Synthesis and thermal behavior of new N-heterotolan liquid crystals

Article abstract of DOI:10.1021/ol047524e

(Chemical Equation Presented) The synthesis of liquid crystal series 9a-d was achieved using the Buchwald protocol and Sonogashira reaction.

Full text of DOI:10.1021/ol047524e

ORGANIC
LETTERS
2005
Vol. 7, No. 6
1027-1030
Synthesis and Thermal Behavior of New
N-Heterotolan Liquid Crystals
Ursula B. Vasconcelos, Emilene Dalmolin, and Aloir A. Merlo*
Chemistry Institute, Federal UniVersity of Rio Grande do Sul, AV. Bento Gonc¸alVes,
9500, Campus do Vale, 91501 970, Porto Alegre, RS, Brazil
aloir@iq.ufrgs.br
Received December 2, 2004
ABSTRACT
The synthesis of liquid crystal series 9a−d was achieved using the Buchwald protocol and Sonogashira reaction.
Liquid crystals are the fascinating condensed state of soft
matter with unique electrical, optical, and mechanical proper-
ties. The anisotropic properties of liquid crystals make them
very attractive materials, which can be found in many
practical technological applications such as displays. The self-
ordering of the LC may be also extended to living processes
such as the cell membrane, which has a bilayer structure
self-organized in water. The biological function of the cell
membrane is related to cyclic or linear topological shape and
is also dependent on the physiological temperature, thus
showing fascinating properties.1
Liquid crystals containing nitrogen heterocycles present
great possibilities in the variations of their permanent dipole
moment (value and direction), as well as in their dielectric
anisotropy.6 N-Heterocycle mesogens are less symmetric and
have lower melting points than analogue phenyl mesogens.
However, they present high birefringence and other proper-
ties.7 N-Heterotolans may be considered as potential candi-
dates for application to liquid crystal displays, and many
synthetic efforts should be put into making them in an
acceptable yield.
To observe the relationship between structure and meso-
morphic properties, we have introduced a pyridine moiety
to produce N-heterotolans using the Buchwald protocol8 and
Sonogashira reaction.9
Among many types of liquid-crystalline architecture, the
tolan (diphenylacetylene) and its N-hetero version (py-
ridylphenylacetylene) play a prominent role in the field of
liquid crystals science. The main outstanding features of
tolans and related systems are high polarizability, stability,
linearity, and phase behavior such as nematic and smectic
phases,2 twist grain boundary phases3 (TGB), an antiferro-
electric smectic phase,4 and NLO properties.5
(3) Bouchta, A.; Nguyen, H. T.; Achard, M. F.; Hardouin, F.; Destrade,
C.; Twieg, R. J.; Maaroufi, A.; Isaert, N. Liq. Cryst. 1992, 12, 575-591.
(4) Faye, V.; Rouillon, J. C.; Nguyen, H. T.; De´tre´, L.; Laux, V.; Isaert,
N. Liq. Cryst. 1998, 24, 747-758.
(5) Walba, D. M.; Rego, J. A.; Clark, N.; Shao, R. Macromolecular
Host-Guest Complexes: Optical and Optoeletronic Properties and Ap-
plications; Jenekhe, S. A., Ed.; Materials Research Society: Pittsburgh,
PA, 1992; Vol. 277, p 205.
(6) Hird, M.; Toyne, K. J.; Gray, G. W. Liq. Cryst. 1993, 14, 741-761.
(7) Pavluchenko, A. I.; Smirnova, N. I.; Petrov, V. F.; Grebenkin, M.
F.; Titov, V. V. Mol. Cryst. Liq. Cryst. 1991, 209, 155-169.
(8) (a) Buchwald, S. L.; Job, G. E.; Nordmann, G.; Wolfer, M. Org.
Lett. 2002, 4, 973-976. (b) Buchwald, S. L.; Job, G. Org. Lett. 2002, 4,
3703-3706. (c) Buchwald, S. L.; Doye, S.; Marcoux, J.-F. J. Am. Chem.
Soc. 1997, 119, 10539-10540. (d) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-
F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805-818. (e) Kiyomori,
A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett. 1999, 40, 2657-
2660. (f) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852-860.
(1) (a) Percec, V.; Horleca, M. N. Biomacromolecules 2000, 1, 6-16.
(b) Goodby, J. W.; Saez, I. M. Chem. Commun. 2003, 1726-1727. (c)
Yamauchi, K.; Kinoshita, M. Prog. Polym. Sci. 1993, 18, 763-804. (d)
Tschierske, C. J. Mater. Chem. 2001, 11, 2647-2671.
(2) (a) Seto, K.; Shimojitosho, H.; Imazaki, H. Bull. Chem. Soc. Jpn.
1990, 63, 1020-1025. (b) Merlo, A. A.; Vasconcelos, U. B.; Ely, F.;
Gallardo, H. Liq. Cryst. 2000, 27, 657-663. (c) Merlo, A. A.; Gallardo,
H.; Ely, F.; Bortoluzzi, A. J. Braz. J. Phys. 2002, 32, 548-551. (d) Gallardo,
H.; Ely, F.; Conte, G.; Merlo, A. A. Liq. Cryst. 2004, 31, 1413-1425. (e)
Young, D. D.; Scharrer, E.; Yoa, M. V. Mol. Cryst. Liq. Cryst. 2003, 408,
21-31.
10.1021/ol047524e CCC: $30.25
© 2005 American Chemical Society
Published on Web 02/19/2005

The first is a copper-catalyzed cross-coupling reaction
developed by the Buchwald group, and the second is a well-
established Sonogashira reaction to introduce an acetylene
unit into the final compounds 9a-d.
Table 1. Arylation Reaction under SNAr and Copper-Catalyzed
Coupling
entry
reaction conditions
DMSO, K2CO3
NaH, DMSO
NaH, DMF
yield
The Ullmann synthesis is a classical methodology for the
construction of aromatic ethers and amines. High tempera-
tures and extended reaction times are needed to ensure
reasonable yields. In addition, a high quantity of copper
catalyst is often needed. As opposed to the traditional copper-
mediated Ullmann ether synthesis, the Buchwald protocol
is an efficient and mild method for N-arylation and O-
arylation coupling of aryl halides with amines and alcohols,
respectively. This prompted us to disclose our preliminary
results in the arylation reaction of 1 and the synthesis of
chiral liquid crystals by double Sonogashira reaction. In our
approach, we were guided by the possibility of constructing
chiral ether 3. The preparation of that key compound
provided us the entry to a new class of precursors to high-
performance liquid crystal materials.
1
2
3a
4b
<50%
<50%
70%
CuI, Cs2CO3, phenanthroline, toluene
60-70%
a Experimental conditions had not been reproduced on the scale of 10
mmol of reagent 1. b Experimental conditions had been reproduced on the
scale of 20 mmol of reagent 1.
or sodium hydride, a more powerful base, provided the
desired product, though in a yield of <50% (entries 1 and
2, Table 1).
The regioselective copper-catalyzed O-arylation of 1
obtained in this work is in accordance with the results
achieved in a previous work reported for the synthesis of
2-alkyl-5-bromopyridine11 and carboalkoxylation12 of 2,5-
dibromopyridine (1). We believe that this method should
provide expedient access to a variety of 2,5-disubstituted
pyridine liquid crystals.
Entry 2 (Table 1) failed to reproduce the desired product
in an acceptable yield. When the solvent was changed to
DMF, the product was obtained in 70% yield (entry 3).
However, it was possible to reproduce this result only in
small quantities, i.e., on the 1 mmol scale. The low yield
(entries 1 and 2) and nonreproducibility (entry 3) may be
associated with harsh reaction conditions involving high
temperature and a strongly basic medium.
Synthesis of the Chiral Intermediate 3 by Buchwald
Protocol. Our synthetic strategy is outlined in the scheme
below. The key intermediate 3 was obtained using the
Buchwald protocol.8 This protocol was particularly suitable
for the conversion of 1 into the chiral precursor 3 in
acceptable yields, according to Scheme 1.
Scheme 1
Ethynylation Reaction of 3 by Sonogashira Coupling.
After accomplishing the synthesis of 3, we started to build
the next key intermediate 4 through a copper-palladium-
catalyzed cross-coupling alkynylation reaction,9 according
to Scheme 2.
We have repeated this protocol several times with different
molar quantities of 1, looking at the yields and regiochemistry
of the reaction. We found that the conversion of 1 into 3
can be made even on the scale of 20 mmol of compound 1
(MM 237 g mol-1) and that the O-arylation reaction of 1
occurs regiospecifically at position 2.10
Scheme 2
Arylation reaction using 2,5-dibromopyridine (1) with (S)-
(-)-2-methyl-1-butanol (2) in the presence of cesium
carbonate as a mild base, as well as 1,10-phenanthroline as
a bidentate nitrogenous ligand and a catalytic amount of
copper iodide, provided the chiral intermediate 3 in the yield
range of 60-70% (entry 4 in Table 1, Scheme 1).
Sonogashira alkynylation with 2-methyl-3-butyn-2-ol
(Mebynol)followedbydeprotectionwithKOHand2-propanol10b
provided (S)-5-ethynyl-2-(2-methylbutoxy) pyridine (4) in
90% yield, [R]D ) +13 (c 1, CH2Cl2).
Under aromatic nucleophilic substitution (SNAr), arylation
reaction of the chiral alcohol 2 using potassium carbonate10a
(9) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467-4470. (b) Sonogashira, K.; Yatake, T.; Tohda, Y.; Takahashi,
S.; Hagihara, N. J. Chem. Soc., Chem. Commun. 1977, 291-292. (c)
Takahashi, K.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N. Synthesis 1980,
627-630. (d) General review, see: Sonogashira, K. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weiheim, 1998; Chapter 5. (e) Negishi, E.-I.; Anastasia, L. Chem. ReV.
2003, 103, 1979-2017. Verkade, J. G.; Urgaonkar, S. J. Org. Chem. 2004,
69, 5752-5755.
(10) (a) Nicoud, J.-F.; Masson, P.; Wong, J. Polym. Bull. 1994, 32, 265-
271. (b) Melissaris, A, P.; Litt, M. H. Macromolecules 1994, 27, 883-
887. (c) Onopchenko, A.; Sabourin, E. T.; Selwitz, C. M. J. Org. Chem.
1979, 44, 1233-1236.
The classical deprotection method10c that uses potassium
hydroxide in toluene under heating failed. Under those
conditions, we observed some decomposition and a degree
of polymerization of the starting material.
Convergent Synthesis of the Chiral Heterotolan Liquid
Crystal 9a-d. As the synthesis of compound 4 was
(11) Tilley, J. W.; Zawoiski, S. J. Org. Chem. 1988, 53, 386-390.
(12) Chambers, R. J.; Marfat, A. Synth. Commun. 1997, 27, 515-520.
1028
Org. Lett., Vol. 7, No. 6, 2005

achieved, we started to synthesize other chemical structures,
8a-d (Scheme 3). Alkylation reaction of methyl p-hydroxy-
benzoate (5) with alkyl bromides resulted in product 6 in
the yield range of 65-80%. Saponification reaction of the
ester 6 provided the p-n-alkoxybenzoic acid (7) in 70-80%
yield.
Table 2. Transition Temperatures (°C) of the Series of
Heterotolans 9a-d and Enthalpy Values (∆H, kcal mol-1
)
entry
R
K
T [∆H]
Sa
T [∆H]
N*
T [∆H]
I
9a
9b
9c
9d
C7H15
C8H17
C9H19
•
•
•
•
101.4 [4.4]
111.9 [6.2]
106.7 [6.4]
85.6 [2.8]
•
•
•
•
132.8 [0.20]
137.4 [0.35]
143.0 [0.52]
144.0 [0.12]
•
•
•
•
151.6 [0.15]
148.6 [0.18]
149.1 [0.25]
144.7a
•
•
•
•
C10H21
a Enthalpy value was not determined, and the N* phase was observed
only through microscopic analysis.
Scheme 3
Mesophase textures14 were identified by microscopy
observations. When the sample was cooled, the isotropic
liquid of heterotolans provided a chiral nematic phase, which
showed typical cholesteric texture, as well as a smectic phase
showing both homeotropic (black) and focal-conic texture
for smectic A phase, respectively.
All heterotolan derivatives display a broad, stable smectic
A phase range, and the temperature range of the smectic A
increases as the alkyl tail changes from 9a to 9d. However,
this homologue series has no smectic C phase.
The opposite behavior was found in the nematic phase. It
was observed that there is a wide nematic range for the first
member of the series. As n increases, the nematic range is
reduced. It was also dependent on the size of the alkyl chain.
The thermal stability of the nematic phase decreased with
an increased alkyl chain length. For example, ∆TSa-N is 18.8
°C for 9a, ∆TSa-N is 11.2 °C for 9b, ∆TSa-N ) 6.1 °C for
9c, and ∆TSa-N ) 0.7 °C for 9d. A narrow enantiotropic
nematic phase was observed in 9d with an increase in the
length of the alkyl chain attached to the benzene moiety.
In contrast, the thermal stability of the smectic A phase
increases as the alkyl tail increases. As pointed out by Gray
and Winsor,15 this behavior has been attributed to the fact
that lateral attractions grow stronger as the alkoxy group is
lengthened, while the terminal attractions grow relatively
weaker; thus, the net result will be an increase in the van
der Waals attraction responsible for the parallel alignment
in the smectic phase. Gray16 discusses the effects of molec-
ular structure changes on the nematic phase and smectic
polymorphism.
Esterification reaction13 using dicyclohexylcarbodiimide
as a dehydrating agent, 4-(N,N-dimethylamino)pyridine
(DMAP) as a catalyst, and p-iodophenol yielded the target
molecules 8a-d in 70-95% yield.
The last step was a second Sonogashira coupling between
4 and 8. The homologous series was obtained in 40-60%
yield as a pale yellow solid after purification through column
chromatography. The cross-coupling product 9a-d is out-
lined in Scheme 4.
Scheme 4
The clearing point (cp N*/isotropic or Sa/isotropic) of
heterotolans 9a-d follows the same tendency. These obser-
vations are a general behavior in the liquid crystal field. This
means that the nematic phase is shifted to the more ordered
smectic phase when the alkyl chain becomes longer, as it
can be seen from enthalpy values compiled in Table 2.
The mesomorphic behavior observed in this liquid-
crystalline series can be compared with the tolan homologue
series reported in our previous paper.2b
Mesomorphic Behavior. Thermal behavior of all N-
heterotolans was characterized by a combination of dif-
ferential scanning calorimetry (DSC) and thermal optical
polarized microscopic techniques and is compiled in Table
2. The DSC thermograms of 9a-d showed that all samples
are thermally stable and present an enantiotropic behavior.
Phase transition temperatures and enthalpy values were
collected from second heating scans.
For the comparison between the transition temperatures,
we notice that the compounds belonging to the heterotolans
(14) Gray, G. W.; Goodby, J. W. G. Smectic Liquid Crystals. Textures
and Structures; Leonard Hill, 1984.
(15) Gray, G. W.; Winsor, P. A. Liquid Crystals and Plastic Crystals;
Ellis Horwood: Chichester, 1974, Vol. 1.
(13) Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978, 17,
522-524.
(16) Gray, G. W. Molecular Structure and the Properties of Liquid
Crystals; Academic Press: New York, 1962.
Org. Lett., Vol. 7, No. 6, 2005
1029

9a-d have lower melting and clearing points than the
equivalent homologue diphenylacetylene with the same
terminal alkyl chain. Furthermore, the nature and range of
the mesophase is changed when the aromatic ring has a
nitrogen atom. The mesomorphic phase in 9a-d is less stable
than those in the corresponding diphenylacetylene. This
corroborates the statement about the influence of the nitrogen
atom and its lone pair of electrons on liquid crystal properties.
The loss of symmetry by the pyridyl ring weakens the
interactions between liquid crystal molecules.
In conclusion, we have synthesized new N-heterotolan
liquid crystals using two powerful methodologies. Using the
Buchwald protocol, we prepared a chiral intermediate 3 as
a promising candidate for a variety of 2,5-disubstituted
pyridine liquid crystals. And, through a double Sonogashira
reaction on 3, we have prepared a final series 9a-d
containing a nitrogen atom at position 2 on the aromatic ring.
The final compounds show an enantiotropic nematic phase,
as well as a smectic A phase.
Acknowledgment. The authors acknowledge PADCT-
CNPq, FAPERGS, and CAPES for financial support. E.D.
is an undergraduate student and thanks PIBIC-UFRGS for
her fellowship.
Supporting Information Available: Experimental details
of representative reactions, as well as spectral and analytical
data on isolated products, including 1H and 13C NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL047524E
1030
Org. Lett., Vol. 7, No. 6, 2005