Synthesis and liquid crystal properties of aryl esters of laterally substituted 5-pyrimidinecarboxylic acids

Article abstract of DOI:10.1023/B:COHC.0000003520.70863.87

(p-R-phenyl)-4-methyl-, 4-methoxy-, and 4-hydroxv-5-pyrimidinecarboxylates have been synthesized and their liquid crystal properties examined. Compounds containing methyl and methoxy groups in the lateral position of the molecule are nematic liquid crysta

Full text of DOI:10.1023/B:COHC.0000003520.70863.87

Chemistry of Heterocyclic Compounds, Vol. 39, No. 8, 2003
SYNTHESIS AND LIQUID CRYSTAL
PROPERTIES OF ARYL ESTERS OF
LATERALLY SUBSTITUTED
5-PYRIMIDINECARBOXYLIC ACIDS
M. A. Mikhaleva
(p-R-phenyl)-4-methyl-, 4-methoxy-, and 4-hydroxy-5-pyrimidinecarboxylates have been synthesized
and their liquid crystal properties examined. Compounds containing methyl and methoxy groups in the
lateral position of the molecule are nematic liquid crystals with a mesophase range of 30-50°C, but the
4-hydroxy derivatives are smectic liquid crystals. With variants of the substituents in a series of
(p-R-phenyl)-4-substituted 5-pyrimidinecarboxylates the mp of individual representatives were
successfully reduced by ~50°C in comparison with the 4-unsubstituted analogs and the range of the
mesomorphic state was extended to 190°C.
Keywords: arylcarboxylates, liquid crystals, lateral substituents, pyrimidines.
Mesomorphic derivatives of 2,5-disubstituted pyrimidines, containing an ester bridge in the structure are
recommended as practically useful components of liquid crystal materials [1,2]. Among the compounds
differing in structure by the mutual disposition of polar groups which influences the many parameters of the
mesomorphic state, there are aryl esters of 2-substituted 5-pyrimidinecarboxylic acids, which are chiral smectic
[3], antiferroelectrical [4], or nematic liquid crystals. For example as was shown in [5], aryl esters of
2-(p-R-phenyl)-5-pyrimidinecarboxylic acids are nematogens, in difference to the analogous compounds with a
reversed disposition of the COO groups (i.e. obtained from 5-hydroxypyrimidines), characterized by the
development of smectic properties [6].
On the other hand the influence of lateral substituents in rod-like liquid crystals on the mesomorphic
state (the effect of a reduction of phase transition temperatures, the change of mesophase ranges and their
thermostability, the predominance of nematics, etc.) with the aim of regulating the parameters of the liquid
crystal state have been widely studied, and definite data have already been accumulated on the change of
properties of a liquid crystal depending on the type and position of a substituent [7-9].
In the present work we have synthesized esters 1b-k and have compared the overall influence of the side
substituent R in the acid portion of the molecule and of the substituent R1 of the phenolic fragment of esters
1b-k on their liquid crystal properties with the unsubstituted analog 1a which has a nematic phase in the range
124.8-195.8°C [5]. The initial esters 2a,c were obtained by condensations known in pyrimidine chemistry of
amidines with the appropriate ethoxymethylene derivatives of acetoacetic and malonic esters [5,10], and esters
2b,d were obtained by conversions of the 4-hydroxy derivative 2c [5].
__________________________________________________________________________________________
Novosibirsk N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy
of Sciences, Novosibirsk 630090; e-mail: oshk@nioch.nsc.ru. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 8, pp. 1184-1189, August, 2003. Original article submitted January 3, 2001.
1032
0009-3122/03/3908-1032$25.00©2003 Plenum Publishing Corporation

Scheme 1
Cl
R
N
N
N
N
R = OH
POCl3
BuO
BuO
COOEt
BuO
BuO
COOEt
2d
2a,c
excess
MeONa
MeONa
10% NaOH
OMe
COOEt
R
N
N
COOH
N
2b
N
3a–c
10% NaOH
p-HOC6H4R1
3c
DCC + DMAP
rt
PPh3–CCl4
rt
TsCl, Py
R
R
O
O
O
N
N
C
C
BuO
1b,d,j,k
COO
BuO
N
N
N
R
1a,c,e–i
BuO
N
R1
4a,c
R
1a R = H; 1b-f, 2a-4a R = Me; 1g-i, 3b R = OMe; 1j-k, 2c-4c R = OH ; 1 b,g,j R1 = Bu;
*
a,c,h R1 = Am; d,i,k R1 = OBu; e R1 = CN; f R1 = COO-p-C6H4Am
Alkaline hydrolysis of the ethyl esters 2a,c gave the corresponding acids 3a,c but on hydrolysis of ester
2b under the same standard conditions [5,10] ready fission of the methoxy group was observed and, in place of
acid 3b, the 4-hydroxy derivative 3c was formed. The desired derivative 3b was successfully obtained by
treating the chloro derivative 2d with an excess of sodium methylate. Under these conditions, contrarily, fission
of the carbethoxy group was observed with retention of the methoxy group in the pyrimidine ring. It is
interesting to note that in [11] the preparation of 4-methoxy-5-methoxycarbonyl-2-phenylpyrimidine was
reported from the corresponding 4-chloro derivative by the action of an excess of sodium methylate.
For the synthesis of aryl esters 1 a method was selected using the PPh3–CCl4 complex at room
temperature [12], previously well recommended when obtaining (aryl)pyrimidinyl-2-carboxylates [13].
However on interacting acid 3a with n-butyl- or n-butyloxyphenol under the conditions in question the
corresponding esters 1b,d were not obtained. In the IR spectra of the reaction products an absorption band was
observed for the C=O group of the initial acid (1690-1700 cm-1), trace amounts of the desired esters (1730 cm-1),
and an absorption band at 1790 cm-1, which we assigned to anhydride 4a. Its formation was confirmed by mass
spectrometric data on determining the molecular mass ([M]+ 554). Analogously the interaction of hydroxy acid
3c with n-butylphenol in the same system gave, according to data of IR and mass spectra, the same set of
reaction products, namely the initial acid 3c ([M]+ 288, 1745 cm-1), traces of ester 1j ([M]+ 420, 1714 cm-1), and
anhydride 4c with νC=O 1773 cm-1. For these cases we selected another method of obtaining aryl esters, the
interaction of acids with phenols in the presence of p-toluenesulfonyl chloride at 90°C [14]. The use in this
_______
* Exist as the 4-oxo-3,4-dihydro derivatives.
1033

reaction of both pure acids 1a,c and of reaction mixtures from previous experiments enabled the synthesis in
good yield of esters 1b,d,j,k. Acid 3b did not react under these conditions and was recovered in significant
amounts from the reaction mixture. To obtain aryl esters of o-methoxy acid 3b the carbodiimide method was
used with dicyclohexylcarbodiimide (DCC) in the presence of 4-dimethylaminopyridine (DMAP) [5,15], which
enabled the synthesis of aryl esters 1g-i. Esters 1c,e,f were synthesized under analogous conditions.
Investigation of the liquid crystal properties of the obtained esters showed that esters 1b-i are nematic
liquid crystals like analog 1a described in the literature. Introduction of the 4-methyl group (esters 1b-d) leads
to a reduction in the phase transition temperature, which corresponds with the data of [8]. In comparison with
TABLE 1. Characteristics of the Synthesized Compounds
Found, %
——————
mp*, °C
I
Com-
pound
Empirical
formula
IR spectrum, Yield,
Calculated, %
, cm-1
%
νC=O
C
H
N
N
S
C26H30N2O3
C27H32N2O3
C26H30N2O4
C23H21N3O3
C34H36N2O5
74.35
74.64
7.16
7.18
6.62
6.69
70
77
122
129
162
194
1740
1738
50
62
1b
1c
1d
1e
1f
74.98
7.62
6.42
75.00
7.40
6.48
71.61
71.89
6.89
6.91
6.68
6.45
103
138
105
1717, 1737 46
70.87
5.36
10.72
1737 *2
72
68
71.32
5.43
10.85
74.21
73.91
6.63
6.52
4.90
5.07
295
1737
(dec.)
C26H30N2O4
C27H32N2O4
C26H30N2O5
C25H28N2O4
72.24
6.98
6.46
80
74
105
113
143
1724, 1751 62
1g
1h
1i
71.89
6.91
6.45
72.20
72.32
7.14
7.14
6.17
6.25
1748
1745
74
83
69.36
6.70
6.20
113
259
69.33
6.67
6.22
71.45
71.42
6.76
6.66
6.55
6.66
270
216 1665, 1714 72
240 1667, 1715 67
1j
(dec.)
C25H28N2O5
68.30
6.46
6.40
280
285
1k
68.80
6.47
6.42
(dec.)
C18H22N2O3
C18H22N2O4
C17H20N2O4
68.62
68.79
6.73
7.01
8.84
8.92
101-102
106-107
225-226
1720
1727
86
87
2a
2b
2c
65.16
6.65
8.92
65.45
64.07
64.55
6.67
6.21
6.33
8.48
8.75
8.86
1660, 1705
53
(69 [5])
C17H19ClN2O3*3 60.61
5.64
8.28
88-88.5
(79 [5])
1714, 1732
62
2d
60.98
5.68
8.37
(52 [5])
C16H18N2O3
C16H18N2O4
C15H16N2O4
67.31
67.13
6.33
6.29
9.72
9.79
219-221
213-214
255-258
1674, 1698 90
1677, 1698 83
1636, 1753 94
3a
3b
3c
63.62
5.98
9.28
63.57
62.45
62.50
5.96
5.70
5.55
9.27
9.45
9.72
_______
* For compounds 1b-k the temperatures for phase transitions are given
(S smectic, N nematic mesophases, I isotropic melt), for compounds 2a-d
and 3a-c the mp are given. Solvents for crystallization were methanol
(1g,d), acetonitrile (1j,k), alcohol–methyl cellosolve (2c, 3a), alcohol–ethyl
acetate (3b), and alcohol (for the remaining compounds).
*2 2222 cm-1 (C≡N).
*3 Cl, found, %: 10.40; calculated, %: 10.63.
1034

the mp of ester 1a the mp of esters 1b,c was reduced by ~50-55°C, but Tc* was reduced by ~70°C caused by
contraction of the mesophase range. A somewhat smaller reduction of both the phase transition temperature and
the mesophase range was observed for the p-butoxyphenyl ester 1d.
Introduction of the p-cyanophenyl group (ester 1e) into the molecular structure did not lead to the
prospect of broadening the range of the nematic state. A significant effect was successfully obtained by the
introduction of a second ester bridge into the rigid framework of ester 1c. Diester 1f is characterized by a
mp 27°C higher than ester 1c and also a significantly more thermostable mesophase and correspondingly to its
almost 4 times greater range.
The presence in aryl esters 1 of a side methoxy group larger in size than a CH3 group and creating an
additional dipole moment at an angle to the long axis of the molecule, leads to destabilization of the
mesomorphous state. As a result compounds 1g-i both due to higher mp and due to reduced thermostability of
the mesophase have a narrower range of the nematic state by 12-29°C compared with analogs 1b-d.
The introduction of lateral methyl and methoxy groups into the acid portion of esters 1b-e,g-i therefore
leads to a reduction in the phase-transition temperatures, and within each series closely similar mesophase
ranges are observed. The size of the effect also depends on the character of the substituent in the p-position of
the phenolic fragment of the ester.
Liquid crystal compounds containing a 4-oxo-3,4-dihydropyrimidine fragment in the molecule are
inclined to strong lateral intermolecular interactions and are characterized by more ordered smectic states [16].
The derivatives of oxodihydropyrimidines obtained in the present work, esters 1j,k, also belong to the high
melting smectogens with a narrow nematic mesophase.
EXPERIMENTAL
The IR spectra of the synthesized compounds were recorded on a Vector 22 spectrometer in KBr disks.
Phase transition temperatures and mesophase textures were determined on a small-scale Boetius type hot stage
with a RNMK 0.5 visual attachment. The characteristics of esters 1 and of the initial compounds 2 and 3 are
given in Table 1. Molecular masses were determined mass spectrometrically on a Finnigan MAT 8200
instrument.
p
Aryl Esters of 4-Methyl- and 4-Hydroxy-2-( -butoxyphenyl)-5-pyrimidinecarboxylic Acids
(1b,d,j,k). p-Toluenesulfonyl chloride (1.9 g, 10 mmol) was added in portions with stirring at room temperature
to a mixture of acid 3a or 3c (5 mmol) and p-butyl- or p-butyloxyphenol (5.3 mmol) in dry pyridine (20 ml) and
the mixture stirred for 1 h. The reaction mixture was then heated at 90°C on a water bath for 2 h, and cooled to
room temperature. The solid ester was filtered off, washed with acidified water, then with water to neutral
reaction, dried, and recrystallized.
p
Aryl Esters of 4-Methyl- and 4-Methoxy-2-( -butoxyphenyl)-5-pyrimidinecarboxylic Acids
(1c,e-i). 4-Dimethylaminopyridine (0,2 g, 2 mmol) and then in portions dicyclohexylcarbodiimide (0.51 g,
2.5 mmol) were added at room temperature to a suspension of acid 3a or 3b (2 mmol) and the appropriate
p-substituted phenol (3 mmol) in methylene chloride (10 ml). A solution formed after a short time, but then a
solid began to precipitate. The suspension was stirred at room temperature for 8 h and left to stand overnight.
The precipitate (~0.5 g) of dicyclohexylurea was filtered off, the filtrate evaporated to dryness, and the residue
triturated with alcohol. The aryl ester was filtered off, washed with alcohol, dried and recrystallized to constant
phase transition temperature.
n
Ethoxymethylene-
2-( -Butoxyphenyl)-4-methyl-5-pyrimidinecarboxylic Acid Ethyl Ester (2a).
acetoacetic ester (18.6 g, 0.1 mol) and p-butyloxybenzamidine hydrochloride (22.8 g, 0.1 mol) were dissolved in
absolute alcohol (200 ml) and a solution of metallic Na (2.75 g, 0.12 mol) in absolute alcohol (50 ml) was added
_______
* Tc is the clear point (N–I transition).
1035

dropwise. The reaction mixture was boiled for 5 h and cooled to room temperature. The precipitated solid was
filtered off, washed with water, dried, and compound 2a (19 g) was obtained.
p
Derivative
2-( -Butoxyphenyl)-4-methoxy-5-pyrimidinecarboxylic Acid Ethyl Ester. (2b).
2d
(8 g,
24 mmol) was added to a solution of sodium methylate (1.35 g, 25 mmol) in methanol (30 ml) and the reaction
mixture was boiled for 2 h. After cooling, the solid was filtered off, washed with methanol, dried, and ester 2b
(7.3 g) was obtained.
p
p
Ethyl Esters of 2-( -Butoxyphenyl)-4-oxo-3,4-dihydro- (2c) and 2-( -Butoxyphenyl)-4-chloro-5-
pyrimidinecarboxylic Acids (2d) were obtained by the method of [5].
p
was obtained by the hydrolysis of
2-( -Butoxyphenyl)-4-methyl-5-pyrimidinecarboxylic Acid (3a)
derivative 2a on boiling in 10% NaOH solution with subsequent acidification of the reaction mixture by analogy
with [10].
p
A solution of metallic Na (1.6 g,
2-( -Butoxyphenyl)-4-methoxy-5-pyrimidinecarboxylic Acid (3b).
35 mmol) in absolute methanol (120 ml) was added to chloro derivative 2d (4.76 g, 14 mmol) and the mixture
was boiled for 1.5 h. The reaction mixture was cooled, and the solid filtered off. It was triturated with water to a
pasty state and the mass acidified with 20% HCl to pH 2-3. The mixture was stirred for 1 h, the solid was
filtered off, washed with water, dried, and acid 3b (3.5 g) was obtained.
p
A 10% solution (78 g) of
2-( -Butoxyphenyl)-4-oxo-3,4-dihydro-5-pyrimidinecarboxylic Acid (3c).
NaOH and alcohol (8 ml) was added to ester 2c (5.6 g, 17.7 mmol) and the mixture boiled for 2 h. The reaction
mixture, which congealed on cooling, was filtered, the solid was triturated with water, and thoroughly washed
several times with water and alcohol. After drying acid 3c (4.8 g) was obtained.
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