JPH0441468A - Tranexamic acid derivative - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R1 is (halogenated) alkyl having 1-16C asymmetric carbon; R2 is H or methyl; R3 is expressed by formula II (p is 1 or 2; q is 2 for p=1 and 1 for p=2; n is 1-16; x is COO or OCO; Y is COO, OCO or O)]. EXAMPLE:A trans-4-(N-methyl-N-(S)-2-methylbutylaminomethyl) cyclohexane carboxylic acid ester. USE:A liquid crystalline compound used for a liquid crystalline indicating element having excellent responsibility and memorial property. Said compound can be mixed with well-known ferroelectric liquid crystal to widen temperature range exhibiting ferroelectricity to upper and lower or to improve responsibility. PREPARATION:Tranexamic acid expressed by formula III and phenol derivative expressed by formula IV are subjected to dehydrating condensation to afford the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention provides novel compounds exhibiting liquid crystals, methods for producing the compounds, and liquid crystal devices using these compounds.

[Conventional technology]

Among the many known liquid crystal compounds is one called nematic liquid crystal. Although this compound currently constitutes the mainstream of compounds or compositions used in liquid crystal display devices, one of its disadvantages is that the response speed is slow and
It is said that a response speed of only the order of 5 ec can be obtained, and that this is approaching the limit for increasing the size of the display.

In order to improve the drawbacks of conventional liquid crystal display elements, Clark and Lagerwell proposed the use of bistable liquid crystals (Japanese Patent Laid-Open No. 1072-1982).
No. 16). Liquid crystals with this bistability are called ferroelectric liquid crystals, and have attracted attention for their high-speed response and memory properties.In recent years, there has been active research into their practical application, and practical ferroelectric liquid crystals There is an urgent need to develop materials.

In general, a ferroelectric liquid crystal is a compound having an optically active site and is expressed in a series of smectic phases having a molecular orientation in which the long axis of the molecule is tilted from the normal direction of the layer. Among them, the chiral smectic C (hereinafter abbreviated as S♂) phase is considered to be practically advantageous because of its relatively low voltage operability.

In this way, ferroelectric liquid crystals have a very fast response speed due to their spontaneous polarization, and can also develop a bistable state with memory properties.Furthermore, due to their excellent viewing angle, they can be used for large-scale applications. Suitable as a material for a nine-panel display with a large capacity.

RB in 1975 as such a ferroelectric liquid crystal.

4-(4-n-decyloxybenzylideneamine) cinnamic acid-2-methylbutyl ester (hereinafter abbreviated as DOBAMBC) synthesized by Meyer et al. (J, Physique 36 L-69 or (
1975) ).

This DOBAMBC contains a Schiff base in its structure, and therefore has a problem in its chemical stability. Therefore, various physically and chemically stable compounds have been searched for as ferroelectric liquid crystal materials, and currently 4-(4-n alkyloxyphenyl)-1-carboxylic acid-2-methylbutyl ester (hereinafter referred to as The main focus has shifted to the search for ester compounds, including CN (abbreviated as CN). However, ester compounds such as CN do not exhibit an S♂ phase, or even if they do, the temperature range in which they exhibit the S♂ phase is narrow, and moreover, they exhibit different phase series when the liquid crystal is heated or cooled. Because it is a monotropic liquid crystal, there are few that can withstand practical use (
Liquid Crystals and Order
d Fluids 4 or (1984+).

On the other hand, as a method for shifting the liquid crystal phase temperature range to a wide range including room temperature, introduction of a hetero ring such as a pyridine:pyrimidine ring or a cyclohexane ring is generally carried out, but the synthesis method is complicated.

In particular, when introducing a cyclohexane ring to improve liquid crystallinity, there are cases in which the smectic property is lost due to the introduction of the cyclohexane ring, and a cis-trans isomer mixture of cyclohexane-1,4-disubstituted products is generated during the synthesis stage. Due to problems such as the need for separation operations, sufficient consideration had not been made.

On the other hand, tranexamic acid is a cyclohexane derivative and is widely used as a hemostatic agent.

However, it has not yet been used for any purpose other than as a medicine.

[Problems to be Solved by the Invention] An object of the present invention is to provide a novel tranexamic acid derivative that is chemically stable and has a wide liquid crystal temperature range.

That is, a novel liquid crystal compound is provided by using tranexamic acid as a raw material for cyclohexane-trans-1,4-disubstituted product, which is inexpensive and easily available, and alkylating the N-terminus and esterifying the C-terminus.

Furthermore, in the production method of the present invention, it is easy to change the type and length of the alkyl group at the N-terminus and the type of ester group at the C-terminus. It is possible to provide a liquid crystal compound that is easy to control. Furthermore, a liquid crystal composition containing at least one of the above compounds as a compounding component is provided.

[Means to solve the problem]

The compounds provided by the present invention have the general formula [wherein R1
is an alkyl group having asymmetric carbon atoms having 1 to 16 carbon atoms, and may be substituted with halogen. R2 is hydrogen or a methyl group, R3 is the general formula (II) (II) where, when p=1, q=2, or when p=2, q=l
, n represents an integer from 1 to 16, and X is C00 or O
represents CO, and Y represents COO1OCO or O] It is a tranexamic acid derivative represented by the following formula.

In the present invention, tranexamic acid is used as a raw material for trans-1,4-disubstituted cyclohexane, and by alkylating the N-terminus and esterifying the C-terminus, we create a compound that exhibits stable liquid crystallinity over a wide temperature range. succeeded in synthesizing.

That is, upon alkylation of an amino group, liquid crystallinity changes depending on the type of alkyl substitution of the amine group. Regarding R1, it is an alkyl group having an asymmetric carbon number of 1 to 16 carbon atoms, and a portion thereof may be substituted with a halogen.

When the number of carbon atoms exceeds 17, it is not only difficult to obtain the raw material, but also the thermal stability of the obtained tranexamic acid derivative as a liquid crystal compound becomes low.The number of carbon atoms is most preferably 5 to IO.

Specific examples of R3 include 2-octyl group, 2-chloropropyl group, fs)-2-methylbutyl group, and (Sl-methylbutyl group is preferred because it can be obtained at low cost).

R2 is hydrogen or a methyl group, but a methyl group is preferable because it is more stable against heat.

2) General formula (III) In the formula, R1 is an alkyl group having an asymmetric carbon having 1 to 16 carbon atoms, and R2, including those substituted with halogen, is a compound or a salt thereof represented by hydrogen or a methyl group, -Ship % formula %) In the formula, p: 1 or 2 q: 2.9 when p = 1, 1 when = 2, an integer from nil to 16 X: COO or 0CO Y: COO1 OCO or O The method for producing a tranexamic acid derivative according to claim 1, which comprises reacting the tranexamic acid derivative with a compound.

R3 is represented by general formula (II).

-... (II) In formula 1, p and q are p=l, q=2 or p=2
, q=l, n represents an integer from 1 to 16, X represents COO or OCO, and Y represents COO1OC
The liquid crystallinity also changes depending on the type of R3 (representing O or O). Regarding n, n=I~16, preferably 5
~12, and as n gets further away from 5 to 12, the liquid crystallinity decreases.

The alkyl group represented by Cn1t2n+1 may be linear or branched, and may contain an asymmetric carbon.

When p and q are 1, q is 2, or when p is 2, q is 1, and R3 has a structure containing three benzene rings.

X represents COO or OCO, and Y represents COO1OCO or 0, but the combination of X and Y can be freely selected.

When there is an ester bond at the end, it is easier to exhibit liquid crystallinity if the orientation of the ester bond is aligned in one direction, but if Y is O, liquid crystallinity is likely to be exhibited regardless of the type of X, especially when ferroelectric There is a tendency to show gender easily.

As a manufacturing method, - Funagura (m) [However, in the formula, R1 is an alkyl group having an asymmetric carbon number of 1 to 16 carbon atoms, and may be substituted with a halogen. R2 is hydrogen or a methyl group. It is synthesized by N-alkylation of tranexamic acid represented by 1, and the compound or its salt corresponding to R3 in -Funazo (T) and -Funazo (1'V)HO-(◎)-pX-(◎
)-9Y-C mountain...

-...-(rV) [In the formula, p and q are p=1% q22 or p=2, q=l
n represents an integer from 1 to 16, X represents C00 or OCO, and Y represents COO1OCO or OCO.
represents. By carrying out dehydration condensation with the phenol derivative represented by J, the tranexamic acid derivative represented by -Funazo (I) can be synthesized.

The reaction process is shown in Figure 1.

First, the production of the compound represented by -Funazo (III) will be explained.

The compound represented by the general formula (1) is a first compound in which the amino group of tranexamic acid is protected with a t-butyloxycarbonyl group, etc.
(See Figure (a)), when R2 is hydrogen, the C-terminus is esterified at the same time as N-alkylation using an alkyl halide corresponding to R3, and when R2 is a methyl group, methyl halide and sodium hydride are used. Thereafter, the t-butyloxycarbonyl group is deprotected (see FIG. 1(b)). Furthermore, when R2 is a methyl group, it is alkylated using an alkyl halide corresponding to R3 and sodium hydride μ.

Finally, the ester can be hydrolyzed to obtain a compound represented by general formula (III) (see FIG. 1(c)).

Next, the compound represented by the general formula (IV) can be obtained by using the combination of X and Y as starting materials (TV-1
) to (IV-4).

First, the Salel compound (I
To synthesize V-1), commercially available ethyl 4-hydroxybenzoate or 4-(4'-hydroxyphenyl)benzoic acid is used as a raw material, and after protecting the hydroxyl group with benzyl ether etc. ) is deprotected by esterification with an alcohol having an alkyl group corresponding to -C1HQ n+ 1 (corresponding to R in Figure 2 (IV-1)) (see Figure 2 C).

Next, the benzoic acid derivative obtained in the above-mentioned process with a protected hydroxyl group is esterified with thionyl chloride, etc., and deprotected to obtain the desired compound (see FIG. 2C).

Next x=coo, Y=O or x=coo, y=oc
.

To synthesize the compound HV-2) represented by
In the case of =O, it is etherified with the corresponding alkyl tosylate or alkyl bromide, and in the case of y=oco, it is esterified with the corresponding fatty acid, followed by deprotection (Fig. 2C).
reference).

The rest is carried out similarly to the case of (IV-1) to obtain the target compound (rV-2).

x=oco, y=o or x=oco, y=oc
The compound (TV-3) represented by o was synthesized using commercially available 4
- Ethyl hydroxybenzoate or ethyl 4-hydroxybenzoate or 4-(4''-hydroxyphenyl)benzoic acid is used as a raw material, and after etherification or esterification in the same manner as in Figure 2C, It can be obtained through a reaction.

Furthermore, the compound (rV-4) represented by x = oco and y = coo can be obtained by esterifying a commercially available dicarboxylic acid with the corresponding alcohol and then undergoing the same reaction as in Figure 2B (see Figure 3). (see figure).

Finally, the tranexamic acid derivative of the general formula (1) can be obtained by reacting the general formula (III) obtained as described above with the compound represented by -Funazou (rV). Specifically, the condensation reaction is carried out in an appropriate solvent (e.g. dichloromethane, carbon tetrachloride, benzene, etc.) using N,N'-dicyclohexylcarbodiimide (hereinafter referred to as
(abbreviated as DCC) etc., or - Shipbuilding (III)
There are methods such as derivatizing the compound into an acid halide using thionyl chloride or the like, and allowing the compound of the general formula (rV) to act on the compound under basic conditions.

The compound produced by the method described above is purified by column chromatography and recrystallization.

[Effect 1] The compound of general formula (I) in the present invention is a tranexamic acid derivative exhibiting very stable liquid crystallinity.

It has a stable liquid crystal phase in a wide temperature range close to room temperature.
A cyclohexane ring sandwiched between an amine and a carboxylic acid is
It is presumed that this is because the steric structure maintains the rigidity of the molecular core, similar to the benzene ring, and the chemical effect is that it lowers the melting point.

On the other hand, there are differences in smectic properties depending on the type of R3. This is because the bending of the molecule caused by the type of benzene ring and its bonding element and the bond angle seen from the long axis of the molecule, that is, changes in the twisted structure of the molecule, affect intermolecular interactions and the regularity of molecular arrangement. It is estimated that this is due to

The compound of the present invention is a novel amino acid derivative that can be used as a liquid crystal display device with excellent responsiveness and memory properties for the above reasons.

In addition, the compound of the present invention can be blended with already known ferroelectric liquid crystals to vertically expand the temperature range in which ferroelectricity is exhibited and to improve responsiveness. It can be blended with ferroelectricity to impart ferroelectric properties.

[Examples] Hereinafter, the compounds of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

Below, Cry, Ch, Iso, SA, Sc
, SX'' phases are crystalline, cholesteric, isolunar, smectic A, xylsmectic C, and chiral smectic X, respectively.

The compound of the present invention was purified by silica gel chromatography and recrystallization with ether and hexane.

The measured values of phase transition points shown below may be slightly influenced by the purity of the material.

In addition, in the following examples, only examples in which 8 optically active forms were used as raw materials will be described, but it should be noted that even when R forms are used as raw materials, substances with the same phase transition temperature can be obtained. is clear from a theoretical point of view.

(1) Synthesis of trans-4-(Nt-butyloxycarbonylaminomethyl)cyclohexanecarboxylic acid 15.7 g of tranexamic acid was mixed with dioxane-water (2:1).
300+n9. Then, under water cooling, a dioxane (50 mI2) solution of 100 IDI2 of a 1 molar aqueous solution of sodium hydroxide and 24.0 g of di-t-butyl dicarbonate was added.
It took several minutes to drip. After returning to room temperature and stirring for 2.5 hours, the reaction solution was diluted by approximately 1/2 on an aqueous solution with an external temperature of 50 to 60°C.
3, and about 851,112 mL of IN hydrochloric acid was added dropwise under water cooling to adjust the pH to 3 to 4. Ethyl acetate (80mQ
x 3), and the organic layer was extracted with purified water (30I112).
After washing with saturated brine (30a112) and drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained crude crystals were washed with isobrobyl ether and then recrystallized from ethyl acetate to obtain 21.2 g of colorless powder trans-4-(N-t-butyloxycarbonylaminomethyl)cyclohexanecarboxylic acid (yield 82%). ) was obtained.

(2) Synthesis of trans-4-(N-t-butyloxycarbonyl-N-methylaminomethyl)cyclohexanecarboxylic acid methyl ester 4.1 g of the compound synthesized in (1) and methyl iodide 8II
Dissolve Iβ in DMF and stir slowly under water cooling for 6 hours.
169 g of 0% sodium hydride was added in portions.

After returning to room temperature and continuing stirring overnight, add 80% ethyl ether.
mg, and 5 nl of water-cooled purified water was added dropwise. The organic layer was mixed with purified water (20 m12
10, dried over magnesium sulfate, and distilled off the solvent under reduced pressure to obtain crude trans-4-' as a yellow oil.
(N-t-butyloxycarbonyl-N-methylaminomethyl)cyclohexanecarboxylic acid methyl ester6.
8 g (100% yield) was obtained.

(3) trans-4-(N-methyl-N-(S)-2-
6.8 g of the compound synthesized in synthesis (2) of methylbutylaminomethyl)cyclohexanecarboxylic acid ester
Add 15 mg of 4N hydrochloric acid-ethyl acetate solution under water cooling,
After stirring for 15 minutes, the solvent was distilled off under reduced pressure, and it was confirmed that there was no irritating odor.

The obtained crude trans-4-(N-methyl-aminomethyl)cyclohexanecarboxylic acid methyl ester hydrochloride was
Dissolved in MFLO1112 and diluted with triethylamine 2 under water cooling.
．． 2 mQ, (S)-2-methylbutyl bromide 3.2
mg was added. 768 mg of 60% sodium hydroxide was added little by little, and the mixture was heated at 80°C for 1 to 2 hours. Cold welding, ethyl ether 80m! 5 mj2 of purified water was slowly added dropwise. The organic layer was washed sequentially with purified water (20 mρ), a saturated aqueous sodium bicarbonate solution (20 m2), and saturated brine (20 mI2), and then dried over magnesium sulfate. , the solvent was distilled off under reduced pressure.

The obtained yellow oil was subjected to column chromatography using 50 g of silica gel, and ethyl acetate-hexane (
1:6), 3.2 g (yield: 61%) of trans-4-(N-methyl-N-(S)-2-methylbutylaminomethyl)cyclohexanecarboxylic acid methyl ester was obtained as a colorless oil.

(4) trans-4-(N-methyl-N-(S)-2-
3.2 g of the compound obtained in synthesis (3) of methylbutylaminomethyl)cyclohexanecarboxylic acid hydrochloride was dissolved in 6N hydrochloric acid,
Stirred at room temperature for 24 hours.

The solvent was distilled off under reduced pressure to obtain 2.9 g of colorless powder trans-4-(N-methyl-N-(S)-2-methylbutylaminomethyl)cyclohexanecarboxylic acid hydrochloride (yield 86%).
I got it.

(5) trans-4-(N-methyl-N-(S)-2-
trans-4-(N-% methylbutylaminomethyl)cyclohexanecarboxylic acid ester synthesis (4)
S)-2-methylbutylaminomethyl)cyclohexanecarboxylic hydrochloride and a phenol derivative corresponding to R3 in Table 1 prepared by a conventional method were mixed with 1 equivalent of DCC and 0.1 equivalent of 4-pyrrolidinopyridine in dichloromethane. The mixture was stirred overnight, and after work-up, recrystallized from hexane to obtain non-CH3CH3 (1) compounds in Examples 1 to 9. Yield was 20-50%.

Table 1 shows the results of measuring the phase transition temperature of these compounds.

The phase transition temperature was determined using a combination of visual observation using a polarizing microscope and a differential scanning calorimeter.

Furthermore, the structure of the obtained compound was confirmed by 'H-NMR and IR. The results are shown in Table 2.

(The following is a blank space) [Effects of the Invention] As exemplified above, the compound of the present invention exhibits ferroelectricity in an extremely wide temperature range. Therefore, we can easily and inexpensively provide novel compounds that are useful as materials for liquid crystal display devices that apply electro-optic effects in practical temperature ranges, either alone or in appropriate combinations with other nematic, smectic, or ferroelectric liquid crystals. can do.

[Brief explanation of drawings]

FIG. 1 shows the synthesis process of the compound represented by -Funazou (III), and FIGS. 2 and 3 show the synthesis process of the compound represented by the general formula (rV).

Claims (1)

[Claims] 1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(I
) In the formula, R_1 is an alkyl group having an asymmetric carbon having 1 to 16 carbon atoms, R_2 including those substituted with halogen is hydrogen or methyl group R_3 is the general formula (II) ▲ Numerical formula, chemical formula, table, etc. Yes▼・・・・・・(II) However, p: 1 or 2 q: 2 when p=1, 1 when p=2 n: An integer from 1 to 16 X: COO or OCO Y: COO , OCO or O 2 . 2) General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(III
) In the formula, R_1 is an alkyl group having an asymmetric carbon having 1 to 16 carbon atoms, and R_2, including those substituted with halogen, is a compound represented by hydrogen or a methyl group or a salt thereof, and the general formula (IV) ▲ There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(IV) In the formula, p: 1 or 2 q: 2 when p=1, 1 when p=2 n: An integer from 1 to 16 The method for producing a tranexamic acid derivative according to claim 1, characterized in that the reaction is carried out with a compound represented by X: COO or OCO and Y: COO, OCO or O 2 . 3) A liquid crystal device containing the tranexamic acid derivative according to claim 1 as at least one component.