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
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220
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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.
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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.