Cholestane-based liquid crystals containing a difluorooxymethylene bridge

Article abstract of DOI:10.1016/j.jfluchem.2005.09.018

A new class of steroid-based liquid crystals was synthesized and characterized with regard to their mesogenic and chiroptical properties. The β-selective formation of the cholestanyl difluoromethyl ether bridge was achieved by an oxidative fluorodesulfura

Full text of DOI:10.1016/j.jfluchem.2005.09.018

Journal of Fluorine Chemistry 127 (2006) 146–149
www.elsevier.com/locate/fluor
Short communication
Cholestane-based liquid crystals containing a
difluorooxymethylene bridge
b
Peer Kirsch a, , Thomas Mergner
*
a Merck Ltd. Japan, Atsugi Technical Center, 4084 Nakatsu, Aikawa-machi,
Aiko-gun, Kanagawa 243-0303, Japan
b Merck KGaA, Liquid Crystals Division, D-64271 Darmstadt, Germany
Received 21 July 2005; received in revised form 16 September 2005; accepted 17 September 2005
Available online 9 November 2005
Abstract
A new class of steroid-based liquid crystals was synthesized and characterized with regard to their mesogenic and chiroptical properties. The
b-selective formation of the cholestanyl difluoromethyl ether bridge was achieved by an oxidative fluorodesulfuration procedure.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Chiral nematic; Cholestane; Fluorodesulfuration, oxidative; Helical twisting power; Liquid crystals; Steroids
1. Introduction
with any type of active matrix LCD technology [2]. Additional
favourable features may be improved solubility and the ease of
adaptation of the electrooptical properties of the chiral dopant
to different types of nematic liquid crystal preparations.
Reinitzer’s discovery in 1888 [1] that cholesteryl benzoate
(1) forms at elevated temperatures an up to then unknown state
of matter – a liquid crystalline mesophase – triggered a
development culminating in the last few years in the ubiquitous
presence of liquid crystal displays (LCD) in our daily lives
[2,3]. The mesophase formed by cholesteryl benzoate was later
classified as ‘‘chiral nematic’’ or simply ‘‘cholesteric’’ (Scheme
1) [4].
2. Results and discussion
From our previous work [7] we knew that liquid crystals
containing a difluorooxymethylene bridge in their mesogenic
core structure do not only fulfil LCD manufacturers’ stability
criteria. In addition – compared to their directly or ester linked
analogues – they usually show a dramatically improved
solubility in combination with a significant extention of their
nematic phase range.
Cholesterol esters, such as the nonanoate 2, are still widely
used as additives for modern liquid crystal mixtures in order to
induce chirality in an otherwise achiral nematic host, rendering
the whole mixture cholesteric [5]. The ability to induce chirality
in a nematic phase is quantified as the helical twisting power
(HTP) [6].
For the design of our new class of chiral dopants, the
cholesteryl moiety containing one double bond was replaced by
a cholestanyl group, in order to avoid complications during the
synthesis of the difluorooxymethylene bridge [7]. Starting from
From a practical point of view, cholesterol esters sometimes
cause problems. This is mostly due to the intrinsic lability of the
ester bond which can either hydrolyse or eliminate the
carboxylic acid component. If not carefully controlled, this
may result in unpredictable changes of the pitch of the
cholesteric phase during the mixture and LCD panel production
process. Therefore, there is a need for chiral dopants which are
easily accessible, chemically more robust and fully compatible
Scheme 1. Cholesteryl benzoate (1), the prototype of ‘‘cholesteric’’, i.e., chiral
nematic, liquid crystals. Other cholesterol esters, such as cholesteryl nonanoate
(2), are currently used as chiral dopants for liquid crystal compositions.
* Corresponding author. Tel.: +81 46 286 2523; fax: +81 46 285 3838.
E-mail address: peer_kirsch@merck.co.jp (P. Kirsch).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.09.018

P. Kirsch, T. Mergner / Journal of Fluorine Chemistry 127 (2006) 146–149
147
cholestanone (3), the ketenedithioketal 4 [8] was synthesized as
the central steroid building block. By a simple four-step one-pot
procedure, the different phenol components could now be
attached via a protonation–equilibration–addition–fluorodesul-
furation reaction sequence, furnishing the liquid crystals 5–8 in
good yields. The exclusive formation of the desired b-
cholestanyl isomers was achieved by allowing the primarily
formed cholestanyl dithianylium salt a/b-isomer mixture (9) to
equilibrate to the thermodynamically preferred b-dithianylium
salt at room temperature for a few minutes (Scheme 2) [7].
All new compounds were fully characterized by mass
spectrometry, 1H, 13C and 19F NMR spectroscopy, and optical
rotation. Their purity was verified to be >98.5% by HPLC. As
expected, the liquid crystals 5–8 showed relatively low melting
points (especially if their high molecular weight is taken into
account) and good solubility in combination with broad
nematic phases. The compounds 7 and 8, derived from a two-
ring phenol component, had smectic A phases in addition.
The dielectric anisotropies (De) of the materials are
determined by the nature of the phenol component used for
their syntheses. Compounds 5 and 6 have strong dipole
moments parallel to their long molecular axes, resulting in
positive dielectric anisotropies. The only weakly polar
compound 7 is dielectrically neutral, whereas the liquid crystal
8 with its dipole moment perpendicular to the long molecular
axis has a negative dielectric anisotropy. The birefringences
Scheme 2. Syntheses of the cholestanone-derived liquid crystals 5–8, and the orientationof their molecular dipole moments (m) relative to the long molecular axes: (a) 2-
trimethylsilyl-1,3-dithiane, n-BuLi, THF; ꢀ70 8C ! RT (79%). (b) 1—CF3SO3H, CH2Cl2, ꢀ15 8C (5 min) ! RT (30 min) ! ꢀ70 8C; 2—X-PhOH (5: 3,4,5-
trifluorophenol, 6: 3-fluoro-4-trifluoromethoxyphenol, 7: 4-(trans-4-propylcyclohexyl)phenol and 8: 4-ethoxy-2,3-difluoro-40-hydroxybiphenyl), NEt3, CH2Cl2,
ꢀ70 8C; 3—NEt3ꢁ3HF, ꢀ70 8C, 4—1,3-dibromo-5,5-dimethyl hydanthoin (DBH), CH2Cl2, ꢀ70 8C ! ꢀ20 8C (5: 66%, 6: 70%, 7: 50% and 8: 67%). The dithianylium
saltintermediates a-9 and b-9 (box) arecontrolling the stereochemistry. A detailedanalysis of the mechanism of the four-step one-potprocedure (b) is provided inref. [7].

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P. Kirsch, T. Mergner / Journal of Fluorine Chemistry 127 (2006) 146–149
(Dn), particularly of the compounds 5–7 containing only one
aromatic moiety, are exceptionally low. This is presumably due
to the combination of low polarizability with a relatively large
lateral extent of the cycloaliphatic steroid skeleton.
(500 MHz, CDCl3, 303 K): d = 6.84 (t, J = 8.1 Hz, 2H, ar-H),
2.09–0.87 (m, 41H), 0.81 (s, 3H, CH3), 0.66 (s, 3H, CH3); 13
C
NMR (75 MHz, CDCl3, 303 K): d = 106.9 (d, J = 23 Hz, ar-C),
56.6, 56.4, 54.4, 45.7, 43.8 (t, J = 25 Hz, CHCF2O), 42.6, 40.1,
39.6, 37.4, 36.2, 35.8, 35.6, 32.0, 28.8, 28.2, 28.0, 27.7, 24.2,
23.9, 22.8, 22.6, 21.0, 18.7, 12.2, 12.1; 19F NMR (235 Hz,
CDCl3, 300 K): d = ꢀ79.16 (d, J = 8.6 Hz, 2F, CF2O), ꢀ133.69
(dd, J = 20.9 and 8.1 Hz, 2F, ar-3,5-F), ꢀ165.13 (tt, J = 20.9 and
5.9 Hz, 1F, ar-4-F); MS (EI, 70 eV): m/z (%) = 568 [M+] (57),
553(20), 428(13), 413(100), 399(19), 345(27), 305(7), 135(6),
123 (24), 109 (21), 95 (28), 81 (25).
Quite surprisingly, the nematic phases of all the supposedly
‘‘cholesteric’’ liquid crystals 5–8 did not show any cholesteric
texture under the polarization microscope. Also, in solution in
achiral nematic host mixtures (ZLI-4792 and MLC-6260) [9]
they showed no propensity to induce a cholesteric phase
detectable under the polarization microscope.
3. Conclusion
6: For mesophases and optical rotation see Table 1; 1H NMR
(500 MHz, CDCl3, 303 K): d = 7.27–7.25 (m, 1H, ar-H;
overlapped by CHCl3 signal at 7.26 ppm), 7.06 (dd, J = 10.7
and 2.8 Hz, 1H, ar-H), 6.97 (d, J = 9.2 Hz, 1H, ar-H), 2.15–0.87
(m, 41H), 0.82 (s, 3H, CH3), 0.66 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 303 K): d = 154.8 (d, 1JCF = 254 Hz, ar-CF),
Oxidative fluorodesulfuration was used as a simple and
convenient method to obtain aromatic b-cholestanyl difluor-
omethyl ethers with complete stereoselectivity. This new class
of chemically very robust liquid crystalline compounds was
characterized with regard to their mesogenic and chiroptical
properties. Even though the practical value of the synthetic
procedure was demonstrated so far only for the preparation of
liquid crystals, the method is expected to be a useful addition
also to the toolbox of bioorganic and medicinal chemistry.
3
150.0 (d, JCF = 10 Hz, ar-C), 124.3 (ar-CH), 117.9 (ar-CH),
111.6 (d, 2JCF = 21.6 Hz, ar-CH), 56.9, 56.7, 54.8, 46.1, 44.2 (t,
2JCF = 26 Hz, CHCF2O), 43.0, 40.4, 39.9, 37.8, 36.6, 36.2,
35.9, 32.4, 29.2, 28.6, 28.4, 28.1, 24.6, 24.3, 23.2, 23.0, 21.5,
19.1, 12.6, 12.5; 19F NMR (235 Hz, CDCl3, 300 K): d = ꢀ59.45
(s, 3F, ar-4-OCF3), ꢀ79.00 (d, J = 8.7 Hz, 2F, CF2O), ꢀ126.06
(mc, 1F, ar-3-F); MS (EI, 70 eV): m/z (%) = 616 [M+] (60), 601
(20), 476 (12), 461 (100), 447 (20), 123 (23), 121 (15), 109 (22),
95 (30), 81 (27), 79 (12).
4. Experimental
Representative synthetic procedure for 5: A solution of 4 [8]
(12.9 g, 24.6 mmol) in CH2Cl2 (110 mL) was treated at ꢀ15 8C
dropwise with triflic acid (2.20 mL, 24.6 mmol). The mixture
was allowed to warm up, stirred for 30 min at room temperature
and then cooled down to ꢀ70 8C. First, a mixture of 3,4,5-
trifluorophenol (5.5 g, 36.8 mmol), NEt3 (6.1 mL, 44.2 mmol)
and CH2Cl2 (40 mL) was added dropwise, followed after 5 min
by NEt3ꢁ3HF (19.9 mL, 123 mmol) and 1,3-dibromo-5,5-
dimethyl hydanthoin (35.1 g, 123 mmol; in small portions) after
additional 5 min. The orange-coloured mixture was stirred for
1 h at ꢀ70 8C, then allowed to warm up to ꢀ20 8C and poured
into ice-cold 1N NaOH (500 mL). The organic layer was
separated, washed with saturated aqueous NaHCO3 and water,
dried over Na2SO4, filtered and evaporated to dryness. The crude
product was chromatographed(silica gel;n-heptane/CH2Cl2 2:1)
and crystallized from i-propanol at 5 8C. Yield: 9.3 g (66%) of 5
as a colourless solid with a purity of 98.6% (HPLC). For
mesophases and optical rotation see Table 1; 1H NMR
7: For mesophases and optical rotation see Table 1; 1H NMR
(500 MHz, CDCl3, 303 K): d = 7.14 (d, J = 8.6 Hz, 2H, ar-H),
7.06 (d, J = 8.6 Hz, 2H, ar-H), 2.46–2.41 (mc, 1H), 2.00–1.95
(mc, 1H), 2.13–2.04 (mc, 1H), 2.00–0.85 (m, 55H), 0.82 (s, 3H,
CH3), 0.66 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3, 303 K):
d = 148.9 (ar-C), 145.1 (ar-C), 127.8 (ar-CH), 121.9 (ar-CH),
2
57.0, 56.8, 54.8, 46.2, 44.4 (t, JCF = 27 Hz, CHCF2O), 43.0,
40.5, 40.1, 40.0, 37.9, 37.4, 36.6, 36.2, 36.0, 34.8, 34.0, 32.5,
29.3, 28.7, 28.4, 28.3, 24.6, 24.3, 23.2, 23.0, 21.6, 21.5, 20.4,
19.1, 14.8, 12.6, 12.5; 19F NMR (235 Hz, CDCl3, 300 K):
d = ꢀ78.29 (d, J = 8.4 Hz, 2F, CF2O); MS (EI, 70 eV): m/z
(%) = 638 [M+] (100), 623 (16), 498 (12), 483 (38), 415 (12),
218 (23), 133 (21), 125 (19), 123 (14), 121 (11), 109 (13), 107
(24), 95 (19), 83 (19), 81 (19).
8: For mesophases and optical rotation see Table 1; 1H NMR
(500 MHz, CDCl3, 303 K): d = 7.45 (d, J = 8.1 Hz, 2H, ar-H),
7.22 (d, J = 8.1 Hz, 2H, ar-H), 7.06 (dt, J = 8.4 Hz, J = 2.0 Hz,
1H, ar-H), 6.78 (t, J = 8.0 Hz, 1H, ar-H), 4.15 (quart,
J = 9.7 Hz, 2H, OCH2), 2.17–1.09 (mc, 1H), 1.99–1.97 (mc,
1H), 1.87–1.98 (m, 3H), 1.70–1.67 (mc, 1H), 1.64–0.87 (m,
38H), 0.83 (s, 3H, CH3), 0.66 (s, 3H, CH3); 13C NMR (75 MHz,
Table 1
The physical properties of the steroid-based liquid crystals 1, 2 and 5–8
20
No.
Phase sequence
Devirt
Dnvirt
HTP
1
½aꢂD
CDCl3, 303 K): d = 150.6 (ar-C), 149.2 (dd, JCF = 249 Hz,
1
2JCF = 11 Hz, ar-CF), 148.1 (ar-C), 142.2 (dd, JCF = 247 Hz,
1
2
5
6
7
8
C 145 N* 179 I
–
–
–
–
–
2JCF = 15 Hz, ar-CF), 132.2 (ar-C), 130.0 (ar-CH), 126.3 (ar-
C), 123.9 (ar-CH), 122.1 (ar-CH), 109.9 (ar-CH), 65.8 (OCH2),
C 81 S? 78 N* 92 I
C 102 N 149.0 I
–
ꢀ4.4
–
7.3
7.2
0.3
ꢀ3.0
0.026
0.034
0.026
0.077
<0.05
<0.05
<0.05
<0.05
+20.2
+19.2
+18.7
+18.0
C 94 N 175.1 I
2
57.0, 56.8, 54.8, 46.1, 44.4 (t, JCF = 26 Hz, CHCF2O), 43.0,
C 112 SA 206 N >300 I
C 105 SA 211 N 312.8
40.5, 40.0, 37.8, 36.6, 36.2, 35.9, 32.5, 29.3, 28.7, 28.4, 28.3,
24.6, 24.3, 23.2, 23.0, 21.5, 19.1, 15.2, 12.6, 12.5; 19F NMR
(235 Hz, CDCl3, 300 K): d = ꢀ78.35 (d, J = 8.6 Hz, 2F, CF2O),
ꢀ142.12 (ddd, J = 19.3 Hz, J = 8.0 Hz, J = 1.1 Hz, 1F, ar-F),
ꢀ159.07 (ddd, J = 22.1 Hz, J = 7.6 Hz, J = 2.7 Hz, 1F, ar-F);
The phase transition temperatures are given in 8C, the helical twisting powers
(HTP) in mmꢀ1, and the optical rotations ½aꢂD20 in degrees [9] (C: crystalline, SA:
smectic A, S?: unidentified smectic phase, N: nematic, N*: chiral nematic and I:
isotropic).

P. Kirsch, T. Mergner / Journal of Fluorine Chemistry 127 (2006) 146–149
149
MS (EI, 70 eV): m/z (%) = 670 [M+] (100), 530 (9), 515 (8), 250
(13), 222 (10), 123 (5), 109 (5), 95 (9).
¨
[5] D. Pauluth, A.E.F. Wachtler, in: A.N. Collins, G.N. Sheldrake, J. Crosby
(Eds.), Chirality in Industry, vol. II, John Wiley & Sons Ltd., New York,
1997, pp. 263–286.
[6] G. Vertogen, W.H. de Jeu, Thermotropic Liquid Crystals: Fundamentals,
Springer, Berlin, 1988.
Acknowledgements
[7] P. Kirsch, M. Bremer, A. Taugerbeck, T. Wallmichrath, Angew. Chem. 113
(2001) 1528–1532;
We thank J. Haas, H. Heldmann and K. Altenburg for the
physical characterization of the liquid crystals.
P. Kirsch, M. Bremer, A. Taugerbeck, T. Wallmichrath, Angew. Chem. Int.
Ed. 40 (2001) 1480–1484.
[8] D. Seebach, M. Kolb, Liebigs Ann. Chem. (1977) 811–829.
[9] The helical twisting powers (HTP) were measured at 20 8C in the Merck
liquid crystal mixtures ZLI-1132 (TNI = 71.0 8C, De = 12.8, Dn = 0.140) (for
2) or MLC-6260 (TNI = 103.5 8C, De = 4.0, Dn = 0.088) (for 5–8) and are
given in mmꢀ1. The ‘‘virtual’’ dielectric (De) and optical anisotropies (Dn)
were extrapolated from a 10% (w/w) solution of the analyte in ZLI-4792
References
[1] F. Reinitzer, Monatsh. Chem. 9 (1888) 421.
[2] P. Kirsch, M. Bremer, Angew. Chem. 112 (2000) 4384–4405;
P. Kirsch, M. Bremer, Angew. Chem. Int. Ed. 39 (2000) 4216–4235.
[3] D. Pauluth, K. Tarumi, J. Mater. Chem. 14 (2004) 1219–1227.
[4] D. Demus, J. Goodby, G.W. Gray, H.-W. Spiess, V. Vill (Eds.), Handbook of
Liquid Crystals, Wiley/VCH, Weinheim, 1998.
20
(TNI = 92.6 8C, De = 5.3, Dn = 0.097). The optical rotations ½aꢂD were
determined from a 0.01 g mLꢀ1 solution in CH2Cl2. The phase transition
temperatures were measured by differential scanning calorimetry (DSC), the
identity of the mesophases was assigned by optical polarization microscopy