3,6-disubstituted cyclohexenones in the synthesis of new three ring liquid crystalline compounds with the negative dielectric anisotropy

Article abstract of DOI:10.1080/15421406.2011.569518

New improved approach for preparation of the three ring liquid crystalline compounds with 2,3-difluorobenzene moiety is proposed. The key stage is the synthesis of 3,6-disubstituted cyclohex-2-en-1-ones via the condensation of the corresponding Mannich sa

Full text of DOI:10.1080/15421406.2011.569518

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3,6-Disubstituted Cyclohexenones in
the Synthesis of New Three Ring Liquid
Crystalline Compounds with the Negative
Dielectric Anisotropy
G. Sasnouski a , V. Bezborodov a , R. Dabrowski b & J. Dziaduszek b
a Institute of Applied Physics Problems, Minsk, Belarus
b Military University of Technology, Warsaw, Poland
Published online: 14 Jun 2011.
To cite this article: G. Sasnouski , V. Bezborodov , R. Dabrowski & J. Dziaduszek (2011) 3,6-
Disubstituted Cyclohexenones in the Synthesis of New Three Ring Liquid Crystalline Compounds with
the Negative Dielectric Anisotropy, Molecular Crystals and Liquid Crystals, 542:1, 56/[578]-61/[583],
DOI: 10.1080/15421406.2011.569518
To link to this article: http://dx.doi.org/10.1080/15421406.2011.569518
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Mol. Cryst. Liq. Cryst., Vol. 542: pp. 56=[578]–61=[583], 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421406.2011.569518
3,6-Disubstituted Cyclohexenones in the Synthesis
of New Three Ring Liquid Crystalline Compounds
with the Negative Dielectric Anisotropy
G. SASNOUSKI,1 V. BEZBORODOV,1
R. DABROWSKI,2 AND J. DZIADUSZEK2
1Institute of Applied Physics Problems, Minsk, Belarus
2Military University of Technology, Warsaw, Poland
New improved approach for preparation of the three ring liquid crystalline
compounds with 2,3-difluorobenzene moiety is proposed. The key stage is the
synthesis of 3,6-disubstituted cyclohex-2-en-1-ones via the condensation of the cor-
responding Mannich salts with 2-substituted acetoacetic esters (or methyl benzyl
ketones) in the presence of base. The chlorination with phosphrous pentachloride
of these cyclohexenones or methylation with methylmagnesium iodide followed oxi-
dative aromatization give new three ring compounds, which could be used in the LC
compositions with negative dielectric anisotropy.
Keywords 2,3-Difluorobenzene derivatives; 3,6-disubstituted cyclohex-2-en-1-
ones; liquid crystal; synthesis
1. Introduction
The liquid crystalline compounds containing 2,3-difluorobenzene moiety are very
useful as the components for LC mixtures because of their negative dielectric ani-
sotropy [1,2]. The synthesis of these compounds was generally realized according
to the scheme, which provides for using of catalytic cross-coupling reaction as a
key stage [3–5]. Some syntheses of the bicyclohexylbenzene LC derivatives have been
carried out starting from 4-alkylbicyclohexyl-4-one [6]. In this article we show a new
pathway to prepare three-ring derivatives possessing 2,3-difluorobenzene moiety. We
believe the advantage of our way is that one provides for complete excluding of
expensive palladium catalysts and low temperatures reactions.
2. Results and Discussion
2.1. Syntheses
We have synthesized a variety of new three-ring derivatives possessing 2,3-difluoro-
benzene moiety using the Michael-type condensation as a key stage. As it was
Address correspondence to G. Sasnouski, Institute of Applied Physics Problems,
Kurchatova 7, 220108 Minsk, Belarus. Tel.: þ375-172785735; Fax: þ375-172124116;
E-mail: g_sasnouski@yahoo.com
56=[578]

3,6-Disubstituted Cyclohexenones in the Synthesis of LC
57=[579]
reported in our previous papers 3,6-disubstituted cyclohexenones arriving from the
condensation of Mannich salts with the 2-substituted acetoacetic esters (or substi-
tuted methyl benzyl ketones) are the convinient semiproducts for the further chemi-
cal transformations in liquid crystals synthesis [7–11]. Earlier we have also reported
the new cyclopropanol approach for the synthesis of three-ring cyclohexylbiphenyl
LC compouds using substituted 1-cyclohexylcyclopropanoles as the precursors
instead of Mannich salts in the condensation with acetoacetic esters or methyl benzyl
ketones [12].
Here three main pathways for the preparation of three ring 3,6-cyclohexenones
with 2,3-difluorobenzene moiety have been developed:
a. Condensation of substituted methyl benzyl ketones with the Mannich salts (2) on
the base of easily available 4-alkoxy-2,3-difluoroacetophenones (1). This method
finally leads to laterally substituted LC terphenyl derivatives (4,5).
=
R C2H5, C4H9; X Cl, OCF3, C2H5, C5H11;
=
b. Condensation of Mannich salt (2) on the base of 4-alkoxy-2,3-difluoroacetophe-
none. (1) with 2-[2-(trans-4-alkylcyclohexyl)ethyl]acetoacetic ester (6). The result-
ing cyclohexenones (7) are precursors for the three ring LC compounds with the
dimethylene bridge (8).
=
R C2H5, C4H9;
c. Starting from alkyl trans-4-alkylcyclohexanecarboxylate as the precursor for
the corresponding cyclopropanol (9) (according Kulinkovich reaction [13]),
which was brominated and then condensed with 4-methoxy-2,3-difluorobenzyl

58=[580]
methyl ketone (11).
G. Sasnouski et al.
2,3-Difluorosubstituted acetophenones (1) prepared from the available
2,3-difluoroalkoxybenzenes in the Friedel-Crafts reaction conditions can be con-
verted in the usual way with dimethylamine hydrochloride and paraform to the
corresponding Mannich salts (2). The condensation of salts (2) with 2-alkylsubstituted
acetoacetic esters in basic media gives three-ring cyclohexenones (7) as well as anal-
ogous condensation of (2) with 4-substituted methylbenzylketones affords the
three-ring cyclohexenones (3).
Using Kulinkovich reaction we have made the successful attempt to apply
this synthetic approach to prepare three-ring cyclohexenones (12) possessing
2,3-difluorobenzene moiety.
For the further transformations of cyclohexenones (3,7,12) standard synthetic
organic chemistry procedures were used. The chlorination with phosphrous
pentachloride of these cyclohexenones or methylation with methylmagnesium iodide
Table 1. Phase transition temperatures [ꢀC] of prepared compounds.
No
3a
R
X
T,ꢀC
No
4a
R
X
T,ꢀC
C2H5 Cl
Cr 145 Iso
Cr 124 Iso
Cr 110 Iso
Cr 121 Iso
Cr 99 Iso
Cr 79 Iso
C2H5 Cl
Cr 152 Iso
3b C2H5 OCF3
3c C4H9 Cl
3d C4H9 OCF3
3e
3f
4b C2H5 OCF3 Cr 118 Iso
4c C4H9 Cl Cr 96 (N 68) Iso
4d C4H9 OCF3 Cr 79 SmA 71 Iso
4e
4f
C4H9 C2H5
C4H9 C5H11
C4H9 C2H5 Cr 78 Iso
C4H9 C5H11 Cr 51 N 60 Iso
No
5a
R
X
T,ꢀC
No
R
T,ꢀC
C4H9 Cl
Cr 79 (N 59) Iso 8a
C2H5
8b C4H9
Cr 74 N 101 Iso
Cr 67 N 98 Iso
5b C4H9 OCF3 Cr 50 Iso
5c C4H9 C2H5 Cr 55 (N 47) Iso
5d C4H9 C5H11 Cr 52 N 72 Iso

3,6-Disubstituted Cyclohexenones in the Synthesis of LC
59=[581]
followed oxidative aromatization give new laterally substituted three ring
compounds (4,5,8,13).
2.2. Mesogenic Properties
Mesogenic properties of the intermediate cyclohexenones (3,7,12) and transform-
ation products prepared on the base of them (4,5,8,13) have been examinated
(Table 1).
The prepared cyclohexenones (3,7,12) are not liquid crystalline. But first of all
these compounds are interesting as precursors for the further chemical transforma-
tions because of reactive enone moiety presence. An initial examination of the meso-
phase behaviour of prepared compounds (4,5,8,13) shows that only compounds with
the enough long chain in the both terminal positions possess liquid crystalline phases
over a narrow temperature range.
3. Experimental
The structures of the prepared compounds are consistent with the analytical data
including H1 NMR and mass spectra. Phase transition temperatures were measured
using a Linkam heating stage in conjugation with a polarising PZO microscope and
also using a Setaram DSC 141.
Here we describe the example of synthetic procedures as the general one for such
compounds. All compounds have been prepared according the analogous instruc-
tions.
All used 4-substituted methylbenzylketones have been prepared by reaction of
the corresponding 4-substituted phenylacetyl chlorides with magnesium malonic
ester followed by hydrolysis in 20% sulphuric acid.
2-(2-(Trans-4-propylcyclohexyl) ethyl) acetoacetic ester (6) has been prepared
starting from trans-4-propylcyclohexane carboxylic acid. Synthesis of 1-(trans-4-
propylcyclohexyl) cyclopropanol starting from methyl trans-4-alkylcyclohexanecar-
boxylate and its further bromination are described in [12].
The Condensation General Procedure. The mixture of 0.05 mol Mannich salt (2),
0.055 mol 2-alkylacetoacetic ester (or 4-substituted methyl benzylketone) and
0.15 mol potassium hydroxide in 150 ml of dioxane was refluxed during 6 h under
stirring. After cooling 300 ml of 10% sulfuric acid solution was added carefully
(evolution of carbon dioxide in the case of acetoacetic ester using) and product
was extracted with methylene chloride. Organic layer was washed with water,
dried over anhydrous magnesium sulfate and filtered through short column with
silica gel. The residue obtained after the solvent evaporation was recrystallized
from ethanol. The yields were 45–60%.
2-Bromoketone (10) obtained from 1-(trans-4-propylcyclohexyl)-1-cyclopropanol
(9) (0.041 mol) was dissolved together with 2,3-difluoro-4-methoxyphenylacetone
(11) (9.0 g, 0.045 mol) in 100 ml of diglyme. After adding of granulated potassium
hydroxide (8.4 g, 0.15 mol) the resulting mixture was then refluxed under stirring
during 4 h. After cooling to room temperature and treatment with 10% solution of
sulphuric acid the product was twice extracted with benzene. After drying over
sodium sulphate and removing of the solvent the ketone (12) has been twice crystal-
lized from ethanol. The yield was 52% (isolated product); m.p. 127–128ꢀC.

60=[582]
G. Sasnouski et al.
Ketone (12) was then chlorinated according below general procedure giving (13);
yield 39%; Cr 101 Iso.
The Chlorination General Procedure. Phosphorous pentachloride (0,015 mol) was
slowly added th the solution of cyclohexenone (3,12) (0,01 mol) in 100 ml of
toluene. The reaction mixture was heated under reflux during 5–6 h and then was
poured into a mixture of 5% sodium hydroxide solution with ice. The organic
layer was separated and washed with water, diluted hydrochloric acid and again
with water. The resulting solution was filtered through short column with silica
gel. After the solvent had been removed the obtained residue was solved in hexane
and purified by filtration throught the column with silica gel. After removing of
solvent the product was recrystallized from isopropyl alcohol-hexane mixture. The
yields were 35–42%.
The Methylation General Procedure. Methylmagnesium iodide (approx. 0.02 mol)
prepared in the usual way in ether was slowly added to the solution of
3,6-disubstituted cyclohexenone (3,7) (0.01 mol) in 30 ml of dry THF at room
temperature. The reaction mixture was stirred for 2 h and then kept overnight.
Diluted sulphuric acid was carefully added and water layer was separated and
twice extracted with ether. Combined organic layer was washed with water and
dried over anhydrous magnesium sulfate. After evaporation of the solvent the
residue was solved in 50 ml of toluene and air was bubbled through the solution
at boiling temperature. The reaction completion was tested by chromatographic
method. Toluene solution was filtered through short column with silica gel and
solvent was removed completely. The residue was solved in hexane and again
filtered through short column with silica gel. After removing of solvent the
product was recrystallized from isopropyl alcohol-hexane mixture. The yields were
60–65%.
4. Conclusions and Perspectives
Thus shown chemical transformations illustrate our approach to be effective and
convenient for the synthesis of various liquid crystalline three-ring derivatives pos-
sessing 2,3-difluorobenzene moiety and additively chlorine atom or methyl group
in the lateral position. Prepared compounds with enough long terminal chains have
low melting points, even terphenyl derivatives. They are easily solved in non polar
organic solvents (hexane, toluene etc) and are easily mixable with another LC com-
pounds and could be useful as component of the liquid crystalline compositions with
negative dielectric anisotropy to adjust their properties.
Acknowledgment
The work was carried under project NATO PDD(TC)-(CBP.EAP.CLG 983701).
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