Synthesis of substituted benzyl ethers of 1-(4-hydroxyphenyl)oct-2-en-1-one

Article abstract of DOI:10.1007/s11178-005-0309-5

A preparation of substituted benzyl ethers of 1-(4-hydroxyphenyl)oct-2-en- 1-one from 3-(4-hydroxy-phenyl)-5-pentyl - 2-isoxazoline was developed for the first time. These ethers can be used as promising additives and useful intermediates for synthesis of

Full text of DOI:10.1007/s11178-005-0309-5

Russian Journal of Organic Chemistry, Vol. 41, No. 8, 2005, pp. 1165−1169. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 8, 2005,
pp. 1187−1190.
Original Russian Text Copyright © 2005 by V. Kovganko, N. Kovganko.
.
Synthesis of Substituted Benzyl Ethers
of 1-(4-Hydroxyphenyl)oct-2-en-1-one
V.N. Kovganko and N.N. Kovganko
Sevchenko Institute of Applied Physical Problems at Belarus State University, Minsk, 220064 Belarus
e-mail: kauhanka@bsu.by
ReceivedApril 24, 2004
Abstract—Apreparation of substituted benzyl ethers of 1-(4-hydroxyphenyl)oct-2-en-1-one from 3-(4-hydroxy-
phenyl)-5-pentyl--2-isoxazoline was developed for the first time. These ethers can be used as promising additives
and useful intermediates for synthesis of fluorine-containing liquid crystals.
Syntheses of liquid crystalline compounds basing on
substituted 2-isoxazolines were formerly reported [1–5].
One of the preparation procedures [1] employed as an
intermediate substituted 2-isoxazoline II. This compound
can be obtained from the easily available 4-hydroxy-
benzaldehyde oxime I. In the first stage of the process
compound I is subjected to successive treatment with
N-chlorosuccinimide and triethylamine to afford the
corresponding nitrile oxide that at subsequent reaction
with 1-heptene furnishes substituted 2-isoxazoline II. The
opening of the heterocycle in the substituted 2-isoxazolines
is widely used in the organic synthesis for preparation of
versatile bifunctional compounds, for instance,
aminoalcohols, β-hydroxyketones, and enones [6, 7]. We
believe that the opening of the 2-isoxazoline ring in
compound II may be used in the synthesis of new liquid
crystalline compounds with various functional groups in
the side chain. The phenol hydroxy group can be used to
connect rigid fragments of the molecule through bridging
ether groups. We report here on the possibility to use this
approach to the synthesis of mesomorphous compounds
by an example of preparation of substituted benzyl ethers
from 1-(4-hydroxyphenyl)oct-2-en-1-one.
By hydrogenolysis of the heterocycle in 2-isoxazoline
II on Raney nickel we obtained β-hydroxyketone III in
76% yield.At treating hydroxyketone III with hydrochloric
acid β-chloroketone IV formed alongside a dehydration
product; the former compound became the main reaction
product at prolonged process time, and it was isolated in
7
0% yield. β-Chloroketone IV arises due to hydrogen
chloride addition across the double bond of the dehydration
product of compound III. We presumed that a double
bond may form in the next benzylation stage, and therefore
(
(
1) NCS
2) Et N
3
H2,
Ni/Ra
(
3)
N O
O OH
N OH
H
C5H
11
HO
HO
HO
C5H
11
C5H
11
I
II
III
O Cl
O
ArCH Cl, K CO
HCl
2
2
3
HO
ArCH O
2
C5H
11
C5H11
_
IV
Vа Vd
F
F
F
Ar =F
(а), NC
(b), MeO
(c), MeO
(d).
1070-4280/05/4108-1165©2005 Pleiades Publishing, Inc.

1166
V. KOVGANKO, N. KOVGANKO
β-chloroketone IV would be suitable for the synthesis of
ethers as chiral additives to nematic mixtures was
described in [8]. We believe that among compounds we
obtained the most promising for this application is benzyl
ether Vb with a terminal cyano group. This compound of
low melting point can be used as isotropic additive for
reducing the temperature of mesophase formation in
nematic liquid crystal mixtures.
the target benzyl ethers.
The structure of compounds III and IV was proved
1
by the data obtained by analysis of IR, UV, and H NMR
spectra. In the IR spectrum of β-hydroxyketone III the
absorption band of the stretching vibrations of the carbonyl
–1
group is observed at 1664 cm . This shift of the C=O
frequency as compared with its usual position in alkyl
It should also be mentioned that the enone moiety
present in the molecules of compounds Va–Vd can be
used to introduce some practically important structural
elements of the liquid crystal compounds, for instance,
fluorine atoms [9–12].
–1
aryl ketones in the region 1680–1700 cm is caused by
involvement of the carbonyl group of compound III into
an intramolecular hydrogen bond with a hydroxy group
3
1
attached to C atom. In the H NMR spectrum the
β-hydroxyketone fragment of compound III gives rise
Thus proceeding from 3-(4-hydroxyphenyl)-5-pentyl-
2-isoxazoline a synthetic procedure was developed for
benzyl ethers of 1-(4-hydroxyphenyl)oct-2-en-1-one
which may be interesting as components of liquid crystal
compositions. The report on application of the approach
we developed to the synthesis of more complex liquid
crystalline compounds with a functionally modified side
chain will be published elsewhere.
2
to two doublets of doublets of protons from C H at δ
2
2
.95 and 3.11 ppm and to a multiplet of the proton
3
C H at δ 4.16–4.25 ppm. In the IR spectrum of
β-chloroketone IV the absorption band of the carbonyl
stretching vibrations appears at 1675 cm . A specific
–1
1
feature of the H NMR spectrum of compound IV
consists in the downfield shift of proton signals from the
β-chloroketone moiety as compared to the corresponding
signals in the spectrum of β-hydroxy-ketone III. Protons
EXPERIMENTAL
2
of C H group give rise to doublets of doublets δ 3.18
2
3
Phase transition temperature was measured on
a heating block coupled with a polarization microscope.
IR spectra were recorded from solutions in chloroform
on a spectrophotometer Specord 75-IR in a cell of potas-
sium bromide. UV spectrum was taken on a spectro-
photometer Specord M40 from a methanol solution.
and 3.50 ppm, and proton C H appears as a multiplet at
δ 4.48–4.57 ppm.
In reaction of compound IV with substituted benzyl
chlorides in the presence of potassium carbonate benzyl
ethers Va–Vd were obtained in 50–80% yields. As we
have presumed the hydrogen chloride is eliminated in the
course of the reaction, and a double bond is formed. The
latter fact is confirmed by the presence in the IR spectra
of compounds Va–Vd of strong absorption bands from
1
H NMR spectra were registered on spectrometer Bruker
Avance 400 (400 MHz), from solutions in deutero-
chloroform, internal reference HMDS. Reactions
progress was monitored and the purity of compounds
obtained was checked by TLC on Kiesel-gel 60 F254
plates (Merck).
–1
C=C bond vibrations at 1610–1620 cm . The vibrations
of the conjugated carbonyl group in the IR spectra of
compounds Va–Vd are observed in the range 1660–
1
-(4-Hydroxyphenyl)-3-hydroxyoctan-1-one
–
1
1
1
670 cm . In the H NMR spectra of benzyl ethers Va–
(
III). A dispersion of 2 g of Raney nickel in 20 ml of
2
3
Vd vinyl protons C H and C H appear as multiplets
at δ 6.84 and 7.05 ppm with a vicinal coupling constant
5.6 Hz. This value of the coupling constant indicates
methanol and 12 ml of water was saturated with hydrogen
at stirring for 1 h. Then a solution of 3.58 g (15.4 mmol)
of 3-(4-hydroxyphenyl)-5-pentyl-2-isoxazoline (II)
prepared by procedure [1] and 9.3 g (150 mmol) of boric
acid in 80 ml of methanol was added. The reaction mixture
was stirred under hydrogen atmosphere till consumption
of hydrogen ended. The catalyst was filtered off, washed
on the filter with 100 ml of dichloromethane, 150 ml of
saturated solution of NaCl was added, and then the
organic layer was separated. The products were
additionally extracted from the water layer into
dichloromethane (2×50 ml). The combined organic
solutions were washed in succession with 50 ml of
1
the formation of a trans-disubstituted double bond.
We established by measuring the temperature of phase
transitions in benzyl ethers Va–Vd that none of the
compounds formed a mesophase. This may be due in
particular to insufficient number of ring structures in the
central part of the molecule. However compounds Va–
Vd have a structure typical for many nematic liquid
crystals. Therefore it is possible to use the compounds
as various isotropic additives to nematic liquid crystal
mixtures. For instance, the application of two-ring benzyl
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

SYNTHESIS OF SUBSTITUTED BENZYL ETHERS OF 1-(4-HYDROXYPHENYL)OCT-2-EN-1-ONE
1167
–
1
saturated sodium hydrogen carbonate solution and 50 ml
of saturated solution of NaCl, dried with sodium sulfate,
and the solvent was distilled off under reduced pressure.
The residue was recrystallized from a mixture toluene−
petroleum ether. Yield 2.77 g (76%), mp 76.5–77.5°C
IR spectrum, cm : 3025, 3015 (C–Harom), 2955, 2930,
2870, 2855 (C–Halkyl), 1660 (C=O), 1610 (C=C), 1595,
1
1570, 1510 (C=C ). H NMR spectrum, δ, ppm: 0.89 t
arom
8
6
7
(3H, C H , J 6.8 Hz), 1.16–1.40 m (4H, C H , C H ),
3
2
2
5
4
1.51 quintet (2H, C H , J 7 Hz), 2.29 q (2H, C H ,
J 7 Hz), 5.08 s (2H, OCH ), 6.87 d (1H, C H,
J 15.6 Hz), 6.94–7.14 m (1H, C H), 6.99 d (2H,
2
2
–
1
2
(
toluene−petroleum ether). IR spectrum, cm : 3575,
460–3100 (OH), 3010 (C–Harom), 2950, 2925, 2850
2
3
3
(
C–Halkyl), 1664 (C=O), 1600, 1590, 1505 (C=Carom).
J 8.8 Hz), 7.04–7.14 m (2H), 7.40 m (2H), 7.93 d (2H,
J 8.8 Hz) (arom. protons).
1
8
H NMR spectrum, δ, ppm: 0.88 t (3H, C H , J 7 Hz),
3
1
.16–1.66 m (8H, CH , H
), 2.95 d.d (1H, J 9,
2
alkyl
1
4-Cyanobenzyl ether of 1-(4-hydroxyphenyl)-oct-
2
J 18 Hz), 3.11 d.d (1H, J 2.4, J 18 Hz) (C H ),
3
6
2
1
2
2
2-en-1-one (Vb). Yield 49%, mp 43°C (2-propanol). IR
3
3
.65 br.s (1H, C OH), 4.16–4.25 m (1H, C H), 6.80–
–1
spectrum, cm : 3025, 3015 (C–Harom), 2960, 2930, 2860
4
'
.98 m (1H, C OH), 6.85 d (2H, J 9 Hz), 7.85 d (2H,
(
1
(
C–Halkyl), 2235 (C≡N), 1665 (C=O), 1610 (C=C), 1600,
J 9 Hz) (arom. protons).
1
570, 1500 (C=C ). H NMR spectrum, δ, ppm: 0.89 t
arom
1
-(4-Hydroxyphenyl)-3-chlorooctan-1-one (IV).
8
6
7
3H, C H , J 7 Hz), 1.16–1.39 m (4H, C H , C H ), 1.51
3 2 2
To a solution of 0.766 g of β-hydroxyketone III in 20 ml
of dioxane was added 1.5 ml of concn. hydrochloric acid.
The mixture obtained was stirred for 22.5 h at 20°C.
Then 40 ml of toluene and 50 ml of saturated sodium
chloride solution were added to the reaction mixture. The
organic layer was separated. The products were
additionally extracted from the water layer into toluene
5
4
quintet (2H, C H , J 7 Hz), 2.29 distorted q (2H, C H ,
J 7 Hz), 5.18 s (2H, OCH ), 6.84 distorted d (1H, C H,
J 15.2 Hz), 7.05 t.d (1H, C H, J 7, J 15.2 Hz), 6.99 d
2
2
2
2
3
1
2
(
2H, J 9 Hz), 7.54 d (2H, J 8 Hz), 7.68 d (2H, J 8 Hz),
.94 d (2H, J 9 Hz) (arom protonû).
-Methoxy-3-fluorobenzyl ether of 1-(4-hydroxy-
phenyl)oct-2-en-1-one (Vc). Yield 58%, mp 59–60°C
7
4
(2×20 ml). The combined toluene solutions were washed
–1
(
2-propanol). IR spectrum, cm : 3035, 3030, 3020 (C–
in succession with 30 ml of saturated sodium hydrogen
carbonate solution and 30 ml of saturated solution of NaCl,
dried with sodium sulfate, and the solvent was distilled
off under reduced pressure. The residue was crystallized
from a mixture toluene−petroleum ether. Yield 0.577 g
Harom), 2965, 2935, 2860 (C–Halkyl), 1670 (C=O), 1620
1
(
C=C), 1600, 1575, 1520, 1510 (C=C ). H NMR
arom
8
spectrum, δ, ppm: 0.89 t (3H, C H , J 6.8 Hz), 1.17–
.38 m (4H, C H , C H ), 1.51 quintet (2H, C H ,
J 7.2 Hz), 2.29 d.q (2H, C H , J 1.6, J 7.2 Hz), 3.89 s
3H, OCH ), 5.03 s (2H, OCH ), 6.87 t.d (1H, C H,
3 2
3
6
7
5
1
2
2
4
2
2
1
2
(
70%), mp 56–57°C (toluene−petroleum ether, decomp.).
2
(
–1
UV spectrum, λ , nm: 221.1, 279.8. IR spectrum, cm :
max
3
J 1.6, J 15.6 Hz), 7.04 t.d (1H, C H, J 7.2,
1
2
1
3
2
1
585, 3100–3500 (O–H), 3025, 3010 (C–Harom), 2960,
930, 2875, 2865 (C–Halkyl), 1675 (C=O), 1605, 1585,
J2 15.6 Hz), 6.93–7.00 m (3H), 7.12 m (1H), 7.16 m
(1H), 7.93 d (2H, J 8.8 Hz) (arom. protons).
1
510 (C=C ). H NMR spectrum, δ, ppm: 0.88 t (3H,
arom
4
-Methoxy-2,3-difluorobenzyl ether of 1-(4-
8
6
7
C H , J 6.8 Hz), 1.20–1.38 m (4H, C H , C H ), 1.40–
1
3
2
2
hydroxyphenyl)oct-2-en-1-one (Vd). Yield 78%,
5
4
.62 m (2H, C H ), 1.69–1.89 m (2H, C H ), 3.18 d.d
2 2
–1
mp 76–77°C (2-propanol). IR spectrum, cm : 3025, 3010
(
(
1H, J 5.6, J 16.4 Hz), 3.50 d.d (1H, J 8, J 16.4 Hz)
1 2 1 2
(
(
1
C–Harom), 2960, 2930, 2875, 2860 (C–Halkyl), 1660
C=O), 1610 (C=C), 1595, 1570, 1510 (C=Carom).
2
3
4'
C H ), 4.48–4.57 m (1H, C HCl), 5.74 br.s (1H, C OH),
2
6
.88 d (2H, J 8.8 Hz), 7.89 d (2H, J 8.8 Hz) (arom.
8
H NMR spectrum, δ, ppm: 0.89 t (3H, C H , J 7 Hz),
3
protons).
6
7
5
1
.12–1.38 m (4H, C H , C H ), 1.51 quintet (2H, C H ,
2 2 2
4
4
-Fluorobenzyl ether of 1-(4-hydroxyphenyl)-oct-
J 7 Hz), 2.29 d.q (2H, C H , J 1, J 7 Hz), 3.90 C (3H,
OCH ), 5.11 C (2H, OCH ), 6.87 t.d (1H, C H, J 1
J 15.6 Hz), 7.04 t.d (1H, C H, J 7, J 15.6 Hz), 7.00 d
2 1 2
2
2
-en-1-one (Va). To a solution of 0.1 g (0.39 mmol) of
,
3
2
3
1
β-chloroketone IV and 0.052 ml (0.43 mmol) of 4-fluoro-
benzyl chloride in 50 ml of methyl ethyl ketone was added
2
1
2
(2H, J 8.8 Hz), 7.94 d (2H, J 8.8 Hz), 6.72–6.78 m (1H),
3
g of potassium carbonate. The reaction mixture was
7.10–7.18 m (1H) (arom. protons).
heated at reflux while stirring for 15 h. Then the inorganic
precipitate was filtered off and washed on the filter
with 50 ml of methyl ethyl ketone. The solvent was distilled
off at reduced pressure, the residue was recrystallized
from 2-propanol. Yield 59%, mp 96–97°C (2-propanol).
REFERENCES
1. Bezborodov, V.S., Kovganko, N.N., and Lapanik, V.I., Vestsi
National Akad. Nauk Belarusi, Ser. Khim. N., 2003, no. 3,
p. 76.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

1168
V. KOVGANKO, N. KOVGANKO
2
3
. Min’ko, A.A., Bezborodov, V.S., Kovganko, N.N., and
Geterotsikl. Soed., 1989, p. 435.
8. Chapman, J., Ellis, C., Duffy, W.L., Friedman, M.R., Xu, H.,
Davey, A.B., and Crossland, W.A., Mol. Cryst. Liq. Cryst.,
Lapanik, V. I., Vestn. BGU, Ser. 1, 2002, no. 3, p. 44.
. Bezborodov, V.S., Kovganko, N.N., and Lapanik, V.I., Vestsi
National Akad. Nauk Belarusi, Ser. Khim. N., 2003, no. 1,
p. 48.
. Bezborodov, V.S., Kauhanka, N.N., Lapanik, V.I., and
Lee, C.J., Liq. Cryst., 2003, vol. 30, p. 579.
2004, vol. 411, p. 49.
9
. Petrov, V.F., Duan, M., Okamoto, H., Mu, J., Shimizu,Y., and
Takenaka, S., Liq. Cryst., 2001, 28, p. 387.
0. Kirsch, P. and Bremer, M., Angew. Chem., Int. Ed., 2000,
vol. 39, p. 4216.
11. Singh, R.P. and Shreeve, J.M., Synthesis, 2002, p. 2561.
12. Kuroboshi, M., Kanie, K., and Hiyama, T., Adv. Synth. Catal.,
2001, vol. 343, p. 235.
4
1
5
. Bezborodov, V., Kauhanka, N., and Lapanik, V., Mol. Cryst.
Liq. Cryst., 2004, vol. 411, p. 103.
6
7
. Kanemasa, S. and Tsuge, O., Heterocycles, 1990, 30, p. 719.
. Lakhvich, F.A., Koroleva, E.V., and Akhrem, A.A., Khim.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005