Strategies for the synthesis of fluorinated liquid crystal derivatives from perbromofluoroaromatic systems

Article abstract of DOI:10.1016/j.tet.2010.10.069

The use of perbromofluorobenzene derivatives as starting materials for the synthesis of a variety of model liquid crystal systems by a combination of nucleophilic aromatic substitution, debromolithiation/trapping, dehydration and reduction processes is de

Full text of DOI:10.1016/j.tet.2010.10.069

Tetrahedron 66 (2010) 9819e9827
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Strategies for the synthesis of fluorinated liquid crystal derivatives from
perbromofluoroaromatic systems
,
a
b
b
Alan M. Kenwright a, Graham Sandford a , Andrzej J. Tadeusiak , Dmitrii S. Yufit , Judith A.K. Howard ,
*
Pinar Kilickiran c, Gabriele Nelles c
a Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK
b Chemical Crystallography Group, Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK
c SONY Deutschland GmbH, Stuttgart Technology Center, Hedelfinger Strasse 61, Stuttgart 70327, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 July 2010
Received in revised form 9 October 2010
Accepted 25 October 2010
Available online 29 October 2010
The use of perbromofluorobenzene derivatives as starting materials for the synthesis of a variety of
model liquid crystal systems by a combination of nucleophilic aromatic substitution, debromolithiation/
trapping, dehydration and reduction processes is described.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Liquid crystal
Nucleophilic aromatic substitution
Perfluoroaromatic
Dibromotetrafluorobenzene
1. Introduction
(SFMs), have significantly contributed to the development of
LC-based devices due to a number of factors including enhanced
Molecules that possess liquid crystalline properties are now
widely used for many display applications in a range of electronic
goods, such as television and laptop computer screens.1e3 Indeed, it
is now fair to say that televisions with flat-screen liquid crystal (LC)
displays have, along with plasma systems, largely replaced cath-
ode-ray tube based technologies. As LC-based display applications
increase in performance (clarity, size, brightness, angle of view, low
power consumption, fast response times, etc.), there exists a con-
tinuing need for the development of materials with liquid crystal-
line properties that can meet consumer demands for enhanced
display technologies.
In general, molecules that exhibit liquid crystalline properties
have narrow, elongated frameworks thatmayalign along theirlinear
axes, parallel to one another, towards a preferred direction in space.4
The design of liquid crystalline molecules must take account of not
only their general linear, rod-like shape but also the relative dipole
moment and position of polar groups within the molecule, the
overall molecular polarizability and the presence of any stereogenic
centres. Recently, liquid crystalline molecules bearing fluorine-
containing substituents,4,5,6 termed superfluorinated materials
performance, increased longevity and the chemical robustness of
appropriate liquid crystal formulations. Dielectrically positive LC
molecules bear polar groups (F, CF3) parallel to the longitudinal axis
of the organic system, whereas dielectrically negative LC molecules
bear polar groups that are perpendicular to the long axis. Both
classes of LC molecule have a variety of uses in display technology
and some examples of commercially important LC systems are
shown in Fig. 1, where the molecular structures comprise of an ar-
omatic polar, fluorine-containing ‘head group’, a rod-like, rigid core
of cyclohexyl units and lipophilic alkyl ‘tail’ units.2
Synthesis of the fluorinated polar head group, usually a fluoroar-
omatic derivative, and attachmentof thehead group tothenon-polar
‘tail’ of the LC molecule is perhaps the most challenging aspect of LC
synthesis and is usually completed by a sequence of reactions in-
volving displacement of hydrogen from mono- or di-fluorinated ar-
omatic substrates by a combination of electrophilic substitution,
palladium catalysed coupling and/or lithiation procedures.4,7 Such
strategies, however, may be limited by low regioselectivity, low yield
and inconvenient reaction conditions and it is often difficult to access
various isomers of all thepolyfluoroaomaticstructural unitspossible.
We decided to explore a complementary approach to the syn-
thesis of LC molecules bearing fluoroaromatic polar head groups by
using perbromofluoroaromatic derivatives as the starting materials.
Such systems are, potentially, very susceptible towards nucleophilic
* Corresponding author. Tel.: þ44 0191 334 2039; fax: þ44 0191 384 4737; e-mail
address: graham.sandford@durham.ac.uk (G. Sandford).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.069

9820
A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
Dielectrically Positive
O
Dielectrically Negative
F
F
F
F
CH3
OEt
O
F
µ
CF3
F3C
µ
Fig. 1. Some commercially important liquid crystal systems.
attack due to the presence of a number of highly electron with-
drawing substituents attached tothe aromatic ring and the presence
of carbonebromine bonds offer opportunities for a variety of useful
synthetic functionalisation procedures. In our initial experiments,
we chose to develop strategies to both new and existing LC materials
by using dibromotetrafluorobenzene systems 1aꢀc as the starting
materials. Sequences of debromolithiation and trapping with ap-
propriate electrophiles, nucleophilic substitution and hydrogena-
tion reactions could, in principle, give rise to many families of LC
systems depending on the structure of the perhalogenated aromatic
starting material, and this approach is shown in Scheme 1, where the
envisaged use of 1,2-dibromotetrafluorobenzene 1a as the starting
material for LC synthesis is illustrated.
F
F
F
F
F
F
X
F
F
F
F
F
F
F
F
F
F
i
ii
iii
X
HO
2
Br
Br
1a
3a
5a
, X = Br, 48%
, X = Br, 64%
7a, 54%
4a, X = H, 5%*
6a, X = H, 3%*
(2.2 : 1)
F
F
F
F
X
F
F
X
F
F
F
F
F
F
Br
F
F
F
i
HO
iii
ii
2
F
F
F
F
n-BuLi
Br
1b
F
F
F
F
F
F
F
F
F
H2 / Pd
Electrophile, E+
Path A
Br
Br
3b, X = Br, 24%
5b, X = Br, 58%
7b, 47%
Br
1a
E
E
4b
6b
, X = H, 2%*
, X = H, 2%*
(4.1 : 1)
X
X
F
F
F
F
F
F
F
Nuc-
Path B
F
F
F
Br
F
F
F
F
F
F
i
ii
iii
HO
2
Nuc
E
Nuc
E
Nuc
F
F
F
F
Br
1c
F
F
F
n-BuLi
H2 / Pd
Electrophile, E+
Br
F
Br
F
Br
3c, X = Br, 94%
5c
, X = Br, 77%
7c, 66%
(2.5 : 1)
4c
, X = H, 4%*
6c, X = H, 3%*
Scheme 1. General strategy for the synthesis of LC molecules from perbromo-
fluorobenzene derivatives.
Reagents and Conditions:
i, (a) n-BuLi, Et2O, 78 oC; (b)
bar), Pd/C, 180 oC
78 o
C
rt; ii, p-TsOH, toluene, reflux; iii, H2 (100
2
,
Whilst all three dibromotetrafluorobenzene systems 1aꢀc
(Scheme 2) have been known for some considerable time, it is
perhaps surprising that a more comprehensive exploration of the
reactivity of these potentially very useful polyfunctional aromatic
synthetic scaffolds has not been developed to any great extent,
although there are a few reports of reactions between these sub-
strates and various nucleophilic species.8e12
2
=
O
* Not isolated; estimated yield by GCMS.
Scheme 2. Synthesis of model LC systems 7 from dibromotetrafluorobenzene systems
1aꢀc.
In this paper, we discuss the synthesis of various model LC-type
molecules using the synthetic strategy outlined in Scheme 1 and
demonstrate the versatility of this approach for the preparation of
new families of model LC molecules bearing various tetrafluoro-
and trifluoro-aryl head groups.
of the corresponding lithiated species upon reaction with cyclo-
hexanone derivative 2, a model substrate for a linear LC ‘tail’ unit,
gave the corresponding cyclohexanol derivative 3a (Scheme 2). The
alcohol was contaminated with small quantities (5% by GC/MS
analysis) of the corresponding tetrafluoroaryl derivative 4a arising
from further debromolithiation and so the mixture 3a/4a was used
in the next synthetic stage without further purification. De-
hydration of the alcohol mixture 3a/4a using p-toluenesulfonic acid
in toluene gave a corresponding alkene mixture 5a/6a, which were
not separated, and the mixture was reduced to give pure LC model
system 7a upon hydrogenation using a Pd/C catalyst and purifica-
tion by column chromatography. The hydrogenation stage was
2. Results and discussion
In our initial investigations we sought to develop the synthesis
of LC systems by debromolithiation/trapping as the first stage of the
synthetic strategy (Path A, Scheme 1). Reaction of n-butyllithium
with 1,2-dibromotetrafluorobenzene 1a and subsequent trapping

A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
9821
surprisingly difficult reflecting the effect of the electron with-
drawing aromatic group on the alkene and high temperatures and
pressures were required to deliver complete conversion to prod-
ucts. It was essential to optimize the hydrogenation reactions to
completeness because the alkenes 5a/6a were very difficult to
separate from the liquid crystal type product 7a. Analogous three-
step processes using 1,3- and 1,4-dibromotetrafluorobenzene
starting materials 1b and 1c gave the LC systems 7b and 7c, re-
spectively (Scheme 2).
diaxially with the large aromatic head group and propyl tail-group
lying equatorially, as would be expected.
Therefore, the strategy outlined in Scheme 1 can be used for the
synthesis of LC systems bearing all three isomers of the tetra-
fluoroaryl head groups (Scheme 2) and, clearly, other tail groups
could be attached to these head groups by reaction of an appro-
priate proprietary cyclohexanone derivative.
The incorporation of additional functionality attached to the
polar fluoroaromatic head group may be achieved by reaction of the
dibromotetrafluorobenzene systems 1aꢀc with appropriate nucle-
ophiles followed by debromolithiation, dehydration and hydroge-
nation procedures discussed above, following Path B (Scheme 1).
Reaction of the dibromotetrafluorobenzene derivatives 1aꢀc
with sodium methoxide following literature procedures8,9 gave the
corresponding methoxydibromoaryl systems 8aꢀc as the major
products, respectively, which were purified by column chroma-
tography and the regioselectivity of these types of processes have
been discussed previously.12
Reaction of 8aꢀc with butyllithium could each lead to two
possible lithiated species and, subsequently, two regioisomeric
products upon trapping the carbanions with an appropriate elec-
trophile. So, in order to establish the outcome of debromolithiation
reactions of 8aꢀc and the effects governing the regioselectivity of
such processes, we reacted each system with n-butyllithium and
trapped the resulting carbanions by hydrogen upon addition of
ethanol/water and the results are shown in Scheme 3.
In all cases, the model LC systems 7aꢀc were isolated as mix-
tures of two configurational isomers, resulting from the non-ster-
eoselective hydrogenation of the precursor alkene derivatives 5/6.
The stereochemistries of the major and minor configurational iso-
mers of 7aꢀc were assigned by consideration of the NMR data.13,14
The carbon NMR spectrum of the product isomer mixture was
firstly fully assigned using HSQC and HMBC 2D NMR techniques.
The HSQC spectrum was then used to assign clean (non-over-
lapping) splitting patterns in the proton NMR spectra through
correlation with individual carbon atom environments. TOCSY 1D
NMR also facilitated the correct assignment of signals in the proton
NMR spectra to the major and minor isomers. The Karplus re-
lationship indicates that a coupling of approximately 12 Hz is ob-
served for two vicinal axial protons with a dihedral angle of 180ꢁ
between them. In the 1H NMR spectrum of, for example, LC model
derivative 7c, a triplet with a 12 Hz 3JHH coupling is observed for the
proton attached to the C-10 position found in both major (3.00 ppm)
and minor (3.04 ppm) isomers suggesting that the benzene ring lies
equatorially in both isomers. Different splitting patterns are, how-
ever, observed for the axial protons attached to the C-30 position of
the major and minor isomers. Three 12 Hz couplings (a quartet at
1.04 ppm) are observed for the major isomer suggesting that the
propyl tail group lies equatorially, but only two (a triplet at
1.60 ppm) are observed for the minor isomer suggesting that the
propyl group lies axially (Fig. 2).
OMe
OMe
OMe
F
F
F
F
F
F
F
F
F
i
+
Br
Br
Br
9b
Br
8a
9a
Furthermore, the 19F NMR spectrum of the LC model derivatives
show two sets of signals corresponding to the major and minor
isomers, allowing ratios of each isomer to be determined accurately
by integration of peak intensities. For example, 7b displays two sets
of signals for both the F-5 fluorine atom (ꢀ117.7 and ꢀ118.0 ppm)
and the F-3 fluorine atom (ꢀ135.8 and ꢀ136.0 ppm) and the peak
integrals indicate the major:minor isomer ratio to be 4.1:1 (Fig. 3).
Only one set of signals were observed for each of the fluorine atoms
at the C-1 and C-2 positions and this may be due to the fact that
they are located at sites more remote from the cyclohexane ring
and, therefore, their electronic environments are unaffected by the
isomeric configurations of the more remote atoms of the molecule.
In all cases, the major isomers of the LC type systems 7aꢀc are
found to be the configurations with the C-10 and C-40 protons lying
88%, 9a : 9b, 85 : 15
OMe
OMe
OMe
F
F
Br
F
F
F
F
Br
F
i
+
F
F
Br
8b
Br
9d
9c
22%, 9c : 9d, 95 : 5
Br
Br
F
F
OMe
F
F
F
OMe
F
F
OMe
F
i
+
F
Br
8c
Br
9f
9e
69%, 9e : 9f, 94 : 6
Reagents and conditions:
i, (a) n-BuLi, Et2O, -78 oC; (b) EtOH, H2O, rt.
H
H
H
H
H
H
F
F
Scheme 3. Debromolithiation and subsequent protonation of 8aꢀc.
H
H
triplet, 3JHH 12 Hz
triplet, 3JHH 12 Hz
Reaction of 8a with n-butyllithium and subsequent protonation
gave a mixture of products 9a and 9b in the ratio 85:15 by 19F NMR
analysis of the crude product mixture, results consistent with
previous observations.8,9 Compounds 9a and 9b could not be sep-
arated by column chromatography and were characterized as
a mixture, whereas anisoles 9c and 9e could be isolated as pure
isomers. Confirmation of the identity of isomers 9c and 9d was
provided through consideration of the 1H NMR spectrum. The
major isomer 9c displays two 3JHF and one 4JHF couplings consistent
H
H
H
H
F
H
H
F
H
3 couplings
H
2 couplings
H
quartet, 3JHH 12 Hz
triplet, 3JHH 12 Hz
major isomer
minor isomer
3
with the structure proposed, whereas anisole 9d has a single JHF
Fig. 2. Couplings between protons in major and minor isomers of 7c.
coupling (ca. 10 Hz), one 4JHF coupling and one small 5JHF coupling.

9822
A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
Fig. 3. Fluorine NMR signals arising from the two configurations of the LC system 7b.
OMe
OMe
OMe
3
4
F
F
F
X
F
F
F
X
F
F
F
Similarly, anisole 9e shows two JHF and one JHF couplings and
OMe
3
4
F
F
F
anisole 9f displays one JHF and two JHF couplings, as would be
expected. The results shown in Scheme 3 indicate that debromo-
lithiation occurs in all cases predominantly at carbonebromine
sites with the greatest number of fluorine atoms that are ortho and
meta to the site of debromolithiation, reflecting the enhanced
electrophilicity of the bromine atoms at these positions.
i
ii
iii
OH
2
Br
Br
8a
Sincethedebromolithiationreactionsdescribedabove(Scheme3)
are sufficiently regioselective to allow the synthesis of various LC
type systems, debromolithiation and trapping of 8aꢀc gave pre-
dominantly 10aec as the major products, contaminated by minor
quantities of11aꢀc, whichwerenot purified atthisstage. Subsequent
processing, bysimilarreactionstothoseshowninScheme2, ledtothe
methoxylated model LC systems 14aꢀc as shown in Scheme 4. As in
the synthesis of LC systems above, some debromination occurred in
the lithiation step and so mixtures were carried through to the end of
each sequence, allowing the isolation of pure LC type material 14aꢀc
at the final stage. Geometric isomers of each system 14aꢀc were
observed and characterized by NMR techniques, as described above.
We then sought to expand this methodology to the synthesis of
LC systems from related tribromotrifluorobenzene 15aꢀc starting
materials. The three possible tribromotrifluorobenzene isomers
15aꢀc were synthesised by perbromination of the corresponding
trifluoraryl derivatives 16aꢀc using N-bromosuccinimide in triflic
acid at room temperature, by adapting related iodination meth-
odology (Scheme 5).15
10a, X = Br, 84%
11a, X = H, 5%*
12a, X = Br, 82%
13a, X = H, 3%*
14a, 40%
(1.3 : 1)
OMe
OMe
OMe
F
X
F
F
X
F
F
OMe
F
F
Br
F
F
F
F
i
HO
iii
ii
2
F
Br
8b
10b
12b
, X = Br, 75%
, X = Br, 85%
14b, 20%
11b, X = H, 4%*
13b, X = H, 4%*
(2.2 : 1)
X
X
F
F
OMe
F
F
OMe
F
F
OMe
F
Br
F
F
OMe
F
F
i
F
ii
iii
HO
2
Br
8c
The strategy outlined above was utilized to synthesise various
LC derivatives 19 proceeding via intermediate alcohol 17 and alkene
18 intermediates by a three step sequence as shown in Scheme 6. In
these final experiments, a larger cyclohexanone derivative 20 was
used as the lipophilic coupling partner and, here, we find that single
geometric isomers may be isolated by recrystallisation of the crude
product mixture for each model LC product. Again, debromoli-
thiation occurs in 15a and 15b at carbonebromine sites with the
greatest number of ortho and meta fluorine atoms, reflecting the
enhanced electrophilicity of the bromine atoms at these positions.
10c, X = Br, 90%
12c, X = Br, 79%
13c, X = H, 4%*
14c
, 23%
11c
, X = H, 6%*
(1.9 : 1)
Reagents and Conditions:
i, (a) n-BuLi, Et2O, 78 oC; (b) 2, 78 o
C
rt; ii, p-TsOH, toluene, reflux; iii, H2 (100
bar), Pd/C, 180 oC
2
=
O
* Not isolated; estimated yield by GCMS.
Scheme 4. Synthesis of methoxy-trifluoroaromatic LC systems 14aꢀc.

A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
9823
F
F
F
F
Br
Br
F
NBS, TfOH
rt
15a
, 27%
F
Br
F
16a
F
Br
Br
F
F
NBS, TfOH
rt
15b
, 49%
Fig. 4. X-ray crystal structure of bicyclohexylaryl 19c.
Br
F
16b
F
F
The structure of the phenylbicyclohexyl derivative 19c was
confirmed by X-ray crystallography and we observe that all the
tertiary hydrogens of the two cyclohexyl rings lie axially (Fig. 4)
giving the structure the most ‘rod-like’ configuration, as would be
expected.
F
Br
Br
F
NBS, TfOH
rt
15c
, 48%
F
F
F
Relatively few crystal structures of 40,4-disubstituted bicyclo-
hexyl derivatives have been reported and, indeed, the Cambridge
Crystallographic Database16 contains only 11 such compounds. In
all reported structures, the substituents are in the equatorial po-
sitions of the bicyclohexyl system, similar to 19c, but, in this case,
the conformation of molecule 19c is quite unusual. Most 40,4-di-
substituted bicyclohexyl structures show s-trans configurations
around the central bond of the bicyclohexyl fragment with corre-
sponding HCCH torsion angles of about 180ꢁ, but in one case,
40-propen-1-yl-bicyclohexyl-4-carbonitrile,17 this torsion angle is
71.2ꢁ, i.e., the cyclohexyl rings are almost perpendicular to each
other. The conformation of molecule 19c is similar where the
central HCCH torsion angle is ꢀ73.1ꢁ.
16c
Br
Scheme 5. Synthesis of tribromotrifluorobenzene systems 15aꢀc.
F
F
F
Br
Br
F
F
Br
Br
F
F
F
F
F
HO
Br
Br
F
F
i
ii
iii
Br
15a
3. Conclusions
We have outlined a general strategy for the synthesis of model
liquid crystal systems 7aꢀc from dibromotetrafluorobenzene 1aꢀc
starting materials. LC molecules bearing all three isomers of the
tetrafluoroaryl unit can be synthesised from the appropriate
starting material and additional functionality can be incorporated
into the aromatic head group by nucleophilic aromatic substitution
processes. Furthermore, we have developed methodology for the
synthesis of tribromotrifluorobenzene systems 15aꢀc and used
these novel precursors for the synthesis of various model LC-type
molecules 19aꢀc. The use of this strategy for the synthesis of many
families of LC systems bearing a range of isomeric fluoroaryl ‘head’
groups complements existing strategies for LC molecule synthesis,
allowing the preparation of many novel SFM derivatives for liquid
crystal display applications.
18a
17a, 87%
, 89%
19a, 45%
Br
Br
F
Br
F
Br
F
F
F
F
F
F
F
F
HO
Br
Br
F
i
ii
iii
Br
F
15b
18b, 84%
19b, 21%
17b, 89%
F
F
F
4. Experimental
4.1. General
Br
F
F
F
F
F
F
F
F
i
iii
All starting materials were obtained commercially (Aldrich,
Lancaster or Fluorochem). All solvents were dried using literature
procedures. NMR spectra were recorded in deuteriochloroform,
unless otherwise stated, on a Varian Mercury 400 NMR spec-
trometer operating at 400 MHz (1H NMR), 376 MHz (19F NMR) and
100 MHz (13C NMR) with tetramethylsilane and trichlorofluoro-
methane as internal standards. Mass spectra were recorded on
a Fisons VG-Trio 1000 Spectrometer coupled with a Hewlett Pack-
ard 5890 series II gas chromatograph using a 25 m HP1 (methyl-
silicone) column. Elemental analyses were obtained on a Exeter
Analytical CE-440 elemental analyser. Melting points and boiling
points were recorded at atmospheric pressure unless otherwise
stated and are uncorrected. Column chromatography was carried
out on silica gel (Merck no. 109385, particle size 0.040e0.063 mm)
and TLC analysis was performed on silica gel TLC plates (Merck).
ii
Br
Br
F
15c
17c
20
19c, 21%
, 74%
18c, 63%
rt; ii, p-TsOH, toluene,
Reagents and Conditions:
i, (a) n-BuLi, Et2O, 78 oC; (b)
,
78 o
C
C
reflux; iii, H2 (100 bar), Pd/C, 180 o
20
O
=
Scheme 6. Synthesis of model LC systems 19aꢀc from tribromotrifluorobenzene de-
rivatives 15aꢀc.

9824
A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
4.2. Synthesis of model liquid crystal systems with fluoroaryl
head groups
ꢀ160.71 (1F, m, F-3); m/z (EIþ) 274 ([M]þ, 82%), 189 (75), 176 (100),
163 (93), 81 (56), 55 (100), 43 (63), 41 (68).
4.2.1. General procedure. A solution of n-butyllithium (2.5 M in
hexanes) in dry diethyl ether (10 mL) was added via a dropping
funnel over 30 min to a solution of the dibromotetrafluoro- or
tribromotrifluorobenzene derivative in dry diethyl ether (40 mL)
cooled to ꢀ78 ꢁC under an atmosphere of dry argon. The solution
was stirred for 30 min and then the cyclohexanone derivative 2 or
20 was added dropwise over 30 min whilst maintaining a reaction
temperature of ꢀ78 ꢁC. The mixture was stirred for 2 h and water
(10 mL) was added. The mixture was stirred for a further 15 min,
allowed to warm to room temperature, poured into dilute HCl
(30 mL) and the product extracted with diethyl ether (3ꢂ30 mL).
The combined ether extracts were washed with water (100 mL) and
dried (MgSO4). The solvent was evaporated to leave the crude
phenyl-4-propylcyclohexanol product, which was identified by GC/
MS and used in the next stage without further purification.
A mixture consisting of the phenyl-4-propylcyclohexanol de-
rivative, p-toluenesulfonic acid monohydrate (0.1 equiv) and tolu-
ene (30 mL) was heated to reflux for 6 h in a Dean and Stark vessel.
After cooling, the solvent was evaporated and column chroma-
tography with hexane as the eluent afforded the phenyl-4-pro-
pylcyclohexene derivative, which was identified by GC/MS and
used in the next stage without further purification.
4.4. Synthesis of 1,2,3,5-tetrafluoro-4-(4-propylcyclohexyl)
benzene 7b from 1,3-dibromotetrafluorobenzene 1b
1,3-Dibromotetrafluorobenzene 1b (6.16 g, 20.0 mmol), n-BuLi
(8.00mL,20.0mmol)andcyclohexanone2(2.80g, 20.0mmol)gave1-
(3-bromo-2,4,5,6-tetrafluorophenyl)-4-propylcyclohexanol 3b (1.77 g,
24%)asaclearoil;m/z(EIþ)370([M]þ, 6%),368([M]þ, 6), 285(82), 283
(85), 272 (59), 270 (58), 257 (55), 255 (55), 98 (90), 96 (77), 85 (69), 55
(79), 43 (100), 41 (68).
The alcohol 3b (1.77 g, 4.79 mmol) and p-TsOH (0.08 g,
0.46 mmol) gave 1-bromo-2,3,4,6-tetrafluoro-5-(4-propylcyclohex-
1-enyl)benzene 5b (0.97 g, 58%) as a clear oil; m/z (EIþ) 352 ([M]þ,
24%), 350 ([M]þ, 25), 295 (77), 293 (84), 243 (82), 241 (77), 201 (51),
96 (68), 81 (100), 68 (86), 55 (55), 41 (51).
The alkene 5b (0.82 g, 2.3 mmol) and Pd/C (0.07 g, 0.2 mmol)
gave 1,2,3,5-tetrafluoro-4-(4-propylcyclohexyl)benzene 7b (0.30 g,
47%) as a clear oil and as a mixture of isomers (4.1:1) (Found: C,
65.40; H, 6.54. C15H18F4 requires C, 65.68; H, 6.61%); Rf (hexane)
0.42; major isomer: dH 0.90 (3H, t, 3JHH 7.3, CH3), 1.05e2.00 (13H, m,
CH, CH2), 2.89 (1H, tt, 3JH5H 12.0, 3JHH 3.9, H-10), 6.69 (1H, dddd, 3JHF
3
4
10.1, JHF 10.1, JHF 6.1, JHF 2.5, H-6); dC 14.5 (s, CH3), 20.1 (s,
CH2CH3), 29.9 (s, C-20), 31.0 (s, C-10), 33.6 (s, C-30), 36.8 (s, C-40), 39.8
2
2
3
A solution of the alkene derivative in dry THF (5 mL) was added
to palladium (30 wt % on carbon, 0.1 equiv). This was placed in an
autoclave under 100 bar pressure of hydrogen at 180 ꢁC for 7 days.
The resulting cooled brown solution was filtered and solvent
evaporated. Column chromatography on silica gel with hexane as
the eluent afforded the model LC system, which was obtained as
a mixture of two configurational isomers (major:minor) identified
by NMR techniques, as described in the text.
(s, CH2CH2CH3), 100.7 (ddd, JCF 30.1, JCF 20.9, JCF 3.8, C-6), 119.8
2
2
3
4
1
(dddd, JCF 20.3, JCF 15.7, JCF 4.6, JCF 1.9, C-4), 137.4 (dddd, JCF
246.9, JCF 17.2, JCF 15.1, JCF 5.2, C-2), 148.8 (dddd, 1JCF 248.0, JCF
15.7, 3JCF 11.1, 3JCF 5.7, C-3),150.2 (dddd, 1JCF 248.0, 2JCF 12.3, 3JCF 10.8,
3JCF 5.4, C-1),155.5 (dddd, 1JCF 244.6, 3JCF 12.3, 3JCF 10.4, 4JCF 3.4, C-5);
dF ꢀ117.70 to ꢀ117.78 (1F, m, F-5), ꢀ135.75 to ꢀ135.81 (1F, m, F-3),
ꢀ137.21 to ꢀ137.29 (1F, m, F-1), ꢀ166.19 to ꢀ166.26 (1F, m, F-2);
minor isomer: dH 0.94 (3H, t, 3JHH 7.2, CH3), 1.00e2.00 (13H, m, CH,
CH2), 2.92 (1H, tt, 3JHH 12.9, 3JHH 3.7, H-10), 6.65e6.70 (1H, m, H-6);
dF ꢀ117.85 to ꢀ117.95 (1F, m, F-5), ꢀ135.95 to ꢀ136.08 (1F, m, F-3),
ꢀ137.15 to ꢀ137.40 (1F, m, F-1), ꢀ166.10 to ꢀ166.35 (1F, m, F-2); m/z
(EIþ) 274 ([M]þ, 53%), 231 (16), 189 (38), 177 (14), 176 (73), 169 (14),
163 (100), 82 (14), 70 (16), 69 (14), 55 (61), 43 (23), 41 (33).
2
2
4
2
4.3. Synthesis of 1,2,3,4-tetrafluoro-5-(4-propylcyclohexyl)
benzene 7a from 1,2-dibromotetrafluorobenzene 1a
1,2-Dibromotetrafluorobenzene 1a (6.16 g, 20.0 mmol), n-BuLi
(8.00 mL, 20.0 mmol) and cyclohexanone 2 (2.80 g, 20.0 mmol)
gave 1-(2-bromo-3,4,5,6-tetrafluorophenyl)-4-propylcyclohexanol 3a
(3.57 g, 48%) as a clear oil; m/z (EIþ) 370 ([M]þ, 2%), 368 ([M]þ, 2),
285 (34), 283 (34), 204 (48), 177 (38), 98 (53), 96 (38), 85 (48), 55
(51), 43 (100), 41 (47).
The alcohol 3a (3.37 g, 9.13 mmol) and p-TsOH (0.15 g,
0.87 mmol) gave 1-bromo-2,3,4,5-tetrafluoro-6-(4-propylcyclohex-
1-enyl)benzene 5a (2.04 g, 64%) as a clear oil; m/z (EIþ) 352 ([M]þ,
19%), 350 ([M]þ,19), 243 (47), 241 (44), 201 (100),187 (45), 151 (65),
96 (73), 81 (98), 68 (64), 67 (70), 55 (49), 41 (47).
The alkene 5a (1.91 g, 5.44 mmol) and Pd/C (0.17 g, 0.50 mmol)
gave 1,2,3,4-tetrafluoro-5-(4-propylcyclohexyl)benzene 7a (0.79 g,
54%) as a clear oil and as a mixture of isomers (2.2:1) (Found: C,
65.79; H, 6.73. C15H18F4 requires: C, 65.68; H, 6.61%); Rf (hexane)
0.35; major isomer: dH 0.90 (3H, t, 3JHH 7.3, CH3), 1.05e1.90 (13H, m,
CH, CH2), 2.81 (1H, tt, 3JHH 12.1, 3JHH 2.8, H-10), 6.77e6.84 (1H, m, H-
6); dC 14.5 (s, CH3), 20.1 (s, CH2CH3), 30.1 (s, C-10), 32.9 (s, C-20), 33.3
(s, C-30), 37.0 (s, C-40), 39.7 (s, CH2CH2CH3), 108.7 (ddd, 2JCF 19.1, 3JCF
4.9, 3JCF 3.5, C-6), 130.9 (dddd, 2JCF 13.8, 3JCF 5.8, 3JCF 3.8, 4JCF 1.1, C-5),
138.6 (dddd, 1JCF 250.4, 2JCF 17.1, 2JCF 13.1, 3JCF 3.4, C-2), 140.7 (dddd,
1JCF 251.4, 2JCF 18.1, 2JCF 12.1, 3JCF 4.2, C-3), 145.4 (dddd, 1JCF 243.4, 2JCF
4.5. Synthesis of 1,2,4,5-tetrafluoro-3-(4-propylcyclohexyl)
benzene 7c from 1,4-dibromotetrafluorobenzene 1c
1,4-Dibromotetrafluorobenzene 1c (3.08 g, 10.0 mmol), n-BuLi
(4.00 mL,10.0 mmol) and cyclohexanone 2 (1.40 g,10.0mmol)gave1-
(4-bromo-2,3,5,6-tetrafluorophenyl)-4-propylcyclohexanol 3c (3.48 g,
94%); m/z (EIþ) 370 ([M]þ, 4%), 368 ([M]þ, 5), 285 (37), 283 (36), 99
(30), 98 (47), 96 (36), 85 (36), 55 (52), 43 (100), 41 (44), 28 (53).
The alcohol 3c (3.48 g, 9.43 mmol) and p-TsOH (0.17 g,
0.99 mmol) gave 1-bromo-2,3,5,6-tetrafluoro-4-(4-propylcyclohex-
1-enyl)benzene 5c (2.55 g, 77%) as a clear oil; m/z (EIþ) 352 ([M]þ,
25%), 350 ([M]þ, 26), 295 (88), 293 (95), 243 (73), 241 (70), 201 (52),
151 (42), 96 (62), 81 (100), 68 (89), 55 (63), 41 (58).
The alkene 5c (2.41 g, 6.8 mmol) and Pd/C (0.20 g, 0.7 mmol)
gave 1,2,4,5-tetrafluoro-3-(4-propylcyclohexyl)benzene 7c (1.24 g,
66%) as a clear oil and as a mixture of isomers (2.5:1) (Found: C,
65.39; H, 6.64. C15H18F4 requires: C, 65.68; H, 6.61%); Rf (hexane)
0.25; major isomer: dH 0.91 (3H, t, 3JHH 7.3, CH3), 1.04 (2H, dddd, 2JHH
13.0, 3JHH 13.0, 3JHH 12.0, 4JHH 3.1, H-30), 1.20e1.90 (11H, m, CH, CH2),
3.00 (1H, tt, 3JHH 12.3, 3JHH 3.7, H-10), 6.87 (1H, tt, 3JHF 9.5, 4JHF 7.0, H-
6); dC 14.5 (s, CH3), 20.1 (s, CH2CH3), 30.8 (m, C-20), 33.5 (s, C-30),
35.9 (s, C-10), 36.8 (s, C-40), 39.8 (s, CH2CH2CH3),103.3 (t, 2JCF 22.8, C-
6), 125.9 (t, 2JCF 16.3, C-3), 145.0 (dddd, 1JCF 244.6, 2JCF 13.4, 3JCF 7.2,
4JCF 3.8, C-2), 146.2 (dddd, 1JCF 247.0, 2JCF 15.9, 3JCF 10.5, 4JCF 3.8, C-1);
dF ꢀ140.51 to ꢀ140.57 (2F, m, F-2), ꢀ143.90 to ꢀ143.98 (2F, m, F-1);
minor isomer: dH 0.94 (3H, t, 3JHH 7.2, CH3), 1.20e1.50 (4H, m, CH2),
3
4
2
3
10.0, JCF 3.4, JCF 1.6, C-1), 147.2 (dddd, 1JCF 245.4, JCF 9.9, JCF 3.8,
4JCF 2.3, C-4); dF ꢀ140.81 ꢀto ꢀ140.88 (1F, m, F-1), ꢀ145.84 ꢀto
ꢀ145.90 (1F, m, F-4), ꢀ157.15 ꢀto ꢀ157.21 (1F, m, F-2), ꢀ160.64 ꢀto
3
ꢀ160.72 (1F, m, F-3); minor isomer: dH 0.93 (3H, t, JHH 7.1, CH3),
1.00e1.95 (13H, m, CH, CH2), 2.80e2.90 (1H, m, H-10), 6.80e6.85
(1H, m, H-6); dF ꢀ140.80 to ꢀ140.85 (1F, m, F-1), ꢀ145.61 to
ꢀ145.69 (1F, m, F-4), ꢀ157.16 to ꢀ157.22 (1F, m, F-2), ꢀ160.65 to
3
3
3
3
1.60 (2H, dddd, JHH 13.4, JHH 13.4, JHH 3.9, JHH 3.9, H-30),

A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
9825
1.75e1.90 (5H, m, CH, CH2), 2.01 (2H, ddd, 2JHH 12.9, 3JHH 12.9, 3JHH
12.9, H-20), 3.03 (1H, tt, 3JHH 12.6, 3JHH 3.7, H-10), 6.87 (1H, tt, 3JHF 9.5,
4JHF 7.0, H-6); dF ꢀ140.49 to ꢀ140.57 (2F, m, F-2), ꢀ144.10 to
ꢀ144.30 (2F, m, F-1); m/z (EIþ) 274 ([M]þ, 70%), 231 (49), 189 (73),
176 (72), 169 (42), 163 (70), 67 (31), 55 (100), 43 (28), 41 (58).
138.4 (ddd, 1JCF 242.4, 2JCF 16.1, 4JCF 4.5, C-4),146.7 (ddd, 2JCF 13.1, 3JCF
9.2, 3JCF 5.3, C-5), 150.0 (ddd, 1JCF 245.4, 2JCF 13.1, 3JCF 11.1, C-3), 156.0
(ddd, 1JCF 241.4, 3JCF 11.1, 4JCF 3.8, C-1); dF ꢀ118.98 to ꢀ119.04 (1F, m,
F-1), ꢀ138.77 to ꢀ138.83 (1F, m, F-4), ꢀ165.69 to ꢀ165.76 (1F, m, F-
3
3); minor isomer: dH 0.94 (3H, t, JHH 7.2, CH2CH3), 1.00e1.95 (13H,
m, CH, CH2), 2.89 (1H, tt, 3JHH 12.8, 3JHH 3.8, H-10), 3.85 (3H, s, OCH3),
6.45 (1H, ddd, 3JHF 11.6, 4JHF 6.8, 5JHF 2.2, H-6); dF ꢀ119.24 to ꢀ119.32
(1F, m, F-1), ꢀ138.96 to ꢀ139.03 (1F, m, F-4), ꢀ165.70 to ꢀ165.76
(1F, m, F-3); m/z (EIþ) 286 ([M]þ, 82%), 202 (49), 201 (90), 188 (100),
175 (87), 173 (31), 145 (36), 55 (50), 43 (50), 41 (44).
4.6. Synthesis of 1,3,4-trifluoro-2-methoxy-5-(4-propyl-
cyclohexyl)benzene 14a from 1,2-dibromo-3,4,6-trifluoro-5-
methoxybenzene 8a
1,2-Dibromo-3,4,6-trifluoro-5-methoxybenzene 8a (1.05 g,
3.28 mmol), n-BuLi (1.60 mL, 4.0 mmol) and cyclohexanone 2 (0.56 g,
4.00 mmol) gave 1-(2-bromo-3,5,6-trifluoro-4-methoxyphenyl)-4-
propylcyclohexanol 10a (1.50 g, 84%); m/z (EIþ) 382 ([M]þ, 23%), 380
([M]þ, 23), 297 (89), 295 (95), 284 (82), 282 (84), 269 (47), 267 (45),
217 (33), 216 (100), 189 (49), 55 (83), 43 (69), 41 (64).
The alcohol 10a (1.43 g, 3.75 mmol) and p-TsOH (0.07 g,
0.41 mmol) gave 1-bromo-2,4,5-trifluoro-3-methoxy-6-(4-pro-
pylcyclohex-1-enyl)benzene 12a (1.13 g, 82%); m/z (EIþ) 364 ([M]þ,
21%), 362 ([M]þ, 23), 268 (64), 266 (64), 253 (33), 213 (36), 169 (38),
43 (58), 41 (100), 40 (41), 39 (35), 29 (74), 28 (47), 27 (51).
4.8. Synthesis of 1,2,4-trifluoro-5-methoxy-3-(4-propyl-
cyclohexyl)benzene 14c from 1,4-dibromo-2,3,5-trifluoro-6-
methoxybenzene 8c
1,4-Dibromo-2,3,5-trifluoro-6-methoxybenzene 8c (1.70 g,
5.31 mmol), n-BuLi (2.10 mL, 5.30 mmol) and cyclohexanone 2
(0.74 g, 5.28 mmol) gave 1-(4-bromo-2,3,6-trifluoro-5-methox-
yphenyl)-4-propylcyclohexanol 10c (1.82 g, 90%); m/z (EIþ) 382
([M]þ, 58%), 380 ([M]þ, 62), 297 (82), 295 (100), 284 (84), 282 (99),
269 (64), 267 (66), 98 (61), 96 (69), 81 (64), 55 (92), 43 (75), 41 (76).
The alcohol 10c (2.30 g, 6.04 mmol) and p-TsOH (0.10 g,
0.71 mmol) gave 1-bromo-2,3,5-trifluoro-6-methoxy-4-(4-pro-
pylcyclohex-1-enyl)benzene 12c (1.74 g, 79%); m/z (EIþ) 364 ([M]þ,
59%), 362 ([M]þ, 61), 321 (78), 319 (79), 307 (88), 305 (92), 268 (95),
266 (100), 255 (73), 253 (75), 182 (55), 169 (44), 55 (60), 41 (64).
The alkene 12c (2.02 g, 5.56 mmol) and Pd/C (0.21 g, 0.6 mmol)
gave 1,2,4-trifluoro-5-methoxy-3-(4-propyl-cyclohexyl)benzene 14c
(0.37 g, 23%) as a clear oil and as a mixture of isomers (1.9:1)
(Found: C, 67.35; H, 7.55. C16H21F3O requires C, 67.11; H, 7.39%); Rf
The alkene 12a (1.41 g, 3.88 mmol) and Pd/C (0.14 g, 0.40 mmol)
gave 1,3,4-trifluoro-2-methoxy-5-(4-propyl-cyclohexyl)benzene 14a
(0.44 g, 40%) as a clear oil and as a mixture of isomers (1.3:1)
(Found: C, 67.26; H, 7.55. C16H21F3O requires C, 67.11; H, 7.39%); Rf
(hexane) 0.35; major isomer: dH 0.90e1.02 (3H, m, CH3), 1.05e1.90
(13H, m, CH, CH2), 2.78 (1H, tt, 3JHH 12.1, 3JHH 3.0, H-10), 3.95e4.02
(3H, m, OCH3), 6.70e6.75 (1H, m, H-6); dC 14.2 (s, CH3), 20.1 (s,
CH2CH3), 30.1 (s, C-20), 31.8 (s, C-10), 33.4 (s, C-30), 37.1 (s, C-40), 39.7
2
3
4
(s, CH2CH2CH3), 62.0 (m, OCH3), 108.3 (ddd, JCF 21.5, JCF 5.4, JCF
3.4, C-6), 129.9 (dd, 2JCF 14.1, 3JCF 6.8, C-5), 135.3 (ddd, 2JCF 15.7, 2JCF
11.5, 3JCF 2.3, C-2),144.6 (ddd, 1JCF 248.8, 2JCF 16.0, 3JCF 6.5, C-3),145.6
(ddd, 1JCF 242.8, 2JCF 11.1, 4JCF 3.5, C-4), 151.4 (ddd, 1JCF 242.6, 3JCF 4.2,
4JCF 3.0, C-1); dF ꢀ134.96 to ꢀ135.02 (1F, m, F-1), ꢀ147.54 to ꢀ147.62
(1F, m, F-3), ꢀ152.67 to ꢀ152.75 (1F, m, F-4); minor isomer: dH
0.90e1.03 (3H, m, CH3),1.05e1.85 (13H, m, CH, CH2), 2.80e2.85 (1H,
m, H-10), 3.99 (3H, s, OCH3), 6.70e6.75 (1H, m, H-6); dF ꢀ135.03 to
ꢀ135.09 (1F, m, F-1), ꢀ147.30 to ꢀ147.38 (1F, m, F-3), ꢀ152.67 to
ꢀ152.73 (1F, m, F-4); m/z (EIþ) 286 ([M]þ, 76%), 201 (76), 188 (100),
175 (83), 173 (61), 145 (56), 55 (70), 43 (78), 41 (68), 29 (48).
3
(hexane) 0.40; major isomer: dH 0.90 (3H, t, JHH 7.3, CH2CH3),
3
3
1.05e2.10 (13H, m, CH, CH2), 2.97 (1H, tt, JHH 12.5, JHH 3.7, H-10),
3.82 (3H, s, OCH3), 6.64 (1H, ddd, 3JHF 11.2, 4JHF 7.7, 4JHF 7.7, H-6); dC
14.5 (s, CH3), 20.1 (s, CH2CH3), 30.3 (s, C-20), 30.8 (s, C-10), 33.6 (s, C-
30), 36.8 (s, C-40), 39.8 (s, CH2CH2CH3), 56.7 (s, OCH3), 99.6 (dd, 2JCF
22.7, 3JCF 2.2, C-6), 124.7 (dd, 2JCF 17.1, 2JCF 15.9, C-3), 142.7 (ddd, 1JCF
236.7, 2JCF 13.8, 3JCF 8.1, C-2), 143.8 (dd, 2JCF 16.8, 3JCF 8.4, C-5), 146.3
(ddd, 1JCF 241.9, 2JCF 6.9, 4JCF 3.5, C-1), 146.5 (ddd, 1JCF 242.3, 3JCF 3.8,
4JCF 3.1, C-4); dF ꢀ141.64 to ꢀ141.71 (1F, m, F-4), ꢀ142.40 to ꢀ142.46
(1F, m, F-2), ꢀ149.67 to ꢀ149.75 (1F, m, F-1); minor isomer: dH 0.93
3
(3H, t, JHH 7.1, CH2CH3), 1.00e2.10 (13H, m, CH, CH2), 3.01 (1H, tt,
4.7. Synthesis of 1,3,4-trifluoro-5-methoxy-2-(4-propyl-
cyclohexyl)benzene 14b from 1,3-dibromo-2,4,5-trifluoro-6-
methoxybenzene 8b
3JHH 12.5, 3JHH 3.7, H-10), 3.82 (3H, s, OCH3), 6.64 (1H, ddd, 3JHF 11.2,
4JHF 7.7, 4JHF 7.7, H-6); dF ꢀ141.78 to ꢀ141.85 (1F, m, F-4), ꢀ142.39 to
ꢀ142.45 (1F, m, F-2), ꢀ149.90 to ꢀ149.97 (1F, m, F-1); m/z (EIþ) 286
([M]þ, 77%), 188 (76), 175 (85), 173 (44), 170 (100), 145 (65), 67 (44),
55 (72), 43 (64), 41 (67), 29 (51).
1,3-Dibromo-2,4,5-trifluoro-6-methoxybenzene 8b (0.89 g,
2.78 mmol), n-BuLi (1.20 mL, 3.0 mmol) and cyclohexanone 2
(0.42 g, 3.00 mmol) gave 1-(3-bromo-2,5,6-trifluoro-4-methox-
yphenyl)-4-propylcyclohexanol 10b (0.80 g, 75%); m/z (EIþ) 382
([M]þ, 54%), 380 ([M]þ, 58), 297 (73), 295 (100), 284 (73), 282 (83),
269 (64), 267 (88), 255 (51), 253 (55), 55 (78), 43 (58), 41 (64).
The alcohol 10b (0.70 g, 1.84 mmol) and p-TsOH (0.03 g,
0.17 mmol) gave 1-bromo-2,4,5-trifluoro-6-methoxy-3-(4-propylcy-
clohex-1-enyl)benzene 12b (0.56 g, 85%); m/z (EIþ) 364 ([M]þ, 72%),
362 ([M]þ, 75), 307 (79), 305 (84), 294 (68), 292 (71), 268 (86), 266
(100), 255 (93), 253 (86), 55 (66), 41 (68).
4.9. Synthesis of 40-propyl-4-(2,3,4-trifluoro-phenyl)-
bicyclohexyl 19a from 1,2,3-tribromo-4,5,6-trifluoro-benzene
15a
1,2,3-Tribromo-4,5,6-trifluoro-benzene 15a (1.37 g, 3.72 mmol),
n-BuLi (1.50 mL, 3.70 mmol) and cyclohexanone 20 (0.82 g,
3.69 mmol) gave 4-(2,3-dibromo-4,5,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-4-ol 17a (1.66 g, 86%); m/z (EIþ) 514 ([M]þ, 1%), 512
([M]þ, 1%), 510 ([M]þ,1%), 83 (35), 81 (42), 69 (84), 67 (50), 55 (100),
43 (43), 41 (88).
The alcohol 17a (1.50 g, 2.93 mmol) and p-TsOH (0.05 g,
0.29 mmol) gave 4-(2,3-dibromo-4,5,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-3-ene 18a (1.32 g, 89%); m/z (EIþ) 496 ([M]þ, 12%), 494
([M]þ, 23%), 492 ([M]þ, 12%), 182 (44), 83 (46), 69 (100), 67 (58), 55
(91), 43 (41), 41 (88).
The alkene 12b (0.81 g, 2.23 mmol) and Pd/C (0.10 g, 0.30 mmol)
gave 1,3,4-trifluoro-5-methoxy-2-(4-propyl-cyclohexyl)benzene 14b
(0.13 g, 20%) as a clear oil and as a mixture of isomers (2.2:1)
(Found: C, 67.39; H, 7.44. C16H21F3O requires: C, 67.11; H, 7.39%); Rf
3
(hexane) 0.40; major isomer: dH 0.90 (3H, t, JHH 7.3, CH2CH3),
1.00e1.95 (13H, m, CH, CH2), 2.86 (1H, tt, 3JHH 12.0, 3JHH 3.8, H-10),
3.84 (3H, s, OCH3), 6.45 (1H, ddd, 3JHF 11.6, 4JHF 6.8, 5JHF 2.2, H-6); dC
14.5 (s, CH2CH3), 20.1 (s, CH2CH3), 30.4 (s, C-20), 31.2 (s, C-10), 33.7 (s,
C-30), 36.9 (s, C-40), 39.8 (s, CH2CH2CH3), 56.6 (s, OCH3), 96.8 (dd,
The alkene 18a (1.70 g, 3.44 mmol) and Pd/C (0.14 g, 0.40 mmol),
following recrystallisation from THF/hexanes, gave 40-propyl-4-
(2,3,4-trifluoro-phenyl)-bicyclohexyl 19a (0.52 g, 45%) as a white
solid; mp 56.5e58.0 ꢁC (Found: C, 74.57; H, 8.70. C21H29F3 requires
3
2
2
3
2JCF 30.2, JCF 3.1, C-6), 115.5 (ddd, JCF 20.6, JCF 16.3, JCF 2.3, C-2),

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A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
3
3
3
3
C, 74.52; H, 8.64%); Rf (hexane) 0.25; dH 0.91 (3H, t, JHH 7.3, CH3),
0.99e1.25 (10H, m, CH2), 1.35e1.90 (11H, m, CH, CH2), 2.79 (1H, tt,
3JHH 12.3, 3JHH 3.0, H-40), 6.85e6.92 (2H, m, H-5,6); dC 14.6 (s, CH3),
20.3 (s, CH2CH3), 30.3 (s), 30.3 (s), 33.3 (s), 33.8 (s), 37.3 (s), 37.9 (s),
2.88 (1H, tt, JHH 11.7, JHH 3.8, H-40), 6.58 (2H, t, JHF 8.8, H-3); dC
14.6 (s, CH3), 20.2 (s, CH2CH3), 30.2 (s), 30.5 (s), 31.3 (s), 33.8 (s),
34.9 (s), 37.8 (s), 40.0 (s), 42.8 (s), 43.6 (s), 100.2e100.3 (m, C-3),
118.5 (td, 2JCF 18.6, 4JCF 4.8, C-1), 160.8 (dt, 1JCF 245.3, 3JCF 16.3, C-4),
161.7 (ddd, 1JCF 264.4, 3JCF 14.9, 3JCF 13.1, C-2); dF ꢀ111.05 to ꢀ111.13
(2F, m, F-2), ꢀ113.12 to ꢀ113.27 (1F, m, F-4); m/z (EIþ) 338 ([M]þ,
30%), 158 (93), 145 (97), 83 (63), 82 (53), 81 (59), 69 (100), 67 (43),
55 (82), 41 (63).
2
3
40.1 (s), 43.0 (s), 43.6 (s), 111.6 (dd, JCF 16.7, JCF 3.8, C-5), 120.8
(ddd, 3JCF 7.6, 3JCF 5.7, 4JCF 4.3, C-6), 132.0 (ddd, 2JCF 12.2, 3JCF 3.6, 4JCF
1.4, C-1), 140.0 (ddd, 1JCF 249.9, JCF 16.4, JCF 15.2, C-3), 149.5 (dd,
2
2
1JCF 247.0, JCF 9.6, C-2), 149.6e149.7 (m, C-4); dF ꢀ139.25 to
2
ꢀ139.31 (1F, m, F-4), ꢀ140.94 to ꢀ141.01 (1F, m, F-2), ꢀ161.82 to
ꢀ161.89 (1F, m, F-3); m/z (EIþ) 338 ([M]þ, 49%), 158 (65), 145 (65),
125 (41), 83 (100), 81 (56), 69 (76), 67 (46), 55 (68), 41 (54).
4.12. Debromolithiation/protonation of 8aec
4.12.1. General procedure. A solution of n-butyllithium (2.5 M in
hexanes) in dry diethyl ether (5 mL) was added via a dropping
funnel over 0.5 h to a solution of the anisole 8 in dry diethyl ether
(10 mL) at ꢀ78 ꢁC under an atmosphere of dry argon. The solution
was stirred for 6 h and then quenched slowly with ethanol
(7.5 mL) followed by water (7.5 mL). The mixture was stirred for
0.5 h, allowed to warm to room temperature, poured into water
(30 mL) and extracted with diethyl ether (3ꢂ30 mL). The com-
bined extracts were washed with water (100 mL) and dried
(MgSO4).
4.10. Synthesis of 40-propyl-4-(2,3,6-trifluoro-phenyl)-
bicyclohexyl 19b from 1,2,4-tribromo-3,5,6-trifluoro-benzene
15b
1,2,4-Tribromo-3,5,6-trifluoro-benzene 15b (2.41 g, 6.54 mmol),
n-BuLi (2.60 mL, 6.5 mmol) and cyclohexanone 20 (1.44 g,
6.48 mmol) gave 4-(3,4-dibromo-2,5,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-4-ol 17b (2.96 g, 89%); m/z (EIþ) 514 ([M]þ, 2%), 512
([M]þ, 4%), 510 ([M]þ, 2%), 178 (60), 81 (59), 69 (94), 67 (61), 55
(100), 43 (53), 41 (66).
The alcohol 17b (2.80 g, 5.47 mmol) and p-TsOH (0.09 g,
0.52 mmol) gave 4-(3,4-dibromo-2,5,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-3-ene 18b (2.03 g, 84%); m/z (EIþ) 496 ([M]þ, 20%), 494
([M]þ, 39%), 492 ([M]þ, 20%), 123 (84), 81 (65), 69 (100), 67 (93), 55
(98), 43 (57), 41 (79).
4.13. 1-Bromo-2,4,5-trifluoro-3-methoxybenzene 9a and
1-bromo-2,3,5-trifluoro-4-methoxybenzene 9b
n-Butyllithium (0.90 mL, 2.50 mmol) and 8a (0.71 g, 2.22 mmol)
gave 1-bromo-2,4,5-trifluoro-3-methoxybenzene 9a and 1-bromo-
2,3,5-trifluoro-4-methoxybenzene 9b (0.47 g, 88%) as a yellow oil
and as a mixture of isomers in the ratio 85:15 by 19F NMR analysis;
found for 9a:18 dH 4.05 (3H, s, OCH3), 7.04e7.12 (1H, m, H-6); dC 62.1
(s, OCH3), 103.2 (ddd, 2JCF 21.4, 3JCF 10.0, 4JCF 4.6, C-1), 113. 7 (d, 2JCF
21.8, C-6),138.7 (ddd, 2JCF 15.7, 2JCF 11.5, 3JCF 2.6, C-3),143.9 (ddd, 1JCF
251.1, 2JCF 14.6, 3JCF14.2, C-4), 147.6 (ddd, 1JCF 248.9, 2JCF 12.0, 4JCF 3.9,
The alkene 18b (2.50 g, 5.06 mmol) and Pd/C (0.17 g, 0.50 mmol),
following recrystallisation from THF/hexanes, gave 40-propyl-4-
(2,3,6-trifluoro-phenyl)-bicyclohexyl 19b (0.36 g, 21%) as a white
solid; mp 86.5e88.0 ꢁC (Found: C, 74.27; H, 8.63. C21H29F3 requires:
3
C, 74.52; H, 8.64%); Rf (hexane) 0.30; dH 0.89 (3H, t, JHH 7.3, CH3),
0.98e1.36 (12H, m, CH2), 1.73e1.90 (11H, m, CH, CH2), 2.95 (1H, tt,
3JHH 12.0, 3JHH 4.0, H-40), 6.74 (dddd, 3JHF 9.4, 3JHH 9.4, 4JHF 3.9, 4JHF
2.1, H-5), 6.92 (ddd, 3JHF 9.0, 3JHH 9.0, 4JHF 4.9, H-4); dC 14.6 (s, CH3),
20.2 (s, CH2CH3), 30.2 (s), 30.4 (s), 31.1 (s), 33.8 (s), 33.6 (s), 37.8
(s), 40.0 (s), 42.7 (s), 43.6 (s), 110.6 (ddd, 2JCF 26.3, 3JCF 6.7, 3JCF 4.3, C-
4), 113.9 (dd, 2JCF 19.6, 3JCF 10.4, C-5), 124.4 (dd, 2JCF 20.1, 2JCF 14.8, C-
1),147.6 (ddd, 1JCF 242.5, 2JCF 14.4, 4JCF 3.4, C-3),149.2 (ddd, 1JCF 247.1,
2JCF 13.9, 3JCF 10.1, C-2), 156.8 (ddd, 1JCF 242.3, 3JCF 7.7, 4JCF 2.9, C-6);
dF ꢀ119.33 to ꢀ119.52 (1F, m, F-6), ꢀ137.82 to ꢀ137.95 (1F, m, F-2),
ꢀ143.3 to ꢀ143.4 (1F, m, F-3); m/z (EIþ) 338 ([M]þ, 29%), 212 (20),
171 (21), 158 (39), 145 (41), 82 (100), 69 (54), 67 (33), 55 (47),
41 (36).
3
4
C-5), 149.4 (ddd, JCF 244.9, JCF 3.5, JCF 3.5, C-2); dF ꢀ126.10 to
ꢀ126.23 (1F, m F-2), ꢀ140.05 to ꢀ140.12 (1F, m, F-5), ꢀ151.73 to
ꢀ151.81 (1F, m, F-4); found for 9b:18 dH 4.03 (3H, s, OCH3), 7.08e7.18
(1H, m, H-6); dC 62.3 (s, OCH3), 101.8 (ddd, 2JCF 20.0, 3JCF 11.2, 3JCF 1.5,
C-1), 114.6 (dd, 2JCF 23.7, 3JCF 3.4, C-6), 137.5 (ddd, 2JCF 15.1, 2JCF 12.1,
1
2
3
3JCF 2.0, C-4), 145.1 (ddd, JCF 253.3, JCF 15.4, JCF 6.5, C-3), 145.9
(ddd, 1JCF 245.3, 2JCF 13.8, 4JCF 3.8, C-2),151.4 (ddd, 1JCF 260.8, 3JCF 4.2,
4JCF 4.2, C-5); dF ꢀ133.02 to ꢀ133.13 (1F, m, F-5), ꢀ133.32 to ꢀ133.41
(1F, m, F-2), ꢀ148.78 to ꢀ148.86 (1F, m, F-3). m/z (EIþ) 242 ([M]þ,
97%), 240 ([M]þ,100), 227 (60), 225 (62),199 (86),197 (88),130 (43),
118 (60), 99 (88), 80 (38), 68 (34).
4.11. Synthesis of 40-propyl-4-(2,4,6-trifluoro-phenyl)-
4.14. 2-Bromo-1,4,5-trifluoro-3-methoxybenzene 9c
bicyclohexyl 19c from 1,3,5-tribromo-2,4,6-trifluoro-benzene
15c
n-Butyllithium (2.00 mL, 5.00 mmol) and anisole 8b (1.54 g,
4.81 mmol) and column chromatography on silica gel with diethyl
ether as the eluent gave 2-bromo-1,4,5-trifluoro-3-methoxybenzene
9c19 (0.26 g, 22%) as a clear oil; dH 4.02 (3H, s, OCH3), 6.77 (ddd, 3JHF
10.0, 3JHF 8.2, 4JHF 6.5, H-6); dC 61.8 (s, OCH3), 99.8 (ddd, 2JCF 23.2, 3JCF
4.6, 4JCF 1.4, C-2), 100.2 (dd, 2JCF 28.6, 2JCF 22.4, C-6), 141.6 (ddd, 1JCF
248.1, 3JCF 14.3, 4JCF 4.9, C-1), 147.3 (ddd, 2JCF 10.3, 3JCF 4.8, 3JCF 3.6, C-
1,3,5-Tribromo-2,4,6-trifluoro-benzene 15c (1.18 g, 3.20 mmol),
n-BuLi (1.30 mL, 3.20 mmol) and cyclohexanone 20 (0.71 g,
3.20 mmol) gave 4-(3,5-dibromo-2,4,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-4-ol 17c (1.20 g, 74%); m/z (EIþ) 514 ([M]þ, 1%), 512
([M]þ, 2%), 510 ([M]þ, 1%), 178 (87), 97 (80), 83 (87), 81 (71), 69
(100), 55 (94), 41 (73).
The alcohol 17c (1.11 g, 2.17 mmol) and p-TsOH (0.03 g,
0.17 mmol) gave 4-(3,5-dibromo-2,4,6-trifluoro-phenyl)-40-propyl-
bicyclohexyl-3-ene 18c (0.67 g, 63%); m/z (EIþ) 496 ([M]þ, 10%), 494
([M]þ, 19%), 492 ([M]þ, 10%), 123 (48), 83 (42), 81 (50), 69 (100), 67
(71), 55 (90), 41 (80).
1
2
3
1
3), 150.4 (ddd, JCF 250.3, JCF 14.2, JCF 13.1, C-5), 154.8 (ddd, JCF
2
4
242.7, JCF 15.3, JCF 3.5, C-4); dF ꢀ108.71 to ꢀ108.79 (1F, m, F-1),
ꢀ134.47 to ꢀ134.58 (1F, m, F-4), ꢀ157.50 to ꢀ157.98 (1F, m, F-5). m/
z (EIþ) 242 ([M]þ, 100%), 240 ([M]þ, 95), 227 (70), 225 (67),199 (90),
197 (82), 130 (79), 118 (68), 99 (89), 81 (64).
The alkene 18c (1.20 g, 2.43 mmol) and Pd/C (0.11 g,
0.30 mmol), following recrystallisation from THF/hexanes, gave 40-
propyl-4-(2,4,6-trifluoro-phenyl)-bicyclohexyl 19c (0.17 g, 21%) as
a white solid; mp 88.0e89.0 ꢁC (Found: C, 74.28; H, 8.64. C21H29F3
requires: C, 74.52; H, 8.64%); Rf (hexane) 0.30; dH 0.89 (3H, t, JHH
7.3, CH3), 0.97e1.36 (12H, m, CH2), 1.73e1.84 (11H, m, CH, CH2),
4.15. 3-Bromo-1,2,5-trifluoro-4-methoxybenzene 9e
n-Butyllithium (2.30 mL, 5.75 mmol) and anisole 8c (1.80 g,
5.63 mmol), after column chromatography on silica gel with diethyl
ether as the eluent, gave 3-bromo-1,2,5-trifluoro-4-methoxybenzene
9e19 (0.93 g, 69%) as a clear oil; dH 3.93 (3H, s, OCH3), 6.97 (1H, ddd,
3

A.M. Kenwright et al. / Tetrahedron 66 (2010) 9819e9827
9827
3
4
2
3JHF 10.9, JHF 10.9, JHF 7.5, H-6); dC 61.8 (s, OCH3), 105.2 (dd, JCF
25.2, 2JCF 22.3, C-6), 107.0 (ddd, 2JCF 18.9, 3JCF 4.6, 3JCF 2.4, C-3), 142.4
(dd, 2JCF 14.4, 3JCF 3.8, C-4), 145.0 (ddd, 1JCF 246.0, 2JCF 14.9, 4JCF 4.3,
366 ([M]þ,12), 210 (26), 208 (27),129 (44),110 (30), 98 (22), 81 (22),
79 (100).
C-2), 146.2 (ddd, 1JCF 249.4, JCF 15.2, JCF 12.1, C-1), 151.1 (ddd, 1JCF
2
3
4.20. X-ray crystallography
3
4
248.7, JCF 10.2, JCF 3.5, C-5); dF ꢀ138.61 to ꢀ138.71 (1F, m, F-2),
ꢀ132.82 to ꢀ132.93 (1F, m, F-1), ꢀ130.93 to ꢀ130.84 (1F, m, F-5);
m/z (EIþ) 242 ([M]þ, 100%), 240 ([M]þ, 93), 227 (74), 225 (70), 199
(75), 197 (71), 130 (40), 118 (47), 99 (63), 81 (37).
The single crystal X-ray data for 19c were collected on a Rigaku
R-AXIS IP Spider diffractometer at 120 K using graphite mono-
ꢀ
chromated Mo K
a
radiation(
l
¼0.71073 A). The structures were
solved by direct method and refined by full-matrix least squares on
F2 for all data using SHELXL software. All non-hydrogen atoms were
refined with anisotropic displacement parameters, H-atoms were
found in the difference Fourier maps and refined isotropically.
Crystallographic data for the structures have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publications CCDC 784207.
4.16. Synthesis of tribromotrifluorobenzene derivatives
15aec
4.16.1. General procedure. Triflic acid (15 mL) was added slowly to
a
cooled (0 ꢁC) and stirred mixture consisting of the tri-
fluorobenzene derivative 16 (1.0 equiv) and NBS (3.1 equiv). The
solution was allowed to warm to room temperature, stirred for 72 h
and poured into ice water (50 mL). The aqueous solution was
extracted with DCM (3ꢂ30 mL) and the organic extracts were dried
(MgSO4), evaporated and the residue recrystallised from ethanol/
water to provide the tribromo-trifluoroaromatic product.
Crystal data for 19c: C21H29F3, M¼338.44, triclinic, space group
ꢀ
Pꢀ1, a¼5.3626(3), b¼7.0644(4), c¼24.8576(10)A,
a¼90.32(3),
3
b¼95.03(3),
g
¼108.57(3)ꢁ, U¼888.68(8) A, F(000)¼364, Z¼2,
ꢀ
Dc¼1.265 mg/m3,
m
¼0.093 mmꢀ1, 11,121 reflections collected, 3830
unique data (Rmerg¼0.0577). Final wR2(F2)¼0.1433 for all data (334
refined parameters), conventional R1(F)¼0.0560 for 2723 re-
4.17. 1,2,3-Tribromo-4,5,6-trifluoro-benzene 15a
flections with Iꢃ2 , GOF¼1.033.
s
1,2,3-Trifluorobenzene 16a (1.32 g, 10 mmol) and N-bromo-
succinimide (5.70 g, 32 mmol) gave 1,2,3-tribromo-4,5,6-trifluoro-
benzene 15a (0.99 g, 27%) as a white solid; mp 70.5e72.0 ꢁC (lit.20
mp 67 e69 ꢁC) (Found: C, 19.33. C6Br3F3 requires: C, 19.54%); dC
Acknowledgements
We thank SONY Deutschland GmbH and EPSRC for funding
(studentship to A.J.T.).
2
1
110.0 (d, JCF 24.5, C-3), 123.1e123.2(m, C-2), 139.6 (dt, JCF 258.7,
1
2
3
2JCF 17.3, C-5), 148.5 (ddd, JCF 251.9, JCF 11.8, JCF 4.3, C-4); dF
ꢀ117.70 (2F, d, 3JFF 21.1, F-4), ꢀ153.65 (1F, t, 3JFF 21.1, F-5); m/z (EIþ)
372 ([M]þ, 20%), 370 ([M]þ, 56), 368 ([M]þ, 56), 366 ([M]þ, 19), 210
(44), 208 (42), 129 (71), 110 (30), 98 (29), 79 (100).
References and notes
1. Collings, P. J.; Hird, M. Introduction to Liquid Crystals. Chemistry and Physics;
Taylor and Francis: London, 1997.
2. Demus, D.; Goodby, J.; Gray, G. W.; Spiess, H. W. Handbook of Liquid Crystals;
Wiley-VCH: Weinheim, 1998.
3. Kelly, S. M. Flat Panel Displays. Advanced Organic Materials; RSC: Cambridge,
2000.
4.18. 1,2,4-Tribromo-3,5,6-trifluoro-benzene 15b
1,2,4-Trifluorobenzene 16b (2.64 g, 20 mmol) and N-bromo-
succinimide (10.68 g, 60 mmol) gave 1,2,4-tribromo-3,5,6-tri-
fluoro-benzene 15b (3.61 g, 49%) as a clear oil (Found: C, 19.55.
4. Kirsch, P.; Bremer, M. Angew. Chem., Int. Ed. Engl. 2000, 39, 4216e4235.
€
5. Kirsch, P.; Binder, W.; Hahn, A.; Jahrling, K.; Lenges, M.; Lietzau, L.; Maillard, D.;
€
Meyer, V.; Poetsch, E.; Ruhl, A.; Unger, G.; Frohlich, R. Eur. J. Org. Chem. 2008,
3479e3487.
2
2
C6Br3F3 requires: C, 19.54%); dC 99.2 (dd, JCF 27.9, JCF 22.0, C-4),
6. Hird, M. Chem. Soc. Rev. 2007, 36, 2070e2095.
7. Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications;
Wiley-VCH: Weinheim, 2004.
108.8 (dd, 2JCF 25.6, 3JCF 4.9, C-2), 113.7 (ddd, 2JCF 20.7, 3JCF 1.6, 3JCF
1
1.1, C-1), 145.8 (A of ABMX, JCF 235.5, C-5/6), 148.0 (B of ABMX,
8. Belf, L. J.; Buxton, M. W.; Fuller, G. J. Chem. Soc. 1965, 3372e3379.
9. Fujii, S.; Maki, Y.; Kimoto, H. J. Fluorine Chem. 1988, 43, 131e144.
10. Peach, M. E.; Sutherland, D. J. J. Fluorine Chem. 1981, 17, 225e231.
11. Sandford, G.; Tadeusiak, A.; Yufit, D. S.; Howard, J. A. K. J. Fluorine Chem. 2007,
128, 1216e1220.
12. Banks, B.; Cargill, M. R.; Sandford, G.; Westemeier, H.; Yufit, D. S.; Howard, J. A.
K.; Kilickiran, P.; Nelles, G. J. Fluorine Chem. 2010, 131, 627e634.
13. Kalinowski, H. O.; Berger, S.; Braun, S. Carbon 13 NMR Spectroscopy; John Wiley:
New York, NY, 1988.
1
3
4
1JCF 251.6, C-5/6), 153.2 (ddd, JCF 246.8, JCF 4.2, JCF 3.1, C-3); dF
5
4
ꢀ95.48 (X of ABMX, JFF 10.0, JFF 6.4, F-3), ꢀ124.54 (A of ABMX,
3JFF 22.5, JFF 10.0, F-6), ꢀ124.97 (B of ABMX, JFF 22.5, JFF 6.4, F-
5); m/z (EIþ) 372 ([M]þ, 52%), 370 ([M]þ, 90), 368 ([M]þ, 100), 366
([M]þ, 78), 289 (73), 210 (88), 208 (83), 129 (88), 110 (76), 79
(100).
5
3
4
14. Kalinowski, H. O.; Berger, S.; Braun, S. NMR Spectroscopy of the Non-Metallic
Elements; John Wiley: New York, NY, 1997.
4.19. 1,3,5-Tribromo-2,4,6-trifluoro-benzene 15c
15. Olah, G. A.; Wang, Q.; Sandford, G.; Prakash, G. K. S. J. Org. Chem. 1993, 58,
3194e3198.
16. Allen, F. H. Acta Cryst, Sect. B 2002, B58, 380e388. For a more general reference
to The CCSD.
17. Gupta, S.; Bhattacharyya, K.; SenGupta, S. P.; Paul, S.; Kalman, A.; Parkanyi, L.
Acta Crystallogr., Sect. C 1999, 55, 403e405.
18. Burdon, J.; King, D. R.; Tatlow, J. C. Tetrahedron 1966, 22, 2541e2549.
19. Bolton, R.; Sandall, J. P. B. J. Chem. Soc., Perkin Trans. 2 1978, 137e141.
20. Heiss, C.; Schlosser, M. Eur. J. Org. Chem. 2003, 447e451.
1,3,5-Trifluorobenzene 16c (2.64 g, 20 mmol) and N-bromo-
succinimide (10.68 g, 60 mmol) gave 1,3,5-tribromo-2,4,6-trifluoro-
benzene 15c (3.54 g, 48%) as a white solid; mp 98.0e99.0 ꢁC (lit.19
mp 94e95 ꢁC) (Found: C, 19.54. C6Br3F3 requires: C, 19.54%); dC
94.8 (td, 2JCF 27.1, 4JCF 5.1, C-1), 156.3 (dt, 1JCF 248.5, 3JCF 5.8, C-2); dF
ꢀ95.79 (s); m/z (EIþ) 372 ([M]þ,13%), 370 ([M]þ, 38), 368 ([M]þ, 38),