JPS62111939A - Optically active beta-fluorohydrin compound - Google Patents

Abstract

NEW MATERIAL:An optically active beta-fluorohydrin compound shown by the formula [R<1> is 2-10C alkyl or aralkyl; R<2> is H, 2-10C alkyl or aralkyl (which may contain carbonyl or thionyl)]. EXAMPLE:(S)-2-Fluoro-3-methylbutanoic acid ethyl ester. USE:Useful as an intermediate for synthesizing optical switch element material, especially an intermediate for ferroelectric liquid crystal compound, namely an asymmetry source. Having strong spontaneous polarization and improved high-speed response, capable of developing a large-sized display, etc. Further useful as an intermediate for synthesizing antibiotics, drugs, physiologically active substances, agricultural chemicals, herbicides, etc. PREPARATION:An optically active alpha-tosyloxycarboxylic acid ester derived from an optically active hydroxycarboxylic acid is reacted with potassium fluoride to give an alpha-fluorocarboxylic acid ester, which is then reacted with aluminum lithium hydride to give a compound shown by the formula.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel optically active β-fluorohydrin compound.

The compound is useful as an intermediate for the synthesis of optical switch element materials, particularly as an intermediate for ferroelectric liquid crystal compounds, that is, as an asymmetric source for liquid crystal compounds. Up to now, optically active alcohols such as amyl alcohol and octyl alcohol have been used as chiral sources for ferroelectric liquid crystal compounds. Since the compound of the present invention has a fluoro group, which is a polar group, directly bonded to the asymmetric site, a compound with stronger spontaneous polarization and superior high-speed response than conventional ferroelectric liquid crystal compounds can be obtained. Make it easier to realize large displays, etc.

Furthermore, the compounds of the present invention are useful as synthetic materials or intermediates such as antibiotics, medicines, physiologically active substances, and medicines and herbicides.

(Conventional technology and problems to be solved by the invention) Currently, the display systems of liquid crystal display elements that are widely put into practical use are the twisted nematic type (TN type) and the dynamic scattering type (DS type). It is. These are nematic liquid crystals,
1, which is a display using a nematic liquid crystal cell as the main component.
One of the disadvantages of conventional nematic liquid crystal cells is the fact that the response speed is slow, and a response speed of only a few m**c can be obtained at most. This is one of the factors that limits the range of applications of nematic liquid crystal cells. However, it has recently been found that a faster response can be obtained by using a smectic liquid crystal cell.

It has become clear that some optically active smectic liquid crystals exhibit ferroelectricity, and there are great expectations for their use. Liquid crystals exhibiting ferroelectric properties, ie ferroelectric liquid crystals, were developed in 1975 by R.B.
It is a compound synthesized by Meyer et al., whose representative example is 2-methylbutyl 4-(4-n-decyloxypenzolidenamino)cinnamate, and exhibits ferroelectricity in its chiral smectic C phase. It is characterized by (J, Physiq, ue, 36.
L-69 (1975)).

In recent years, N. A. C1ark et al. (Appl. Phys,
Lett. 36°89 (1,980) is DOB
In the thin film cell of AMBC, we found a diurnal speed response on the order of μsec. Taking advantage of this, the high-speed response of ferroelectric liquid crystals can also be used as materials for displays such as LCD televisions, optical printer heads, optical Fourier transform elements, light valves, and other OSI electronics-related elements. It is attracting attention as a material.

An essential condition for obtaining a liquid crystal compound exhibiting ferroelectric liquid crystal is the presence of an optically active group in the compound.

Although it can be obtained in the known manner so far, it is a semi-functional alcohol with poor reactivity, and chemical modification near the optically active site is limited, making it difficult to design the molecules of liquid crystal compounds. It was making it difficult. Typical examples of such chemical modification of optically active sites include J, W, and G.
The only example is the carburization reaction of amyl alcohol by OODBY et al. (Mol.Cryst, Liq,
Cryst, e1984, (110), 175-20
3) The effects of the optically active group or the substituents in its vicinity include two factors: steric factors and electronic factors at or near the chiral source. As an effect of the physical properties of the liquid crystal material, the former influences the symmetry of the liquid crystal molecules, making it possible, for example, to control the temperature range in which the liquid crystal phase is exhibited. The latter effect changes the dipole moment of the optically active group or its vicinity, making it possible to control the direction and strength of spontaneous polarization, the pitch length, direction, viscosity, etc. Therefore, if the effects of optically active groups or substituents near them can be effectively controlled, the characteristics, temperature range, response speed, viscosity, and pitch length imposed on ferroelectric liquid crystal materials to realize large liquid crystal panel displays can be improved. It becomes easy to design molecules that satisfy the following conditions, or to design formulations using these compounds.

Examples of the effects of the optically active group or the substituent in its vicinity include the following.

That is, compound (A) (A) announced by P. Keller et al. in 1976 exhibits chiral smectic C'MJ in the temperature range from 65°C to 83°C, and compared to DOBAMBC (B),
(B) We have succeeded in increasing the dielectric constant and spontaneous polarization.

This suggests that if a highly polar Peter atom is introduced at or near the chiral source, the dipole moment will increase and, as a result, the spontaneous polarization can be increased.

Therefore, it can be seen that the effect of the substituent at or near the optically active site has a large influence on the physical properties of the ferroelectric liquid crystal. However, as mentioned above, only a limited number of optically active materials have been used in the development of ferroelectric liquid crystals, such as amyl alcohol and octyl alcohol.

(Means for Solving the Problems) The present inventors have investigated various asymmetric sources and have developed a liquid crystal compound that has performance equivalent to or better than liquid crystal compounds obtained from non-i-form alcohols such as amyl alcohol and octyl alcohol. Discovering an optically active β-fluorohydrin compound having
We have arrived at the present invention.

That is, it is an optically active β-fluorohydrin compound represented by general formula (1).

RCHFCH20R2 (1) [However, R is an alkyl group or an aralkyl group having 2 to 10 carbon atoms. R2 is a hydrogen atom or has 2 to 10 carbon atoms
An alkyl or aralkyl group of Cal? It may contain a nyl group or a thionyl group. ] The optically active β-fluorohydrin compound of the present invention is useful as an intermediate for a ferroelectric liquid crystal compound. Optical activity β
-A liquid crystal compound using a fluorohydrin compound has higher spontaneous polarization than other chain optically active alcohols. In other words, a compound made from amyl alcohol (C
) exhibits a ferroelectric liquid crystal phase at n = 7 to 11, but the spontaneous polarization is less than 1 nC/c-.

In comparison, compound (D) using the optically active β-fluorohydrin compound of the present invention exhibits a spontaneous polarization as high as 72 n07 cm, several tens of times as high.

The magnitude of such spontaneous polarization is due to the fact that the optically active group is formed by a carbon-fluorine bond, which has a large dipole moment.

The β-fluorohydrin compound of the present invention can be synthesized as follows.

An optically active α-tosyloxycaldate ester, which is easily derived from an optically active amino acid or an optically active hydroxycalzenic acid, is used as a precursor of an optically active α-fluorocaldate ester, and a polar compound such as DMF or acetonitrile is used. Potassium fluoride in solvent at 100-150°C, 24
- By reacting for 48 hours, α
-Fluorocargenic acid ester was obtained. At this time, the reaction is promoted by adding 18-crown-6-ether as a catalyst to the tosyloxycaldic acid ester and 10-110-1O0'-cent. This reaction is a nucleophilic substitution reaction, and by selecting a sulfonic acid ester as a leaving group, the absolute configuration of the product is reversed through a SnZ type reaction, but an optically active compound can be obtained without compromising optical purity. can be obtained. In addition, by adding crown ether to the reaction solution, "nake"
A d 1on ' type fluorine anion is generated and facilitates the nucleophilic substitution reaction.

This reaction was previously used by Kobayashi et al. to introduce fluorine atoms into steroid compounds;
Yashi et al., Tatrahedron Let, p.
2023 (1979)) The stereochemistry of the reaction was not studied, and when optically active α-tosyloxycaldic acid ester is used, the reaction proceeds stereoselectively.

Fluorination in the reaction is common, e.g. t f
Examples of starting materials include d' valine, leucine, inleucine, alanine, phenylalanine, glutamic acid, aspartic acid, lysine primary amino acids, lactic acid, tartaric acid, and malic acid. Examples of sulfonic acid esters used as leaving groups include toluenesulfonic acid, benzenesulfonic acid, methylsulfonic acid, etc. Carpic acid esters are not particularly limited, but methyl esters, ethyl esters, isopropyl esters, etc. are usually used. It's practical.

α-Fluorocal obtained as described above? The target compound, an optically active β-fluorinated compound, was obtained by reacting the phosphoric acid ester with lithium aluminum hydride in anhydrous ether under ice-cooling.

(Effects of the Invention) A liquid crystal compound can be synthesized using the optically active β-fluorohydrin compound of the present invention as a raw material. (R)-2-fluoro-3-methylbutyl 4/-(4'l-octylcar?nyloxyphenyl)benzoic acid ester, which was synthesized from this compound, exhibited a chiral smectic C phase at 47 to 60°C and spontaneously Polarization is 72 nC/m
"Met.

The optically active β-fluorohydrin compound of the present invention could be obtained as an optically active substance with good purity by using optically active amino acids and other compounds as raw materials.

The present invention will be explained in detail below with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Synthesis of (S)-2-fluoro-3-methylbutanoic acid ethyl ester D-baIJy was used as a raw material in an 11-three-bottle flask equipped with a stirrer, using a known method (K, Koga et al., Chem.

Pharrn, Bull, 27.747 (1979
)), (R) (+) 3-methyl-2-tosyloxybutanoic acid ethyl ester ([α),
-+32.6° (C=6.54.chloroform))7
5.74F (0,252 mol), potassium fluoride 4
6.47F (0,780mol), 18-crown-
6-ether 15.9 (0,056 mo1.), DMF
500 rLl was added, and the mixture was heated and stirred at 100° C. for 24 hours. After the reaction was completed, the reaction solution was slowly poured into ice water (approximately 1 F) and extracted with ether. The ether layer was thoroughly washed with saturated brine, dried over magnesium sulfate, and dried at a concentration of about 1 F/l/L.
f was distilled off, and the residue was distilled under reduced pressure to obtain the target compound.

(86-87℃/76cm Hg) Yield 20.66g Proton N dish δ value (ppm) 0.95, 1.05 (6H, d, 6I (Z, CH (CH
3) 2) 1.28 (3H, t, 7 Hz -C0
0CH2CH3) 1.85-2.50 (L H.

m, CH(CI(3)2) 4.20 (2H,q
, 7H1,C00CH,CI(3)4.60 (IH
,dd, 48Hz, 5Hz, (IjFCO
OEt) Elemental analysis (as C7H1302F) CH Theoretical value (CH) 56.74 8.84 Measured value (CH)
56.70 8.82 Example 2 Synthesis of (S)-2-fluoro-3-methylbutanol In a 50d flask equipped with a condenser, 301 nl of anhydrous ether and lithium aluminum hydride were added dropwise to a magnetic stirrer. (26 mmol) e was added, and the (S) obtained in Example 1 was added under an arganese atmosphere and cooled with water.
2-Fluoro-3-methylbutanoic acid ethyl ester5.
S' (33.7 mmol) and anhydrous ether extracted
Dropped carefully. After completion of the dropwise addition, the reaction vessel was returned to room temperature and stirred for about 3 hours. After the reaction was completed, the reaction solution was poured into ice water for hydrolysis. After neutralizing the solution with dilute hydrochloric acid, it was extracted with ether.

The ether layer was washed with saturated brine, dried over magnesium sulfate, the ether was distilled off, and the resulting residue was distilled at normal pressure (130-132°C/760wHg) to obtain the target compound (S) -2-fluoro- 3-methylbutanol 2.9
7. ! i', (83 percent) was obtained.

Proton-based δ value (ppm) 0.92-LO2(6H, d-5Hz -CH(C
H3)2) 1.90(I H-my CH(C
H3)2) 2.28 (II(-s', CH2
9H) 3.30-3.90 (2H1m -(JtFC
HzOH) 4.20 (IH.

nh * 岨FCH2QH) Elemental analysis value (C3l (1, as OF) CI (Theoretical value (CH) 56.58 10.45 Measured value (
56.55 10.43 Furthermore (S) -
2-Fluoro-3 methyl! In order to check the optical purity of tanol, it was subjected to diester condensation with (+)-α-methoxy-α-trifluorophenyl acetic acid by a conventional method, isolated as diastereomers, and purified at 400 MHz 7'oton NM.
As a result of determining the optical purity from the area ratio of the peaks using Rfc, the optical purity of the compound was (α-methoxy proton, 83.56, 3.57) 93 ee.

Example 3 As a result of carrying out the same reaction as in Example 1 and Example 2 using L-valine as a starting material, (R) -2 was obtained in the same yield.
-Fluoro-3-methylbutanol was obtained.

Example 4 354 μm (1 mmol) of 4-(4'-octylcarbonyloxyphenyl)benzoic acid was dispersed in carbon tetrachloride, 2 ml of thionyl chloride was added, and the mixture was refluxed for about 5 hours to obtain acid chloride. This acid chloride was dissolved in 2-lysine and (S)-2-fluoro-3-methylbutanol 0
．． 1rR1! (1 mmol). After leaving the apparatus at room temperature for about - days, the solvent was distilled off, all insoluble matter was filtered off, the resulting reaction residue was separated by chromatography, and recrystallized from ethanol to give (R)-2-fluoro-3-methylbutyl. 250 m9 of 4'-(4#-octylcarbonyloxyphenyl)benzoic acid ester was obtained. The compound exhibited chiral smectic C phase at 47-60°C.

Further, in place of 4-(4'-octylcarbonyloxyphenyl)benzoic acid, compounds having different carbon numbers in the alkyl groups were used to synthesize liquid crystal compounds having different carbon chains in the alkyl groups. The structural formula and physical properties of the obtained liquid crystal compound are shown in Table 1.

Example 5 4'((R)-2-fluoro-3-methylbutoxy)
Synthesis of phenyl 4-octyloxybenzoate ester (a) Synthesis of 2-fluoro-3-methyl-1-tosyloxybutane 2-fluoro-3-methylbutanol 5.571 (52
, 4 mmol) fz, dissolved in 20 rnl of pyridine, cooled to 0°C, and dissolved p-) toluenesulfonic acid chloride 30.17 (157.2 mmol) and pyridine 1.
00d was added dropwise. After the dropwise addition was completed, the mixture was left at room temperature for 2 days, and then poured into dilute hydrochloric acid for hydrolysis. Extracted with chloroform, washed with saturated aqueous sodium bicarbonate, dried over calcium chloride, distilled off the chloroform, and purified by column chromatography (Silica Del). 10.1.9 (b) 2-fluoro-3methyl-1-tosyloxybutane obtained in 4(-2-fluoro-3-methylbutoxy÷phenol synthesis (1L)) 10.1 El (38.8 mmol) ,
Hydroquinone 6.4, li' (58,2 mmol
) and 12 g of potassium carbonate in 50 d of DMF
(86,8d) was added and stirred at 70°C for about 20 hours.

After hydrolysis with dilute hydrochloric acid, extraction with ether, drying with magnesium sulfate, distillation of ether, and column chromatography (Silica Del), a sample was obtained. 3.5
(c) 4' combination (R) -2-fluoro-3-methylbutoxy)phenyl 4+2-fluoro-3-methylbutoxy ÷ obtained in synthesis (b) of 4-octyloxy7benzoate ester
400rn9 of phenol, 200ml of phenol, and 20M of carbon tetrachloride were added, and the same acid chloride obtained from 500~ of 4-octyloxybenzoic acid and 20M of carbon tetrachloride were added dropwise at 0°C. - After stirring day and night, hydrolysis and extraction with chloroform were performed. After drying with CaCt2, chloroform was removed. The residue was purified by column chromatography and recrystallized from EtOH.
(R) -2-Fluoro-3-methylbutoxy)phenyl 4-octyloxybenzoic acid ester (380 ml) was obtained. The physical properties of the compound are shown in Table 2.

Furthermore, in (c), 4-dodecyloxybenzoic acid is used instead of 4-octyloxybenzoic acid to give 4'(-(R
) -2-fluoro-3-methylbutoxy)phenyl
4-octyloxybenzoic acid ester was synthesized and its physical properties are shown in Table 2.

Claims (2)

[Claims] (1) An optically active β-fluorohydrin compound represented by the following general formula (1). R^1■HFCH_2OR^2(1) (However, R^1 is an alkyl group or aralkyl group having 2 to 10 carbon atoms. R^2 is a hydrogen atom or an alkyl group or aralkyl group having 2 to 10 carbon atoms, and carbonyl or thionyl group.) (2) A patent where R^1 is a general formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) (However, n is 0, 1 or 2, and m is 0 or 1.) Optically active β- according to claim 1
Fluorohydrin compounds.