Synthesis and mesomorphic behaviour of new mesogenic compounds possessing a cholesteryl ester moiety connected to a pyrimidine core

Article abstract of DOI:10.1016/j.tetlet.2009.02.065

New mesogenic compounds containing a cholesteryl ester and a pyrimidine moiety connected through a polymethylene spacer have been prepared. The mode of linkage has been made via -C{double bond, long}C- and -C{double bond, long}N- to understand the structu

Full text of DOI:10.1016/j.tetlet.2009.02.065

Tetrahedron Letters 50 (2009) 1992–1995
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and mesomorphic behaviour of new mesogenic compounds
possessing a cholesteryl ester moiety connected to a pyrimidine core
a
b
a
K. C. Majumdar a, , Shovan Mondal , Nilasish Pal , Randhir Kumar Sinha
*
a Department of Chemistry, University of Kalyani, Kalyani, West Bengal 741 235, India
b Sripat Singh College, Jiaganj, Murshidabad, West Bengal, India
a r t i c l e i n f o
a b s t r a c t
Article history:
New mesogenic compounds containing a cholesteryl ester and a pyrimidine moiety connected through a
polymethylene spacer have been prepared. The mode of linkage has been made via –C@C– and –C@N– to
understand the structure-property relationship. Only two compounds with a pentamethylene spacer
show mesomorphic behaviour. The mesomorphic behaviour has been investigated by polarizing optical
microscopy, differential scanning calorimetry and HRXRD studies. Enantiotropic smectic A, twist grain
boundary (TGB) and chiral nematic mesophases are exhibited by the newly synthesized compounds.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 20 November 2008
Revised 6 February 2009
Accepted 11 February 2009
Available online 14 February 2009
Keywords:
Mesogen
Schiff’s base
Pyrimidine
Cholesterol
Chiral liquid crystals (LCs) have occupied one of the fascinating
fields of research over the last few decades.1 Chiral LC phases are
formed either by self-assembly or when a chiral material is doped
with a host showing a non-chiral LC phase. They are intrinsically
characterized by an array of unique properties and structure which
are promising from both advanced technology and fundamental
points of view.2 Chiral moieties have a tendency to stabilize frus-
trated fluid phases such as blue phases (BPs) and twist grain
boundary (TGB) phases.3 They also generate chiral nematic (N*),
chiral smectic C (SmC*) and chiral smectic A (SmA*) phases which
have been used in thermochromic, electro-optic devices and in
light modulation applications.4 Due to the commercial availability
of cholesterol as an inexpensive natural product, its rigid structure
with eight chiral centres and the ease with which the structure can
be derivatized, it has been incorporated extensively in chiral liquid
crystalline material. The ability of cholesterol in inducing a liquid
crystalline property in its various derivatives motivated many
researchers to synthesize thousands of monomers, oligomers and
polymers derived from cholesterol.5 Among them, dimeric com-
pounds consisting of either two identical (symmetric) or two
non-identical (non-symmetric) mesogenic units interlinked
through a central spacer are a relatively new class of liquid crystal-
line compounds, which encouraged not only experimentalists but
also theoreticians to study the structure-liquid crystalline property
relationship.6 These dimers offer a unique and practical means of
accomplishing a multifunctional system through an appropriate
selection of mesogens.7 In general, cholesterol dimers contain a
cholesterol moiety and another mesogen, such as a Schiff’s base,8
and an azobenzene,9 stilbene10 or tolane unit.11 Those containing
the Schiff’s base mesogen exhibit a very wide variety of mesopha-
ses. Since these dimers exhibit novel liquid crystalline phases as
well as interesting thermal phase behaviour, they serve as useful
models for semiflexible, main chain liquid crystalline polymers.
Uracil and barbituric acid are found in various natural products
and have numerous applications in organic synthesis.12 Itahara
et al. reported13 on the liquid crystalline materials formed by con-
necting adenine or thymine (1) to cholesteryl benzoate or related
steroid groups through a polymethylene spacer.
The nature of phase variation in different substituted or unsub-
stituted dimers is strongly influenced by the functional group pres-
ent in the aromatic moiety, the nature of substituents in the end
alkyl chain and by the length of the end alkyl chain. Uracil and bar-
bituric acid do not possess any end alkyl group, but possess a
strong dipolar effect. In continuation of our ongoing research on
the synthesis of heterocycles containing liquid crystalline materi-
als,14 and for understanding the structure-liquid crystalline prop-
erty relationship, we have undertaken a study on the synthesis
and characterization of new mesogenic compounds containing
uracil and barbituric acid moieties connected to a cholesteryl ester
moiety either through a pentamethylene spacer or through a
decamethylene spacer.
The methodology for the synthesis of dimeric materials 7a–d and
8a,b is depicted in Scheme 1. The reaction between cholesterol and
n-bromohexanoyl chloride in THF at room temperature gave the
corresponding ester derivatives 3a,b. The p-hydroxybenzaldehydes
* Corresponding author. Tel.: +91 33 2582 7521; fax: +91 33 2582 8282.
E-mail address: kcm_ku@yahoo.co.in (K.C. Majumdar).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.065

K. C. Majumdar et al. / Tetrahedron Letters 50 (2009) 1992–1995
1993
O
N
Me
HN
O
O
(CH2)n
O
O
1
O
(i)
Br
O
+
(CH2)n
Cl
HO
O
(H2C)n
Br
3 (a,b)
a, n = 5
b, n = 10
2 (a,b)
a, n = 5
b, n = 10
(ii)
O
4 (a,b)
a, n = 5
b, n = 10
O
(H2C)n
O
OHC
R
O
N
O
5a,b
a, R = Me
b, R = Et
O
(iii)
N
H3C
NH2
R
N
(iv)
R
O
N
O
O
O
O
N
O
N
CH3
6
O
(H2C)n
N
R
7 (a,b)
a, R = Me, n = 5
b, R = Me, n = 10
c, R = Et, n = 5
d, R = Et, n = 10
O
O
H3C
O
O
(H2C)n
N
O
N
O
8 (a,b)
a, n = 5
b, n = 10
CH3
Scheme 1. Reagents and conditions: (i) THF, pyridine, rt, 12 h (ii) p-hydroxybenzaldehyde, K2CO3, acetone, reflux, 12 h (iii) AcOH, EtOH, reflux, 1–12 h (iv) EtOH, reflux, 1–
12 h.
were then subjected to alkylation with cholesteryl ester derivatives
in refluxing dry acetone in the presence of anhydrous K2CO3 to
afford the corresponding aldehyde derivatives 4a,b.15 The
aldehydes 4a,b on condensation with different amino uracils and
a heating rate of 5 °C minꢀ1. The transition temperatures and asso-
ciated enthalpies obtained are shown in Table 1. Textural analysis
was done with the help of a polarizing optical microscope (POM).
Compound 7a shows the enantiotropic phase sequence of
crystal ? smectic A1 ? TGB ? cholesteric ? isotropic, while the
compounds of the same series 7b, c and d containing a decameth-
ylene spacer do not show any mesomorphic behaviour when
barbituric acid afforded the compounds 7a–d16 and 8a,b17
.
The phase transitions of the new mesogenic compounds 7a and
8a were measured using differential scanning calorimetry (DSC) at
Table 1
Phase transition temperatures and enthalpies of the new mesogenic compounds
Compound
Heating
H/kJ molꢀ1
Cr 151.6(32.6) SmA1 154.3(4.4) Ch 158.3(2.9) I
Cr 84.2(0.1) SmAd 133.3(11.7) TGB 135.4(0.9) Ch 140.5(0.3) I
Cooling
Phase transition temperature/°C (
7a
8a
D
)
I 157.4(3.2) Ch 151.9(0.8) SmA1 141.1(37.3) Cr
I 138.8(0.4) Ch 132.9(0.9) SmAd 119.6(0.3) Cr
Ch = cholesteric and I = isotropic.

1994
K. C. Majumdar et al. / Tetrahedron Letters 50 (2009) 1992–1995
placed in a thin cell with a cell gap of d = 5 0.2
l
m with homoge-
molecular length L. For 8a, the d value 37.41 Å is greater than L,
but is less than 2L (d/L ꢁ 1.34). It is well known that when the
reflection within the SmA layer corresponds to d ꢁ L, the smectic
A layer is called the monolayer (A1), and when the layer-spacing
is intermediate between L and 2L then it is called a partial bilayer
(Ad) phase.19,20 Therefore, we can designate the SmA phase of
compound 7a as SmA1 (A1) and that of compound 8a as SmAd
(Ad).
neous planar boundary conditions. Compound 8a also exhibits the
same phase sequence as 7a, while 8b is a non-mesomorphic com-
pound. The difference in the Smectic A phase of 7a and 8a is that
the former shows a monolayer smectic A1 (SmA1), while the latter
exhibits a partial bilayer smectic Ad (SmAd) which is described la-
ter. On cooling the isotropic phase of compound 7a, an oily streak
texture appeared which changed instantly to a fan-like texture, a
characteristic texture of the N* phase (Fig. 1, a and b). On further
cooling the sample, hometropic texture of the SmA phase
(Fig. 1c) appeared. However, if the transition is maintained over
a length of time, either on slow cooling or on repeated heating
and cooling cycles, a filament texture appears, very similar to the
so-called fingerprint texture of the characteristic TGB phase. Com-
pound 8a also shows similar phase transitions. The difference in
the textural appearance of SmA of 8a is that it is not fan-shaped,
but is like a stripe of bâttons arranged in layers (Fig. 1, a–c). The
replacement of the N-methyl group with an N-ethyl group resulted
in non-mesophase behaviour. On the other hand, when the central
spacer is changed from n = 5 to n = 10, surprisingly, no mesomor-
phic behaviour is observed.
Itahara et. al.13 explained the thermotropic behaviour of their
mesogenic compounds containing adenine and thymine by consid-
ering Watson–Crick base pairing (H-bonding). However, in the
present instance, the compounds cannot form Watson–Crick base
pairing or similar hydrogen bonds. The liquid crystalline behaviour
in this case is a consequence of the supramolecular interaction of
the dipoles inherent in the molecular structure. The direction of
the dipoles of 7a and 8a was calculated by Density Functional The-
ory (DFT), which may determine the presence of dipolar interac-
tion within the molecules. All calculations have been performed
by the Chem3D (version 10) with GAUSSIAN 03 Interface.21 We have
computed the DFT (B3LYP) level of theory using the basis set 6-
31G to obtain the dipole moment and dipolar orientation of 7a
and 8a molecules. The dipole moments of 7a and 8a have been cal-
culated as 6.62 D and 7.82 D, respectively. The direction of the di-
pole moment of 7a is supposed to be axial, having a value of
3.7109, ꢀ5.465 and ꢀ0.3931 in the X, Y and Z directions, respec-
tively. The maxima of the dipole must be in between the negative
direction of Y and X. The net dipole of the 8a molecule is supposed
to be along the X direction (X, Y, Z: ꢀ7.4585, ꢀ2.2411, ꢀ0.7065).
However, if the molecules have a strong longitudinal dipole mo-
ment, near-neighbour antiparallel correlations will exist which
can result in subtle changes in the structure that can exhibit more
than one form of the SmA phase. Usually, the dipoles of the mono-
layer A1 phase can point up or down with equal probability within
each layer.22 The appearance of the SmAd phase of compound 8a at
sufficiently high temperature (125 °C) may be due to the overlap of
two neighbouring rod-shaped molecules in antiparallel orientation
The powder X-ray diffraction pattern of 7a and 8a was per-
formed at 143 °C and 125 °C, respectively. The pretty similar
appearance of a sharp signal in the small angle region signifies
the layered structure for the smectic phase; the other two sharp
signals at 2h = 5.8996° and 8.8223° with a d spacing of 14.98 Å
and 10.023 Å, respectively, for 7a may be due to the fluctuation
of crystal in smectic layers whose temperature is very close to
smectic in crystal transition. The Debye–Scherrer pattern of 7a
shows a layer thickness of 29.44 Å with a Cu K
wavelength k = 1.5418 Å, corresponding to 2h = 3.001°, and
a radiation of
a
fairly sharp diffuse scattering at wide angle 2h ꢁ 17.5°. The latter
corresponds to an in-layer short-range liquid-like order. The small
angle reflection of 8a is at 2h = 2.361° with a layer thickness
d = 37.41 Å. The molecular lengths (L) calculated from chem3D
software are 29.87 Å and 27.73 Å for 7a and 8a, respectively.18
The d value of 7a (29.44 Å) at 143 °C is approximately equal to
as in the case of highly polar rod-shaped molecules23,24
.
Figure 1.

K. C. Majumdar et al. / Tetrahedron Letters 50 (2009) 1992–1995
1995
9. (a) Mallia, V. A.; Tamaoki, N. J. Mater. Chem. 2003, 13, 219; (b) Mallia, V. A.;
Tamaoki, N. Chem. Mater. 2003, 15, 3237.
10. Cha, S. W.; Jin, J.-I.; Laguerre, M.; Achard, M. F.; Hardouin, F. Liq. Cryst. 1999, 26,
1325.
11. Lokanath, N. K.; Sridhar, M. A.; Prasad, J. S.; Yelamaggad, C. V.; Rao, D. S. S.;
Prasad, S. K. Mol. Cryst. Liq. Cryst. 2001, 364, 567.
12. Zajac, M. A.; Zakrzewski, A. G.; Kowal, M. G.; Narayan, S. Synth. Commun. 2003,
33, 3291.
13. Itahara, T.; Sunose, M.; Kameda, T.; Ueda, T. Chem. Phys. Chem. 2002, 4, 378.
14. (a) Majumdar, K. C.; Chakravorty, S.; Pal, N.; Rao, N. V. S. Tetrahedron 2009,
65, 152; (b) Majumdar, K. C.; Chattopadhyay, B.; Chakravorty, S.; Pal, N.;
Sinha, R. K. Tetrahedron Lett. 2008, 49, 7149; (c) Majumdar, K. C.; Pal, N.;
Debnath, P.; Rao, N. V. S. Tetrahedron Lett. 2007, 48, 6330; (d) Majumdar,
K. C.; Pal, N.; Nath, S.; Choudhury, S.; Rao, N. V. S. Mol. Cryst. Liq. Cryst.
2007, 461, 37; (e) Majumdar, K. C.; Pal, N.; Rao, N. V. S. Liq. Cryst. 2006,
33, 531.
In conclusion, we have developed nucleobase derivatives by
connecting pyrimidine moieties with cholesterol for new liquid
crystalline materials. There are several reports of the formation
of lyotropic liquid crystals by DNA and nucleotides.25,26 However,
unsuccessful attempts27,28 were made to prepare thermotropic li-
quid crystals of nucleobase derivatives, and there is only one report
by Itahara et al. who succeeded in the preparation of thermotropic
liquid crystals adjoining adenine and thymine with cholesterol and
observed only the cholesteric phase.13 We have synthesized new
mesogenic compounds derived from cholesterol with uracil and
barbituric acid linked with an alkyl chain spacer giving rise to
monolayer SmA1 and partial bilayer SmAd associated with the
TGB and cholesteric phases. The presence of two sharp signals in
the XRD profile besides the small angle peak and diffuse peak im-
plies that the smectic layer is fluid with a long range order in both
the compounds (7a and 8a). The remaining compounds of both the
series do not exhibit any mesomorphic behaviour. The stacking of
bâttonets in the SmAd phase suggests attractive interaction be-
tween the adjoining bâttons. The variation of the smectic A phase
is observed when cholesterol is linked with uracil in place of bar-
bituric acid.
15. Yelamaggad, C. V.; Srikrishna, A.; Shankar Rao, D. S.; Krishna Prasad, S. Liq.
Cryst. 1999, 26, 1547.
16. Typical procedure for the synthesis of compound 7a: A mixture of compound 5a
(128 mg, 0.827 mmol) and cholesteryl benzoate 4a (500 mg, 0.827 mmol) was
refluxed in absolute ethanol in the presence of a catalytic amount of glacial
acetic acid for 2 h. The schiff base 7a was obtained as a precipitate from the hot
reaction mixture. It was repeatedly washed with hot ethanol and dried in
vacuum.
Compound 7a: Yield 96%; IR (KBr): 2945, 1733, 1693, 1655 cmꢀ1
;
1H NMR
(400 MHz, CDCl3): dH = 0.66ꢀ2.32 (m, 51H), 3.40 (s, 3H), 3.46 (s, 3H), 3.99 (t,
J = 6.4 Hz, 2H), 4.59–4.62 (m, 1H), 5.35 (d, J = 4.0 Hz, 1H), 6.91 (d, J = 8.7 Hz,
2H), 7.43 (s, 1H), 7.74 (d, J = 8.7 Hz, 2H), 9.50 (s, 1H). 13C NMR (100 MHz,
CDCl3): dC = 12.2, 19.1, 19.7, 23, 23.2, 24.2, 25.2, 26, 28.4, 28.5, 28.6, 29.3, 32.2,
32.3, 35, 36.2, 37, 37.5, 38.6, 39.9, 40.1, 42.7, 50.4, 56.5, 57, 68.1, 74.2, 115, 123,
123.3, 130.3, 139.9, 140, 160.5, 161.1, 161.9, 173.4. HRMS: m/z calcd for
Acknowledgements
C46H67N3O5 [M+H]+: 742.5153; found: 742.5156; ½a D
ꢀ17.8 (c 0.16, CHCl3).
ꢂ
The financial support from the Department of Science and Tech-
nology through the SERC project No. SR/S1/OC-44/2005 is grate-
fully acknowledged. S.M. is thankful to DST (New Delhi) and
R.K.S. is grateful to CSIR (New Delhi) for fellowships. We also thank
the Material Science Department of the IACS (Kolkata) for HRXRD
facilities.
Anal. Calcd for C46H67N3O5: C, 74.46; H, 9.10, N, 5.66. Found: C, 73.89; H, 8.93;
N, 5.79.
17. Typical procedure for the synthesis of compound 8a: A mixture of compound 6
(106 mg, 0.827 mmol) and cholesteryl benzoate 4a (500 mg, 0.827 mmol) was
refluxed in absolute ethanol for 2 h. The product 8a was obtained as
a
precipitate from the hot reaction mixture. It was repeatedly washed with hot
ethanol and dried in vacuum.
Compound 8a: Yield 98%; IR (KBr): 2943, 1730, 1669 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): dH = 0.66ꢀ2.33 (m, 51H), 3.38 (s, 3H), 3.40 (s, 3H), 4.05 (t, J = 6.4 Hz, 2H),
4.59–4.61 (m, 1H), 5.36 (d, J = 4.0 Hz, 1H), 6.94 (d, J = 8.9 Hz, 2H), 8.31 (d,
J = 9.0 Hz, 2H), 8.50 (s, 1H). 13C NMR (100 MHz, CDCl3): dC = 19.3, 21, 22.5, 22.8,
23.8, 24.3, 24.7, 25.5, 27.8, 28, 28.2, 28.3, 28.7, 29, 31.8, 31.9, 34.5, 35.8, 36.2,
36.6, 37, 38.1, 39.5, 39.7, 42.3, 50, 56.1, 56.7, 68, 73.8, 114.1, 114.4, 122.6, 125.4,
138.1, 139.6, 151.4, 158.9, 161, 163.2, 163.9, 172.9. HRMS: m/z calcd for
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