Liquid crystalline 4,4'-diaryl-2,2'-bithiazoles

Article abstract of DOI:10.1080/15421406.2011.570142

Several new non-symmetrically substituted 4,4'-diphenyl-2,2'-bithiazole derivatives were synthesized with the use of a novel synthetic methodology comprising modified Hantzsch synthesis and palladium-catalyzed Kharash cross-coupling reaction at the key steps. Mesogenic properties of the new compounds were studied by optical and calorimetric methods. The most promising for practical applications are easily accessible non-symmetrical 4,4'-diaryl-2,2'-bithiazoles containing alkyl and alkoxy substituents at the para-positions of the aryl moieties that exhibit wide-range high-temperature smectic-C phases. Copyright Taylor & Francis Group, LLC.

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Liquid Crystalline 4,4′-diaryl-2,2′-
bithiazoles
V. V. Mikhailenko a , A. I. Krivoshey a , V. V. Vashchenko a , M. F.
Prodanov a & N. Yu. Gorobets a
a State Scientific Institution “Institute for Single Crystals,” National
Academy of Sciences of Ukraine, Kharkov, Ukraine
Version of record first published: 14 Jun 2011.
To cite this article: V. V. Mikhailenko , A. I. Krivoshey , V. V. Vashchenko , M. F. Prodanov & N. Yu.
Gorobets (2011): Liquid Crystalline 4,4′-diaryl-2,2′-bithiazoles, Molecular Crystals and Liquid Crystals,
542:1, 115/[637]-122/[644]
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Mol. Cryst. Liq. Cryst., Vol. 542: pp. 115=[637]–122=[644], 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421406.2011.570142
Liquid Crystalline 4,40-diaryl-2,20-bithiazolesy
V. V. MIKHAILENKO, A. I. KRIVOSHEY,
V. V. VASHCHENKO, M. F. PRODANOV, AND
N. YU. GOROBETS
State Scientific Institution ‘‘Institute for Single Crystals,’’ National
Academy of Sciences of Ukraine, Kharkov, Ukraine
Several new non-symmetrically substituted 4,40-diphenyl-2,20-bithiazole derivatives
were synthesized with the use of a novel synthetic methodology comprising modified
Hantzsch synthesis and palladium-catalyzed Kharash cross-coupling reaction at the
key steps. Mesogenic properties of the new compounds were studied by optical and
calorimetric methods. The most promising for practical applications are easily
accessible non-symmetrical 4,40-diaryl-2,20-bithiazoles containing alkyl and alkoxy
substituents at the para-positions of the aryl moieties that exhibit wide-range
high-temperature smectic-C phases.
Keywords Bithiazoles; Hantzsch synthesis; Kharash cross-coupling reaction;
smectic C phase
1. Introduction
Readily available by cost effective synthetic methods, 4,40-diaryl-2,20-bithiazoles 1
consisting of symmetrical molecules were shown to possess nematic and smectic A
thermotropic mesophases [1]. However, the relatively high phase transition tempera-
tures of these symmetric compounds 1 do not enable their practical use as smectic
hosts. Moreover, the synthetic approach applied restricts variability of the molecular
structure of such compounds and consequently decrease possibility to tune their
mesogenic properties.
Thus, the aim of this work is to improve the mesogenic properties of 4,40-diaryl-
2,20-bithiazoles 1 (i.e., to reduce their melting points and, preferably, to increase the
mesomorphic range) by varying the molecular structure of such compounds. For this
purpose, non-symmetrically substituted bithiazoles 2a—d and 3, and also symmetri-
cally substituted compound 4 were synthesized with the use of novel synthetic
yDedicated to the memory of Professor Lidiya Kutulya (1939–2010).
Address correspondence to A. I. Krivoshey, State Scientific Institution ‘‘Institute for
Single Crystals’’, National Academy of Sciences of Ukraine, Lenin ave. 60, 61001 Kharkov,
Ukraine. Tel.: þ38-057-341-01-28; Fax: þ38-057-340-93-43; E-mail: krivoshey@isc.kharkov.
com
115=[637]

116=[638]
V. V. Mikhailenko et al.
methods, and their mesogenic properties were investigated.
Variations of the molecular structure of compounds 2—4 (with the reference to
the known symmetrical compound 1b) consist in the introduction of terminal alkyl
and=or alkoxy substituents of different length, lateral fluorination and changing the
molecular shape of these compounds by terminal metha-substitution.
2. Experimental Methods
1H NMR spectra were recorded on a Varian Mercury VX-200 (200 MHz) and a
Bruker Avance-400 (400 MHz) spectrometers in CDCl3 or C6D6=CCl4 using signal
of residual protons as inner standard [2]. Mass spectra were recorded on a Varian
1200 L GC-MS instrument either in GC-MS mode or with the use of direct exposure
probe (DEP) method with EI at 70 eV. HPLC analyses were performed on a Bischoff
HPLC system equipped with 4.0 ꢀ 250 mm Prontosil 120-5-C18H reversed phase col-
umn using acetonitrile and mixtures of acetonirtile with chloroform as eluents; for
preparative HPLC the 20 ꢀ 200 mm Prontosil 120-10-C18H reversed phase column
was used.
Optical textures and phase transition temperatures were studied using a Kofler
hot stage and LOMO polarizing microscope. DSC measurements were done by
means of Mettler TA-3000 thermoanalitical instrument at 5ꢁC=min heating=cooling
rate.
Bromine, rubeanic acid, bromopentane, bromooctane, magnesium turnings and
PdCl2dppf (complex with DCM) are commercially available and were used without
additional purification. All used solvents were distilled immediately before use. THF
was distilled over potassium-benzophenone prior to use.
Synthesis of Thioamides 7 and 8 (General Procedure). A solution of the
corresponding a-bromo acetophenone 5 or 6 (30 g, 0.1 mol) in DMF (80 mL) was
added dropwise for 3 h to a stirred solution of rubeanic acid (26 g, 0.2 mol, 2
equiv) in DMF (180 mL). The mixture was stirred for three days. Then the
precipitate of symmetrically substituted bithiazole by-product (9 or 10
correspondingly) was filtered off and the solution obtained was treated with

Liquid Crystalline 4,40-diaryl-2,20-bithiazoles
117=[639]
stirring with the solution of KOH (9 g) in water (40 mL). The precipitate formed was
filtered, washed with diluted aqueous KOH (3 ꢀ 50 mL) and water and dried in air at
ambient temperature. Then the precipitate was re-crystallized from isopropyl
alcohol-acetone mixture (3:2 vol.) and filtered while hot. The crystals formed at
cooling of the filtrate were collected and dried. Yields: 42% (7), 63% (8).
Synthesis of Bithiazoles 12a—d and 13b (General Procedure). The corresponding
acyl bromide 11a—d (6 mmol) and thioamide 7 or 8 (6 mmol) were mixed together
in DMF (20 mL) and the mixture was stirred overnight. The precipitate formed
was filtered off, washed with butanol (2 ꢀ 20 mL) and recrystallized from the
mixture of acetonitrile and chloroform (3:1 vol.). Yields: 44% (12a), 50% (12b),
64% (12c), 67% (12d), 54% (13b).
Synthesis of the Target Compounds 2 and 3 (General Procedure). The corresponding
alkylmagnesium bromide (obtained from corresponding alkyl bromide, magnesium
turnings (1.2 equiv) in THF (1 mL per 1 mmol of alkyl bromide) by well-known
Grignard methodology) was added dropwise under atmosphere of dry argon to
the stirred mixture of the corresponding aryl bromide (0.5 equiv based on alkyl
bromide), PdCl2dppf (0.05 equiv based on aryl bromide) in THF (1 mL per
1 mmol of aryl bromide) (CAUTION! The reaction mixture undergoes
spontaneous heating) and then was left overnight with stirring. Methanol was
added to the mixture dropwise (2 mL per 1 mmol of alkyl bromide) and the
suspension obtained was evaporated to dryness. The residue was diluted with
dichloromethane and filtered through the short pad of Celite, and the filtrate was
evaporated to dryness. The residue was transferred onto silica and extracted with
hot heptane=benzene (3:1 vol.) in the modified Soxhlet apparatus, and then
further purified by appropriate methods (see below).
4-(4-Nonylphenyl)-2-(4-(4-pentylphenyl)thiazol-2-yl)thiazole
2a. Re-crystallized
from isopropyl alcohol. Yield 55%. Purity 98.8% (HPLC). 1H NMR (CDCl3,
400 MHz, d, ppm, J=Hz): 7.89 (4H, d, J ¼ 8.0), 7.53 (2H, s), 7.27 (4H, d, J ¼ 8.2),
2.66 (4H, t, J ¼ 7.6), 1.66 (4H, m), 1,35 (8H, m), 1,28 (8H, m), 0.91 (3H, t,
J ¼ 6.8), 0.89 (3H, t, J ¼ 7.1). MS (m=z, (I, %)): 516 (Mþ, 100), 459 (21), 403 (48),
347 (22), 147 (45).
2-(4-(4-(Hexyloxy)phenyl)thiazol-2-yl)-4-(4-octylphenyl)thiazole 2b. Re-
crystallized from acetonitrile=acetone=CHCl3 (3:1:1 vol.). Yield 78%. Purity 98.4%
1
(HPLC). H NMR (C6D6=CCl4 (1:3 vol.), 200 MHz, d, ppm, J=Hz): 7,77 (2H, d),
7.76 (2H, d), 7.06 (2H, d, J ¼ 8.3), 6.91 (1H, s), 6.83 (1H, s), 6.78 (2H, d, J ¼ 8.8),
3.66 (2H, t, J ¼ 6.4), 2.47 (2H, t, J ¼ 7.6), 1.54 (4H, m), 1.19 (16H, m), 0.82 (3H, t),
0.81 (3H, t). MS (m=z, (I, %)): 532 (Mþ, 100), 447 (38), 349 (77), 335 (60), 147 (15).
2-(4-(3-Fluoro-4-(hexyloxy)phenyl)thiazol-2-yl)-4-(4-octylphenyl)thiazole 2c. Re-
crystallized from acetonitrile=acetone (3:1 vol.). Yield 72%. Purity 95.0% (HPLC).
Analyticaly pure sample (purity 99.2% (HPLC)) was obtained by preparative
1
HPLC. H NMR (CDCl3, 400 MHz, d, ppm, J=Hz): 7.88 (2H, d, J ¼ 7.5), 7.72
(1H, d, J ¼ 12.2), 7.67 (1H, d, J ¼ 8.0), 7.53 (1H, s), 7.46 (1H, s), 7.27 (2H, d,
J ¼ 7.6), 7.02 (1H, t (dd), J ¼ 8.5), 4.08 (2H, t, J ¼ 6.5), 2.65 (2H, t, J ¼ 7.6), 1.85
(2H, m), 1.65 (2H, m), 1.50 (2H, m), 1.31 (14H, m), 0.92 (3H, t), 0.89 (3H, t). MS
(m=z, (I, %)): 550 (Mþ, 100), 465 (66), 366 (32), 147 (15).

118=[640]
V. V. Mikhailenko et al.
2-(4-(2,3-Difluoro-4-(hexyloxy)phenyl)thiazol-2-yl)-4-(4-octylphenyl)thiazole 2d.
Re-crystallized from acetonitrile=acetone (3:1 vol.). Yield 60%. Purity 93.0%
(HPLC). Analytically pure sample (purity 95.8% (HPLC)) was obtained by
preparative HPLC. 1H NMR (CDCl3, 400 MHz, d, ppm, J=Hz): 7.97 (1H, dd,
J ¼ 8.5), 7.88 (2H, d, J ¼ 12.2), 7.75 (1H, s), 7.53 (1H, s), 7.27 (2H, d. J ¼ 7.6),
6.84 (1H, t (dd), J ¼ 7.8), 4.09 (2H, t, J ¼ 6.5), 2.66 (2H, t, J ¼ 7.5), 1,85 (2H, m),
1.65 (2H, m), 1.50 (2H, m) 1.32 (14H, m), 0.93 (3H, t), 0.90 (3H, t). MS (m=z, I,
%): 568 (Mþ, 100), 483 (95), 384 (15), 147 (25).
2-(4-(4-(Hexyloxy)phenyl)thiazol-2-yl)-4-(3-octylphenyl)thiazole 3. Re-crystallized
from isopropyl alcohol=CHCl3 (3:1 vol.). Analyticaly pure sample (purity 96.1%
(HPLC)) was obtained by preparative HPLC. Yield 24%. 1H NMR (C6D6=
CCl4 (1:3 vol.), 200 MHz, d, ppm, J=Hz): 7.72 (2H, d, J ¼ 8.7), 7.67 (1H, s), 7.61
(1H, d, J ¼ 7.8), 7.14 (1H, t), 7.06 (1H, s), 6.96 (1H, d), 6.94 (1H, s), 6.75 (2H, d,
J ¼ 8.7), 3.71 (2H, t, J ¼ 6.4), 2.51 (2H, t, J ¼ 7.6), 1.56 (4H, m), 1.18 (16H, m),
0.81 (3H, t), 0.79 (3H, t). MS (m=z, (I, %)): 532 (Mþ, 100), 350 (42).
Synthesis of Symmetrically Substituted Bithiazoles 1b and
4
(General
Procedure). The corresponding a-bromoacetophenone 11b or 14 (15 mmol),
rubeanic acid (0.09 g, 7.5 mmol) and DMF (5 mL) were mixed together and the
mixture was stirred overnight. The precipitate formed was filtered and
recrystallized from isopropyl alcohol.
4-(4-(Hexyloxy)phenyl)-2-(4-(4-(hexyloxy)phenyl)thiazol-2-yl)thiazole 1b. Yield
1
68%. Purity 99.4% (HPLC). H NMR (C6D6=CCl4 (1:3 vol.), 200 MHz, d, ppm,
J=Hz): 7.75 (4H, d, J ¼ 8.2), 6.88 (2H, s), 6.76 (4H, d, J ¼ 8.0), 3.68 (4H, t,
J ¼ 6.0), 1.59 (4H, quintet), 1.21 (12H, m), 0.81 (6H, t). MS (m=z, (I, %)): 520
(Mþ, 100), 435 (15), 350 (65).
4-(3-Octylphenyl)-2-(4-(3-octylphenyl)thiazol-2-yl)thiazole 4. Yield 33%. Purity
1
99.7% (HPLC). H NMR (CDCl3, 400 MHz, d, ppm, J=Hz): 7,80 (2H, s), 7.79 (2H,
d), 7.58 (2H, s), 7.37 (2H, t, J ¼ 8.1), 7.20 (2H, d, J ¼ 7.3), 2.70 (4H, t, J ¼ 7,4), 1.69
(4H, quintet), 1.33 (20H, m), 0.89 (6H, t). MS (m=z, (I, %)): 544 (Mþ, 100), 445 (18).
3. Results and Discussion
3.1. Synthesis
A novel synthetic procedure comprising modified Hantzsch methodology and
palladium-catalyzed Kharash cross-coupling reaction at the key steps was used for
the synthesis of non-symmetrically substituted bithiazoles 2a—d and 3 (Scheme 1).
Our modification of Hantzsch synthesis (with respect to the known method
[1,3,4]) consists of using DMF as solvent. This allows carrying out the reaction at
room temperature which is found to be favorable for the enhancement of the reac-
tion selectivity. Thus, the intermediate bromophenyl thioamides 7 and 8 are obtained
under these conditions in moderate to good yields from the reaction of a-bromo acet-
openones 5 and 6 correspondingly with a double excess of rubeanic acid. Moreover,
low solubility of the symmetrically substituted bithiazole by-products 9 and 10 in
DMF at room temperature allows them to be easily removed by simple filtration
of the reaction mixture. Using similar modified protocol for the next step, bithiazoles
12a—d and 13b are synthesized in moderate to good yields. And again, the low

Liquid Crystalline 4,40-diaryl-2,20-bithiazoles
119=[641]
Scheme 1. Synthesis of non-symmetrically substituted bithiazoles 2a—d and 3.
Scheme 2. Synthesis of symmetrically substituted bithiazoles 1b and 4.
Table 1. Phase transition temperatures of bithiazoles 1b, 2—4a
Entry Compound Cr
SmC
SmA
N
I
1b
2
.
.
107
181 (þ97.9)
.
.
180
206
.
.
197
.
.
1b
2a
2b
2c
2d
.
197
230 (þ4.6)
230 (ꢂ.4.3)
190 (þ16.5)
189 (ꢂ16.8)
200 (þ12.6)c
198 (ꢂ12.3)c
189 (þ17.7)
187 (ꢂ17.8)
167 (þ13.5)
166 (ꢂ15.0)
3
4
5
6
.
.
.
.
117 (þ37.7)
115 (ꢂ34.7)
131 (þ39.9)
121 (ꢂ36.2)
132 (þ64.9)
120 (ꢂ57.9)
129 (þ62.9)
122 (ꢂ60.3)
112 (þ91.0)
101 (þ100.4)
.
.
.
.
.
.
.
.
.
.
165
147
198
196
.
7
8
3
4
.
.
.
.
a
ꢁ
Phase transition temperatures (enthalpies) are given in C (J=g) according to DSC (in the
corresponding cells, top data set corresponds to heating, lower data set corresponds to cool-
ing) or according to microscopic investigation at cooling (values shown in italics).
bData from [1].
cSum of coalescent peaks of SmA $ N and N $ I phase transitions.

120=[642]
V. V. Mikhailenko et al.
solubility of compounds 12a—d and 13b in DMF favors their simple isolation and
purification. The target non-symmetrically substituted bithiazoles 2a—d and 3 were
obtained by Kharash cross-coupling reaction [5] of aryl bromides 12a—d and 13b
with corresponding alkyl Grignard reagents in the presence of catalytic amount of
PdCl2dppf.
The symmetrically substituted bithiazoles 1b and 4 were also synthesized by
modified Hantzsch procedure from the corresponding a-bromo acetopenones 11b
and 14 and 0.5 equiv of rubeanic acid in moderate to good yields (Scheme 2).
3.2. Mesomorphic Properties
Characteristic optical textures and phase transitions of mesophases formed by the
new compounds 2—4 were studied by polarizing microscopy. Temperatures and
enthalpies of the first order phase transitions were measured using DSC technique.
The determined phase transition temperatures for the new compounds 2—4 and
the previously described compound 1b are given in Table 1. Typical optical textures
are shown in Figure 1.
Figure 1. Typical optical textures of bithiazoles 1b, 2—4; (a) compound 1b, glass plates,
216ꢁC, nematic phase; (b) compound 2a, glass plates, 143ꢁC, SmA phase; (c) compound 2b,
glass plates, 158ꢁC, SmC phase at different boundary conditions; (d) compound 2c,
free-suspended film, 147ꢁC, SmC phase. (Figure appears in color online.)

Liquid Crystalline 4,40-diaryl-2,20-bithiazoles
121=[643]
Surprisingly, in our hands, known compound 1b which was synthesized and
investigated in our laboratory (Table 1, entry 2) exhibits mesomorphic behavior
rather different from the one described in the literature [1] (entry 1). The differences
are revealed both in the aspect of phase sequence and in the phase transition tem-
peratures of the compound 1b.
When two terminal alkyl substituents of different length are introduced into
the 4,40-diaryl-2,20-bithiazole core (compound 2a, Table 1, entry 3), a substantial
reduction of the melting temperature and some increase of the mesomorphic range
as well as suppression of SmC and N phases formation occur in comparison to
the reference compound 1b. In comparison with 2a, the substitution of the terminal
alkyl substituent with an alkoxy group (compound 2b, entry 4) leads to some
increase of the melting temperature and narrowing of the mesomorphic range, how-
ever the SmC phase again occurs. The substitution of the lateral hydrogen atom
with fluorine (2c, entry 5) does not lead to the essential reduction of the melting tem-
perature but substantially decreases mesomorphic range as well as ability of this
compound to form the SmC and completely suppresses the N phase formation.
The introduction of the second fluorine atom (2d, entry 6) furthermore decreases
the mesomorphic range and completely suppresses the ability to form SmC and N
phases. The change of the shape of 4,40-diaryl-2,20-bithiazole molecules by metha-
substitution in the aryl moieties (compounds 3 and 4, entries 7 and 8 respectively)
leads to the complete suppression of mesomorphic properties.
It is worth mentioning that despite of rather high clearing temperature observed
for compounds 2a—d, they do not show any changes in the phase transition tem-
peratures even after several heating-cooling cycles. As an exeption, the most
high-thermal range compound 1b exhibits some decrease in isotropic transition
temperature after several heating-cooling cycles, however only slight changes in its
composition are detectable by HPLC analyses.
4. Conclusions and Perspectives
Non-symmetrical substitution of 4,40-diaryl-2,20-bithiazole molecules with terminal
alkyl and=or alkoxy groups of different length in comparison to symmetrical substi-
tution lead to the substantial reduction of the melting temperature and some increase
of the mesomorphic range. At least one alkoxy substituent in 4,40-diaryl-
2,20-bithiazole molecules is required for the formation of SmC phase. Lateral fluor-
ination of 4,40-diaryl-2,20-bithiazole molecules does not lead to essential reduction of
the melting temperature but substantially decreases the mesomorphic range and abil-
ity to form SmC phase. Change in the molecular shape of 4,40-diaryl-2,20-bithiazole
molecules by metha-substitution at the aryl moieties leads to suppression of the
mesomorphic properties.
The most promising for practical applications are easy accessible non-
symmetrical 4,40-diaryl-2,20-bithiazoles comprising alkyl and alkoxy substituents in
para-positions of the aryl moieties.
Acknowledgment
Authors gratefully acknowledge Dr. V. Musatov and Dr. A. Uglov for providing
NMR measurements, Dr. E. Vashchenko for mass-spectra recording, Dr. O.
Vashchenko for providing DSC measurements, and Dr. M. Pivnenko for helpful

122=[644]
V. V. Mikhailenko et al.
discussion. Financial support from STCU-NASU (Grant No. 5205) is also gratefully
acknowledged.
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[3] Singh, S. P., Naithani, R., Aggarwal, R., & Prakash, O. (2001). Syn. Comm., 31, 3747.
[4] Arcadi, A., Attanasi, O. A., Filippone, P., Perrulli, F. R., Rossi, E., & Santeusanio, S.
(2004). Synlett, 2681.
[5] Stanforth, S. P. (1998). Tetrahedron, 54, 263.