The influence of vicinal threo-difluorination on electro-optic and mesogenic properties of propyleneoxy-linked nematic liquid crystals

Article abstract of DOI:10.1016/j.tet.2014.05.027

A protocol for the preparation of a series of liquid crystals is presented, where the structures carry a central propyleneoxy motif carrying two vicinal threo-C-F bonds. The negative dielectric anisotropy (-Δε) of the resultant liquid crystals has been explored. The stereoelectronic relationship between the vicinal C-F bonds was anticipated to orientate the fluorine atoms gauche to each other when the propylene chain is extended. This is shown to be the case. This orientation of the C-F bonds generates a net dipole perpendicular to the molecular axis, a prerequisite for the design of dielectrically negative liquid crystals. However the molecules adopt a conformation where one C-F bond reinforces the net molecular dipole, and the other has a counter effect, thus the introduction of the motif has an almost neutral effect on dielectric anisotropy (Δε_virt) of these candidate liquid crystals. However, introduction of the difluoro motif raises the melting points of the liquid crystals and increases their conformational rigidity.

Full text of DOI:10.1016/j.tet.2014.05.027

Tetrahedron 70 (2014) 4626e4630
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The influence of vicinal threo-difluorination on electro-optic and
mesogenic properties of propyleneoxy-linked nematic liquid
crystals
,
a
a,
Nawaf Al-Maharik a, Peer Kirsch b , Alexandra M.Z. Slawin , David O’Hagan
*
*
a EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews, Fife KY16 9ST, UK
b Merck KGaA, Liquid Crystals R&D Chemistry, Frankfurter Str. 250, D-64293 Darmstadt, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A protocol for the preparation of a series of liquid crystals is presented, where the structures carry
a central propyleneoxy motif carrying two vicinal threo-CeF bonds. The negative dielectric anisotropy
Received 10 February 2014
Received in revised form 28 April 2014
Accepted 12 May 2014
(ꢀ
D 3 ) of the resultant liquid crystals has been explored. The stereoelectronic relationship between the
vicinal CeF bonds was anticipated to orientate the fluorine atoms gauche to each other when the pro-
pylene chain is extended. This is shown to be the case. This orientation of the CeF bonds generates a net
dipole perpendicular to the molecular axis, a prerequisite for the design of dielectrically negative liquid
crystals. However the molecules adopt a conformation where one CeF bond reinforces the net molecular
dipole, and the other has a counter effect, thus the introduction of the motif has an almost neutral effect
Available online 17 May 2014
on dielectric anisotropy (
D 3 virt) of these candidate liquid crystals. However, introduction of the difluoro
motif raises the melting points of the liquid crystals and increases their conformational rigidity.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
molecular components in particular for LCD-TV and PC mon-
itors.6e10 Such compounds have a molecular dipole moment, which
Novel liquid crystals (LCs) are in high demand presently as
a consequence of the exponential growth in global personal device
ownership, such as smart phones.1,2 As the specifications for dis-
play screens for such devices are increasingly being improved, new
component materials are required to follow or even anticipate the
on-going technological developments in order to keep pace with
product diversification and consumer demand.3,4 Organofluorine
compounds constitute an important subclass of the materials used
in display screen development.5 This is because the CeF bond is
polarised and contributes a large dipole moment, however, the
fluorine atom itself is not polarisable, and displays only weak in-
termolecular interactions. This latter property often confers low
viscosity on organofluorine compounds and thus they orientate
rapidly under the influence of changing electric fields. Another
effect of fluorination is its positive impact on mesogenic properties,
such as wide nematic phase ranges and high clearing tempera-
tures.5 Also the strength of the CeF bond adds durability and thus
reliability over the product lifetime. In this context, dielectrically
negative LC materials have become attractive in the design of
is orientated perpendicular to the molecular axis. This can be
contrasted with dielectrically positive compounds, which have the
molecular dipole orientated along the molecular axis.11
It became an objective to prepare a series of dielectrically neg-
ative LC candidates carrying a vicinal difluoro motif on an aliphatic
linker.12 Given that the central alkyl chain will preferentially adopt
an anti-zig-zag conformation, then a threo (rather than erythro)
arrangement of CeF bonds is required to place the two vicinal CeF
bonds gauche to each other. Additional stability for this arrange-
ment is expected as it is well known that vicinal CeF bonds have
a conformational preference, which predisposes them to align
gauche to each other. This comes from the stereoelectronic gauche
effect, which recognises that CeH bonds adopt preferred anti ori-
entations to CeF bonds, such that the electron density of the CeH
bond can hyperconjugate into the sꢁ
antibonding orbital.13,14
CeF
The stabilising effect is relatively weak contributing up to
1.0 kcal molꢀ1 for
a
gauche over anti preference in 1,2-
difluoroethane, but it should enhance or ‘rigidify’ the inherent
zig-zag conformation of the alkyl linker. It is expected that the
gauche orientation of the CeF bonds will raise the overall molecular
dipole perpendicular to the long molecular axis of the liquid crystal.
We report in this study the synthesis of the six LC candidates 1e6,
five of which have a vicinal threo-difluoro motif. Their LC charac-
teristics are then compared relative to each other (Fig. 1).
* Corresponding authors. Tel.: þ44 1334 467176; fax: þ44 1334 463808 (D.O’H.);
e-mail addresses: peer.kirsch@merckgroup.com (P. Kirsch), do1@st-andrews.ac.uk
(D. O’Hagan).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.05.027

N. Al-Maharik et al. / Tetrahedron 70 (2014) 4626e4630
4627
Fig. 1. Target liquid crystalline (LC) candidates with 2e6 containing the difluoro threo-vicinal motif.
2. Results and discussion
particularly relative to analogue 3, to determine the influence of the
fluorine atoms on the LC properties. The synthesis route to 6 is il-
lustrated in Scheme 2. In this case allylic alcohol 10 was hydroge-
nated to generate alcohol 18, and the alcohol was then subjected to
etherification with phenol 12c, to generate 6. An analytically pure
sample was also prepared by semi-preparative HPLC for LC prop-
erty analysis.
The properties of the prepared compounds 1e6 were assessed
for their LC characteristics, and the data is summarised in Table 1.
The liquid crystals 1e6 do not show any mesophases. This is also
reflected in the low virtual clearing temperatures, which are all
below ꢀ10 ꢂC. However, the melting points of the
difluoropropyleneoxy-linked materials 1e5 are all significantly
higher (>53 ꢂC) than for the non-fluorinated propyl-ether linked
compound 6 (33 ꢂC). This is an indication of fluorine-induced in-
termolecular electrostatic interactions, stabilising the crystal
lattice.
The target LCs 1e6 have a common general structure. They all
possess a propyl-cyclohexyl motif linked through the propyl chain
to a phenol ether. For structures 2e6, the difluorovicinal motif was
introduced by conversion of an epoxide ring in intermediates
13aee by sequential stereospecific conversion of the original
epoxide CeO bonds to CeF bonds.15,16 Thus epoxides 13aee
were key intermediates. They were prepared by the Hor-
nereWordswortheEmmons reaction of cyclohexylaldehyde 7 and
phosphonate 8.17 The resultant (E)-
a,b-unsaturated ester 9 formed
as a 1:4 mixture of isomers due to the configuration of substituents
across the cyclohexyl ring. This isomeric ratio could be improved by
epimerisation to a 1:9 ratio after treatment of 9 with base (KOH/
EtOH)18 (Scheme 1).
Reduction to allylic alcohol 10 was straightforward, and then
epoxidation with m-CPBA generated epoxy alcohol 11, which was
isolated as a single diastereoisomer after chromatography. Epoxy
alcohol 11 served as a common intermediate to the vicinal
difluorinated LC targets 2e6. At this stage it was treated with
a series of different phenols, 12aee under conditions described
previously6 to generate ethers 13aee. The epoxide functionality of
13aee was then taken through to the corresponding vicinal
difluoro motifs in a three step protocol.7,9 This involved epoxide
ring opening with Et3N$3HF, to give a mixture of fluorohydrin
regio-isomers, namely 14aee and 15aee. These reactions did not
show any particular selectivity and the regio-isomers were gener-
ally formed in 1:1 ratios. Regio-isomers 14aed were purified by
chromatography whereas regio-isomer 14e was inseparable from
15e, and in that case both isomers were treated together to gen-
erate a mixture of 16e and 17e. Compounds 14aed were obtained
after two rounds of chromatography and were converted to their
corresponding triflates 16aed. The triflates were then treated,
without further purification, with Et3N$3HF (65 ꢂC) to generate the
desired vicinal difluoro products 1e5. This protocol displayed
complete stereointegrity, and only the threo-vicinal difluoro iso-
mers were formed. On the other hand, when trifates 17a, 17c and
17e generated from regio-isomers 15a, 15c and 15e were subjected
to identical fluorination conditions, these substrates gave complex
rearrangement product mixtures. The products were not charac-
terised, but the presence of significant levels of fluoromethyl
groups was obvious in the 19F NMR spectra of the product mixtures.
Samples of each of the difluoro ethers 1e5 derived from 16aed,
were further purified by preparative HPLC, such that analytically
pure samples (w400 mg) were available for LC property analyses.
The non-fluorinated analogue 6 was also prepared. This was
required such that it could be assessed as a comparative compound,
Compound 1 is distinct in that it does not carry a polar terminal
group, therefore, the dielectric anisotropy of 1 is mainly caused by
the electronegative threo-difluoro motif in the linker. This moder-
ate negative dielectric anisotropy (
D 3 virt) indicates that the overall
molecular dipole moment is oriented in a perpendicular manner
relative to the long molecular axis, as is well known for other liquid
crystals with a vicinal-difluoroalkylene subunit.4 In the case of
compounds 2 and 5, the polar fluorine substituents on the aromatic
head groups twist the overall dipole moment more in line with the
long molecular axis, rendering liquid crystal 2 dielectrically nearly
neutral in spite of the presence of seven electronegative hetero-
atoms. This indicates that the angle between the overall dipole
moment vector and the director of the nematic phasedapproxi-
mated by the long molecular axisdis around 53ꢂ, where
D 3 be-
comes zero, independent from the molecular dipole moment.5 In
contrast, compounds 3, 4 and 6 with a 2,3-difluorophenyl head
group show strong negative dielectric anisotropy. In general 1-
alkoxy-2,3-difluorobenzenes prefer an anti arrangement of the
arylealkoxy bond by about 10:1 over the syn conformation, which
is reflected nicely in the crystal structure of 4.6 A comparison be-
tween 3 and 6 allows some conclusions to be drawn on the pre-
ferred conformation; the virtual clearing point of 3 is 18.1 K higher
than that of the analogue 6 with the non-fluorinated linker. This
can be seen as evidence for the conformational rigidification of the
linker group by threo-difluorination.
Unexpectedly, the comparison of the dielectric anisotropies of 3
(
D
3
¼ꢀ5.69) and 6 (
D
3
¼ꢀ5.77) are very similar. A closer look at
virt
virt
the crystal structure of 3 suggests a rationale assuming this is
a highly populated conformer in the LC phase; the all-gauche
conformation around the fluorine and oxygen atoms in the linear

4628
N. Al-Maharik et al. / Tetrahedron 70 (2014) 4626e4630
Scheme 1. Synthesis route to LC candidates 1e5 carrying a threo-vicinal difluoro motif in the aliphatic linker.
Scheme 2. Preparation of reference liquid crystal 6 without an aliphatic vicinal threo-difluoro motif.
linker chain shows a uniform handedness (gþgþgþ or gꢀgꢀgꢀ). In
the 2,3-difluorophenylene unit, the ether oxygen and the 3-fluorine
substituent are pointing their local dipole moments roughly in the
same direction, whereas the 4-fluorine of the linker is pointing in
the opposite direction. This results in a partial cancellation of the
overall dipole moment and a reduction of the overall dielectric
anisotropy. In summary, this means that the difluoropropyleneoxy
chain is moderately effective in rigidifying the liquid crystal’s
mesogenic core structure, but it is counter-productive for in-
creasing the negative dielectric anisotropy. Geometrically it is im-
possible to combine in such a 3,4-difluoropropyl ether, an all-
gauche conformationda gþgꢀgþ or gꢀgþgꢀ, the conformation nec-
essary to avoid the dipole cancellation of the electronegative het-
eroatoms with the required linear zig-zag conformation of the

N. Al-Maharik et al. / Tetrahedron 70 (2014) 4626e4630
4629
Table 1
two vicinal fluorines of the hydrocarbon would orientate to in-
crease the molecular dipole and as a consequence increase the ꢀve
dielectric anisotropy of the various analogues. A direct comparison
of the properties of compounds 3 and 6, which differ only in the
influence of the vicinal threo-difluorines, indicated that these
The phase transition temperatures are given in ꢂC
No.
Phase transitions (Mp in ꢂC)
TNI,virt
D
3
Dnvirt
virt
1
2
3
4
5
6
C 53 I
C 54 I
C 63 I
C 73 I
C 69 I
C 33 I
ꢀ32.1
ꢀ71.0
ꢀ33.7
ꢀ10.1
d
ꢀ4.71
ꢀ0.43
ꢀ5.69
ꢀ7.35
d
d
d
0.0855
0.090
d
fluorines had a neutral impact on the ꢀDε dielectric anisotropy.
Essentially one CeF bond has a reinforcing effect and the second
orientated to counter the overall molecular dipole. This was ap-
parent from X-ray structures. It is found, however, that melting
points increase when the vicinal difluoro linker is introduced, in-
dicative of increased electrostatic interaction between molecules,
and thus a rigidifying effect of this motif. This information will be
used to refine the design of more effective ꢀve dielectric aniso-
tropic liquid crystalline candidates.
ꢀ51.8
ꢀ5.77
0.0898
C¼crystalline, Mp¼melting point, I¼isotropic. The virtual parameters TNI,virt and
D
nvirt were determined by linear extrapolation from a 10% w/w solution in the
commercially available Merck mixture ZLI-4792 (TNI¼92.8 ꢂC,
D
3
¼5.3, n¼0.0964).
D
The extrapolated values are corrected empirically for differences in the order pa-
rameter.
D
3
virt was extrapolated from ZLI-2857 (TNI¼82.3 ꢂC,
D
3 ¼ꢀ1.4, n¼0.0776).
D
The phase transition onset temperatures (Mps) were determined by differential
scanning calorimetry (DSC). The heating/cooling rate was 10 K/min.
Experimental details are provided in Supplementary data.
linker group, thus there are limitations to this motif in maximising
the molecular dipole moment. The highest dielectric anisotropy is
Acknowledgements
found with 4 (
D
3
¼ꢀ7.35), which is clearly a consequence of the
virt
D.O’H. thanks the European Research Council for an Advanced
Investigator Grant and the Royal Society for a Wolfson Merit Award.
P.K. thanks Andreas Ruhl and David Till of Merck, Darmstadt, for
technical assistance.
additional oxygen atom of the para-substituted ethoxy ether,
pointing its dipole to reinforce that of the CeF bonds of the
difluoroaryl moiety (see X-ray of 4, Fig. 2).
Fig. 2. X-ray-derived structures of three (3, 6 and 4) of the prepared liquid crystals. For structures 3 (CCDC 997680) and 4 (CCDC 997681), the 4-fluoro substituent of the pro-
pyleneoxy linker group is pointing into a direction opposite to the other carboneheteroatom bonds, resulting in a partial cancellation of the local dipole moments and concomitant
reduction of the overall molecular dipole moment. Structure 6 (CCDC 997682) is a reference compound indicating, by comparison that the threo-difluoro linker does not change the
overall conformation of these liquid crystals.
3. Conclusion
Supplementary data
In conclusion we have demonstrated a relatively efficient syn-
thesis protocol to prepare samples of nematic liquid crystals, car-
rying a vicinal threo-difluoro motif. The idea was to explore if the
Supplementary data associated with this article can be
found in the online version, at http://dx.doi.org/10.1016/
j.tet.2014.05.027.

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N. Al-Maharik et al. / Tetrahedron 70 (2014) 4626e4630
10. Kirsch, P.; Bremer, M.; Huber, F.; Lannert, H.; Ruhl, A.; Lieb, M.; Wallmichrath, T.
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