3,5-disubstituted isoxazolines as potential molecular kits for liquid-crystalline materials

Article abstract of DOI:10.1002/ejoc.200801026

A collection of 3,5-disubstituted isoxazolines have been synthesized by 1,3-dipolar [3+2] cycloaddition reactions. Some isoxazolines were selected and transformed into liquid crystals. These new liquid crystals exhibit nematic and smectic C mesophases.

Full text of DOI:10.1002/ejoc.200801026

FULL PAPER
DOI: 10.1002/ejoc.200801026
3,5-Disubstituted Isoxazolines as Potential Molecular Kits for Liquid-
Crystalline Materials
Aline Tavares,[a] Paulo H. Schneider,[a] and Aloir A. Merlo*[a]
Keywords: Heterocycles / Cycloaddition / Coupling reactions / Liquid crystals
A collection of 3,5-disubstituted isoxazolines have been syn-
thesized by 1,3-dipolar [3+2] cycloaddition reactions. Some
isoxazolines were selected and transformed into liquid crys-
tals. These new liquid crystals exhibit nematic and smectic
C mesophases.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
emerge. In this sense, the isoxazoline moiety can be consid-
ered a useful molecular kit for the preparation of interesting
organic materials.[13]
Introduction
The 1,3-dipolar [3+2] cycloaddition of nitrile oxides to
olefins offers a convenient one-step route to the construc-
tion of a variety of five-membered heterocycles known as
isoxazolines.[1] Pharmacologically, this class of heterocycle
has been reported to possess interesting biological activities
as well as analgesic, anti-inflammatory and hypoglycemic
properties.[2–5] Isoxazolines are also synthetically versatile
intermediates that readily undergo further transformations,
such as alkylation,[6] dehydrogenation to isoxazoles[7] and
reductive cleavage to expose functionalities such β-hydroxy
ketones, α,β-unsaturated ketones,[8] β-amino acids or γ-
amino alcohols.[9]
Nitrogen- and oxygen-containing heterocycles also play
an important role in the synthesis of novel liquid-crystalline
(LC) materials. One important heterocycle moiety used in
LC materials is the isoxazole ring and its variants. Although
the [3+2] cycloaddition approach has been used to synthe-
size isoxazole directly from activated alkynes and nitrile
oxides, the literature reports only moderate yields and low
regioselectivities.[10–12] To increase both the yield and re-
gioselectivity of the cycloaddition step, we envisage that
isoxazoline as an intermediate emerges as an excellent alter-
native to the preparation of the isoxazole ring in fair-to-
good yields and high regioselectivity. The oxidation reac-
tion of the corresponding 3,5-disubstituted isoxazol-
ine[13b,13d] prepared by cycloaddition is an easy and efficient
approach to the synthesis of the isoxazole ring. Moreover,
by attaching suitable aryl groups at the C-3 and C-5 posi-
tions of the isoxazoline ring, interesting LC properties can
In this article we describe the 1,3-dipolar cycloaddition
of nitrile oxides to dipolarophiles to produce 3,5-disubsti-
tuted isoxazoline rings which are potential candidates for
liquid-crystalline materials. For this purpose we selected
three 3,5-disubstituted isoxazoline compounds synthesized
in this work to demonstrate that these heterocycles can
serve as molecular kits in the synthesis of new compounds
with mesogenic properties. Four LC compounds were pre-
pared by a simple and easy modification of the original
isoxazoline ring (Figure 1) by adding two “molecular
wings” bearing one or more aromatic rings at the 3- and 5-
positions of the isoxazoline system.
Figure 1. General structure of the isoxazoline liquid crystals.
Results and Discussion
Synthesis of the Isoxazolines 6–12
Two main methodologies were used to prepare the
isoxazoline LC materials. First, to form the isoxazoline, a
[3+2] cycloaddition reaction between a nitrile oxide (gener-
ated by in situ oxidation of the corresponding aldoxime)
and an alkene was performed. The Sonogashira reaction
was then used as the second methodology to install the tri-
ple bond into the molecular wings of the final compounds.
The preparation of the aldoximes 3a–d is outlined in
Scheme 1. They were prepared from aldehyde 1 in two steps
following classical procedures. In the first step, p-hydroxy-
[a] Organic Department, Chemistry Institute, UFRGS,
Bento Gonçalves avenue, 9500, Campus do Vale, Porto Alegre,
RS, Brazil, 91501970
Fax: +55-51-3308-7304
E-mail: aloir@iq.ufrgs.br
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2009, 889–897
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
889

A. Tavares, P. H. Schneider, A. A. Merlo
FULL PAPER
benzaldehyde (1) was alkylated by treatment with alkyl bro- Table 1. 1,3-Dipolar [3+2] cycloaddition of oximes 3a–d and 4e–g
with dipolarophiles 5a–g.[a]
mides to yield the corresponding p-alkoxybenzaldehydes
2a–d in 70–90% yields. In the second step the oximes were
synthesized by the reaction of 2a–d with a solution of hy-
droxylamine hydrochloride in good yields (73–93%).
Entry
Aldoxime
Dipolarophile
Adduct
Yield [%][b]
1
2
3
4
5
6
7
3a
3b
3c
3d
4e
4f
6a
6b
6c
80
66
83
89
47
–
5a
Y = CO2H
6d
6e
Scheme 1. Synthesis of aldoximes 3a–d.
6f[c]
6g
4g
25
Oximes containing a polar group (X) at the para position
of the aromatic ring 4e (X = Br), 4f (X = CN) and 4g (X
= NO2) were also prepared in good yields by exposure of
the corresponding 4-substituted benzaldehyde to a solution
of hydroxylamine hydrochloride.
8
9
10
11
3a
3b
3c
3d
7a
7b
7c
7d
36
36
38
41
5b
5c
5d
Y = CH2OH
12
13
14
15
3a
3b
3c
3d
8a
8b
8c
8d
31
65
38
62
n
The oximes prepared in this work were obtained as a
mixture of E and Z isomers. The structural assignments of
Y = CO2 Bu
these intermediates were made based on their H and 13C
1
NMR chemical shifts. The signal of the iminyl hydrogen of 16
3a
3b
4f
9a
9b
50
78
–
17
18
19
Y = CONH2
the Z isomer always appears at a higher field than that of
9f[c]
9g
the E isomer, in accordance with the reported oxime ana-
4g
45
logues derived from anisaldehyde.[15a,15b] The 13C NMR res-
20
3c
3a
3b
5e
5f
Y = CN
10c
11a[d]
12b
43
30
60
onance line of the iminyl carbon atom follows the same
tendency. For instance, the chemical shift of the iminyl car-
bon of the E isomer is always shifted downfield, whereas
that of the Z isomer is shifted upfield. The chemical shift
is an indication of the charge distribution on the iminyl car-
21
Y = CH2CO2H
Y = p-MeC6H4
22
5g
[a] Reaction conditions: dipolarophile (2.3 mmol), NCS
(2.3 mmol), oxime (2 mmol), pyridine (3 mmol), solvent (8 mL). [b]
bon atom. In this situation, the charge distribution values Isolated yields. [c] No reaction. [d] 2:1 Cycloadduct, see discussion
in the text.
observed for the E isomers were smaller than the those of
the Z isomers.[14–19]
The 1,3-dipolar [3+2] cycloaddition reactions were car-
ried out with seven different benzaldehyde oximes 3a–d and
4e–g and seven dipolarophiles 5a–g (Scheme 2, Table 1).
of the cyano aldoxime 4f with dipolarophile 5a and 5d, no
cycloadducts were observed (entries 6 and 18).
1
The 13C and H NMR spectra of the isoxazolines exhib-
The yields of the isoxazolines 6–12 obtained are reported
ited well-defined resonance lines for the C-3 and C-5 carbon
1
in Table 1. All the cycloadducts were characterized by H
1
atoms and for the corresponding hydrogen atoms. The H
and 13C NMR spectroscopic techniques and melting points.
NMR spectrum of cycloadduct 7a, for instance, showed
1
The regiochemistries were established by H and 13C NMR
four sets of doublet of doublets centred at δ = 3.24, 3.36,
spectroscopy. In all cases the reactions of the benzaldehyde
3.68 and 3.86 ppm, which belong to ABX and AMX pat-
terns arising from chemically and magnetically non-equiva-
lent protons. The resonance lines of the selected carbon
atoms of the isoxazoline ring confirm the correct regio-
oximes with 5a–g (via the nitrile oxide intermediate) were
completely regioselective giving only 3,5-disubstituted isox-
azolines with no traces of the 3,4-regioisomers detected.[20]
chemistry of the [3+2] cycloaddition event. Thus, from the
13C NMR spectrum of 7a we can observe only two signals
centred at δ = 36.5 and 80.9 ppm, which are consistent with
the 3,5 regioisomer[20,21] (see the Supporting Information).
The cycloaddition reaction between the oxime 3a and the
dipolarophile 5f reported in Table 1 gave the product 11a
(Figure 2) exclusively in 30% yield and not the expected
3,5-disubstituted isoxazoline. The structure of the new con-
Scheme 2. Preparation of isoxazolines 6–12.
In nearly all cases, the yields were in the range of 40 densed product 11a, which was characterized as the 2:1
to 90%. Low yields were obtained with the allylic alcohol cycloadduct, was confirmed by NMR, mass spectrometry,
dipolarophile 5b, which gave the 3,5-disubstituted isoxazol- elemental analysis and thermal analysis. These results can
ines 7a–d and is known to be considerably less reactive than be rationalized by the low dipolarophilic reactivity of the
the other dipolarophiles used in this work. In the reactions vinylacetic acid (5f) in comparison with the 3,5-disubsti-
890
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 889–897

3,5-Disubstituted Isoxazolines as Liquid-Crystalline Materials
tuted isoxazoline formed in situ. Once the 3,5-disubstituted
isoxazoline has formed by the reaction of the aryl nitrile
oxide and 5f, polarization of the C=N bond by the oxygen
atom enhances the dipolarophilic character of the C=N
bond and drives the addition of a second equivalent of aryl
nitrile oxide to the initially formed isoxazoline.[22]
Figure 3. Terminal acetylenes 15 and 16.
The second Sonogashira reaction allowed further elong-
ation of the acetylene derivatives 15 and 16 by connection
of another aromatic ring. Thus, the reaction of the pro-
tected bromophenol[26] 17b and 15 under palladium/copper
cross-coupling conditions[24,27] gave the desired phenol 18
after hydrolysis of the acetyl group in good yields
(Scheme 3).
Figure 2. The 2:1 cycloadduct 11a.
Synthesis of Selected Liquid-Crystalline Materials
Having accomplished the preparation of 3,5-disubsti-
tuted isoxazolines (Table 1) we could then explore the po-
tential of this heterocycle as a molecular kit for obtaining
a new class of calamitic liquid crystals. In this way, potential
LC materials can be obtained from these key intermediates
by an elongating molecular strategy. The elongation builds
on the rigid isoxazoline core to form a more polarizable
and mesogenic one. Our idea was to explore the synthetic
potential of this class of compounds bearing a functional
group by attaching a suitable aromatic moiety. The isoxazol-
ines 6a and 7a were chosen because they possess carboxy
and hydroxy functional groups, which could be used to ob-
tain the desired LC materials. In addition, simple oxidation
of the isoxazoline ring, such as 12b, affords the liquid crys-
tal compound in a straightforward fashion.
Scheme 3. Synthesis of 18.
The chemical linkage between 18 and 6a to obtain the
final liquid crystal compound 19 was mediated by the DCC/
DMAP protocol[28] in 70% of yield (Figure 4). Thermal
analysis (DSC) and polarized optical microscopy studies
(POM) showed that 19 is a thermotropic liquid crystal.
When compound 19 was cooled from the isotropic phase, it
clearly presented typical schlieren textures with singularity
points and two- and four-brush defects characteristic of the
nematic phase. The optical, thermal and thermodynamic
data for the liquid crystals prepared in this work are sum-
marized in Table 2.
By a Sonogashira reaction an arylacetylenic group was
installed on one side of the isoxazoline ring. Figure 3 shows
the two acetylene derivatives used to elongate the isoxazol-
ines 6a and 7a. Compounds 15 and 16 were synthesized in
three steps following
a methodology described pre-
viously.[23] Thus, the alkylation of 6-bromo-2-naphthol (13)
or p-bromophenol (14) with n-alkyl bromide gave the corre-
sponding alkyl aryl ethers in 85–95% yields. Installation of
the acetylene unit was accomplished by Sonogashira alk-
ynylation[24] of the alkyl aryl ethers derived from 13 or 14
with 2-methyl-3-butyn-2-ol (mebynol). The terminal acetyl-
enes 15 and 16 were smoothly obtained by the release of
acetone using KOH and 2-propanol.[25]
Figure 4. Chemical structure of 19.
Table 2. Transition temperatures and enthalpies (∆H) for compounds 19, 21, 23 and 24.[a]
Entry
Phase transition temperature [°C]
∆H [kcalmol–1]
Heating
Cooling
Melt[d]
Iso phase K[e]
19
21
23
24
K 144.5[b] N 148.0 I
K 138.4 I
K 102.5 I
I 144.9 N 136.9 K
I 134.3[c] N 120.2 K
I 75.7[c] SmC[f] 71.2 K
I 131.1 N 82.2 K
6.74
I 0.015 N 6.59 K
I 0.67 N 13.53 K
I 2.81 SmC 11.79 K
I 0.076 N 5.87 K
13.91
13.40
5.82
K 105.9 N 132.2 I
[a] Scan rate: 10 °Cmin–1 for all samples. K denotes crystal phase, SmC = smectic C phase and N = nematic phase. [b] Data obtained
from POM study. [c] Monotropic behaviour. [d] Enthalpies (second heating/cooling stage) were determined from the crystal phase to the
LC phase. [e] Cooling. [f] On slow cooling the samples crystallized. On fast cooling the sample displayed an unstable mesophase SmC
during the crystallization process.
Eur. J. Org. Chem. 2009, 889–897
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
891

A. Tavares, P. H. Schneider, A. A. Merlo
FULL PAPER
The DSC traces (Figure 5) for 19 exhibit I Ǟ N Ǟ K the nematic↔isotropic transition of 21 is larger than con-
on cooling. However, this compound showed enantiotropic ventional transition enthalpies
nematic↔isotropic
behaviour when analyzed by POM. On slow heating the (Ͻ0.50 kcalmol–1) of calamitic liquid crystals. This may
sample 19 enters into the nematic phase at 144.5 °C and indicate that relatively strong intermolecular interactions
melts to an isotropic liquid at 148.0 °C. The temperature exist in the nematic phase and could be attributed to an
range for the mesophase is small for 19 (∆T = 3.5 °C). The inversion of the carboxylate group in 21 compared with in
transition enthalpy for the isotropic-to-nematic transition 19.
of 19 is rather low (0.015 kcalmol–1). This value is consis-
tent with a less-ordered nematic mesophase.
Figure 6. Chemical intermediates 20 and 22 and final liquid crystal
isoxazolines 21 and 23.
Liquid crystal 23 was prepared from 7a by a short and
fast method. The esterification reaction (DCC/DMAP) be-
tween 7a and the popular acid 22 widely used in LC synthe-
sis[29] gave the LC product. The phase behaviour of com-
pound 23 is similar to that of compound 21. On heating
the sample 23 melts to the isotropic state at 102.5 °C. How-
ever, on cooling, the sample enters into the smectic C phase
at 75.7 °C and finally crystallizes at 71.2 °C (Table 2, Fig-
ure 5). The schlieren texture observed for this sample shows
a disclination point at which four black brushes (disclin-
ation lines) meet and this was assigned as the smectic C
phase. In the smectic C phase, only four-fold singularities
were observed; nematics may in addition show singularities
with two brushes, as shown by compound 19. For compari-
son, the mesophase range of LC 21 is larger than that of
LC 23 due to the phenylacetylene substructure present in
21. The transition enthalpy for the isotropic-to-smectic
transition of 23 is higher than that for 21. The enthalpy
value suggests a more ordered phase on going from the iso-
tropic to the smectic phase compared with compound 21.
Figure 5. DSC curves for the LC compounds 19, 21, 23 and 24 on
second heating and cooling.
The final demonstration of the potential of isoxazolines
The isoxazoline 7a was selected to prepare the liquid- in LC materials is outlined in Scheme 4. Isoxazoline 12b
crystalline compounds 21 and 23. Figure 6 shows the chem- was oxidized to the isoxazole 24 by exposure to manga-
ical structures of the final liquid crystals as well as the op- nese(IV) dioxide.[30] Compound 24 was easily purified by
tical texture micrographs of their mesophases. For these simple filtration to remove the inorganic materials and
purposes, the ester linkage was introduced by esterification recrystallized from ethanol. The optical, thermal and
of the bromo acid 20 with 7a by the DCC/DMAP protocol. thermodynamic data (Table 2) and the DSC traces (Fig-
Application of the same cross-coupling reaction conditions ure 5) for compound 24 clearly reveal that it exhibits a large
to the alkyne 16 and the ester derivative from acid 20 af- enantiotropic nematic mesophase. When the sample is
forded the liquid-crystalline compound 21 in 40% yield cooled from its isotropic phase, the nematic phase appears
(two steps). The data collected in Table 2 for this compound exhibiting planar thread-like texture, which is characteristic
show that the mesophase appears only during the cooling of a liquid-crystalline nematic phase.[31] On heating, sample
cycle. No mesophase was observed on heating when the 24 enters into the nematic phase at 105.9 °C and finally
sample was analysed by POM. Compound 21 displayed a melts to an isotropic liquid at 132.2 °C. The temperature
planar thread-like texture, which is characteristic of a li- range for the mesophase is 26.3 °C. The two peaks observed
quid-crystalline nematic phase. Note that the enthalpy for at 105.9 and 132.2 °C were associated with KǞN and
892
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 889–897

3,5-Disubstituted Isoxazolines as Liquid-Crystalline Materials
with a Shimadzu GC-17A gas chromatograph equipped with a DB-
17 MS capillary column. ESI-MS data were collected with a
Waters® Micromass® Q-Tof microTM mass spectrometer with a Z-
spray electrospray source. Samples were infused from a 100 µL gas-
tight syringe at 5 µLmin–1 through a syringe pump. Instrument set-
tings were unexceptional: capillary voltage 4500 V, cone voltage
50 V, source temperature 100 °C, desolvation gas temperature
100 °C. Nitrogen was used as the desolvation gas. CHN analyses
were performed with a Perkin–Elmer 2400 CHN Elemental Ana-
lyzer. All reactions involving the Sonogashira coupling were per-
formed in a one-neck round-bottomed flask equipped with septum
stoppers and charged with triethylamine (Et3N), aromatic iodide
and alkyne under argon for 30 min. Copper(I) iodide (CuI), tri-
phenylphosphane (PPh3) and bis(triphenylphosphane)palladi-
um(II) chloride [PdCl2(PPh3)2] were then added.
NǞI transitions, respectively. As expected for iso-
tropic↔nematic transition enthalpies, the value of
0.076 kcalmol–1 is in accordance with a less-ordered ne-
matic mesophase.
Scheme 4. Preparation of isoxazole LC 24.
Alkylation Reactions: The 4-(n-alkyloxy)benzaldehydes 2a–d were
prepared from benzaldehyde (1) following previously reported pro-
cedures.[23b,32]
Conclusions
We have synthesized and characterized a number of Synthesis of Aldoximes: The 4-(n-alkyloxy)benzaldehyde oximes
3a–d and 4e–g were synthesized from the corresponding 4-substi-
tuted benzaldehydes according literature procedures.[13a,33–36] See
the Supporting Information for experimental procedure and spec-
tral characterization.
isoxazolines with aryl and polar groups at the 3- and 5-
positions by 1,3-dipolar [3+2] cycloaddition reactions of ni-
trile oxides and alkenes. The straightforward access to 2-
isoxazolines is excellent for obtaining molecular kits for the
preparation of versatile intermediates that can be trans-
formed into LC materials. In this work, isoxazolines 6a and
7a were chosen and chemically modified by linkage of an
arylacetylenic moiety at the polar group. Also we selected
isoxazoline 12b and performed the oxazolineǞoxazole
transformation by an oxidation reaction. In this way four
new LC materials 19, 21, 23 and 24 were synthesized. In all
the chemical operations, the compounds exhibited meso-
morphic behaviour; the nematic phase was observed for
compounds 19, 21 and 24 and the smectic C phase was
detected for compound 23. With the less reactive di-
polarophile vinylacetic acid (5f), the 2:1 cycloadduct was
obtained exclusively and not the expected 1:1 cycloadduct.
The synthesis of new liquid crystals derived from the isox-
azolines listed in Table 1 is in progress and will be reported
in due course.
Cycloaddition Reactions: A solution of the corresponding oxime
(2 mmol) in CHCl3 (2 mL) was added dropwise to an ice-cooled
solution of CHCl3 (8 mL), dipolarophile (2.3 mmol), pyridine
(3 mmol) and N-chlorosuccinimide (NCS) (2.3 mmol) under argon
for 40 min. The reaction was then stirred at room temperature for
4 h. The solution was washed with water and dried with Na2SO4.
The filtrate was evaporated under a reduced pressure and the resi-
due purified by recrystallization from toluene.
3-[4-(Heptyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylic
Acid
(6a): Yield 240 mg, 80%; white solid; m.p. 149 °C. 1H NMR
(CDCl3): δ = 0.89 (m, 3 H, CH3), 1.38 [m, 8 H, (CH2)4], 1.79 (m,
2 H, CH2CH2O), 3.62 (d, J = 9.0 Hz, 2 H, CH2CH), 3.98 (t, J =
6.6 Hz, 2 H, CH2O), 5.12 (t, J = 9.0 Hz, 1 H, CH2CH), 6.90 (d, J
= 8.7 Hz, 2 H, Ar), 7.60 (d, J = 8.7 Hz, 2 H, Ar), 8.10 (br., 1 H,
OH) ppm. 13C NMR (CDCl3/[D6]DMSO): δ = 13.7, 22.2, 25.5,
28.6, 28.7, 31.3, 38.8, 67.7, 77.4, 114.3, 120.5, 128.0, 155.3, 160.5,
172.0 ppm. IR: ν = 3182, 2925, 2854, 1720, 1610, 1517, 1461, 1377,
˜
1252, 1183, 1043, 1010, 897, 829, 721, 666 cm–1. C17H23NO4
(305.37): calcd. C 66.86, H 7.59, N 4.59; found C 66.96, H 7.62, N
4.71.
Experimental Section
3-[4-(Octyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylic Acid (6b):
Instruments and Techniques: 4-Hydroxybenzaldehyde, 1-bromoal-
kanes, hydroxylamine hydrochloride, acrylic acid, N-chlorosuc-
cinimide (NCS), KOH, sodium acetate, ethanol, chloroform, butyl
acrylate, acrylonitrile, 4-bromobenzaldehyde, acetonitrile and tolu-
ene were from Aldrich and used without further purification. Pyr-
idine and allylic alcohol were distilled under reduced pressure. All
other commercial solvents and reagents were used without further
purification. The melting points and mesophase transition tem-
peratures and textures of the samples were measured with a Mettler
Toledo FP82HT Hot Stage FP90 Central Processor and DSC 2910
TA Instruments. NMR spectra were obtained with a Varian
300 MHz instrument. Chemical shifts are given in parts per million
(δ) and are referenced to tetramethylsilane (TMS). Infrared spectra
were recorded with a Perkin–Elmer Spectrum One FTIR spectrom-
eter using NaCl plates in the case of solids and as thin films sup-
ported between NaCl plates in the case of liquids and are reported
in wavenumbers (cm–1). Low-resolution mass spectra were obtained
with a Shimadzu GC-MS-QP5050 mass spectrometer interfaced
1
Yield 105 mg, 66%; white solid; m.p. 143 °C. H NMR (CDCl3): δ
= 0.89 (m, 3 H, CH3), 1.39 [m, 10 H, (CH2)5], 1.79 (m, 2 H,
CH2CH2O), 3.63 (d, J = 9.0 Hz, 2 H, CH2CH), 3.98 (t, J = 6.6 Hz,
2 H, CH2O), 5.13 (t, J = 9.0 Hz, 1 H, CH2CH), 5.80 (br., 1 H,
OH), 6.90 (d, J = 8.7 Hz, 2 H, Ar), 7.60 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (CDCl3/[D6]DMSO): δ = 13.7, 22.2, 25.6, 28.7,
28.8, 29.0, 31.4, 38.9, 67.7, 77.4, 114.3, 120.5, 128.1, 155.3, 160.5,
172.1 ppm. IR: ν = 3184, 2925, 2854, 1720, 1610, 1519, 1461, 1377,
˜
1253, 1183, 1045, 1010, 895, 828, 721, 665 cm–1. C18H25NO4
(319.40): calcd. C 67.69, H 7.89, N 4.39; found C 67.58, H 7.92, N
4.51.
3-[4-(Nonyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylic Acid (6c):
1
Yield 138 mg, 83%; white solid; m.p. 141 °C. H NMR (CDCl3): δ
= 0.88 (m, 3 H, CH3), 1.38 [m, 12 H, (CH2)6], 1.78 (m, 2 H,
CH2CH2O), 3.62 (d, J = 9.0 Hz, 2 H, CH2CH), 3.98 (t, J = 6.6 Hz,
2 H, CH2O), 5.11 (t, J = 9.0 Hz, 1 H, CH2CH), 6.70 (br., 1 H,
OH), 6.90 (d, J = 8.7 Hz, 2 H, Ar), 7.59 (d, J = 8.7 Hz, 2 H,
Eur. J. Org. Chem. 2009, 889–897
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
893

A. Tavares, P. H. Schneider, A. A. Merlo
FULL PAPER
Ar) ppm. 13C NMR (CDCl3/[D6]DMSO): δ = 13.8, 22.3, 25.6, 28.8,
28.9, 29.0, 29.1, 31.5, 38.9, 67.8, 77.4, 114.3, 120.6, 128.1, 155.3,
N=CCHHCH), 3.36 (dd, J = 16.8, 10.5 Hz, 1 H, N=CCHHCH),
3.67 (dd, J = 12.0, 4.8 Hz, 1 H, CHCHHOH), 3.86 (dd, J = 12.0,
160.5, 172.2 ppm. IR: ν = 3183, 2925, 2854, 1721, 1608, 1518, 1461, 3.3 Hz, 1 H, CHCHHOH), 3.97 (t, J = 6.6 Hz, 2 H, CH2O), 4.84
˜
1377, 1253, 1182, 1045, 1010, 898, 828, 721, 667 cm–1. C19H27NO4 (m, 1 H), 6.89 (d, J = 9.0 Hz, 2 H, Ar), 7.58 (d, J = 8.7 Hz 2 H,
(333.43): calcd. C 68.44, H 8.16, N 4.20; found C 68.32, H 8.09, N
4.32.
Ar) ppm. 13C NMR (CDCl3): δ = 13.9, 22.5, 25.8, 29.0, 29.1, 29.2,
29.3, 31.7, 36.5, 63.3, 68.0, 80.9, 114.4, 121.5, 128.0, 156.4,
160.5 ppm. IR: ν = 3294, 3189, 2923, 2854, 1611, 1515, 1463, 1377,
˜
3-[4-(Decyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylic Acid (6d):
Yield 309 mg, 89%; white solid; m.p. 138 °C. 1H NMR (CDCl3): δ
= 0.88 (m, 3 H, CH3), 1.38 [m, 14 H, (CH2)7], 1.79 (m, 2 H,
CH2CH2O), 3.62 (d, J = 9.0 Hz, 2 H, CH2CH), 3.98 (t, J = 6.6 Hz,
2 H, CH2O), 5.12 (t, J = 9.0 Hz, 1 H, CH2CH), 6.90 (d, J = 8.7 Hz,
2 H, Ar), 7.59 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3/
[D6]DMSO): δ = 13.8, 22.3, 25.6, 28.8, 28.9, 29.0, 29.2, 30.6, 31.5,
1254, 1182, 1048, 876, 820, 721, 666 cm–1. C19H29NO3 (319.44):
calcd. C 71.44, H 9.15, N 4.38; found C 71.65, H 9.25, N 4.50.
{3-[4-(Decyloxy)phenyl]-4,5-dihydroisoxazol-5-yl}methanol
(7d):
1
Yield 273 mg, 41%; white solid; m.p. 95 °C. H NMR (CDCl3): δ
= 0.89 (m, 3 H, CH3), 1.43 [m, 14 H, (CH2)7], 1.79 (m, 2 H,
CH2CH2O), 2.05 (br., 1 H, OH), 3.24 (dd, J = 16.5, 7.8 Hz, 1 H,
N=CCHHCH), 3.37 (dd, J = 16.5, 10.5 Hz, 1 H, N=CCHHCH),
3.67 (dd, J = 12.0, 4.8 Hz, 1 H, CHCHHOH), 3.86 (dd, J = 12.0,
3.3 Hz, 1 H, CHCHHOH), 3.98 (t, J = 6.6 Hz, 2 H, CH2O), 4.84
(m, 1 H), 6.90 (d, J = 9.0 Hz, 2 H, Ar), 7.58 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (CDCl3): δ = 14.0, 22.6, 25.9, 29.1, 29.2, 29.3,
29.4, 29.5, 31.8, 36.5, 63.5, 68.0, 80.9, 114.5, 121.5, 128.1, 156.6,
38.9, 67.7, 77.4, 114.3, 120.5, 128.1, 155.3, 160.5, 172.1 ppm. IR: ν
˜
= 3183, 2925, 2854, 1720, 1610, 1517, 1461, 1377, 1251, 1183, 1042,
1010, 898, 830, 721, 665 cm–1. C20H29NO4 (347.45): calcd. C 69.14,
H 8.41, N 4.03; found C 69.23, H 8.33, N 4.12.
3-(4-Bromophenyl)-4,5-dihydroisoxazole-5-carboxylic Acid (6e):
Yield 127 mg, 47%; brown solid; m.p. 173–175 °C. 1H NMR
(CDCl3): δ = 3.62 (d, J = 9.3 Hz, 2 H, CH2CH), 5.16 (t, J = 9.3 Hz,
1 H, CH2CH), 7.55 (s, 4 H, Ar) ppm. 13C NMR (CDCl3/[D6]-
160.6 ppm. IR: ν = 3294, 3187, 2923, 2854, 1610, 1515, 1463, 1377,
˜
1256, 1182, 1047, 877, 820, 721, 667 cm–1. C20H31NO3 (333.47):
calcd. C 72.04, H 9.37, N 4.20; found C 71.98, H 9.24, N 4.45.
DMSO):
δ = 38.5, 77.8, 124.4, 127.4, 128.1, 131.7, 155.0,
171.8 ppm. IR: ν = 3200–3100, 2924, 2854, 1726, 1592, 1462, 1377,
˜
Butyl 3-[4-(Heptyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylate
(8a): Yield 112 mg, 31%; yellow solid; m.p. 34 °C. 1H NMR
(CDCl3): δ = 0.91 [m, 6 H, (CH3)2], 1.38 [m, 10 H, (CH2)5], 1.67
(m, 2 H, CH2CH2OCO), 1.79 (m, 2 H, CH2CH2O), 3.60 (d, J =
10.2 Hz, 1 H, CHHCH), 3.61 (d, J = 8.4 Hz, 1 H, CHHCH), 3.98
(t, J = 6.6 Hz, 2 H, CH2O), 4.20 (t, J = 6.6 Hz, 2 H, CH2OCO),
1225, 899, 824 cm–1. C10H8BrNO3 (270.08): calcd. C 44.47, H 2.29,
N 5.19; found C 44.56, H 2.41, N 5.25.
3-(4-Nitrophenyl)-4,5-dihydroisoxazole-5-carboxylic Acid (6g): Yield
118 mg, 25%; white solid; m.p. 130 °C. 1H NMR (CDCl3/[D6]-
DMSO): δ = 3.69 (d, J = 9.3 Hz, 2 H, CH2CH), 5.25 (m, 1 H,
CH2CH), 7.45 (br., 1 H, OH), 7.87 (d, J = 8.4 Hz, 2 H, Ar), 8.27 5.13 (dd, J = 8.4, 10.2 Hz, 1 H, CHHCH), 6.90 (d, J = 9.0 Hz, 2
(d, J = 8.4 Hz, 2 H, Ar) ppm. C10H8N2O5 (236.18): calcd. C 50.85,
H, Ar), 7.60 (d, J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ
H 3.41, N 11.86; found C 50.78, H 3.49, N 12.01.
= 13.5, 13.9, 18.9, 22.4, 25.8, 28.9, 29.0, 30.3, 31.6, 39.0, 65.6, 68.0,
77.7, 114.5, 120.7, 128.3, 155.5, 160.8, 170.3 ppm. IR: ν = 2923,
˜
{3-[4-(Heptyloxy)phenyl]-4,5-dihydroisoxazol-5-yl}methanol
(7a):
2854, 1737, 1610, 1519, 1456, 1377, 1264, 1210, 1017, 879, 828,
722, 664 cm–1. C21H31NO4 (361.48): calcd. C 69.78, H 8.64, N 3.87;
found C 69.58, H 8.59, N 3.98.
1
Yield 419 mg, 36%; white solid; m.p. 96 °C. H NMR (CDCl3): δ
= 0.89 (m, 3 H, CH3), 1.41 [m, 8 H, (CH2)4], 1.79 (m, 2 H,
CH2CH2O), 2.10 (br., 1 H, OH), 3.24 (dd, J = 16.5, 7.8 Hz, 1 H,
N=CCHHCH), 3.36 (dd, J = 16.5, 10.5 Hz, 1 H, N=CCHHCH),
3.67 (dd, J = 12.0, 4.8 Hz, 1 H, CHCHHOH), 3.85 (dd, J = 12.0,
3.3 Hz, 1 H, CHCHHOH), 3.97 (t, J = 6.6 Hz, 2 H, CH2O), 4.83
(m, 1 H), 6.89 (d, J = 9.0 Hz, 2 H, Ar), 7.58 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (CDCl3): δ = 13.9, 22.5, 25.8, 28.9, 29.0, 31.6,
Butyl
3-[4-(Octyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylate
(8b): Yield 244 mg, 65%; yellow solid; m.p. 35 °C. 1H NMR
(CDCl3): δ = 0.91 [m, 6 H, (CH3)2], 1.38 [m, 12 H, (CH2)6], 1.67
(m, 2 H, CH2CH2OCO), 1.79 (m, 2 H, CH2CH2O), 3.60 (d, J =
9.9 Hz, 1 H, CHHCH), 3.61 (d, J = 8.1 Hz, 1 H, CHHCH), 3.98
(t, J = 6.6 Hz, 2 H, CH2O), 4.20 (t, J = 6.6 Hz, 2 H, CH2OCO),
5.13 (dd, J = 8.1, 9.9 Hz, 1 H, CHHCH), 6.90 (d, J = 9.0 Hz, 2 H,
Ar), 7.60 (d, J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ =
13.5, 14.0, 18.9, 22.5, 25.9, 29.0, 29.1, 29.2, 30.3, 31.7, 39.0, 65.6,
36.5, 63.4, 68.0, 80.9, 114.5, 121.5, 128.1, 156.5, 160.5 ppm. IR: ν
˜
= 3294, 3187, 2923, 2854, 1610, 1517, 1463, 1377, 1253, 1181, 1049,
875, 820, 721, 665 cm–1. C17H25NO3 (291.39): calcd. C 70.07, H
8.65, N 4.81; found C 70.12, H 8.71, N 4.89.
68.0, 77.7, 114.5, 120.6, 128.3, 155.5, 160.8, 170.4 ppm. IR: ν =
˜
{3-[4-(Octyloxy)phenyl]-4,5-dihydroisoxazol-5-yl}methanol
(7b):
1
2923, 2854, 1738, 1612, 1519, 1458, 1377, 1264, 1210, 1019, 881,
827, 722, 666 cm–1. C22H33NO4 (375.51): calcd. C 70.37, H 8.86, N
3.73; found C 70.18, H 8.69, N 3.90.
Yield 219 mg, 36%; white solid; m.p. 94 °C. H NMR (CDCl3): δ
= 0.89 (m, 3 H, CH3), 1.41 [m, 10 H, (CH2)5], 1.78 (m, 2 H,
CH2CH2O), 2.99 (br., 1 H, OH), 3.24 (dd, J = 16.8, 8.1 Hz, 1 H,
N=CCHHCH), 3.34 (dd, J = 16.8, 10.5 Hz, 1 H, N=CCHHCH),
3.67 (dd, J = 12.0, 4.8 Hz, 1 H, CHCHHOH), 3.83 (dd, J = 12.0,
3.3 Hz, 1 H, CHCHHOH), 3.96 (t, J = 6.6 Hz, 2 H, CH2O), 4.81
(m, 1 H), 6.87 (d, J = 9.0 Hz, 2 H, Ar), 7.56 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (CDCl3): δ = 13.9, 22.5, 25.8, 29.0, 29.1, 29.2,
31.7, 36.5, 63.4, 68.0, 80.9, 114.5, 121.4, 128.1, 156.5, 160.5 ppm.
Butyl
3-[4-(Nonyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylate
(8c): Yield 151 mg, 38%; yellow solid; m.p. 40 °C. 1H NMR
(CDCl3): δ = 0.91 [m, 6 H, (CH3)2], 1.38 [m, 14 H, (CH2)7], 1.67
(m, 2 H, CH2CH2OCO), 1.79 (m, 2 H, CH2CH2O), 3.60 (d, J =
9.9 Hz, 1 H, CHHCH), 3.61 (d, J = 8.4 Hz, 1 H, CHHCH), 3.98
(t, J = 6.6 Hz, 2 H, CH2O), 4.20 (t, J = 6.6 Hz, 2 H, CH2OCO),
5.13 (dd, J = 8.4, 9.9 Hz, 1 H, CHHCH), 6.91 (d, J = 9.0 Hz, 2 H,
Ar), 7.60 (d, J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ =
13.5, 14.0, 18.9, 22.5, 25.8, 29.0, 29.1, 29.2, 29.4, 30.3, 31.7, 39.0,
IR: ν = 3294, 3189, 2923, 2854, 1608, 1517, 1463, 1377, 1254, 1181,
˜
1049, 876, 820, 721, 668 cm–1. C18H27NO3 (305.42): calcd. C 70.79,
H 8.91, N 4.59; found C 70.65, H 8.86, N 4.80.
{3-[4-(Nonyloxy)phenyl]-4,5-dihydroisoxazol-5-yl}methanol
(7c): 65.6, 68.0, 77.7, 114.5, 120.7, 128.3, 155.5, 160.8, 170.4 ppm. IR: ν
˜
1
Yield 122 mg, 38%; white solid; m.p. 98 °C. H NMR (CDCl3): δ
= 2923, 2854, 1737, 1610, 1517, 1456, 1377, 1264, 1210, 1017, 880,
= 0.89 (m, 3 H, CH3), 1.43 [m, 12 H, (CH2)6], 1.79 (m, 2 H, 828, 722, 667 cm–1. C23H35NO4 (389.54): calcd. C 70.92, H 9.06, N
CH2CH2O), 2.10 (br., 1 H, OH), 3.24 (dd, J = 16.8, 8.1 Hz, 1 H, 3.60; found C 70.98, H 9.12, N 3.69.
894
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 889–897

3,5-Disubstituted Isoxazolines as Liquid-Crystalline Materials
Butyl
3-[4-(Decyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxylate
(CH3)2], 1.38 [m, 16 H, (CH2)8], 1.79 [m, 4 H, (CH2CH2O)2], 2.87
(dd, J = 15.6, 7.5 Hz, 1 H, NCCHHCH), 3.05 (dd, J = 15.6, 6.0 Hz,
(8d): Yield 250 mg, 62%; yellow solid; m.p. 44 °C. 1H NMR
(CDCl3): δ = 0.91 [m, 6 H, (CH3)2], 1.38 [m, 16 H, (CH2)8], 1.67
1
H, NCCHHCH), 3.28 (dd, J = 16.8, 6.9 Hz, 1 H,
(m, 2 H, CH2CH2OCO), 1.79 (m, 2 H, CH2CH2O), 3.60 (d, J = CHCHHCO2H), 3.59 (dd, J = 16.8, 10.5 Hz, 1 H, CHCHHCO2H),
10.2 Hz, 1 H, CHHCH), 3.61 (d, J = 8.4 Hz, 1 H, CHHCH), 3.98 3.98 [m, 4 H, (CH2O)2], 5.17 (m, 1 H), 6.89 (d, J = 8.4 Hz, 2 H,
(t, J = 6.6 Hz, 2 H, CH2O), 4.20 (t, J = 6.6 Hz, 2 H, CH2OCO),
Ar), 6.93 (d, J = 8.4 Hz, 2 H, Ar), 7.60 (d, J = 8.7 Hz, 2 H, Ar),
5.13 (dd, J = 8.4, 10.2 Hz, 1 H, CHHCH), 6.90 (d, J = 9.0 Hz, 2 7.85 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3/[D6]DMSO):
H, Ar), 7.60 (d, J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ
= 13.5, 14.0, 18.9, 22.5, 25.9, 29.0, 29.1, 29.2, 29.4, 29.5, 30.3, 31.7,
39.0, 65.6, 68.0, 77.7, 114.5, 120.7, 128.3, 155.5, 160.8, 170.3 ppm.
δ = 14.0, 22.5, 25.8, 25.9, 28.9, 29.0, 29.1, 31.7, 37.5, 40.4, 68.1,
68.2, 76.3, 114.4, 114.6, 121.3, 122.4, 128.3, 129.5, 156.4, 160.8,
162.7, 166.3, 168.8 ppm. IR: ν = 3228, 2924, 2854, 1787, 1684,
˜
IR: ν = 2923, 2854, 1737, 1611, 1519, 1457, 1377, 1264, 1210, 1018, 1608, 1517, 1464, 1377, 1254, 1176, 1098, 1015, 876, 834, 812, 722,
˜
879, 829, 722, 667 cm–1. C24H37NO4 (403.56): calcd. C 71.43, H
9.24, N 3.47; found C 71.52, H 9.34, N 3.59.
666 cm–1. HRMS (ESI): calcd. for [M]+ 552.3199; found [M + 1]+
553.3298; calcd. for [M + Na]+ 575.3097; found 575.3068. EIMS:
m/z (%) = 233, 135 (100), 134, 107, 106, 90, 78. C32H44N2O6
(552.71): calcd. C 69.54, H 8.02, N 5.07; found C 68.93, H 8.03, N
4.79.
3-[4-(Heptyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxamide (9a):
Yield 152 mg, 50%; white solid; m.p. 185 °C. 1H NMR (CDCl3/
[D6]DMSO): δ = 0.88 (m, 3 H, CH3), 1.39 [m, 8 H, (CH2)4], 1.79
(m, 2 H, CH2CH2O), 3.68 (m, 2 H, CH2CH), 3.99 (t, J = 6.6 Hz, 5-(4-Methylphenyl)-3-[4-(octyloxy)phenyl]-4,5-dihydroisoxazole
1
2 H, CH2O), 5.11 (dd, J = 6.6, 9.9 Hz, 1 H, CH2CH), 5.57 (s, 1 H,
NHH), 6.79 (s, 1 H, NHH), 6.92 (d, J = 9.0 Hz, 2 H, Ar), 7.59 (d,
J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3/[D6]DMSO): δ =
12.2, 20.4, 23.8, 26.8, 26.9, 29.6, 65.9, 76.7, 112.8, 119.1, 126.5,
(12b): Yield 220 mg, 60%; white solid; m.p. 110–113 °C. H NMR
(CDCl3): δ = 0.89 (m, 3 H, CH3), 1.38 [m, 10 H, (CH2)5], 1.80 (m,
2 H, CH2CH2O), 2.31 (s, 3 H, CH3), 3.30 (dd, J = 16.6, 7.8 Hz, 1
H, CHHCH), 3.71 (dd, J = 16.4, 10.7 Hz, 1 H, CHHCH), 4.0 (t,
153.9, 158.6, 170.7 ppm. IR: ν = 3394, 3186, 2925, 2854, 1655, J = 6.4 Hz, 2 H, CH2O), 5.60 (dd, J = 10.8, 8.0 Hz, 1 H, CHHCH),
˜
1610, 1460, 1377, 1255, 1114, 1048, 906, 875, 822, 722, 667 cm–1. 6.93 (d, J = 8.8 Hz, 2 H, Ar), 7.28 (d, J = 8.4 Hz, 2 H, Ar), 7.32
C17H24N2O3 (304.39): calcd. C 67.08, H 7.95, N 9.20; found C
67.06, H 7.89, N 9.30.
(d, J = 8.6 Hz, 2 H, Ar), 7.68 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C
NMR (CDCl3): δ = 14.1, 21.1, 22.6, 25.9, 29.1, 29.2, 29.3, 31.8,
43.3, 68.0, 82.2, 114.5, 121.6, 125.8, 128.1, 129.3, 137.8, 137.9,
3-[4-(Octyloxy)phenyl]-4,5-dihydroisoxazole-5-carboxamide
(9b):
155.7, 160.6 ppm. IR: ν = 2922, 2853, 1904, 1701, 1605, 1515, 1460,
˜
Yield 496 mg, 78%; white solid; m.p. 185 °C. 1H NMR (CDCl3/
[D6]DMSO): δ = 0.88 (m, 3 H, CH3), 1.37 [m, 10 H, (CH2)5], 1.80
(m, 2 H, CH2CH2O), 3.64 (m, 2 H, CH2CH), 3.99 (t, J = 6.6 Hz,
2 H, CH2O), 5.11 (dd, J = 6.6, 10.5 Hz, 1 H, CH2CH), 5.58 (s, 1
H, NHH), 6.79 (s, 1 H, NHH), 6.92 (d, J = 8.1 Hz, 2 H, Ar), 7.59
1376, 1255, 1174, 1112, 1044, 1021, 904, 837, 812, 714, 657 cm–1.
C24H31NO2 (365.52): calcd. C 78.87, H 8.55, N 3.83; found C
78.89, H 8.53, N 3.79.
2-Ethynyl-6-(octyloxy)naphthalene (15): Compound 15 was synthe-
(d, J = 8.1 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3/[D6]DMSO): δ = sized according to previously reported procedures.[23–25] Yield
12.1, 20.3, 23.7, 26.8, 26.9, 27.0, 29.5, 65.8, 76.7, 112.7, 119.0,
1
1.55 g, 69%; white solid; m.p. 36 °C. H NMR (CDCl3): δ = 0.89
(m, 3 H, CH3), 1.40 [m, 10 H, (CH2)5], 1.83 (m, 2 H, CH2CH2O),
3.10 (s, 1 H, HCC), 4.04 (t, J = 6.6 Hz, 2 H, CH2O), 7.07 (d, J =
2.4 Hz, 1 H, Ar), 7.15 (dd, J = 9.0, 2.4 Hz, 1 H, Ar), 7.47 (dd, J =
126.4, 153.4, 158.5, 170.5 ppm. IR: ν = 3394, 3187, 2924, 2854,
˜
1655, 1610, 1460, 1377, 1256, 1114, 1049, 906, 875, 823, 722,
667 cm–1. C18H26N2O3 (318.42): calcd. C 67.90, H 8.23, N 8.80;
found C 67.92, H 8.16, N 8.85.
8.4, 1.5 Hz, 1 H, Ar), 7.65 (m, 2 H, Ar), 7.93 (s, 1 H, Ar) ppm. 13
C
NMR (CDCl3): δ = 14.1, 22.6, 26.1, 29.1, 29.2, 29.3, 31.8, 68.1,
76.6, 84.2, 106.4, 116.7, 119.7, 126.7, 128.1, 129.0, 129.2, 132.1,
3-[4-(Nitrophenyl)]-4,5-dihydroisoxazole-5-carboxamide (9g): Yield
106 mg, 45%; white solid; m.p. 220 °C (thermal degradation above
the isotropic temperature). 1H NMR (CDCl3/[D6]DMSO): δ = 3.67
(m, 2 H, CH2CH), 5.15 (dd, J = 11.4, 6.6 Hz, 1 H, CH2CH), 6.41
(s, 1 H, NHH), 6.84 (s, 1 H, NHH), 7.78 (d, J = 9.0 Hz, 2 H, Ar),
134.4, 157.9 ppm. IR: ν = 3314, 2904, 2109, 1630, 1602, 1500, 1466,
˜
1377, 1266, 1225, 1173, 1030, 891, 849, 812, 722, 646 cm–1.
1-Ethynyl-4-(octyloxy)benzene (16):[23–25] Compound 16 was syn-
8.21 (d, J = 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3/[D6]DMSO): thesized according to previously reported procedures.[23–25] Yield
1
δ = 36.9, 78.4, 122.4, 126.4, 133.5, 146.9, 153.8, 170.7 ppm. IR: ν =
1.10 g, 60%; colourless liquid. H NMR (CDCl3): δ = 0.90 (m, 3
˜
3310, 3192, 1670, 1578, 1346, 875, 851, 752, 722 cm–1. C10H9N3O4 H, CH3), 1.38 [m, 10 H, (CH2)5], 1.77 (m, 2 H, CH2CH2O), 2.99
(235.20): calcd. C 51.07, H 3.86, N 17.87; found C 51.12, H 3.89,
N 17.94.
(s, 1 H, HCC), 3.94 (t, J = 6.6 Hz, 2 H, CH2O), 6.82 (d, J = 8.4 Hz,
2 H, Ar), 7.41 (d, J = 8.4 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3):
δ = 14.1, 22.6, 26.0, 29.1, 29.2, 29.3, 31.8, 68.1, 75.6, 83.7, 113.9,
3-[4-(Nonyloxy)phenyl]-4,5-dihydroisoxazole-5-carbonitrile
(10c):
114.4, 133.5, 159.5 ppm. IR: ν = 3318, 2927, 2856, 2108, 1607,
˜
1
Yield 136 mg, 43%; white solid; m.p. 65 °C. H NMR (CDCl3): δ
= 0.92 (m, 3 H, CH3), 1.35 [m, 12 H, (CH2)6], 1.80 (m, 2 H,
CH2CH2O), 3.68 (dd, J = 16.5, 6.6 Hz, 1 H, CHHCH), 3.75 (dd,
J = 16.5, 10.2 Hz, 1 H, CHHCH), 3.99 (t, J = 6.6 Hz, 2 H, CH2O),
1507, 1469, 1289, 1248, 1170, 1026, 832, 724, 641 cm–1.
4-Bromophenyl Acetate (17b): This compound was prepared ac-
cording to a previous report.[26] Yield 3.78 g, 88%; pale-yellow li-
5.34 (dd, J = 6.6, 10.2 Hz, 1 H, CHHCH), 6.93 (d, J = 8.7 Hz, 2 quid. 1H NMR (CDCl3): δ = 2.29 (s, 3 H, CH3), 6.98 (d, J = 8.7 Hz,
H, Ar), 7.59 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ
2 H, Ar), 7.48 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3):
= 14.0, 22.5, 25.8, 29.0, 29.1, 29.2, 29.4, 31.7, 41.3, 66.2, 68.1,
δ = 20.9, 118.7, 123.3, 132.3, 149.6, 168.9 ppm. IR: ν = 1761, 1485,
˜
114.8, 117.2, 119.4, 128.6, 155.8, 161.4 ppm. IR: ν = 2924, 2853,
1369, 1197, 1068, 1013, 908, 843, 794, 710, 674 cm–1.
˜
1607, 1516, 1461, 1377, 1362, 1257, 1175, 1014, 935, 876, 860, 839,
812, 723, 666 cm–1. C19H26N2O2 (314.43): calcd. C 72.58, H 8.33,
N 8.91; found C 72.51, H 8.58, N 8.94.
4-[(6-Octyloxy-2-naphthyl)ethynyl]phenol (18): This compound was
prepared according to a literature procedure.[27] Yield 204 mg,
65%; brown solid; m.p. 126–128 °C. 1H NMR (CDCl3/[D6]-
DMSO): δ = 0.89 (m, 3 H, CH3), 1.38 [m, 10 H, (CH2)5], 1.82 (m,
2 H, CH2CH2O), 4.06 (t, J = 6.3 Hz, 2 H, CH2O), 6.84 (d, J =
3,7a-Bis[4-(heptyloxy)phenyl]-7,7a-dihydro-6H-isoxazolo[2,3-d]-
[1,2,4]oxadiazol-6-ylacetic Acid (11a): Yield 83 mg, 30%; white so-
lid; m.p. 110–113 °C. 1H NMR (CDCl3): δ = 0.89 [m, 6 H, 8.1 Hz, 2 H, Ar), 7.12 (m, 2 H, Ar), 7.40 (d, J = 8.1 Hz, 2 H, Ar),
Eur. J. Org. Chem. 2009, 889–897
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
895

A. Tavares, P. H. Schneider, A. A. Merlo
FULL PAPER
7.50 (d, J = 8.4 Hz, 1 H, Ar), 7.64 (d, J = 8.4 Hz, 1 H, Ar), 7.68
(d, J = 9.0 Hz, 1 H, Ar), 7.91 (s, 1 H, Ar) ppm. 13C NMR (CDCl3/
[D6]DMSO): δ = 13.9, 22.5, 25.9, 29.0, 29.1, 29.2, 31.6, 67.9, 87.9,
89.3, 106.4, 113.9, 115.6, 118.3, 119.4, 126.5, 128.2, 128.7, 128.9,
0.89 (m, 3 H, CH3), 1.38 [m, 10 H, (CH2)5], 1.80 (m, 2 H,
CH2CH2O), 2.41 (s, 3 H, CH3), 4.00 (t, J = 6.6 Hz, 2 H, CH2O),
6.72 (s, 1 H), 6.97 (d, J = 8.7 Hz, 2 H, Ar), 7.28 (d, J = 8.1 Hz, 2
H, Ar), 7.72 (d, J = 8.1 Hz, 2 H, Ar), 7.78 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (CDCl3): δ = 14.1, 21.5, 22.6, 26.0, 29.1, 29.2,
29.3, 31.8, 68.1, 96.7, 114.8, 121.5, 124.9, 125.7, 128.1, 129.6, 140.4,
130.5, 132.9, 133.7, 157.3, 157.5 ppm. IR: ν = 2925, 2855, 1727,
˜
1466, 1377, 1251, 1182, 898, 876, 829, 721, 666 cm–1.
160.6, 162.6, 170.3 ppm. IR: ν = 2924, 2854, 1618, 1464, 1377,
˜
4-[(6-Octyloxy-2-naphthyl)ethynyl]phenyl
3-(4-Heptyloxyphenyl)-
1270, 1180, 951, 875, 837, 807, 722, 666 cm–1. C24H29NO2 (363.50):
calcd. C 79.30, H 8.04, N 3.85; found C 79.24, H 8.09, N 3.80.
4,5-dihydroisoxazole-5-carboxylate (19): Compound 19 was pre-
pared according to the DCC/DMAP/DCM reaction protocol fol-
lowing a previously described experimental procedure.[28] Yield
115 mg, 70%; white solid; m.p. 144.5 °C. 1H NMR (CDCl3): δ =
0.88 [m, 6 H, (CH3)2], 1.38 [m, 18 H, (CH2)9], 1.82 [m, 4 H,
(CH2CH2O)2], 3.75 (m, 2 H, CH2CH), 3.98 (t, J = 6.6 Hz, 2 H,
CH2O), 4.07 (t, J = 6.6 Hz, 2 H, CH2O), 5.37 (dd, J = 7.2, 11.1 Hz,
1 H, CH2CH), 6.92 (d, J = 8.7 Hz, 2 H, Ar), 7.14 (m, 4 H, Ar),
7.50–7.72 (m, 7 H, Ar), 7.96 (s, 1 H, Ar) ppm. 13C NMR (CDCl3):
δ = 14.0, 14.1, 22.5, 22.6, 25.9, 26.1, 28.9, 29.0, 29.1, 29.2, 29.3,
31.7, 31.8, 39.2, 68.0, 68.1, 77.7, 87.9, 90.4, 106.5, 114.7, 117.6,
119.7, 120.5, 121.3, 121.6, 126.8, 128.3, 128.5, 128.8, 129.2, 131.3,
Supporting Information (see also the footnote on the first page of
this article): Spectral and analytical data for the isolated products,
including 1H and 13C NMR, IR, DSC and polarizing optical
micrographs of the texture of the LCs, are supplied.
Acknowledgments
This work was supported by the Conselho Nacional de Desenvolvi-
mento Científico e Tecnológico (project MCT/CNPq no. 555785/
2006-8) and the Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior (CAPES) for a fellowship.
132.7, 134.2, 149.9, 155.6, 157.9, 161.0, 168.5 ppm. IR: ν = 2924,
˜
2854, 1763, 1596, 1464, 1378, 1224, 1045, 897, 859, 818, 722,
666 cm–1. C43H49NO5 (659.85): calcd. C 78.27, H 7.48, N 2.12;
found C 78.48, H 7.58, N 2.07.
[1] a) S. Kobayashi, K. A. Jorgensen, Cycloaddition Reactions in
Organic Synthesis, Wiley-VCH, Weinheim, 2002; b) K. V. Go-
thelf, K. A. Jorgensen, Chem. Rev. 1998, 98, 863–909; c) A.
Padwa, W. H. Pearson, The Chemistry of Heterocyclic Com-
pounds: Synthetic Applications of 1,3-Dipolar Cycloaddition
Chemistry Toward Heterocycles and Natural Products, Wiley,
New York, 2002, vol. 59; d) K. B. G. Torssell, Nitrile Oxides,
Nitrones and Nitronates in Organic Synthesis, VCH, New York,
1988; e) R. Huisgen, J. Org. Chem. 1976, 41, 403–419; f) K. N.
Houk, J. Sims, R. E. Duke, R. W. Strozier, J. K. George, J. Am.
Chem. Soc. 1973, 95, 7287–7301; g) A. Ros, E. Alvarez, H.
Dietrich, R. Fernández, J. M. Lassaletta, Synlett 2005, 2899–
2904; h) H. Yamamoto, S. Hayashi, M. Kubo, M. Harada, M.
Hasegawa, M. Noguchi, M. Sumimoto, K. Hori, Eur. J. Org.
Chem. 2007, 2859–2864.
[2] a) P. A. Kozikowski, Acc. Chem. Res. 1984, 17, 410–416; b)
J. A. Bull, E. P. Balskus, R. A. J. Horan, M. Langner, S. V. Ley,
Angew. Chem. Int. Ed. 2006, 45, 6714–6718.
[3] a) P. Conti, C. Dallanoce, M. De Amici, C. De Micheli, K.-N.
Klotz, Bioorg. Med. Chem. 1998, 6, 401–408; b) L.-H. Zhang,
J. C. Chung, T. D. Costello, I. Valvis, P. Ma, S. Kauffman, R.
Ward, J. Org. Chem. 1997, 62, 2466–2470; c) N. Zanatta,
J. M. F. M. Schneider, P. H. Schneider, A. D. Wouters, H. G.
Bonacorso, M. A. P. Martins, L. A. Wessjohann, J. Org. Chem.
2006, 71, 6996–6998.
[4] a) D.-H. Ko, M. F. Maponya, M. A. Khalil, E. T. Oriaku, Z.
You, H. Lee, J. Med. Chem. Res. 1998, 8, 313–323; b) J. Wityak,
T. M. Sielecki, D. J. Pinto, G. Emmett, J. Y. Sze, J. Liu, A. E.
Tobin, S. Wang, B. Jiang, P. Ma, S. A. Mousa, R. R. Wexler,
R. E. Olson, J. Med. Chem. 1997, 40, 50–60.
[5] a) P. J. Zimmermann, J. Y. Lee, I. Hlobilova, R. Endermann,
D. Habich, V. Jager, Eur. J. Org. Chem. 2005, 3450–3460; b)
S. A. Mousa, J. Wityak, Cardiovasc. Drug Rev. 1998, 16, 48–61.
[6] V. Jäger, W. Schwab, Tetrahedron Lett. 1978, 19, 3129–3132.
[7] K. P. Park, C.-Y. Shiue, L. B. Clapp, J. Org. Chem. 1970, 35,
2065–2067.
[3-(4-Heptyloxyphenyl)-4,5-dihydroisoxazol-5-yl]methyl 4-[(Octyl-
oxyphenyl)ethynyl]benzoate (21): Compound 21 was prepared ac-
cording to the DCC/DMAP/DCM reaction protocol following a
previously described experimental procedure.[28] Yield 63.0 mg,
1
40%; orange solid; m.p. 138.4 °C. H NMR (CDCl3): δ = 0.89 [m,
6 H, (CH3)2], 1.38 [m, 18 H, (CH2)9], 1.79 [m, 4 H, (CH2CH2O)2],
3.24 (dd, J = 16.5, 6.6 Hz, 1 H, N=CCHHCH), 3.52 (dd, J = 16.5,
10.5 Hz, 1 H, N=CCHHCH), 3.98 [m, 4 H, (CH2O)2], 4.43 (dd, J
= 12.0, 5.4 Hz, 1 H, CHCHHOCO), 4.50 (dd, J = 12.0, 4.2 Hz, 1
H, CHCHHOCO), 5.08 (m, 1 H), 6.87 (d, J = 9.0 Hz, 2 H, Ar),
6.92 (d, J = 8.7 Hz, 2 H, Ar), 7.45 (d, J = 9.0 Hz, 2 H, Ar), 7.51
(d, J = 8.4 Hz, 2 H, Ar), 7.62 (d, J = 9.0 Hz, 2 H, Ar), 7.97 (d, J
= 8.4 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 14.0, 22.5, 22.6,
25.8, 25.9, 28.9, 29.0, 29.1, 29.3, 31.6, 31.7, 37.5, 65.7, 68.0, 77.8,
87.3, 92.9, 114.3, 114.5, 114.6, 121.3, 128.1, 128.3, 128.6, 129.6,
131.2, 133.1, 155.8, 159.6, 160.7, 165.7 ppm. IR: ν = 2924, 2855,
˜
1723, 1600, 1517, 1465, 1377, 1286, 1251, 1177, 1108, 1045, 890,
834, 765, 721, 695, 666 cm–1. C40H49NO5 (623.82): calcd. C 77.01,
H 7.92, N 2.25; found C 76.96, H 8.07, N 2.14.
[3-(4-Heptyloxyphenyl)-4,5-dihydroisoxazol-5-yl]methyl 4-Decyloxy-
benzoate (23): Compound 23 was prepared according to the DCC/
DMAP/DCM reaction protocol following a previously described
experimental procedure.[28] Yield 83.0 mg, 60%; white solid; m.p.
1
102.5 °C. H NMR (CDCl3): δ = 0.89 [m, 6 H, (CH3)2], 1.38 [m,
22 H, (CH2)11], 1.79 [m, 4 H, (CH2CH2O)2], 3.22 (dd, J = 16.5,
6.9 Hz, 1 H, N=CCHHCH), 3.49 (dd, J = 16.5, 10.8 Hz, 1 H,
N=CCHHCH), 3.98 [t, J = 6.6 Hz, 4 H, (CH2O)2], 4.44 (m, 2 H,
CHCH2OCO), 5.06 (m, 1 H), 6.85 (d, J = 8.7 Hz, 2 H, Ar), 6.91
(d, J = 8.4 Hz, 2 H, Ar), 7.61 (d, J = 8.7 Hz, 2 H, Ar), 7.95 (d, J
= 9.0 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 14.0, 14.1, 22.5,
22.6, 25.9, 28.9, 29.0, 29.1, 29.2, 29.3, 29.5, 31.7, 31.8, 37.6, 65.2,
68.0, 68.1, 78.0, 114.0, 114.6, 121.5, 121.6, 128.2, 131.7, 155.8,
[8] a) P. Aschwanden, L. Kvaerno, R. W. Geisser, F. Kleinbeck,
E. M. Carreira, Org. Lett. 2005, 7, 5741–5742; b) J. W. Bode,
E. M. Carreira, Org. Lett. 2001, 3, 1587–1590.
160.7, 163.1, 166.0 ppm. IR: ν = 2924, 2854, 1715, 1606, 1510,
˜
1466, 1377, 1249, 1169, 1127, 1014, 882, 834, 768, 722, 699, 666,
649 cm–1. C34H49NO5 (551.76): calcd. C 74.01, H 8.95, N 2.54;
found C 74.15, H 9.13, N 2.54.
[9] a) A. A. Fuller, B. Chen, A. R. Minter, A. K. Mapp, J. Am.
Chem. Soc. 2005, 127, 5376–5383; b) J. A. Kenar, J. Am. Oil
Chem. Soc. 2002, 79, 351–356.
[10] a) V. Kumar, R. Aggarwal, S. P. Singh, J. Fluorine Chem. 2006,
127, 880–888; b) M. Tanaka, T. Haino, K. Ideta, K. Kubo, A.
Mori, Y. Fukazawa, Tetrahedron 2007, 63, 652–665; c) C. K. Y.
Lee, A. J. Herlt, G. W. Simpson, A. C. Willis, C. J. Easton, J.
3-(4-Octyloxyphenyl)-5-(4-methylphenyl)isoxazole (24): This com-
pound was prepared according to a previous report.[30] Yield
131 mg, 90%; white solid; m.p. 105.9 °C. 1H NMR (CDCl3): δ =
896
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 889–897

3,5-Disubstituted Isoxazolines as Liquid-Crystalline Materials
Org. Chem. 2006, 71, 3221–3231; d) F. Machetti, L. Cecchi, E.
Trogu, F. De Sarlo, Eur. J. Org. Chem. 2007, 4352–4359; e)
H. A. Gallardo, R. Cristiano, F. Ely, Liq. Cryst. 2005, 32, 15–
25; f) H. A. Gallardo, R. Cristiano, A. A. Vieira, R. A. W.
Neves Filho, R. M. Srivastava, Synthesis 2008, 605–609; g)
H. A. Gallardo, R. Cristiano, F. Ely, Liq. Cryst. 2006, 33, 381–
390.
C. K. Y. Lee, A. B. Holmes, B. Al-Duri, G. A. Leeke, R. C. D.
Santos, J. P. K. Seville, Chem. Commun. 2004, 22, 2622–2623.
For regioselective copper(I)-catalyzed cycloaddition reactions,
see: T. V. Hansen, P. Wu, V. V. Fokin, J. Org. Chem. 2005, 70,
7761–7764.
a) J. A. Passo, G. D. Vilela, P. H. Schneider, O. M. S. Ritter,
A. A. Merlo, Liq. Cryst. 2008, 35, 833–840; b) V. N. Kovganko,
N. N. Kovganko, Russ. J. Org. Chem. 2006, 42, 696–700; c)
O. M. S. Ritter, F. C. Giacomelli, J. A. Passo, N. P. Silveira,
A. A. Merlo, Polym. Bull. 2006, 56, 549–561; d) U. M. Kau-
hanka, M. M. Kauhanka, Liq. Cryst. 2006, 33, 121–127; e)
K. B. Umesha, K. M. L. Raí, N. Mahadeva, Indian J. Chem.,
Sect. B: Org. Chem. Incl. Med. Chem. 2004, 43, 2635–2640; f)
V. Bezborodov, N. Kauhanka, V. Lapanik, Mol. Cryst. Liq.
Cryst. 2004, 411, 1145–1152; g) V. N. Kovganko, N. N. Kov-
ganko, Russ. J. Org. Chem. 2005, 41, 1165–1169; h) M. Tanaka,
T. Haino, K. Ideta, K. Kubo, A. Mori, Y. Fukuzawa, Tetrahe-
dron 2007, 63, 652–665.
[21] a) F. A. C. Andrade, J. Braz. Chem. Soc. 1998, 9, 85–86; b)
A. A. Merlo, O. M. S. Ritter, F. V. Pereira, C. H. Vieira, N. P.
Silveira, J. Braz. Chem. Soc. 2001, 12, 184–191.
[22] a) J.-P. Gilbert, R. Jacquier, C. Pétrus, Bull. Soc. Chem. Fr.
1979, 281–288; b) J.-F. Wang, D.-Q. Wei, C.-F. Wang, Y. Ye,
Y.-X. Li, Y. Luo, W.-W. Wang, L.-Z. Liu, Y.-F. Zhao, J. Theor.
Comput. Chem. 2007, 6, 861–867; c) We have synthesized com-
pounds 11a–d. Each compound displayed the same spectro-
scopic data. A complete thermal study of the LC properties of
this class of compounds is underway and will be reported soon.
[23] a) U. B. Vasconcelos, E. Dalmolin, A. A. Merlo, Org. Lett.
2005, 7, 1027–1030; b) U. B. Vasconcelos, A. A. Merlo, Synthe-
sis 2006, 7, 1141–1147; c) U. B. Vasconcelos, G. D. Vilela, A.
Schrader, A. C. A. Borges, A. A. Merlo, Tetrahedron 2008, 64,
4619–4626.
[24] a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
1975, 16, 4467–4470; b) R. Chinchilla, C. Nájera, Chem. Rev.
2007, 107, 874–922; c) R. Cristiano, D. M. P. O. Santos, G.
Conte, H. Gallardo, Liq. Cryst. 2006, 33, 997–1003; d) D. M.
Price, S. M. Dirk, F. Maya, J. M. Tour, Tetrahedron 2003, 59,
2497–2518.
[11]
[12]
[13]
[25] A. P. Melissaris, M. H. Litt, Macromolecules 1994, 27, 883–
887.
[26] B. Neises, W. Steglich, Angew. Chem. Int. Ed. Engl. 1978, 17,
569–583.
[27] S. Takahashi, Y. Kuroyama, K. Sonogashira, N. Hagihara,
Synthesis 1980, 627–630.
[14]
[15]
J. B. Stothers, Carbon-13 NMR Spectroscopy, Academic Press,
New York, 1972.
[28] B. Neises, W. Steglich, Angew. Chem. Int. Ed. Engl. 1978, 17,
522–524.
a) M. S. Gordon, S. A. Sojka, J. G. Krause, J. Org. Chem. 1984,
49, 97–100; b) N. A. Owston, A. J. Parker, J. M. J. Williams,
Org. Lett. 2007, 9, 3599–3601; c) A. Danoff, M. Franzen-Sie-
veking, R. L. Lichter, S. N. Y. Fanso-Free, Org. Magn. Reson.
1979, 12, 83–86; d) B. A. Halkier, C. E. Olsens, B. L. Moller, J.
Biol. Chem. 1989, 264, 19487–19494; e) G. C. Levy, R. L. Lich-
ter, G. L. Nelson, Carbon-13 Nuclear Magnetic Resonance
Spectroscopy, Wiley-Interscience, New York, 1980; f) J. Este-
ban, A. M. Costa, F. Urpí, J. Vilarrasa, Tetrahedron Lett. 2004,
45, 5563–5567.
[29] N. Gimeno, M. B. Ros, M. R. De la Fuente, J. L. Serrano,
Chem. Mater. 2008, 20, 1262–1271.
[30] a) R. J. K. Taylor, M. Reid, J. Foot, S. A. Raw, Acc. Chem.
Res. 2005, 38, 851–869; b) R. M. Srivastava, A. A. Lima, O. S.
Viana, M. J. C. Silva, M. T. J. A. Catanho, J. O. F. Morais, Bi-
oorg. Med. Chem. 2003, 11, 1821–1827.
[31] a) G. W. Gray, J. W. Goodby, Smectic Liquid Crystals: Textures
and Structures, Leonard Hill, Glasgow and London, 1984; b)
L. Li, C. D. Jones, J. Magolan, R. P. Lemieux, J. Mater. Chem.
2007, 17, 2313–2318.
[32] C. Weygand, R. Gabler, J. Prakt. Chem. 1940, 155, 332–341.
[33] K.-C. Liu, B. R. Shelton, R. K. Howe, J. Org. Chem. 1980, 45,
3916–3918.
[16] G. J. Karabatsos, R. A. Taller, F. M. Vane, J. Am. Chem. Soc.
1963, 85, 2326–2327.
[17] G. Heinisch, W. Holzer, Tetrahedron Lett. 1990, 31, 3109–3112.
[18] M. De Rosa, K. Brown, M. McCoy, K. Ong, K. Sanford, J.
Chem. Soc. Perkin Trans. 1 1993, 1787–1790.
[19] B. C. Gunn, M. F. G. Stevens, J. Chem. Soc. Perkin Trans. 1
1973, 1682–1688.
[20] L. J. Kateley, W. B. Martin, D. C. Wiser, C. A. Brummond, J.
Chem. Educ. 2002, 79, 225–227.
[34] R. F. Collins, J. Pharm. Pharmacol. 1962, 14, 48–58.
[35] A. V. Narsaiah, Adv. Synth. Catal. 2004, 346, 1271–1274.
[36] L. Field, P. B. Hughmark, S. H. Shumaker, W. S. Marshall, J.
Am. Chem. Soc. 1961, 83, 1983–1987.
Received: October 20, 2008
Published Online: January 2, 2009
Eur. J. Org. Chem. 2009, 889–897
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
897