Synthesis and mesomorphic properties of new 3-aryl-5-cyano-4,5- dihydroisoxazoles

Article abstract of DOI:10.1023/B:RUJO.0000019743.40861.ce

New 3-aryl-5-cyano-4,5-dihydroisoxazoles possessing liquid crystalline properties were synthesized in two ways. The key stage in both procedures is 1,3-dipolar cycloaddition of nitrile oxides to acrylonitrile.

Full text of DOI:10.1023/B:RUJO.0000019743.40861.ce

Russian Journal of Organic Chemistry, Vol. 39, No. 12, 2003, pp. 1777 1780. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 12, 2003,
pp. 1848 1851.
Original Russian Text Copyright
2003 by Bezborodov, Kovganko, Lapanik.
Synthesis and Mesomorphic Properties
of New 3-Aryl-5-cyano-4,5-dihydroisoxazoles
V. S. Bezborodov, N. N. Kovganko, and V. I. Lapanik
Sevchenko Research Institute of Applied Physical Problems, Belarussian State University,
ul. Kurchatova 7, Minsk, 220064 Belarus
e-mail: bezborodov@bsu.by
Received December 29, 2002
Abstract New 3-aryl-5-cyano-4,5-dihydroisoxazoles possessing liquid crystalline properties were synthesized
in two ways. The key stage in both procedures is 1,3-dipolar cycloaddition of nitrile oxides to acrylonitrile.
Mesomorphic heterocyclic compounds attract
strong interest from the viewpoint of creation of
materials for electrooptical display devices (LCD)
[1, 2]. These substances give rise to smectic or
nematic phase at low temperature and over a wide
temperature range [3]; they are characterized by high
positive or negative dielectric anisotropy and are
efficient components of liquid crystalline composi-
tions with a low threshold and saturation voltage.
in 68% yield by reaction with hydroxylamine hydro-
chloride in the presence of sodium acetate. Generation
of nitrile oxide from IVa was effected by chlorination
with N-chlorosuccinimide and subsequent dehydro-
chlorination with triethylamine in the presence of
acrylonitrile. As a result, the target 5-cyano-4,5-di-
hydroisoxazole Va was synthesized in 66% yield.
Ester Vb was obtained using an analogous reaction
sequence.
We previously described the synthesis and liquid
crystalline properties of 3-alkyl-5-aryl-4,5-dihydro-
isoxazoles [4] and 5-alkyl-3-aryl-4,5-dihydroisoxa-
zoles [5]. The key stage in the synthesis of these
compounds was 1,3-dipolar cycloaddition of nitrile
oxide generated from the corresponding hydroxamoyl
chloride to 1-heptene (1-hexene) or methyl 4-vinyl-
benzoate, respectively.
The goal of the present study was to synthesize
new 3-aryl-5-cyano-4,5-dihydroisoxazoles V and
examine their liquid crystalline properties. Unlike
ferroelectric mesomorphic derivatives of pyrazole and
isoxazole [6], compounds V could be utilized in liquid
crystalline devices based on nematic materials.
We tried to obtain 3-aryl-5-cyano-4,5-dihydro-
isoxazoles V in two ways. The first of these includes
building up of dihydroisoxazole ring at the last stage
via 1,3-dipolar cycloaddition of nitrile oxide generated
from oxime IV to acrylonitrile. It is known that such
reactions occur in a regioselective fashion, yielding
the corresponding 5-cyano derivatives [7]. Following
this approach, 4-hydroxybenzaldehyde I was treated
with 4-(octyloxy)benzoyl chloride (IIa) in the pres-
ence of pyridine to obtain 90% of ester IIIa. The
latter was converted into the corresponding oxime IVa
The second approach is based on esterification of
5-cyano-4-(4-hydroxyphenyl)-4,5-dihydroisoxazole
VII with acids VIIIa VIIIc. As above, phenol VII
was prepared from 4-hydroxybenzaldehyde oxime
(VI). It shoud be noted that the chlorination of VI in
the presence of pyridine led to formation of a complex
mixture of products, from which we failed to isolate
dihydroisoxazole VII. When hydrogen chloride was
used as catalyst [8], compound VII was synthesized in
56% yield. We also made an attempt to obtain phenol
VII from acetoxy derivative Vc. However, hydrolysis
of Vc with potassium hydroxide in aqueous methanol
gave a mixture of poorly soluble products. Analogous
results were obtained in the debenzylation of com-
pound XI with hydrogen over Pd/C. According to the
TLC data, a mixture of products was also formed in
the synthesis of VII from benzyloxy derivative XI.
Presumably, strong electron-acceptor character of the
cyano group favors decomposition of the isoxazole
ring in the above reactions. Esters Vd Vf were syn-
thesized by esterification of phenol VII with acids
VIIIa VIIIc in the presence of N,N -dicyclohexyl-
carbodiimide (Scheme 1).
The structure of the products was confirmed by
1
the IR and H NMR spectra. The IR spectra of oximes
1070-4280/03/3912-1777$25.00 2003 MAIK Nauka/Interperiodica

1778
BEZBORODOV et al.
Scheme 1.
II V, R = 4-C8H17OC6H4 (a), 4-C9H19OC6H4 (b), Me (c); Vd, VIIIa, R = 4-C7H15C6H4; Ve, VIIIb, R = 4-C8H17C6H4;
Vf, VIIIc, R =
.
IV, VI, and X lack aldehyde absorption bands but
Esters Va, Vb, and Vd Vf were found to exhibit
properties of liquid crystals. 4-Alkoxybenzoic acid
derivatives Va and Vb give rise to monotropic
smectic phase A. Compound Ve, which is a derivative
of 4-alkylbenzoic acid, gives hard smectic phase E
whose structure is similar to crystalline phase. trans-
4-Pentylcyclohexanecarboxylate Vf forms thermo-
tropic smectic phase A in the temperature range from
1
contain bands in the region 3120 3580 cm , which
correspond to stretching vibrations of the oxime
1
hydroxy group. In the H NMR spectra of dihydro-
isoxazole derivatives V, VII, and XI we observed two
doublets at
3.64 3.83 ppm from the methylene
protons on C4 and a doublet of doublets at 5.29
5.74 ppm from the 5-H proton.
Table 1. Yields, phase transition temperatures, and IR spectra of oximes IVa IVc, VI, and X
Compound
no.
Yield,
%
mp or phase transition
temperature,
1
IR spectrum, , cm
C
IVa
IVb
IVc
VI
68
96
56
71
98
Cr 88 N 122 I
Cr 93 N 130 I
96 97 (toluene)
3580, 3480 3200 (O H), 3010 (C Harom), 2930, 2860 (C Haliph),
1725, 1255, 1070 (COOAr), 1600, 1500 (C Carom), 1165 (C O)
3575, 3490 3140 (O H), 3005 (C Harom), 2930, 2855 (C Haliph),
1725, 1250, 1065 (COOAr), 1600, 1500 (C Carom), 1160 (C O)
3575, 3500 3120 (O H), 3025 (C Harom), 1750 (C=O), 1600, 1500
(C Carom
)
107 108
(toluene ethyl acetate)
109 110 (toluene)
3595 3040 (O H), 1675 (C N), 1600, 1500 (C Carom
)
X
3570, 3465 3120 (O H), 3000 (C Harom), 1600, 1500 (C Carom),
1170 (C O)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

SYNTHESIS AND MESOMORPHIC PROPERTIES
1779
Table 2. Yields, phase transition temperatures, and IR and 1H NMR spectra of dihydroisoxazoles Va Vf, VII, and XI
Comp.
no.
Yield, mp or phase transition
1
IR spectrum, , cm
1H NMR spectrum, , ppm (J, Hz)
%
temperature,
C
Va
66
Heating:
Cr 132 I
Cooling:
3005 (C Harom), 2920, 0.87 t (3H, CH3, J = 4.5), 1.15 1.90 m (12H,
2850 (C Haliph),
CH2), 3.67 d (2H, 4-H, J = 8.3), 3.98 t (2H,
OCH2, J = 6.3), 5.31 t (1H, 5-H, J = 8.3),
1730, 1255, 1065
Cr 86 SmA 132 I
(COOAr), 1600, 1500
6.91 d (2H, Harom, J = 9.0), 7.24 d (2H, Harom,
(C Carom),
(C O)
1165
J = 9.0), 7.66 d (2H, Harom, J = 9.0), 8.07 d
(2H, Harom, J = 9.0)
Vb
55
Heating:
Cr 136.5 I.
Cooling:
3005 (C Harom), 2925, 0.83 t (3H, CH3, J = 4.5), 1.15 1.90 m (14H,
2850 (C Haliph),
CH2), 3.68 d (2H, 4-H, J = 8.3), 3.98 t (2H,
OCH2, J = 6.3), 5.32 t (1H, 5-H, J = 8.3),
1720, 1245, 1065
Cr 87 SmA 136.5 I
(COOAr), 1600, 1500
6.91 d (2H, Harom, J, 9.0), 7.24 d (2H, Harom,
(C Carom),
(C O)
1165
J = 9.0), 7.66 d (2H, Harom, J = 9.0), 8.07 d
(2H, Harom, J = 9.0)
Vc
Vd
46
77
137 138
(2-propanol)
3025 (C Harom), 1755 2.25 s (3H, AcO), 3.64 d (1H, 4-H, J = 8.2),
(OAc), 1600, 1500
3.65 d (1H, 4-H, J = 9.0), 5.29 d.d (1H, 5-H,
J1 = 8.2, J2 = 9.0), 7.11 d (2H, Harom, J = 9.0),
7.61 d (2H, Harom, J = 9.0)
(C Carom
)
121 (2-propanol)
3025 (C Harom), 2955, 0.83 t (3H, CH3, J = 7.2), 1.20 1.33 m (8H, CH2),
2930, 2855
1.60 quint (2H, CH2, J = 7.2), 2.64 t (2H, CH2,
J = 7.2), 3.66 d.d (1H, 4-H, J1 = 6.8, J2 = 16.4),
3.71 d.d (1H, 4-H, J1 = 10.4, J2 = 16.4),
5.32 d.d (1H, 5-H, J1 = 6.8, J2 = 10.4), 7.25 d
(2H, Harom, J = 2.0), 7.27 d (2H, Harom, J =
2.0), 7.67 d (2H, Harom, J = 8.8), 8.04 d (2H,
Harom, J = 8.8)
(C Haliph), 1730,
1265, 1065 (COOAr),
1600, 1505
(C Carom), 1165
(C O)
Ve
Vf
83
81
Cr 92 98 SmE 110 I 3015 (C Harom), 2920, 0.82 t (3H, CH3, J = 7.2), 1.15 1.33 m (10H,
2865 (C Haliph),
1725, 1250, 1050
(COOAr), 1600, 1500
CH2), 1.59 quint (2H, CH2, J = 7.2), 2.64 t (2H,
CH2, J = 7.2), 3.66 d.d (1H, 4-H, J1 = 6.8, J2 =
16.4), 3.71 d.d (1H, 4-H, J1 = 10.4, J2 = 16.4),
5.32 d.d (1H, 5-H, J1 = 6.8, J2 = 10.4), 7.24 d
(2H, Harom, J = 2.0), 7.27 d (2H, Harom, J =
2.0), 7.67 d (2H, Harom, J = 8.8), 8.04 d (2H,
Harom, J = 8.8)
(C Carom
)
Cr 107 SmA 121 I 3020, (C Harom), 2960, 0.88 t (3H, CH3, J = 5.8), 1.14 1.38 m (10H,
2930, 2855
CH2), 1.43 2.35 m (7H, CH and CH2), 2.48 t.t
(1H, CHCOO, J1 = 3.4, J2 = 11.9), 3.70 d (1H,
4-H, J = 7.0), 3.71 d (1H, 4-H, J = 8.9),
5.35 d.d (1H, 5-H, J1 = 7.0, J2 = 8.9), 7.14 d
(2H, Harom, J = 8.8), 7.66 d (2H, Harom, J 8.8)
3.82 d (1H, 4-H, J = 8.9), 3.83 d (1H, 4-H, J =
7.0), 5.74 d.d (1H, 5-H, J1 = 7.0, J2 = 8.9),
(C Haliph), 1740,
1160, 1115 (COOAr),
1600, 1505
(C Carom
)
VII
XI
56
43
150.5 151.5
(toluene ethyl acetate)
3530 3050 (O H),
1600, 1505
(C Carom
)
6.85 d (2H, Harom, J = 8.8), 7.55 d (2H, Harom
J = 8.8), 10.10 br.s (1H, ArOH)
,
147 (2-propanol
3010 (C Harom), 1695 3.64 d (1H, 4-H, J = 7.2), 3.65 d (1H, 4-H, J =
methyl ethyl ketone)
(C N), 1600, 1500
(C Carom), 1165
(C O)
9.5), 5.07 s (2H, PhCH2O), 5.28 d.d (1H, 5-H,
J1 = 7.2, J2 = 9.5), 6.97 d (2H, Harom, J = 9.0),
7.28 7.41 m (5H, Harom), 7.55 d (2H, Harom
,
J = 9.0)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1780
BEZBORODOV et al.
107 to 121 C. It should be noted that the obtained
compounds are characterized by a high positive di-
electric anisotropy ( > 10); therefore, they can be
used in the preparation of nematic liquid crystalline
compositions with a low threshold voltage.
portions of water, and dried over sodium sulfate. The
solvent was removed under reduced pressure, and the
residue was subjected to column chromatography on
aluminum oxide using methylene chloride as eluent.
Yield of Va 1.36 g (66%).
Compounds Vb, Vc, VII, and XI were synthesized
in a similar way (Table 2).
EXPERIMENTAL
4-(5-Cyano-4,5-dihydroisoxazol-3-yl)phenyl
4-heptylbenzoate (Vd). A catalytic amount of 4-di-
methylaminopyridine was added to a mixture of
0.393 g of 4-heptylbenzoic acid, 0.352 g of 3-(4-hy-
droxyphenyl)-4,5-dihydroisoxazole-5-carbonitrile
(VII), and 0.394 g of N,N -dicyclohexylcarbodiimide
in 15 ml of methylene chloride. The mixture was
stirred for 20 h at room temperature, and the precip-
itate was filtered off through a layer of aluminum
oxide and washed with two portions of methylene
chloride. The filtrate was evaporated under reduced
pressure, and the residue was recrystallized from
2-propanol. Yield 0.537 g (77%).
The melting points and phase transition tempera-
tures were determined on a heating device coupled
with a polarization microscope. The IR spectra were
1
recorded on a Specord 75IR spectrometer. The H
NMR spectra were measured on Tesla BS-567A
(80 MHz) and Tesla BS-567 (100 MHz) instruments
using HMDS as internal reference.
Esters IIIa IIIc were synthesized by reaction of
4-hydroxybenzaldehyde (I) with carboxylic acid
chlorides IIa IIc according to the procedure described
in [9]. Chlorides IIa and IIb were prepared by treat-
ment of the corresponding acids with thionyl chloride.
The properties of esters IIIa and IIIb were in agree-
ment with published data [9].
4-(Hydroxyiminomethyl)phenyl 4-octyloxyben-
zoate (IVa). A solution of 12.8 g of aldehyde IIIa in
100 ml of 2-propanol was heated to the boiling point,
and a solution of 3.0 g of hydroxylamine hydro-
chloride and 3.6 g of sodium acetate in a mixture of
20 ml of 2-propanol and 40 ml of water was added
dropwise. The mixture was stirred for 1.5 h on heating
under reflux, 50 ml of water was added to the hot
mixture, and the mixture was cooled to 20 C. The
precipitate was filtered off, and an additional amount
of the product was isolated from the mother liquor.
Yield 9.0 g (68%).
Esters Ve and Vf were synthesized in a similar way
(Table 2).
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1. Nagashima, Y., Ichihashi, T., Noguchi, K., Iwa-
moto, M., Aoki, Y., and Nohira, H., Liq. Cryst., 1997,
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and Lapanik, V.I., Vestn. Bel. Gos. Univ., Ser. 1,
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Oximes IVb, IVc, VI, and X were synthesized in
a similar way (Table 1).
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Vestsi Nats. Akad. Navuk Belarusi, Ser. Khim. Navuk,
2003, p. 48.
4-(5-Cyano-4,5-dihydroisoxazol-3-yl)phenyl
4-octyloxybenzoate (Va). To a solution of 1.8 g of
oxime IIIa in 15 ml of chloroform and 5 ml of di-
methylformamide we added 0.8 g of N-chlorosuccin-
imide and one drop of pyridine. The mixture was
cooled with ice to 0 C, and 5 ml of acrylonitrile was
added. A solution of 0.85 ml of triethylamine in 10 ml
of chloroform was then added dropwise over a period
of 1.5 h. The mixture was stirred for an additional
1 h and filtered, and the filtrate was treated with
dilute (1:9) hydrochloric acid, washed with three
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Tetrahedron, 1981, vol. 37, p. 2815.
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