. 29. B.E. Segelstein, T.W. Butler, B.L. Chenard, J. Org. Chem., 1995, 60, 12-13. 30. C.C. Dong, P. Styring, J. W. Goodby, L. K. M. Chan, J. Mater. Chem., 1999, 9, 1669. 31. G-X. Sun, B. Chen, H. Tang, S-Y. Xu, J. Mater. Chem., 2003, 13, 742. 32. H. M. Vorbrodt, Ph.D. Thesis, University of Halle, Germany, 1987. 33. H. M. Vorbrodt, S. Deresch, H. Kreese, A. Wiegeleben, D. Demus, H. Zaschke, J. Prakt. Chem., 1981, 323, 902. 34. C. C. Dong, Ph.D. Thesis, University of Hull, England, 1990. 35. A. Boller, M. Schadt, A. Villiger, GB Patent 2085877, 1981. 36. D. Demus, H. Zaschke, C. Tschierske, H. Maike, German Patent DD227720A1, 1985. 37. S. Trombotto, unpublished results. 38. H. Zasche, J. Prakt. Chem., 1975, 317, 617. 39. K. Terashima, M. Ichihashi, F. Takeshita, M. Kikuchi, K. Furukawa, European Patent 0293763, 1987. 40. K. Terashima, M. Ichihashi, F. Takeshita, M. Kikuchi, K. Furukawa, European Patent 0293764, 1987. 41. S. M. Kelly, J. Funfschilling, Liq. Cryst., 1995, 19, 519. 42. C. S. Oh, Mol. Cryst. Liq. Cryst. 1972, 19, 95. 43. D. L. Fishel, P. R Patel, Mol. Cryst. Liq. Cryst. 1972, 17, 139. 44. K. Seto, S. Takahashi, T. Tahara, J. Chem. Soc., Chem Comm., 1985, 122. 45. V. S. Bezborodov, V. I. Lapanik, Liq. Cryst., 1991, 10, 803. 46. C. C. Dong, P. Styring, L. K. M. Chan, J. W. Goodby, Mol. Cryst. Liq. Cryst., 1997, 302, 289. 47. D. Demus, Mol. Cryst. Liq. Cryst., 2001, 346, 25. 48. G. W. Gray, S. M. Kelly, J. Mater. Chem., 1999, 9, 2037. 49. W. Schroth, S. Dunger, F. Billig, R. Spitzer, R. Herzschuh, A. Vogt, T. Jende, G. Israel, J. Barche, D. Strohl, J. Sieler, Tetrahedron, 1996, 52, 12677. 280 50. N. L. Campbell, W. L. Duffy, G. I. Thomas, J. H. Wild, S. M. Kelly, K. Bartle, M. O’Neill, V. Minter. R. P. Tuffin, J. Mater. Chem., 2002, 12, 2706. 51. M. R. Friedman, K. J. Toyne, J. W. Goodby, M. Hird, J. Mater. Chem., 2001, 11, 2759. 52. M. R. Friedman, K. J. Toyne, J. W. Goodby, M. Hird, Liq. Cryst., 2001, 28, 901. 53. M. R. Friedman, Ph.D. Thesis, University of Hull, England, 2001. 54. M. Marcos, A. Omenat, J. L. Serrano, Liq. Cryst., 1993, 13, 843. 55. S. M. Kelly, M. Schadt, H. Seiberle, Liq. Cryst., 1992, 11, 761. 56. G. Heppke, D. Lotzsch, F. Oestreicher, Z. Naturforsch., 1987, 42a, 279. 57. J. W. Goodby, A. J. Slaney, C. J. Booth, I. Nishiyama, J. D. Vuijk, P. Styring, K. J. Toyne, Mol. Cryst. Liq. Cryst., 1994, 243, 213. 58. D. Demus, Z. Chem., 1986, 26, 6. 281 Chapter Five: Summary and Conclusions 282 5.1: General Summary and Conclusions The aim of this work was to synthesise compounds suitable for future display devices based on the nematic liquid crystal phase. Primarily, materials were targeted for the Vertically Aligned Nematic (VAN) device so a high optical anisotropy (birefringence) and a negative dielectric anisotropy were the physical properties most desired. In order to meet these requirements many compounds based on the highly successful 1,2difluorobenzene group were synthesised. Difluoroterphenyls, difluorophenylnaphthalenes benzodioxinanes, and benzodioxaborinanes were all prepared and the mesogenic properties evaluated. Additionally, materials with high helical twisting powers (HTP) when used as dopants in suitable nematic hosts were targeted, as they could be used in Supertwisted Nematic (STN) devices. 283 5.2: Materials for Vertically-Aligned Nematic (VAN) Applications 5.2.1: Difluoroterphenyls Many new 2,3-difluoroterphenyls and 2’,3’-difluoroterphenyls with dialkyl, and alkylalkoxy terminal chains have been prepared, using well established synthetic routes [1]. The transition temperatures of the new compounds are consistent with the literature materials, giving valuable information on the effect of chain length on mesogenic properties. The new 2’,3’-difluoroterphenyls with short terminal chains are nematogens with large nematic ranges, making them very good candidates for nematic hosts. Compound 72, having a melting point of 40.0 °C, is likely to be the compound with the most potential. Novel 2,3-difluoroterphenyls and 2’,3’-difluoroterphenyls with alkylsulphanyl terminal chains were successfully synthesised; and it was found that the phase behaviour of these compounds differed significantly from the dialkyl, and alkyl-alkoxy homologues. The compounds with fluoro substituents on the centre ring generate the nematic and smectic A phases, and those with fluoro substituents on the outer ring generate the crystal E and smectic A phases. No tilted phases were observed in the pure compounds, however when the alkylsulphanyl compounds were mixed with a weakly smectic C commercially available host, 56 the semectic C phase was exhibited showing that the dipole moment of the sulphur atom is significant enough to stabilise the smectic C phase, particularly in conjunction with outeredge fluoro substituents. This is a very interesting result, and the alkylsulphanyl materials could have potential in ferroelectric mixtures. Four terphenyls with no lateral substituents were also prepared, as predicted they possess very high melting and clearing points. 284 5.2.2: Difluorophenylnaphthalenes Several 2,3-difluorophenylnaphthalenes with both alkoxy, and alkyl chains attached to the naphthalene core have been prepared. An important product of this research was the development of a new synthetic route to 6-alkylnaphthols, which is superior to the previous method [2]. All of the novel 2,3-difluorophenylnaphthalenes are nematogens with low nematic to isotropic transition temperatures relative to the melting points. This limits their use as host materials, but they have potential as components of mixtures. Additionally, two parent compounds were prepared, as well as, one 2- fluorophenylnaphthalene, and one 2,3-difluorobiphenylnaphthalene material, all were nematogens with higher melting points than the 2,3-difluorophenylnaphthalenes. 5.2.3: Benzodioxinanes No mesomorphic compounds containing a benzodioxinane ring have previously been reported. However, it was thought that attaching a phenyl or biphenyl unit to the benzodioxinane ring should produce compounds with mesogenic behaviour. Phenylbenzodioxinanes were prepared first, by coupling the appropriate phenylboronic acid to the bromine of alkyl-substituted bromobenzodioxinanes. These were made, in turn by the condensation reaction of 5-bromo-2-hydroxybenzyl alcohol and an aldehyde. Eight 2,3-difluorophenylbenzodioxinanes were prepared, however none displayed any enantiotropic phase morphology. The 2-fluorophenylbenzodioxinanes prepared later show more potential, as all but the compound with the longest terminal chains (159) displayed the nematic phase. Observed melting points are very low, and four of the seven materials showed smectic A behaviour. For comparison six parent materials were synthesised, of these only two (151 and 153) were mesogenic, exhibiting crystal E and smectic A phases. 285 Six 2,3-Difluorobiphenylbenzodioxinanes with dialkyl terminal chains were prepared, as it was thought that the extra phenyl ring would increase the mesogenic range, relative to the 2,3-difluorophenylbenzodioxinanes. This proved to be the case; all six exhibited a nematic phase, with high clearing points and all except the dipropyl homologue showed a smectic A phase. The next step in the evolution of the project was to invent molecules with a ring on both sides of the benzodioxinane core. Attaching a phenyl ring onto the acetal side of the core proved a synthetic challenge, however, it was accomplished be using very mild conditions for the acetal formation step. A compound was prepared with a difluorophenyl unit attached to the aromatic side of the benzodioxinane core, and a phenyl ring with no lateral substituents on the other (179). An isomeric molecule, with the difluorophenyl unit on the acetal side of the core was synthesised (182), as well as a parent compound (178) and one with a difluorophenyl unit on both sides (183). All four compounds are nematogens, and it was found that the clearing point of 179 is actually greater than that of 182, when it was predicted to be lower, from interannular twisting effects. The final series of compounds based on the benzodioxinanes core to be prepared were the phenyl-2-cyclohexylbenzodioxinanes. Two compounds were synthesised with a single fluoro substituent on the inner-edge of the phenyl ring, four with the difluorophenyl unit and one parent compound. It was found that the parent material exhibited the smectic A phase only; the mono-fluorinated species with a propoxy chain is a nematogen only, but the octyloxy homologue showed the smectic A and C phases, as well as the nematic phase. All four of the difluoro compounds show the smectic A and nematic phases, as expected. In addition to these compounds a material with a lateral fluoro substituent on the benzodioxinane ring itself was synthesised via a novel route using phenyl boronic acid as a template [3]. This species also has a fluoro substituent on the phenyl ring, and is a nematogen with similar melting and clearing points to the structural isomer with a difluoro unit. The synthesis of a new core unit a benzodioxaborinine ring was attempted. However, it was found the products were very thermally unstable, and decomposed to the diol starting material. 286 5.2.4: Other Core Units A range of materials with different core units were also synthesised. One biphenylpyrimidine species was prepared, it displays similar mesogenic behaviour homologues literature compounds, exhibiting both smectic A and C phases [4]. Three diarylbenzo[b]furan compounds with an ethylsulphanyl terminal chain were prepared, as it was thought that they would possess a high birefringence. The mesogenic behaviour of the series proved very interesting; the homologue with a propyl terminal chain (221) is non-mesogenic, the pentyl derivative is a nematogen, and the heptyl species exhibits the smectic A phase only. Two difluorobiphenyldioxaborinane materials with dialkyl chains were prepared. They were found to be nematogens, as expected from previous work [5]. The melting points of both compounds are low, and clearing points relatively high. However, the reactivity of the boronic ester group, and hence poor chemical stability of the system, limits their use in commercial applications. Two compounds with a difluorophenyl unit attached to both sides of a thiophene ring were invented. These are very interesting materials as both are nematogens, and their clearing points are close to that of the parent species, despite possessing four lateral substituents. 287 5.3: Chiral Dopants Nine materials, intended for use as chiral dopants were synthesised by an esterification of different acids and chiral alcohols, using the DCC-DMAP method. Despite all of them possessing either a biphenyl, or cyclohexylphenyl unit only the compound with the lowest melting point (228) exhibits any mesomorphic behaviour, and it is only a monotropic smectic A phase. However, as they are to be used in very small quantities within a mixture it is not necessary that they are liquid crystalline. A low melting point is desired; compounds 247 and 248 both satisfy this requirement, and compound 238 is a liquid, despite its high molecular weight. 288 5.4: Physical Properties Some interesting mixtures have been found, and some some promising physical properties have been found. Such results have been obtained very recently by collaborators at QinetiQ and cannot be included here, but will be published in due course. 289 5.5: References 1. G. W. Gray, M. Hird, D. Lacey, K. J. Toyne, J. Chem. Soc., Perkin. Trans. 2, 1989, 2041. 2. D. Coates, G. W. Gray, Mol. Cryst. Liq. Cryst., 1977, 119, 122. 3. G. Casiraghi, G. Casnati, G. Puglia, G. Sartori, Synthesis, 1980, 124. 4. K. Terashima, M. Ichihashi, F. Takeshita, M. Kikuchi, K. Furukawa, European Patent 0293763, 1987. 5. C. C. Dong, P. Styring, L. K. M. Chan, J. W. Goodby, Mol. Cryst. Liq. Cryst., 1997, 302, 289.