Sonogashira coupling applied in the synthesis of 1,2,4-oxadiazole-based nonsymmetrical liquid crystals

Article abstract of DOI:10.1055/s-2008-1032156

A series of highly π-conjugated nonsymmetrical liquid crystals, based on the core 3,5-(disubstituted)-1,2,4-oxadiazole with a shape similar to a hockey stick, were successfully synthesized by convergent Sonogashira coupling reaction between the building blocks of aryl iodides and the corresponding terminal arylacetylenes, using 3-[4-(decyloxy)phenyl]-5-(haloaryl)-1,2,4-oxadiazoles or decyl 4-iodobenzoate (10) and terminal arylacetylenes. This versatile synthetic route yielded luminescent mesogens with smectic and nematic phases, typical of calamitic compounds. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032156

PAPER
605
Sonogashira Coupling Applied in the Synthesis of 1,2,4-Oxadiazole-Based
Nonsymmetrical Liquid Crystals
S
ynthesis of 1,2,4-
u
O
xadiazole-B
g
ased
N
onsy
o
mmetrical LC
s
Gallardo,*a Rodrigo Cristiano,a André A. Vieira,a Ricardo A.W. Neves Filho,b Rajendra M. Srivastava*b
a
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
Fax +55(48)37216850 ; E-mail: hugo@qmc.ufsc.br
b
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE 50740-540, Brazil
Received 9 October 2007; revised 22 November 2007
RO
Abstract: A series of highly p-conjugated nonsymmetrical liquid
crystals, based on the core 3,5-(disubstituted)-1,2,4-oxadiazole with
a shape similar to a hockey stick, were successfully synthesized by
convergent Sonogashira coupling reaction between the building
blocks of aryl iodides and the corresponding terminal arylacety-
lenes, using 3-[4-(decyloxy)phenyl]-5-(haloaryl)-1,2,4-oxadiazoles
or decyl 4-iodobenzoate (10) and terminal arylacetylenes. This ver-
satile synthetic route yielded luminescent mesogens with smectic
and nematic phases, typical of calamitic compounds.
N
O
OCnH2n+1
N
N
L
1a L = H; n = 10
1b L = H; n = 12
1c L = NO2; n = 10
RO
RO
RO
N
Key words: Sonogashira coupling, liquid crystals, 1,2,4-oxadi-
azoles, acetylenes
O
OR
1d
N
In an attempt to optimize molecular properties for display
and optical applications, considerable attention has been
given to the design and synthesis of liquid crystalline
compounds with suitable selection of the core fragment,
linking group, and terminal functionality.1 Highly p-con-
jugated liquid crystal molecules containing heterocycles
have attracted increasing interest in the field of organic
light emitting diodes (OLEDs), where electron-deficient
heteroaromatic rings can lead to a good charge-transport-
ing materials allied with its inherent self-organization
ability, and strong fluorescence.2 1,3,4-Oxadiazole-based
liquid crystals with high thermal stability and very effi-
cient blue luminescence have been synthesized.3 In addi-
tion, the carbon–carbon triple bond is a good spacer group
in liquid crystals, which produces a highly p-polarizable
and conjugated moiety. Liquid crystals containing a car-
bon–carbon triple bond are very interesting materials due
to their large birefringence,4 large index of refraction par-
allel to the director, large electric polarizability and the
ability to form optical films transparent in the visible. The
Sonogashira coupling5 between aryl halides and terminal
acetylenes, the most common employed synthetic tech-
nique to build carbon–carbon triple bonds, has been wide-
ly used in the synthesis of functional materials.6
N
NR
N
O
1e
O
N
N
O
OR
1f
R = C10H21
Figure 1 Structures of the final synthesized compounds 1a–f
moieties were linked to the central core by a carbon–car-
bon triple bond. These aromatic groups [phenyl, 2-naph-
thyl,
carbonyl)phenyl], were chosen by considering an elonga-
tion of the liquid crystal molecule rod, thus increasing the
length-to-breadth ratio, and also an extension in the p-
conjugated system, with strong electron-donating (e.g.,
OR, NR2) and electron-withdrawing (e.g., NO2, C=O)
substituents.
4-(piperazin-1-yl)phenyl,
or
4-(alkoxy-
The initial synthesis of the intermediates containing the
1,2,4-oxadiazole ring (compounds 6a,b) was carried out
as shown in Scheme 1. First, N-hydroxyimidamide 3 was
prepared from 4-(decyloxy)benzonitrile (2)8 by the
Tiemann reaction9 using hydroxylamine hydrochloride,
and potassium hydroxide in a methanol–water mixture.
Herein, we report an efficient synthesis of a series of liq-
uid crystalline compounds 1a–f, which possess a 1,2,4-
oxadiazole heterocyclic nonsymmetrical core and similar
hockey stick shape (Figure 1).7 In our attempts to gain a
better understanding of the chemical structure versus ther-
mal/optical property relationships, different aromatic
The formation of the 1,2,4-oxadiazole ring was accom-
plished by the reaction between N-hydroxyimidamide 3
and the freshly prepared acyl chlorides 5a,b in pyridine
under reflux, affording the bromide and iodide derivatives
6a,b in 95% and 65% yields, respectively.
SYNTHESIS 2008, No. 4, pp 0605–0609
x
x
.
x
x
.2
0
0
8
Advanced online publication: 31.01.2008
DOI: 10.1055/s-2008-1032156; Art ID: M07407SS
© Georg Thieme Verlag Stuttgart · New York
The synthesis of the final compounds 1a–e is outlined in
Scheme 2. The terminal arylacetylenes 7a–e were ob-

606
H. Gallardo et al.
PAPER
Table 1 Sonogashira Coupling Results, Optical Data, and Liquid
Crystalline Profile of Final Compounds 1a–e
C10H21
O
CN
HO2C
X
X
4a X = Br
4b X = I
2
3
a
a
Compd Yield labs
lem
Transition temperaturesb (°C)
(%)
81
82
74
80
77
81
(nm) (nm)
a
b
1a
1b
1c
1d
1e
1f
333
333
321
346
349
320
413
412
390
437
468
413
Cr 104 SmC 169 N 195 I
Cr 105 SmC 162 N 184 I
Cr 86 SmC 149 SmA 158 I
Cr 102 SmC 190 N 228 I
Cr 124 SmC 171 SmA 256 Ic
Cr 99 SmC 162 N 177 I
NOH
NH2
C10H21
O
ClOC
5a X = Br
5b X = I
X
c
N
6a X = Br (95%)
6b X = I (65%)
C10H21
O
O
N
a In CHCl3 soln.
b Observed by optical microscopy on heating. Cr = crystal phase;
SmC = smectic C phase; SmA = smectic A phase; N = nematic
phase; I = isotropic liquid.
Scheme 1 Reaction conditions: (a) NH2OH·HCl, MeOH–H2O
(1:1), reflux, 12 h, 85%; (b) SOCl2, CH2Cl2, reflux, 18 h, 100%; (c)
pyridine, reflux 16 h.
c Decomposition starts.
different approach was necessary for the synthesis of the
final compound 1f. In this case we simply reversed the
functionalities, building the carbon–carbon triple bond on
the part of the molecule containing the heterocycle. First-
ly, this was attempted by the reaction of 6a with 2-meth-
ylbut-3-yn-2-ol, which gave the respective alkynol 11.
However, in the deprotection step using the protocol of
Trofimov et al.11 the arylacetylene product was not
formed, and decomposition in the reaction media was also
observed. The synthesis was then performed by Sono-
gashira coupling of aryl bromide 6a with (trimethylsi-
lyl)acetylene giving intermediate 12 in 80% yield. The
elimination of the trimethylsilyl group was carried out by
reaction with potassium carbonate in a mixture of metha-
nol and dichloromethane at room temperature, affording
the terminal arylacetylene 13 in 98% yield. The final step
consisted of the Sonogashira coupling, under the same
conditions as those used for the other final compounds
1a–e, between arylacetylene 13 and decyl 4-iodobenzoate
(10), obtained from the Fischer esterification of acid 4b,
to give compound 1f.
tained from their respective aryl halides via Sonogashira
coupling with commercially available 2-methylbut-3-yn-
2-ol followed by protective group elimination. Com-
pounds 1a–e were synthesized by Sonogashira coupling
between an aryl iodide containing the 1,2,4-oxadiazole
ring (compound 6b) and the respective terminal arylacet-
ylenes 7a–e. These reactions were carried out using 10
mol% of the catalyst dichlorobis(triphenylphosphine)pal-
ladium, 5 mol% of the co-catalyst copper (I) iodide, and
triphenylphosphine as an additive, in a triethylamine–
tetrahydrofuran mixture (7:3). All reactions were carried
out at room temperature due to the better reactivity of the
aryl iodide compared to the aryl bromide for Sonogashira
coupling. The reaction yields for the Sonogashira cou-
pling are shown in Table 1.
As demonstrated in Scheme 3, attempts to esterify car-
boxylic acid 8 to obtain the terminal arylacetylene 9
failed. This may be due to the high instability of com-
pound 8, which easily polymerizes on heating.10 Thus, a
I
PdCl2(PPh3)2,
CuI, Ph3P
N
aromatic
+
C10H21O
O
Et3N–THF (7:3)
r.t., 18 h
N
7a–e
6b
O
N
aromatic
N
1a–e
H21C10O
OC10H21
OCnH2n+1
d
aromatic
=
L
a (L = H; n = 10)
N
NC10H21
b (L = H; n = 12)
c (L = NO2; n = 10)
e
Scheme 2
Synthesis 2008, No. 4, 605–609 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,2,4-Oxadiazole-Based Nonsymmetrical LCs
607
O
O
OH
OR
8
9
R = C10H21
a, b
O
O
c
I
I
OH
OR
4b
10
g
1f
RO
N
N
O
13
f
OR
RO
N
O
N
O
TMS
OH
N
N
11
12
d
e
6a
Scheme 3 Reaction conditions: (a) EtOH, H2SO4 (cat.), toluene, reflux, 7 h, 87%; (b) (i) 2-methylbut-3-yn-2-ol, PdCl2(PPh3)2, CuI, Ph3P,
Et3N–THF (2:3), reflux, 3 h; (ii) KOH, i-PrOH, reflux 7 h, 59%; (c) decan-1-ol, H2SO4 (cat.), toluene, reflux, 18 h, 82%; (d) 2-methylbut-3-yn-
2-ol, PdCl2(PPh3)2, CuI, Ph3P, Et3N–pyridine, reflux, 3 h; (e) (trimethylsilyl)acetylene, PdCl2(PPh3)2, CuI, Ph3P, Et3N–pyridine, 50 °C, 24 h,
80%; (f) K2CO3, CH2Cl2–MeOH, r.t., 98%; (g) PdCl2(PPh3)2, CuI, Ph3P, Et3N–THF (3:1), r.t., 20 h, 81%.
The structures of all synthesized compounds were fully by polarizing optical microscopy analysis. They also ex-
1
characterized by IR, H and 13C NMR spectra, and ele- hibited strong blue fluorescence in solution.
mental analysis.
A preliminary study of the liquid crystalline profile of the
final molecules 1a–f was performed by polarizing optical
microscopy (POM), and the results are shown in Table 1.
All these compounds exhibited liquid crystal phases, in
particular the smectic C (SmC) and nematic (N) phases
with Schilieren textures, typical of calamitic compounds.
In contrast, compounds 1c and 1e did not show nematic
All reagents were obtained from commercial sources and used with-
out further purification. Chromatography was performed using sili-
ca gel (60–120 mesh). IR spectra were recorded on a Perkin-Elmer
model 283 spectrophotometer in KBr discs. 1H NMR spectra were
obtained with a Varian Mercury Plus 400-MHz instrument using
TMS as the internal standard. 13C NMR spectra were recorded on a
Varian Mercury Plus 100 MHz spectrometer. Elemental analysis
was performed with a Carlo Erba instrument model E-1110. The
phase, and the smectic A phase observed presented a fan- melting points, thermal transitions, and mesomorphic textures were
determined using an Olympus BX50 microscope equipped with a
shaped texture. This may be explained by the presence of
Mettler Toledo FP-82 hot-stage and a PM-30 exposure control unit.
a lateral nitro group and piperazine ring, respectively,
An HP UV-vis model 8453 spectrophotometer was used to record
absorption spectra. Fluorescence spectra were recorded on a Hita-
chi-F-4500. Sonogashira couplings were carried out under an argon
which increased the lateral interaction and lead to a lay-
ered phase.
atmosphere. Terminal arylacetylenes 7a–e were prepared according
With exception of compound 1c, which showed very poor
fluorescence due to the nitro lateral group, all the other fi-
nal compounds exhibited strong blue fluorescence with
maximum emission wavelengths between 410 and 470
nm. The absorption and emission spectra data in chloro-
form solution are listed in Table 1.
to published methods.3c,12
4-(Decyloxy)-N-hydroxybenzimidamide (3)
This intermediate was synthesized following the published proce-
dure for 4-alkoxy-N-hydroxybenzimidamide;13 yield: 85%; mp
109–110 °C.
In summary, we successfully employed a palladium-cata- IR (KBr): 3447, 3348, 2919, 2852, 1651, 1609, 1391, 1252, 826.
cm–1.
lyzed cross-coupling reaction (Sonogashira reaction) to
1H NMR (400 MHz, CDCl3): d = 7.54 (d, J = 8.8 Hz, 2 H), 6.87 (d,
J = 8.8 Hz, 2 H), 6.34 (s, 1 H), 5.15 (s, 2 H), 3.93 (t, J = 6.8 Hz, 2
H), 1.81 (q, J = 6.8 Hz, 2 H), 1.77 (m, 2 H), 1.27 (m, 12 H), 0.88
(t, J = 6.8 Hz, 3 H).
prepare nonsymmetrical liquid crystalline compounds
based on 5-[4-(arylethynyl)phenyl]-3-[4-(decyloxy)phe-
nyl]-1,2,4-oxadiazole; they possess a similar hockey-
stick-shaped structure. These final compounds 1a–f
showed liquid crystal phases, in particular smectic and
nematic phases typical of calamitic structures, observed
Anal. Calcd for C17H28N2O2: C, 69.83; H, 9.65; N, 9.58. Found: C,
69.26; H, 9.91; N, 9.33.
Synthesis 2008, No. 4, 605–609 © Thieme Stuttgart · New York

608
H. Gallardo et al.
PAPER
3-[4-(Decyloxy)phenyl]-5-(4-iodophenyl)-1,2,4-oxadiazole (6b);
Typical Procedure
IR (KBr): 2920, 2851, 2206, 1597, 1597, 1250, 840 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 8.0 Hz, 2 H), 8.10 (d,
J = 8.2 Hz, 2 H), 7.65 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 2 H),
7.01 (d, J = 8.4 Hz, 2 H), 6.88 (d, J = 8.4 Hz, 2 H), 4.01 (m, 4 H),
1.81 (m, 4 H), 1.27 (m, 32 H), 0.86 (t, J = 5.6 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 174.9, 162.4, 159.9, 133.5, 132.1,
130.9, 129.3, 129.1, 128.2, 123.5, 119.3, 115.0, 114.8, 93.4, 87.6,
68.4, 46.3, 32.1, 29.9, 29.6, 29.4, 26.2, 22.9, 14.3.
Freshly prepared 4-iodobenzoyl chloride14 (5b, 1.41 g, 5.3 mmol)
and 3 (1.6 g, 5.5 mmol) were stirred under reflux in pyridine for 16
h. After cooling, the mixture was poured into cold H2O. The precip-
itate was then filtered and recrystallized (EtOH) to give light brown
crystals; yield: 65%; mp 104 °C.
IR (KBr): 2923, 2853, 1606, 1477, 1262, 1360 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.06 (d, J = 9.2 Hz, 2 H), 7.92 (s,
4 H), 6.98 (d, J = 9.2 Hz, 2 H), 4.02 (t, J = 6.8 Hz, 2 H), 1.81 (m, 2
H), 1.43 (m, 2 H), 1.28 (m, 12 H), 0.89 (t, J = 7.2 Hz, 3 H).
Anal. Calcd for C44H58N2O3: C, 79.72; H, 8.82; N, 4.23. Found: C,
79.22; H, 8.61; N, 4.15.
13C NMR (100 MHz, CDCl3): d = 174.9, 169.0, 161.9, 138.6, 129.6,
129.3, 124.0, 119.1, 115.0, 100.2, 68.4, 32.1, 29.8, 29.7, 29.6, 29.5,
29.4, 26.2, 22.9, 14.3.
5-(4-{[4-(Decyloxy)-3-nitrophenyl]ethynyl}phenyl)-3-[4-(decyl-
oxy)phenyl]-1,2,4-oxadiazole (1c)
Yield: 74%.
Anal. Calcd for C24H29IN2O2: C, 57.15; H, 5.80; N, 5.55. Found: C,
57.01; H, 5.20; N, 5.13.
IR (KBr): 2922, 2849, 2207, 1607, 1535, 1356, 1261, 1016, 846 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.21 (d, J = 8.0 Hz, 2 H), 8.09 (d,
J = 8.0 Hz, 2 H), 7.91 (s, 1 H), 7.67 (m, 3 H), 7.07 (d, J = 8.4 Hz, 1
H), 6.99 (d, J = 8.4 Hz, 2 H), 4.13 (t, J = 6.4 Hz, 2 H), 4.02 (t, J =
6.6 Hz, 2 H), 1.82 (m, 4 H), 1.28 (m, 28 H), 0.88 (t, J = 6.4 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 174.9, 169.0, 161.8, 152.9, 138.6,
137.2, 132.3, 129.6, 129.3, 129.0, 128.3, 127.3, 124.2, 119.2, 115.0,
114.9, 114.7, 90.4, 89.2, 70.2, 68.4, 32.1, 29.8, 29.8, 29.7, 29.6,
29.5, 29.5, 29.48, 29.4, 29.1, 26.0, 22.9, 14.4.
5-(4-Bromophenyl)-3-(4-(decyloxy)phenyl)-1,2,4-oxadiazole
(6a)
Following the typical procedure for 6b using 4-bromobenzoyl chlo-
ride (5a) gave 6a as colorless crystals; yield: 2.08 g (95%); Cr 90 °C
N, 109 °C I.
IR (KBr): 2916, 2851, 1598, 1477, 1359, 1253, 1014, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.08 (d, J = 8.4 Hz, 4 H), 7.68 (d,
J = 8.4 Hz, 2 H), 7.01 (d, J = 8.4 Hz, 2 H), 4.02 (t, 2 H), 1.81 (m, 2
H), 1.27 (m, 14 H), 0.88 (t, J = 7.2 Hz, 3 H).
Anal. Calcd for C42H53N3O5: C, 74.20; H, 7.86; N, 6.18. Found: C,
74.11; H, 7.56; N, 6.07.
13C NMR (100 MHz, CDCl3): d = 174.5, 168.8, 161.7, 129.4, 128.5,
128.1, 127.5, 123.4, 118.9, 114.7, 68.2, 21.9, 29.5, 29.4, 29.2, 26.0,
22.7, 14.1.
5-(4-{[6-(Decyloxy)naphthalen-2-yl]ethynyl}phenyl)-3-[4-(dec-
yloxy)phenyl]-1,2,4-oxadiazole (1d)
Yield: 80%.
Anal. Calcd for C24H29BrN2O2: C, 63.02; H, 6.39; N, 6.12. Found:
C, 62.98; H, 6.21; N, 6.25.
IR (KBr): 2919, 2847, 1606, 1465, 1364, 1253, 1172, 1021, 842 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.21 (d, J = 8.4 Hz, 2 H), 8.11 (d,
J = 8.8 Hz, 2 H), 8.02 (s, 1 H), 7.74–7.70 (m, 4 H), 7.55 (dd, J = 8.8,
1.1 Hz, 1 H), 7.19 (dd, J = 8.8, 2.1 Hz, 1 H), 7.12 (d, J = 2.1 Hz, 1
H), 7.01 (d, J = 8.8, 2 H), 4.08 (t, J = 6.0 Hz, 2 H), 4.03 (t, J = 6.6
Hz, 2 H), 1.84 (m, 4 H), 1.48 and 1.27 (m, 28 H), 0.89 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 175.1, 169.0, 161.8, 158.4, 134.7,
132.3, 131.9, 129.6, 129.3, 129.0, 128.3, 127.1, 123.7, 120.1, 119.3,
117.4, 114.9, 106.8, 93.9, 88.5, 68.4, 32.1, 29.8, 28.8, 29.6, 29.5,
29.4, 26.3, 26.26, 22.9, 17.8, 14.4.
Synthesis of 1a–e; General Procedure
A mixture of 6b (0.3 g, 0.6 mmol), PdCl2(PPh3)2 (41.66 mg, 0.06
mmol). and Ph3P (15.59 mg, 0.06 mmol) in Et3N–THF (7:3, 30 mL)
was stirred at r.t. for 15 min. CuI (5.65 mg, 0.03 mmol) was then
added and the mixture was further stirred for 20 min. The corre-
sponding terminal arylacetylene 7a–e (0.71 mmol) dissolved in
Et3N (5 mL) was added dropwise and the mixture was stirred at r.t.
for 16 h. The progress of the reaction was followed by TLC (hex-
ane–EtOAc, 95:5). The mixture was filtered through a Celite pad
and washed with THF (50 mL). The solvents were evaporated under
reduced pressure and the crude product was recrystallized (hex-
anes–CHCl3) to afford the desired product.
Anal. Calcd for C46H56N2O3: C, 80.66; H, 8.24; N, 4.09. Found: C,
80.72; H, 8.80; N, 4.23.
3-[4-(Decyloxy)phenyl]-5-(4-{[4-(4-decylpiperazin-1-yl)phe-
nyl]ethynyl}phenyl)-1,2,4-oxadiazole (1e)
Yield: 77%.
IR (KBr): 2921, 2848, 2208, 1602, 1514, 1357, 1246, 816, 759 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.16 (d, J = 8.0 Hz, 2 H), 8.08 (d,
J = 8.0 Hz, 2 H), 7.64 (d, J = 8.0 Hz, 2 H), 7.45 (d, J = 8.0 Hz, 2 H),
6.99 (d, J = 8.4 Hz, 2 H), 6.87 (d, J = 8.4 Hz, 2 H), 4.02 (t, J = 6.4
Hz, 2 H), 3.49 (t, J = 6.4 Hz, 4 H), 3.15 (q, J = 7.2 Hz, 2 H), 2.91 (t,
J = 6.4 Hz, 4 H), 2.66 (m, 2 H), 1.81 (m, 2 H), 1.26 (m, 28 H), 0.88
(m, 6 H).
3-[4-(Decyloxy)phenyl]-5-(4-{[4-(decyloxy)phenyl]ethynyl}phe-
nyl)-1,2,4-oxadiazole (1a)
Yield: 81%.
IR (KBr): 2919, 2849, 2204, 1597, 1505, 1248, 840 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 8.4 Hz, 2 H), 8.10 (d,
J = 8.4 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 8.0 Hz, 2 H),
7.01 (d, J = 8.4 Hz, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 4.02 (m, 4 H),
1.81 (m, 4 H), 1.28 (m, 28 H), 0.89 (t, J = 6.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 175.1, 169.0, 161.8, 159.9, 133.5,
132.1, 129.3, 128.2, 123.5, 119.3, 114.9, 114.8, 93.4, 87.6, 86.8,
68.3, 32.1, 29.8, 29.5, 29.4, 26.2, 22.9, 14.4.
13C NMR (100 MHz, CDCl3): d = 175.1, 168.9, 161.8, 150.6, 133.2,
132.1, 129.3, 128.2, 123.3, 119.2, 115.7, 114.9, 113.5, 93.7, 87.8,
68.4, 58.6, 47.3, 46.3, 32.1, 29.9, 29.6, 29.5, 29.5, 29.4, 27.4, 26.2,
25.6, 22.9, 14.36, 8.8.
Anal. Calcd for C42H54N2O3: C, 79.46; H, 8.57; N, 4.41. Found: C,
79.62; H, 8.42; N, 4.07.
Anal. Calcd for C46H62N4O2: C, 78.59; H, 8.89; N, 7.97. Found: C,
78.81; H, 8.57; N, 7.56.
3-[4-(Decyloxy)phenyl]-5-(4-{[4-(dodecyloxy)phenyl]eth-
ynyl}phenyl)-1,2,4-oxadiazole (1b)
Yield: 82%.
Synthesis 2008, No. 4, 605–609 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,2,4-Oxadiazole-Based Nonsymmetrical LCs
609
3-[4-(Decyloxy)phenyl]-5-{4-[(trimethylsilyl)ethynyl]phenyl}-
1,2,4-oxadiazole (12)
IR (KBr): 2919, 2849, 1710, 1609, 1467, 1272, 1108, 841, 762 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.21 (d, J = 8.4 Hz, 2 H), 8.09 (d,
J = 8.8 Hz, 2 H), 8.05 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H),
7.62 (d, J = 8.4 Hz, 2 H), 7.00 (d, J = 8.8 Hz, 2 H), 4.33 (t, J = 6.4
Hz, 2 H), 4.02 (t, J = 6.4 Hz, 2 H), 1.79 (m, 4 H), 1.28 (m, 28 H),
0.88 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 174.9, 169.0, 166.2, 161.8, 132.5,
131.8, 130.6, 129.8, 129.3, 127.3, 124.3, 119.1, 114.9, 92.0, 91.3,
92.1, 91.4, 68.4, 65.7, 46.1, 32.1, 29.8, 29.8, 29.6, 29.5, 28.9, 26.2,
22.9, 14.3, 8.9.
A mixture of 6a (2 g, 4.4 mmol), PdCl2(PPh3)2 (30.00 mg, 0.04
mmol), Ph3P (10.48 mg, 0.04 mmol), CuI (5.65 mg, 0.03 mmol),
and (trimethylsilyl)acetylene (0.59 g, 6.0 mmol) in Et3N–pyridine
(8:2, 50 mL) was stirred at 50 °C for 24 h. The progress of the reac-
tion was followed by TLC (hexane–EtOAc, 95:5). The mixture was
filtered through a Celite pad and washed with THF (100 mL). The
solvents were vaporized under reduced pressure and the crude prod-
uct was recrystallized (EtOH); yield: 80%; mp 107–108 °C.
IR (KBr): 2920, 2850, 2154, 1610, 1466, 1263, 844, 760 cm–1.
Anal. Calcd for C43H54N2O4: C, 77.91; H, 8.21; N, 4.23. Found: C,
77.65; H, 8.32; N, 4.37.
1H NMR (400 MHz, CDCl3): d = 8.14 (d, J = 8.0 Hz, 2 H), 8.08 (d,
J = 8.0 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.00 (d, J = 8.8 Hz, 2 H),
4.03 (t, J = 6.4 Hz, 2 H), 1.82 (m, 2 H), 1.28 (m, 14 H), 0.89 (t, J =
6.4 Hz, 3 H), 0.28 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 174.9, 168.9, 161.7, 132.6, 129.2,
132.6, 129.2, 128.0, 127.7, 124.0, 119.1, 114.9, 104.0, 98.4, 68.3,
32.1, 29.7, 29.6, 29.5, 29.3, 26.2, 22.9, 14.3, 0.0.
Acknowledgment
The authors thank to Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq, Brazil) and Merck (Germany) for
funding.
Anal. Calcd for C29H38N2O2Si: C, 73.37; H, 8.07; N, 5.90. Found:
C, 73.64; H, 8.33; N, 6.10.
References
3-[4-(Decyloxy)phenyl]-5-(4-ethynylphenyl)-1,2,4-oxadiazole
(13)
Compound 12 (1 g, 2.1 mmol) and K2CO3 (0.58 g, 4.2 mmol) in
CH2Cl2–MeOH (3:2) were vigorously stirred overnight at r.t. The
mixture was filtered and solvents evaporated under reduced pres-
sure to give the crude product, which was purified by recrystalliza-
tion (EtOH); yield: 98%; Cr 93 °C N, 107 °C I.
(1) (a) Spieker, B.; Hahn, A.; Vill, V. Synthesis 2002, 2129.
(b) Feuerbacher, N.; Vögtle, F.; Windscheidt, J.; Poetsch, E.;
Nieger, M. Synthesis 1999, 117. (c) Pickaert, G.; Ziessel, R.
Synthesis 2004, 2716. (d) Lee, A. S. Y.; Wu, C. C.; Lin, L.
S.; Hsu, H. F. Synthesis 2004, 568. (e) Lee, S. K.; Naito, Y.;
Shi, L.; Tokita, M.; Takezoe, H.; Watanabe, J. Liq. Cryst.
2007, 935. (f) Prajapati, A. K.; Patel, H. N. Liq. Cryst. 2007,
903.
IR (KBr): 3279, 2923, 2851, 1612, 1266, 846, 760 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.18 (d, J = 8.0 Hz, 2 H), 8.08 (d,
J = 8.0 Hz, 2 H), 7.65 (d, J = 8.8 Hz, 2 H), 7.01 (d, J = 8.8 Hz, 2 H),
4.02 (t, J = 6.4 Hz, 2 H), 3.28 (s, 1 H), 1.81 (m, 2 H), 1.28 (m, 14
H), 0.88 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 174.9, 169.0, 161.8, 132.9, 129.3,
128.2, 126.7, 124.5, 119.1, 114.9, 82.8, 80.7, 77.6, 77.2, 76.9, 68.4,
32.1, 29.9, 29.6, 29.4, 26.2, 22.9, 14.3.
(2) (a) Vlachos, P.; Mansoor, B.; Aldred, M. P.; O’Neill, M.;
Kelly, S. M. Chem. Commun. 2005, 2921. (b) O’Neill, M.;
Kelly, S. M. Adv. Mater. (Weinheim, Ger.) 2003, 1135.
(3) (a) Cristiano, R.; Santos, D. M. P. O.; Gallardo, H. Liq.
Cryst. 2005, 7. (b) Cristiano, R.; Ely, F.; Gallardo, H. Liq.
Cryst. 2005, 15. (c) Cristiano, R.; Vieira, A. A.; Ely, F.;
Gallardo, H. Liq. Cryst. 2006, 381. (d) Gallardo, H.;
Magnago, R.; Bortoluzzi, A. J. Liq. Cryst. 2001, 1343.
(4) Wu, S.-T.; Finkenzeller, U.; Rieffenrath, J. J. Appl. Phys.
1989, 4372.
Anal. Calcd for C26H30N2O2: C, 77.58; H, 7.51; N, 6.96. Found: C,
77.19; H, 7.73; N, 6.67.
(5) (a) Sonogashira, K. J. Organomet. Chem. 2002, 46.
(b) Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874.
(6) (a) Vieira, A. A.; Cristiano, R.; Bortoluzzi, A. J.; Gallardo,
H. J. Mol. Struct. 2007, in press; DOI: 10.1016/
j.molstruc.2007.05.006. (b) Vasconcelos, U. B.; Dalmolin,
E.; Merlo, A. A. Org. Lett. 2005, 7, 1027. (c) Tong, L. H.;
Pascu, S. I.; Jarrosson, T.; Sanders, J. K. M. Chem. Commun.
2006, 1085.
Decyl 4-Iodobenzoate (10)
In a round-bottom flask coupled with a Dean–Stark apparatus, a
mixture of 4-iodobenzoic acid (4b, 1 g, 4.0 mmol), decan-1-ol (0.97
g, 6.1 mmol), and H2SO4 (catalytic amount) in toluene was refluxed
for 18 h. The reaction was completed when 0.1 mL of H2O was
trapped. The solvents were concentrated under reduced pressure,
then the crude product was purified by column chromatography (sil-
ica gel, hexane–EtOAc, 8:2) to afford 10 as a brown oil; yield: 1.28
g (82%).
(7) Dingemans, T. J.; Murthy, N. S.; Samulski, E. T. J. Phys.
Chem. B 2001, 8845.
(8) Lee, J. W.; Kang, S. U.; Lim, J. O.; Choi, H. K.; Jin, M. K.;
Toth, A.; Pearce, L. V.; Tran, R.; Wang, Y.; Szabo, T.;
Blumberg, P. M. Bioorg. Med. Chem. 2004, 12, 371.
(9) Tiemann, F. Ber. Dtsch. Chem. Ges. 1884, 17, 126.
(10) Melissaris, A. P.; Litt, M. H. J. Org. Chem. 1992, 57, 6998.
(11) Mal’kina, A. G.; Brandsma, L.; Vasilevsky, S. F.; Trofimov,
B. A. Synthesis 1986, 589.
(12) (a) Merlo, A. A.; Braun, J. E.; Vasconcelos, U. B.; Ely, F.;
Gallardo, H. Liq. Cryst. 2000, 657. (b) Ely, F.; Conte, G.;
Merlo, A. A.; Gallardo, H. Liq. Cryst. 2004, 1413.
(13) Grassmann, S.; Sadek, B.; Ligneau, X.; Elz, S.; Ganellin, C.
R.; Arrang, J. M.; Schwartz, J. C.; Stark, H.; Schunack, W.
Eur. J. Pharm. Sci. 2002, 15, 367.
IR (KBr): 2922, 2853, 1721, 1586, 1272, 1108, 753 cm–1.
Decyl 4-[(4-{3-[4-(Decyloxy)phenyl]-1,2,4-oxadiazol-5-yl}phe-
nyl)ethynyl]benzoate (1f)
A mixture of 10 (0.1 g, 0.25 mmol), PdCl2(PPh3)2 (18 mg, 0.03
mmol), and Ph3P (7.00 mg, 0.03 mmol) in Et3N–THF (7:3, 30 mL)
was stirred at r.t. for 15 min. CuI (5.65 mg, 0.03 mmol) was then
added as solid and the mixture was stirred for an additional 20 min.
Compound 13 (0,2 g, 0.5 mmol) dissolved in THF (8 mL) was add-
ed dropwise. The mixture was stirred at r.t. for 20 h. The progress
of the reaction was followed by TLC (hexane–EtOAc, 95:5). The
mixture was filtered through a Celite pad and washed with THF (50
mL). The filtrate was concentrated under reduced pressure to give
the crude product, which was recrystallized (hexane–CHCl3) to af-
ford the product; yield: 81%.
(14) Break, P.; Musick, T. J.; Chen, C. W. J. Am. Chem. Soc.
1988, 110, 3538.
Synthesis 2008, No. 4, 605–609 © Thieme Stuttgart · New York