Synthesis of new family of thiazoline and thiazole esters and investigation of their thermal properties

Article abstract of DOI:10.5935/0103-5053.20140132

A new family of thiazoline and thiazole esters has been synthesized and their thermal properties are presented and discussed. Thiazoline esters were obtained by cyclization reaction from 4-substituted benzenenitrile and amino acid L-cysteine followed by esterification reaction with selected alcohols and phenol. Subsequent oxidation step to transform thiazoline esters into thiazole esters was applied mediated by BrCCl3/DBU. The final thiazoline and thiazole esters are composed by terminal flexible hydrogenated alkyl chain from one side and to the other side by terminal segments of flexible alkyl chains (hydrogenated chain), (perfluoralkyl)alkyl chains (semifluorinated alkane) p-alkoxyphenyl chains. Some liquid crystals compounds for thiazoline and thiazole esters showed to be relevant. One of the thiazoline esters display a monotropic smectic A (SmA) mesophase while some thiazole esters show stable SmA mesophase. As expected semifluorinated alkane chain induce the formation of orthogonal mesophase by means of segregation effect.

Full text of DOI:10.5935/0103-5053.20140132

http://dx.doi.org/10.5935/0103-5053.20140132
J. Braz. Chem. Soc., Vol. 25, No. 8, 1493-1503, 2014.
Printed in Brazil - ©2014 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their
Thermal Properties
Juliana M. F. M. Schneider, Eric S. Sales, Paolo R. Livotto,
Paulo H. Schneider and Aloir A. Merlo*
Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS),
90040-060 Porto Alegre-RS, Brazil
Uma nova família de ésteres tiazolínicos e tiazóis foram sintetizados e as propriedades térmicas
são apresentadas e discutidas. Os ésteres tiazolínicos foram obtidos pela reação de ciclização
de benzonitrilas 4-substituídas com o amino ácido L-cisteína seguido da reação de esterificação
com álcoois e fenol previamente selecionados. A oxidação dos ésteres tiazolínicos mediado
pelo reagente BrCCl3/DBU permitiu a transformação dos respectivos ésteres tiazolínicos em
ésteres tiazóis . Os compostos finais dos ésteres tiazolínicos e tiazóis são formados por cadeias
alquílicas, (perfluoroalquil)alquílicas e p-alcoxifenilas. Alguns cristais líquidos mostraram serem
mais relevantes. Um deles apresentou mesofase esmética A (SmA) monotrópica enquanto que
outros apresentaram mesofase estável SmA. Como esperado, as cadeias de alcanos semifluorados
induziram a formação de mesofase ortogonal via efeito de segregação.
A new family of thiazoline and thiazole esters has been synthesized and their thermal
properties are presented and discussed. Thiazoline esters were obtained by cyclization reaction
from 4-substituted benzenenitrile and amino acid L-cysteine followed by esterification reaction
with selected alcohols and phenol. Subsequent oxidation step to transform thiazoline esters into
thiazole esters was applied mediated by BrCCl3/DBU. The final thiazoline and thiazole esters
are composed by terminal flexible hydrogenated alkyl chain from one side and to the other side
by terminal segments of flexible alkyl chains (hydrogenated chain), (perfluoralkyl)alkyl chains
(semifluorinated alkane) p-alkoxyphenyl chains. Some liquid crystals compounds for thiazoline
and thiazole esters showed to be relevant. One of the thiazoline esters display a monotropic
smectic A (SmA) mesophase while some thiazole esters show stable SmA mesophase. As
expected semifluorinated alkane chain induce the formation of orthogonal mesophase by means
of segregation effect.
Keywords: thiazoline and thiazole esters, liquid crystals, semifluorinated alkane and SmA
mesophase
Introduction
important and versatile interface. Since the discovery of
interesting electro-optical properties in the middle sixties
and the production of the first LCD panel in the beginning
of the seventies, many other practical applications of these
molecules have been largely studied.
As they show a variety of physical properties, these
molecules find application in diverse fields of science,
such as display technologies,2 light emitting diodes3 and
photo/semiconducting materials.4 Thus, great effort has
been made in developing synthetic strategies for acquisition
of new and diverse mesomorphic compounds.
Liquid crystals (LC) have been long recognized as one
of the most extensive and attracting fields of materials
research. The first studies, dating from 150 years ago,
prompted nowadays researches worldwide increasing
scientific interest, focusing on obtaining and monitoring
new LC compounds.1
The most common application of liquid crystal
technology is in liquid crystal displays (LCDs). From the
ubiquitous wrist watch and pocket calculator to an advanced
computer screen, this type of display has evolved into an
Heterocyclic compounds are of great importance in many
fields of chemistry. It is very common the observation of
interesting biological activity on compounds bearing these
*e-mail: aloir.merlo@ufrgs.br

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Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their Thermal Properties
J. Braz. Chem. Soc.
structures.5 Insertion of a heterocyclic unit in the skeleton
of a mesogenic molecule aggregates many advantages,
once one could enhance design possibilities and count up
several changes in liquid crystalline properties. Also it is
well-known that a minor change in molecular geometry
may bring about substantial variations on mesomorphic
behavior.6 Furthermore, the presence of heteroatom alters
considerably the polarity and polarisability of the molecule,
and the heterocycle core has the ability of impart lateral
and/or longitudinal dipoles.7 In particular 1,3 thiazoles
derivatives show bond angles of 153° and 133°, depending
on the substitution pattern, and a dipole moment of 1.6 D.8
In addition, the presence of the electron-rich sulfur atom
attains modifications on the ionization potential that could
induce smectic mesophases.9
Moreover, mesophase morphologies can be further
tuned by replacement of a flexible non branched alkyl
chain for a perfluorinated segment.10 The increased rigidity,
linearity and low surface energy of the perfluorinated
chain compared to the hydrocarbon one, settles particular
properties modifications, as the fluorophobic effect, which
reduces the miscibility of the fluorinated moieties with
other sides of the molecule.11 Thus, fluoro substituents
and perfluorochains have been incorporated to LC
compounds leading to a variety of modifications on these
substances behaviors, as broad mesomorphic ranges,
different mesophase morphologies, lower melting points
and transition temperatures as well as stabilization of
preexisting mesophases, due to the combination of small
size, intense polarity and high strength of the C-F bond.10
Such attributes can be successfully comprised in the
structure of mesogens and are of major significance in
terms of primary structure property relationships, any more
than crucial to the development of novel liquid crystal
materials.12 For the thiazole building block showed in
Figure 1, the general structure carries always on a flexible
alkyl chain from one side of the molecule and a carboxylic
group at the other side to be derivatized into aliphatic or
aromatic esters and amides. Among the wide range of
methodologies for preparation of thiazoline derivatives,13
the one based on cyclization of nitriles with the natural
amino acid L-cysteine was elected,14,15 once it employs
readily accessfull and low cost starting materials. Also,
this method delivery the target precursor bearing the
desirable carboxyl group mentioned above, which enables
the possibility to attach a variety of substituents by means
of esterification procedures employing different alcohols
phenols.
synthetic organic chemistry.As demonstrated in this work,
a sequential oxidation of the thiazoline to thiazole ring
leads to an enhancement of geometrical anisometry of the
rigid core contributing for emergence of mesomorphic and
photoluminescent properties. Thereby, we wish to report a
simple and straightforward methodology for the synthesis
of a new class of compounds derived from the thiazoline
precursor using the chain elongation strategy as well as
to investigate the liquid-crystalline behavior of the final
thiazole esters.
General structure of target thiazole esters is presented in
Figure 1. Primitive core is formed by aromatic and thiazole
ring connected by a single bond.Variable connection means
the chemical communication between additional group on the
right side and the primitive core intermediated by carboxyl
group presented in the target esters. Thiazolines 6a-k and
thiazoles 7a-k are composed of a flexible hydrogenated
alkyl chain on the left side of Figure 1, except for those from
4-bromophenyl nitrile. On the right side of Figure 1, terminal
segments connected by carboxyl group are composed of
flexible alkyl chains (hydrogenated chain), (perfluoralkyl)
alkyl chains (semifluorinated alkane)16 and p-alkoxyphenyl
chains. Figure 1 shows the general structure of the new
thiazole esters synthesized in this work.
Figure 1. General structure for the target thiazoles.
Results and Discussion
Synthesis
The synthesis of key intermediate thiazoline carboxylic
acids 4a-c is outlined in Scheme 1. The strategy applied
here begins with the commercially available nitriles 1a
and 1b, which were submitted to the alkylation reaction
with 1-bromoctane under basic conditions, affording the
alkylated nitriles 2a and 2b in almost quantitatively yields.
From this point, in Scheme 1, 4-bromobenzonitrile (2c)
was added to our plan of the synthesis of 4a-c. Next step
nitriles 2a-c were submitted to cyclization reaction with
amino acid L-cysteine (3) to generate the key intermediates
thiazoline derivatives 4a-c. In general, the most common
procedure for this reaction involves a system of water/
alcohol under buffer control by several days.17 In our hands
Thiazolines synthesis and their subsequent oxidation
to heteroaromatic thiazole rings are an interesting way to
prepare building block to be used in many branchs of the

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the experimental condition describe above to yield the
corresponding thiazoline carboxylic acids 4a-c gave very
low yields of the described thiazoline derivatives. In order
to achieve better results, we changed the initial protocol
reaction to one that has been used by Loughlin et al..18
Under the new experimental conditions, we prepared
the intermediate 4a-c in a good yield. Thus, exposing
nitriles 2a-c to L-cysteine mediate by sodium bicarbonate,
morpholine and reflux in an alcoholic solvent (ethanol or
isopropanol), the cyclizated products 4a-c were afforded
in excellent overall yields. This is an interesting and an
alternative way to prepare thiazolines in a simple and almost
inexpensive methodology.
After accomplished successfully the synthesis of
4a-c, the esters formation was initiated to complete our
synthetic plan. Esterification reactions with activation of
acids by carbodiimides are probably the most versatile
procedures for preparation of ester compounds.19 The
chemical linkage between 4a-c and 5a-d to obtain the
final thiazoline esters 6a-k was firstly attempted using the
dicyclohexylcarbodiimide/4-N,N-dimethylaminopyridine
(DCC/DMAP) protocol.20 However, due to the troublesome
to remove the by-product urea, we changed DCC to
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI)
to promote the ester ligation. Thus, thiazoline esters 6a-k
were synthesized as outlined in Scheme 2, by activation of
acids 4a-c with EDCI followed by the reaction with several
alcohols 5a-d in dichloromethane and DMAP as a catalyst.
Table 1 summarizes the results for the thiazoline esters
6a-k. It is noteworthy to mention that EDCI/DMAP couple
worked successfully for a variety of chosen alcohols, such
as alkyl and (perfluoralkyl)alkyl and phenols, delivering
the intermediates compounds 6a-k to be transformed into
LC in good yields by oxidation process.
The 2,5-disubstituted thiazole core in the final
compounds 7a-k was accomplished as described in
Scheme 3. Several methods were evaluated to perform
this transformation, such as reactions with 2,3-dichloro-
5,6-dicyanobenzoquinone (DDQ),21 NiO222 and MnO2.23
First attempts employing this later strategy resulted in poor
yields of target final products, as well as a complex mixture
of by-products detected by thin layer chromatography
(TLC) analysis of crude reaction extract. In order to
improve the obtention of these target mesogens, the
Scheme 1. Preparation of thazoline precursors 4a-c.
Scheme 2. Obtention of thiazoline esters 6a-k.

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Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their Thermal Properties
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Scheme 3. Oxidation of thiazoline esters 6a-k to the final mesogens 7a-k intermediate by BrCCl3/DBU.
oxidative dehydrogenation step was most conveniently
performed using a mixture of bromotrichloromethane and
1,8-diazabicyclo[5.4.0]undec-7-ene (BrCCl3/DBU).24 In
comparison to the ones mentioned above, this synthetic
protocol is advantageous for its milder conditions and
tolerating to a large variety of functional groups. Therefore,
the bromination takes place first in 6a-k and then, the
dehidrobromination in presence of DBU in dry DCM
furnished the final products 7a-k in good to excellent
yields (Table 2).25
the longest and more anisotropic 6k it was not able to show
some evidence of liquid-crystalline behavior.
A briefly comment is addressed to 6i, which displays a
monotropic SmA mesophase. The monotropic nature of the
mesophase to 6i means that mesophase appeared only upon
cooling, it is thermally unstable with an unpredictable and
short mesophase temperature range. The mesophase range
is too narrow with DT = 2 °C. Why 6i, among all compounds
listed in Table 1, displays a LC behavior? The answer of this
question may be associated to perfluoroalkyl chain effect,
close to the thiazoline ring. The molecular segregation is
the driving force for the formation of liquid-crystalline
phase of 6i. Incompatibility of totally flexible alkyl chain,
rigid anisometric core and less flexible semifluorinated
alkane chain are responsible for the formation of positional
ordered liquid-crystalline phases27 as observed for 6i and
the thiazole series in Table 2. We have to say more about
the mesomorphic properties (see thiazole discussion) but
the linearity deviation and non-coplanarity of the thiazoline
ring (broken anisometry) is the main force of the absence
of the mesophase in this series.28
Figure 2 displays a typical growth of SmA bâtonnets
(bright) from the isotropic phase (black) upon cooling
at 161 °C of thiazoline 6i. Bright and black colors in
Figure 2 are observed due to crossed polarizers, using
optical microscopy and the molecular orientation of the
samples sandwiched between the glass plates. Upon cooling
coalescing, bâtonnets will form full focal conic SmA fan
texture. Sometimes, black areas from isotropic state remain
black due to the perpendicular orientation of the molecules.
Black areas of the sample have a homeotropic alignment.
In this case, the long molecular axis is perpendicular to the
glass plates. When the growth of bâtonnets is completed,
the fan focal-conic is observed. The color is a consequence
of the orientation of the director which basically lies in the
plane of the substrate and the structured layers are curved
across the fans.29
Liquid crystal properties
Transition temperatures of thiazoline and thiazol esters
are tabulated in Table 1 and 2, respectively. Table 1 and 2
display the transition temperatures of eleven thiazoline and
thiazol esters synthesized in this work. The primitive core
(rigid core) contains at least a phenyl group connected to
heterocyclic moiety. Esters here are composed of flexible
alkyl chains (hydrogenated chain), (perfluoralkyl)alkyl
chains (semifluorinated alkane)16 and p-alkoxyphenyl
chains. Thiazolines esters are not LC as we can see in
Table 1, except for 6i, which displayed smecticA mesophase
(SmA) upon cooling. They are mostly crystalline solid with
melting point (mp) in the range between 40 °C to 140 °C,
and only 6a is liquid at room temperature. Melting point
was dependent on how flexible is the aliphatic chain ester.
For example, 6a is a liquid, while 6b and 6c are solids
with mp being bigger than 6c, which is, of course, more
anisotropic but not liquid crystal. This tendency in the mp
extends to the others thiazolines in Table 1. As it moves
from more flexible alkyl chain to (perfluoralkyl)alkyl chains
the stiffness becomes higher. Also, for 6c, 6g and 6k, the
phenyl group contributes to the stiffness of the compounds.
So in this sense, mp tends to be higher as the molecular rigid
core becomes more anisotropic.Additionally, 6d, 6e and 6f
are good examples to compare the stiffness effect caused
by fluorine atom at alkyl chain. The higher mp is seen in
the more rigid thiazoline 6e. Additional phenyl group has
a higher contribution to molecular stiffness as expected;
comparing 6d and 6g, 6d and 6h and 6g with 6k.26 This
is irrespective on the relative position of the phenyl group
into the rigid rod core. The behavior was observed even in
Table 2 displays the thermal data of thiazoles 7a-k that
were obtained by oxidation process from thiazolines 6a-k.
As expected, some thiazoles in Table 2 display liquid-
crystalline behavior as evidenced by the texture observed
using polarized optical microscopy (POM). The phase
transition temperatures (in °C) were obtained by POM and

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Table 1. Transition temperature (°C) for thiazoline esteres 6a-ka
entry
Chemical structure
Yield / %
71
Heating/cooling
Oil (liquid)
6a
Cr 56 I
I 30 Cr
6b
6c
70
62
Cr 107 I
I 91 Cr
6d
6e
6f
78
60
58
Cr 43 I b
Cr 97 I
I 87 Cr
Cr 62 I
I 43 Cr
Cr 104 I
I 86 Cr
6g
83
Cr 108 I
I 95 Cr
6h
6i
56
76
72
Cr 168 I
I 163 SmA 161 Cr
Cr 139 I
I 131 Cr
6j
Cr 153 I
I 145 Cr
6k
80
aData were acquired by POM analysis; bno recrystalization was observed; Cr = crystal phase; SmA = smectic A mesophase.
by differential scanning calorimetry (DSC) experiments.
To the first four thiazoles 7a-d, no liquid-crystalline
behavior was observed. Even for 7c, a more anisotropic
one, a transition crystal to isotropic state at 128 °C was
obtained. The relative compound 6c (Table 1), the melting
point is DT = 21 °C below 7c, showing that in the crystal
state, the packing of molecules of thiazoles is better than
thiazolines molecules.30 The increase in the melting point
is also observed in 7a-d in comparison to the 6a-d. The
tendency noted to these compounds is also seen in the others

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Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their Thermal Properties
J. Braz. Chem. Soc.
Table 2. Transition temperature (°C) for thiazoles ester 7a-ka
entry
Chemical structure
Yield / %
82
Heating/cooling
Cr 65 I / I 49 Cr
7a
7b
7c
66
51
Cr 109 I / I 81 Cr
Cr 128 I / I 114 Cr
Cr 62 I / I 46 Cr
7d
7e
7f
74
74
76
Cr 119 SmA 129 I
I 126 SmA 117 Cr
Cr 78 SmA 85 I
/ I 80 SmA 65 Cr
7g
50
Cr 108 I / I 95 Cr
Cr 119 I
I 115 SmX 109 Cr
7h
7i
70
73
75
Cr 175 SmA 205 I
I 197 SmA 163 Cr
Cr 142 Cr1 152 SmA 191 I
I 181 SmA 154 Cr1 128 Cr
7j
7k
58
Cr 143 I / I 135 Cr
aData were acquired by POM analysis; Cr = crystal phase; SmA = smecticA mesophase; SmX = mesophase with texture not related with the model pattern;
probably is a SmA mesophase.
compounds in Table 2. However, compounds 7e, 7f, 7h,
7i and 7J have also an additional mesophase intercalated
between the crystal and isotropic phase. The LC thiazoles
above display a structured orthogonally layer which was
characterized as smectic A mesophase according to the
texture analysis of POM. This smectic fluid A mesophase

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1499
be more elongated as possible to compensate bent-shape of
thiazole ring.8,31 The mesophase nature is also dependent on
the terminal group connected to the rigid and anisometric
core. In the current study, SmA mesophase was found
particularly due to the presence of two aliphatic chains
with distinct chemical nature. We can see from Table 2
the predominance of orthogonal SmA mesophase for all
LC compounds listed. The significance of semifluorinated
alkyl chain is clearly seen when we compare compounds
7a, 7d and 7h. They have flexible hydrogenated alkyl
chain in both sides of arylthiazol esters except for 7a. For
the longer aryl moiety 7h, which at first would favor the
appearance of stable mesophase, it is possible to observe
only a monotropic SmA mesophase. Usually, molecules
with longer molecular length, tend to be more elongated
and consequently more anisotropic due to length-to-breadth
ratio of two molecular axes. Also, it is well-known for
biphenyl and others systems that, the increase of carbon
atoms in the flexible alkyl chain favors the formation of
smectic mesophases, usually SmA and SmC.32 The result
founded in 7h definitively emphasizes the function of
perfluoroalkyl chain plays on the mesomorphic properties
in this study. For aryl esters 7c, 7g and 7k, and even for
7k, which has a more anisometric core, no mesophase was
observed. Again, the result observed to 7c, 7g and 7k is
suggesting the importance of perfluoroalkyl chain on the
mesomorphic behavior. Obviously it is possible to assume
that the absence of mesophase to these compounds in terms
of an equilibrium of Z- and E-rotamers, that are observed
in esters when they entry to the mesophase, similarly to the
behavior of liquid crystal dimers where the mesophases are
governed by the populations of linear and bent molecules.33
Attempt to correlate carbonyl group frequency (nC=O cm-1) in
the IR spectrum of 6c/7c, 6g/7g and 6k/7k in the solid state
(KBr pellets) with the composition of the rotamers E and Z
of esters has failed. The band of carbonyl group associated
to those compounds in solid state looks like strong and
Figure 2. Growth of SmA bâtonnets (bright) of fan focal-conic texture of
SmA mesophase upon cooling at 161 °C of thiazoline 6i.
is characterized by positional order of molecules’ centers
of mass in one dimension in addition to the long range
orientational order of the director phase n which is
associated parallel to the long molecular axis. Locally, the
SmA mesophase can be regarded as a two dimensional
liquids due to the molecules’ centers of mass are arranged
in layers and their projection onto the smectic layer plane
are isotropically distributed with no positional correlation
being observed within or across the layer planes.29
Figure 3 displays (left) the growth of SmA bâtonnets
(bright) of fan focal-conic texture of SmA mesophase upon
cooling at 176 °C of thiazole 7j; typical fan-shaped texture
of a SmA phase upon cooling at 187 °C of thiazole 7i
(right). Lighter and darker regions seen in Figure 3 (right),
in the fans, are due to the molecular layers of sample and
cross polarizers that are used in POM study.
As expected, LC properties of thiazoles are affected
mainly by the flatness and coplanarity of the heterocyclic
ring. Strong p-stacking in the lattice is observed in crystal
phase with 3.73 Å the distance between two adjacent
thiazole rings.30 Of course, to be a classical rod-shape
liquid crystal the molecular shape of the structures has to
Figure 3. Growth of SmA bâtonnets (bright) of fan focal-conic texture of SmA mesophase upon cooling at 176 °C of thiazole 7J (left); typical fan-shaped
texture of a SmA phase upon cooling at 187 °C of thiazole 7i (right).

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Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their Thermal Properties
J. Braz. Chem. Soc.
sharp. Thus, it is impossible to assume that the non liquid-
crystalline behavior of 7c, 7g, 7k is due to the composition
of the rotamers in the equilibrium between the more
anisotropic Z-rotamer and the less anisotropic E-rotamer.
Now we are turning our attention to the four LC: 7e, 7f,
7i and 7j. All LC compounds listed in Table 2 have one
semifluorinated alkyl chain connected to the carboxyl group
of thiazole ring and a flexible hydrogenated alkyl chain on
the opposite side. They are LC with SmA mesophase as
expected considering that the individual molecules possess
specific groups which repel or attract each other strongly.
This effect begins among a few molecules at molecular level
on cooling and very fast amplifies to large scale, where the
nanoscale segregation is the driven force. The aggregation
is promoting by these groups favoring the smectic ordering.
Terminal groups such as siloxanes, fluorinated, halogenated
and even diol favor the smectic ordering.34 The mesophase
range for 7i and 7j is bigger than 7e and 7f as a consequence
of the more anisometric biphenyl group in 7i and 7j. For
example, 7i displays a mesophase range of 30 °C, while
for 7e is 10 °C. Transition temperatures associated to the
Cr → SmA and SmA → I phase transition reveals the effect
of proximity of perfluoroalkyl chain to carboxyl group.
Transition temperatures depend on how close to the
carboxyl group is the perfluoralkyl chain. Comparing 7i with
7j and 7e with 7f it is possible to note that 7i and 7e display
higher transition temperature from crystal to mesophase and
mesophase to isotropic phase. Only 7j displays a second
transition Cr → CrX and it has the biggest mesophase range
(DT=39°C)forSmAmesophasetoisotropicstate.According
to Höpken et al.,35 the thermal behavior of (perfluoroalkyl)
alkane can be explained in terms of conformational aspect
of hydrogenated and perfluorated chains. Alkyl chain tends
to be more amorphous in the mesomorphic state while
perfluorinated alkyl chain tends to be more organized,
which of course affect the transition temperatures. In the
solid state both chains self-organize in crystalline way. Of
course, alkyl chain may assume predominantly an extend
all-trans conformation while perfluoralkyl chain tends to be
kink due to the gauche effect.36 When the solid enters to the
mesophase, the hydrocarbon portion must have liquid-like
conformational freedom, while perfluoralkyl chains behave
as a hard molecular segment owing its polar nature. Due to
stiffness, fluorinated segments are packed regularly in the
solid state, which favors the high melting point and even
the high clearing point. In another way, when the sample on
cooling enters into the mesophase state, the conformational
disordering of the hydrocarbon segments upon the transition
from isotropic state to the smectic mesophase is bigger than
the perfluoralkyl segments. The molecular aggregation is
faster to the perfluoralkyl chains favoring the attraction
between rigid segments. Soft segments in the mesophase are
still mobile and conformationally disordered. And finally,
when the sample starts to crystallize again, hard molecular
segments are packed more efficiently than the soft molecular.
It is important to mention that in the mesophase more
mobility is expected to more amorphous segments. Thus,
the contribution of one and two methylene carbon atoms
is causing the behavior observed to that thiazoles LC ester
7e, 7f, 7i and 7j.
Conclusion
We have synthesized a new family of thiazoline
and thiazole esters 6a-k and 7a-k. The final thiazoline
and thiazole esters are composed by terminal flexible
hydrogenated alkyl chain from one side and to the other side
by terminal segments of flexible alkyl chains (hydrogenated
chain), (perfluoralkyl)alkyl chains (semifluorinated alkane)
p-alkoxyphenyl chains. 6i was the only compound belonging
to the family of thiazoline esters to display monotropic SmA
mesophase. Thiazole esters family presented enantiotropic
SmA mesophase for 7e, 7f, 7h, 7i and 7j. The combination
of better conjugation of thiazole ring and polar effect of
semifluorinated alkane chain induces the formation of
structured layer mesophase by means of segregation effect.
Experimental
General methods
All starting materials were purchased from commercial
suppliers (SigmaAldrich Chemical Co.,Acros Organics and
ABCR Chemicals) and used without further purification.
All reactions were carried out under a nitrogen atmosphere
in oven-dried glassware with magnetic stirring. Solvents
were dried, purified and degassed under classical methods.
Solvents used in extraction and purification were distilled
prior to use. TLC was performed using silica gel 60 F254
aluminum sheets and the visualization of the spots has
been done under UV light (254 nm) or stained with iodine
vapor. Products were purified by flash chromatography on
silica gel 60 M, 230-400 mesh. Melting and mesophase
transition temperatures and textures of the samples points
were measured using an Olympus BX43 microscope
equipped with a Mettler Toledo FP82HT Hot Stage FP90.
1H (13C) NMR spectra were recorded at 300 (75) MHz on
a Varian Inova and 400 (100) MHz Bruker spectrometer
1
using CDCl3 as solvent. The H and 13C chemical shifts
were reported in parts per million (d) referenced to residual
solvent signals at dH/C 7.26/77.00 (CDCl3) relative to
tetramethylsilane (TMS) as internal standard. Coupling

Vol. 25, No. 8, 2014
Schneider et al.
1501
constants J [Hz] were directly taken from the spectra and
are not averaged. Splitting patterns are designated as s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet)
and br (broad). Low-resolution mass spectra were obtained
with a Shimadzu GC-MS-QP5050 mass spectrometer
interfaced with a Shimadzu GC-17A gas chromatograph
equipped with a DB-17 MS capillary column. HRMS
spectra were obtained from a Fourier transform ion
cyclotron resonance (FT-ICR) mass spectrometer equipped
with an Infinity™ cell, a 7.0 Tesla superconducting magnet,
an RF-only hexapole ion guide and an external electrospray
ion source (off axis spray) and with ESI(+)-MS and tandem
ESI(+)-MS/MS using a hybrid high-resolution and high
accuracy MicroTOF-Q II mass spectrometer (Bruker
Daltonics), or on a Micromass Q-TOFmicro instrument.
the organic layer was dried with Na2SO4. The solvent was
evaporated and the remaining product was purified by
chromatography (hexanes/AcOEt = 80:20).
Representative data for (R)-3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluorooctyl 4,5-dihydro-2-[4-(octyloxy)phenyl]
thiazole-4-carboxylate (6f)
o
1
Yield 58%; white solid; mp 62 C; H NMR
(CDCl3, 400 MHz) d 7.80 (d, 2H, J 8.8 Hz, Ar-H), 6.89
(d, 2H, J 8.9 Hz, Ar-H), 5.26 (t, 1H, J 8.9 Hz, NCH),
4.57-4.47 (m, 2H, SCH2), 3.98 (t, 2H, J 6.6 Hz, OCH2),
3.72-3.53 (m, 2H, OCH2), 2.68-2.45 (m, 2H, OCH2CF2),
1.85-1.71 (m, 2H, CH2), 1.55-1.16 (m, 10H, (CH2)5),
0.88 (t, 3H, J 6.8 Hz, CH3); 13C NMR (CDCl3, 100 MHz)
d 170.72, 170.59, 162.09, 130.35, 124.99, 120.00-107.00
(6C), 114.23, 77.93, 68.14, 57.36, 35.20, 31.84, 30.38 (t,
CF2, J 21.7 Hz), 29.51, 29.50, 29.32, 29.27, 29.07, 25.93,
22.62, 13.99.
General procedure for the synthesis of thiazolines 4a-c
A solution of L-cysteine hidrochloride (60 mmol;
10.8 g), NaHCO3 (60 mmol; 5.3g), the appropriate nitrile
(20 mmol) in 85 mL of ethanol was refluxed for 30 min.
After, the pH was adjusted to 8.0 by adding a few drops
of morpholine, and the reflux was continued for additional
12 h. The ethanol was removed, the residue dissolved
in distilled water and acidified to pH 1.5 by adding
concentrated HCl. The product was extracted with CH2Cl2
(3 × 50 mL), the organic layers where combined, dried
over MgSO4 and the solvent removed under vacuum. The
products were obtained with satisfactory purity and were
used in the next step without further purification.
General procedure for the synthesis of tiazoles 7a-k
The thiazoline ester (1 mmol) (6a-k) and dry CH2Cl2
(5 mL) were added to a round bottomed flask under
N2 atmosphere. The system was cooled to 0 °C, and
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (2 mmol) was
added and the reaction mixture was stirred for 20 min.
Bromotrichloromethane (BrCCl3) (2 mmol) was then
added and stirred for additional 16 h at room temperature.
The reaction was quenched with saturated NH4Cl and the
organic layer washed with water (2 × 10 mL), saturated
NaCl (2 × 10 mL) and dried over Na2SO4. The solvent was
finally evaporated and the remaining product was purified
by chromatography (CHCl3).
Representative data for (R)-2-[4-(octyloxy)phenyl]-4,5-
dihydrothiazole-4-carboxylic acid (4b)
1
Beige solid; mp 103.5 °C; yield: 88%; H NMR
Representative data for 3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluorooctyl 2-(4-bromophenyl)thiazole-4-carboxylate
(7b)
(DMSO-d6, 300 MHz) d 0.84 (t, 3H, J 6.4, CH3), 1.38-1.24
(m, 10H, (CH2)2), 1.72-1.65 (m, 2H, CH2), 3.63-3.60 (m,
2H, CH2S), 3.99 (t, 2H, J 6.5, OCH2), 5.23 (t, 1H, J 8.3,
CHN), 6.99 (d, 2H, J 8.9, Ar-H), 7.71 (d, 2H, J 8.9, Ar-H);
13C NMR (DMSO-d6, 75.5 MHz) d 171.96, 167.45, 161.38,
129.91, 124.82, 114.48, 78.25, 67.77, 34.94, 31.25, 28.74,
28.67, 28.57, 25.47, 22.09, 13.93.
Yield 66%; IR (KBr) n/cm-1 2919, 2850, 2364, 1745,
1509, 1454, 1344, 1245, 1211, 1072, 1014, 827, 634;
1H NMR (CDCl3, 300 MHz) d 8.11 (s, 1H, CHS), 7.81 (d,
2H, J 8.4 Hz, Ar-H), 7.52 (d, 2H, J 8.4 Hz, Ar-H), 4.62 (t,
2H, J 6.5 Hz, OCH2), 2.80-2.34 (m, CF2CH2, 2H); 13C NMR
(CDCl3, 75 MHz) d 167.86, 160.62, 147.14, 132.23, 131.48,
128.33, 128.04, 125.28, 122-106 (6C), 57.24, 30.55 (t,
J 21.7 Hz). HRMS (ESI) m/z, calcd for C18H10BrF13NO2S
[M+H+]: 629.9408; found: 629.9404.
General procedure for esterification of thiazolines 6a-k
To a stirred solution of the corresponding thiazoline
4a-c (2.0 mmol) in dry CH2Cl2 (8 mL) under N2 atmosphere
at room temperature, were added subsequently the
corresponding alcohol (2.0 mmol) EDCI (2.0 mmol) and
catalytic amount of DMAP. After 16 h, the organic phase
was transferred to an extraction funnel, washed with
saturated NaHCO3 (2 × 10 mL), water (2 × 10 mL) and
Supplementary Information
Supplementary data (experimental description,
1H NMR and 13C NMR spectrum) are available free of
charge at http://jbcs.sbq.org.br as PDF file.

1502
Synthesis of New Family of Thiazoline and Thiazole Esters and Investigation of their Thermal Properties
J. Braz. Chem. Soc.
Acknowledgments
15. Loughlin, W.A.; Knevitt, S.A.; Hosking, R. E.; Marshall, R. L.;
Aust. J. Chem. 2000, 53, 457.
The authors gratefully acknowledge the INCT-Catálise,
Edital 01/12-PPG-Química-UFRGS and Fapergs-Edital
PqG 2012. The authors are also grateful to Sidnei Moura
e Silva [Universidade de Caxias do Sul (UCS)] for the
HRMS analysis. Eric S. Sales thanks to PIBIC-UFRGS
for fellowship.
16. Höpken, J.; Möller, M.; Macromolecules 1992, 25, 2482.
17. Lu,Y.; Li, C.-M.; Wang, Z.; Ross, C. R.; Chen, J.; Dalton, J. T.;
Li, W.; Miller, D. D.; J. Med. Chem. 2009, 52, 1701; Bergeron,
R. J.; Wiegand, J.; Dionis, J. B.; Egii-Karmakka, M.; Frei,
J.; Huxley-Tencer, A.; Peter, H. H.; J. Med. Chem. 1999, 34,
2072.
18. Loughlin, W.A.; Knevitt, S.A.; Hosking, R. E.; Marshall, R. L.;
Aust. J. Chem. 2000, 53, 457.
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