JP2879456B2 - Optically active fluoroalcohol and method for producing the same - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel optically active fluoroalcohol. The compound is useful as a synthetic intermediate for pharmaceuticals, agricultural chemicals, other physiologically active substances, and functional materials. In particular, it is useful as an intermediate for synthesizing ferroelectric liquid crystal compounds that have received attention as functional materials. The compound of the present invention is a novel optically active compound having two asymmetric carbon atoms in the molecule and having a fluoro group which is a polar group. The compound is referred to as biphenyl, phenylpyrimidine, phenylpyridine derivative or the like. Can lead to various ferroelectric liquid crystal compounds.

[Background Art] Optically active substances having a fluoro group in the molecule have attracted attention in the fields of industrial raw materials, agricultural chemicals, functional materials, etc. because of their unique physical properties. In the field of pharmaceuticals, bioactive substances such as fluorosteroids (Ch
emical Times, 2241 (1986), Chemical Times, 8 (198
7)) etc. are known.

On the other hand, in ferroelectric liquid crystal materials in the field of functional materials, 2-methyl-1-butanol, 4-
Compounds synthesized using optically active alcohols such as methyl-1-hexanol and 2-hexanol and optically active carboxylic acids such as 2-methylbutanoic acid and 4-methylhexanoic acid are mainly used. In order to improve this, various optically active alcohols, carboxylic acids, and the like have been researched and developed in recent years for the purpose of developing a material having a large spontaneous polarization related to the response speed. For example,
Optically active 2-fluoro-1-octanol (Japanese Unexamined Patent Publication No.
93248, JP-A-62-198633), optically active 1,1,1-trifluoro-2-octanol (JP-A-63-307837) and optically active 3 having two asymmetric carbons in the molecule. -Methyl-2-chloro-pentanol (JP-A-60-16878)
0), optically active 3-methyl-2-chloro-1-octanol (JP-A-63-165371) has been reported. However, the number is small, and development of various optically active alcohols useful as intermediates for synthesizing ferroelectric liquid crystal materials is desired.

Thus, the present inventors have conducted intensive studies with the aim of providing a novel optically active alcohol useful for synthesizing a ferroelectric liquid crystal compound having a high response speed, and succeeded in providing a novel compound according to the present invention. did.

DISCLOSURE OF THE INVENTION The present inventors have found that the formula (1) (However, R ¹ is an alkyl group having 3 to 12 carbon atoms,
R ² represents an alkyl group having 1 or 2 carbon atoms.

(Showing an asymmetric carbon atom).

The novel optically active fluoroalcohol has two asymmetric carbons substituted with a fluoro group and a hydroxyl group in the molecule, and the carbon substituted with the fluoro group has the absolute configuration of (R) or (S). An optically active fluoroalcohol wherein the carbon substituted by the hydroxyl group is a racemic carbon, the carbon substituted by the fluoro group is a racemic carbon, and the carbon substituted by the hydroxyl group has the absolute configuration of (R) or (S). And an optically active fluoroalcohol having an absolute configuration of (R) or (S), wherein the carbon substituted for the fluoro group and the carbon substituted for the hydroxyl group are each independently an absolute configuration of (R) or (S). An optically active fluoroalcohol in which a carbon atom having a fluoro group as a substituent has an absolute configuration of (R) or (S), and a carbon atom having a hydroxyl group as a substituent is a racemic carbon atom. Can be synthesized by alkylating an optically active fluoroaldehyde with an organometallic reagent that can be used as an alkylating agent. An optically active fluoroalcohol in which the carbon atom having a fluoro group as a substituent is a racemic carbon atom and the carbon atom having a hydroxyl group as a substituent has the absolute configuration of (R) or (S) is obtained by converting a racemic fluoroaldehyde into an optically active fluoroalcohol. It can be synthesized by asymmetric alkylation with a dialkylzinc reagent in the presence of an active amino alcohol catalyst. A carbon atom having a fluoro group as a substituent has an absolute configuration of (R), and a carbon atom having a hydroxyl group as a substituent has an absolute configuration of (S), or a carbon atom having a fluoro group as a substituent. Has an absolute configuration of (S), and a carbon atom having a hydroxyl group as a substituent has an absolute configuration of (R). The optically active fluoroalcohol uses an optically active fluoroaldehyde, and the aldehyde is used as an alkylating agent. It can be synthesized by diastereoselective alkylation with a usable organometallic reagent or asymmetric alkylation with a dialkylzinc reagent in the presence of an optically active amino alcohol catalyst. An optically active fluoroalcohol, which is a diastereomer having a different absolute configuration at a carbon atom having a hydroxyl group as a substituent, is converted into a sulfonic acid ester, and then converted to an inverted carboxylic acid ester by reacting with a carboxylate, This can be synthesized by hydrolysis. In addition, the present inventors have found that, in the synthesis of the optically active fluoroalcohol (1), an intermediate thereof represented by the formula (2) (Wherein R ¹ is an alkyl group having 3 to 12 carbon atoms, (Indicating an asymmetric carbon atom).

To date, racemic fluoroaldehydes, for example, 2-fluoroheptanal, have been synthesized by reacting 1-trimethylsilyloxy-2-heptene with fluorine gas in Freon 11 (Tetrahedron Leh).
tters., 27 , 2715 (1986)). However, optically active fluoroaldehyde cannot be synthesized by this method, and has never been reported before. The present inventors have succeeded in easily providing a novel optically active fluoroaldehyde by reduction of an optically active α-fluorocarboxylic acid ester or oxidation of an optically active 2-fluoro-1-alkanol.

Hereinafter, the synthetic route of the optically active fluoroalcohol according to the present invention is represented by a formula, and their synthesis methods will be described.

(Wherein R ¹ is an alkyl group having 3 to 12 carbon atoms,
R ² represents an alkyl group having 1 or 2 carbon atoms, and R ³ represents
It represents an alkyl group having 1 to 18 carbon atoms.

In the above process diagram, the optically active α-hydroxycarboxylic acid ester of the formula (B) is obtained by converting the optically active α-hydroxycarboxylic acid of the formula (A) to an alcohol under the catalyst such as p-toluenesulfonic acid. And by heating and stirring.

The optically active α-tosyloxycarboxylic acid ester of the formula (C) can be synthesized by reacting the compound of the formula (B) with tosylic acid chloride.

The optically active α-fluorocarboxylic acid ester of the formula (D) is prepared by heating the compound of the formula (C) with potassium fluoride in a polar solvent such as dimethylformamide as a catalyst in the presence of 18-crown-6-ether. Can be synthesized.

The optically active α-fluoro alcohol of the formula (F) is obtained by reducing the compound of the formula (D) with a reducing agent such as lithium aluminum hydride in a solvent such as ether, It can be synthesized by adding hydrogen fluoride to 1,2-epoxyalkane.

The optically active fluoroaldehyde of the formula (G) is represented by the formula (D)
Is synthesized by reducing the compound of formula (F) in a solvent such as ether with a reducing agent such as diisobutylaluminum hydride, or oxidizing the compound of formula (F) with oxalyl chloride, dimethyl sulfoxide and triethylamine. be able to. The racemic fluoroaldehyde of the formula (G) can be similarly synthesized from a racemic compound of the formula (D) or a racemic compound of the formula (F).

An optically active fluoroalcohol of the formula (H) in which the carbon atom having a fluoro group as a substituent has the absolute configuration of (R) or (S) and the carbon atom having a hydroxyl group as a substituent is a racemic carbon has a formula (H) It can be synthesized by adding an organic metal reagent usable as an alkylating agent, for example, an alkyl magnesium reagent, an alkyl lithium reagent, an alkyl titanium reagent, an alkyl lead reagent, an alkyl zinc reagent, etc., to the optically active fluoroaldehyde of G). it can. The carbon atom having a fluoro group as a substituent is racemic carbon, and the carbon atom having a hydroxyl group as a substituent is (R)
Alternatively, the optically active fluoroalcohol of the formula (H) having the absolute configuration of (S) can be prepared by adding a racemic fluoroaldehyde of the formula (G) to an optically active dibutyl norefedrin (J. Chem. Soc., Chem. Commun., 1960 (198
7)), optically active pyrrolidyl methanol (J. Am. Chem. So
c., 109 .7111 (1987) ), optically active 1-piperidino-3,3
-Dimethyl-2-butanol (J. Am. Chem. Soc., 110,787
7, (1988)) and asymmetric addition of a dialkylzinc reagent using an optically active amino alcohol as a catalyst. Whether the carbon atom having a fluoro group as a substituent has the absolute configuration of (R) and the carbon atom having a hydroxyl group as a substituent has an absolute configuration of (S),
Alternatively, the optically active fluoroalcohol of the formula (H) wherein the carbon atom having a fluoro group as a substituent has the absolute configuration of (S) and the carbon atom having a hydroxyl group as a substituent has the absolute configuration of (R) is represented by the formula An organic metal reagent which can be used as the alkylating agent is diastereoselectively added to the optically active fluoroalcohol of (G), or the optically active aminoalcohol is used as a catalyst,
It can be synthesized by asymmetric addition of a dialkylzinc reagent.

The optically active fluoroalcohol of the formula (I), which has a diastereomeric relationship with the optically active fluoroalcohol of the formula (H), is obtained by converting the optically active fluoroalcohol of the formula (H) into methane in a solvent such as methylene chloride. After reaction with a sulfonic acid halide such as sulfonic acid chloride to convert to a sulfonic acid ester, this is reacted with a carboxylate such as potassium acetate in a solvent such as dimethyl sulfoxide to form a carbon atom having a hydroxyl group as a substituent. Can be obtained by hydrolysis.

Note that the absolute configuration of the carbon atom having a hydroxyl group as a substituent in the optically active fluoroalcohol in the present specification is not absolutely derivable from the sample, and physical properties such as specific rotation have not been compared. Has not decided. However, in the alkylation reaction of an optically active α-halogenated carbonyl compound having an asymmetric carbon atom having a halogen atom as a substituent at the α-position, the optically active α-halogenated carbonyl compound, in its transition state, has a carbonyl oxygen and a halogen atom. Has been reported to be oriented to the anti-periplanar, and that alkylation proceeds from a direction with less steric hindrance (Asymmetric Synthesised b
y JDMorrison, Academic Press, Ner York (1983))
Further, when dimethylzinc or diethylzinc is asymmetrically added to n-heptanal under the optically active N, N-dibutylnorefedrine catalyst having the absolute configuration of (1S, 2R), the absolute configuration of (S) It has been reported that an optically active alcohol having an absolute configuration of (1R, 2S) can be obtained by using a catalyst having an absolute configuration of (1R, 2S) (J. Chem. Soc., Chem. Commun., 1690 (1
987)); Yugobutsu, 47 11 Judging from (1989), for example, (S)-2-fluoro octa knurls in the absence of catalyst, as an alkylating agent, a methylating agent such as methyl titanium triisopropoxide Act on, or
It is considered that addition of dimethylzinc under the catalyst of (1R, 2S) -N, N-dibutylnorefedrine produces optically active 3-fluoro-2-nonanol having the absolute configuration of (2R, 3S). When dimethylzinc is added to racemic 2-fluorooctanal under an optically active N, N-dibutylnorefedrine catalyst having an absolute configuration of (1R, 2S), it has an absolute configuration of (2S). Since the formation of optically active 3-fluoro-2-nonanol is expected, the absolute configuration of the novel optically active fluoroalcohol according to the present invention has not been absolutely confirmed, but is shown accordingly. It is a thing.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 (a) 8.0 g (50 mmol) of (R) -2-hydroxyoctanoic acid,
0.1 g of p-toluenesulfonic acid was dissolved in 100 ml of isopropyl alcohol and heated under reflux for 4 hours. After the reaction,
The isopropyl alcohol is distilled off, and the residue is n-hexane.
Dissolved in 100 ml, 30 ml of 2% aqueous sodium hydrogen carbonate solution,
Then, it was washed with 30 ml of pure water. Then, after drying over sodium sulfate, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain the title (R) -2-hydroxyoctanoic acid isopropyl ester.

Boiling point (78-80 ° C / 0.7mmHg) Yield 9.2g (b) (R) -2- obtained in the above (a) was added to 50 ml of pyridine.
Hydroxyoctanoic acid isopropyl ester 7.3g (36mm
ol) (93% ee in optical purity) was dissolved, and 8.4 g (44 mmol) of tosylate chloride was added dropwise at -5 ° C to 0 ° C. 0 ° C
After stirring for 2 hours, the mixture was poured into ice water. After extraction with chloroform, the extract was dried over magnesium sulfate, chloroform was distilled off, and the residue was purified by column chromatography (silica gel, chloroform), followed by distillation under reduced pressure to obtain the title (R) -2-tosyloxyoctane. The acid isopropyl ester was obtained.

Boiling point (160-165 ° C / 0.7mmHg) Yield 11.3g (c) In 20 ml of dimethylformamide, 3.4 g (9.5 mmol) of (R) -2-tosyloxyoctanoic acid isopropyl ester obtained in the above (b) and 1.6 g (28 mmol) of potassium fluoride were obtained.
l), 0.8 g (30 mmol) of 18-crown-6-ether was added, and the mixture was heated and stirred at 100 ° C for 41 hours. After completion of the reaction, the reaction mixture was poured into ice water and extracted with ether. After the ether layer was dried over sodium sulfate, the ether was distilled off.
The residue was purified by column chromatography (silica gel, hexane-chloroform) and distilled under reduced pressure.
The title (S) -2-fluorooctanoic acid isopropyl ester was obtained.

Boiling point (88-90 ° C / 6mmHg) Yield 0.87g (d) 0.22 g (0.1 mmol) of (S) -2-fluorooctanoic acid isopropyl ester obtained in the above (c) was mixed with 1 m of ether.
This was added dropwise at 0 ° C. to 0.017 g (0.5 mmol) of lithium aluminum hydride suspended in 3 ml of ether. After stirring at room temperature for 18 hours, the reaction solution was ice-cooled 2N
Charged into hydrochloric acid. After ether extraction, the extract was dried over sodium sulfate, and ether was distilled off. The residue was distilled under reduced pressure to obtain the title (S) -2-fluoro-1-octanol.

Boiling point (115-120 ° C / 13mmHg) Yield 0.15g (e) -1 0.65 g (3.2 mmol) of (S) -2-fluorooctanoic acid isobutyl ester obtained in the above (c) was added to 10 ml of ether.
And 3 ml (1 mol-L, 3 mmol) of an n-hexane solution of diisobutylaluminum hydride was added dropwise at -70 ° C. After stirring at -70 ° C for 1 hour, the reaction mixture was poured into a saturated aqueous ammonium chloride solution. After ether extraction
The ether layer was dried over sodium sulfate, and ether was distilled off. The residue is distilled under reduced pressure to obtain the title (S).
-2-Fluoroctanal was obtained.

Boiling (37-40 / 5 mmHg) Yield 0.39g proton NMRδ value (ppm) 0.7-2.0 (9H, m , CH 3 CH 2 CH 2 -) 2.5 (2H, m, -CH 2 CH 2 CHF-)
_{3.5 (2H, m, -CH 2} CHF-) 4.4 5.2 (1H, dt, J = 48,6Hz, -CHF
−) 9.7 (1H, d, J = 6 Hz, −CH = 0) ▲ [α] ²⁵ _D ▼ = −24.8 ° (c = 2.0, EtOH) (e) -2 To 300 ml of methylene chloride, 40 ml of oxalyl chloride (0.47 mmo
l) was mixed and cooled to -78 ° C. Methylene chloride 1
66.4 ml of dimethyl sulfoxide dissolved in 00 ml (0.94 mol
l) was added dropwise and stirred for 15 minutes. Next, 29.6 g of (S) -2-fluoro-1-octanol obtained in the above (d) was obtained.
(0.20 mol) was dissolved in 200 ml of methylene chloride, and this was slowly added dropwise. After further stirring at -78 ° C for 1 hour,
195 ml (1.40 mol) of triethylamine were added dropwise. After the reaction solution was poured into water, the layers were separated. Methylene chloride 30
The mixture was extracted with 0 ml, and the organic layers were combined, washed with 2N hydrochloric acid and 2N aqueous sodium hydrogencarbonate, then with saturated saline, and dried over sodium sulfate. After distilling off chloroform, the residue was distilled under reduced pressure to obtain the title (S) -2-fluorooctanal.

Boiling point (37-38 ° C / 5mmHg) Yield 23.2g (f) -1 In an argon atmosphere, 2.0 g (7.6 mmol) of (1R, 2S) -N, N-dibutylnorefedrine (J. Chem. Soc., Chem. Comm.
un., 1690 (1987)) (S) -2- obtained in the above (e).
12.6 g (86 mmol) of fluorooctanal and dry n-
Hexane (150 ml) was stirred at room temperature for 30 minutes. After cooling to 0 ° C, 170 ml of a 1N dimethyl zinc n-hexane solution (170 mmo
l) was added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 2 days, and then the mixture was poured into ice-cooled 2N hydrochloric acid. After layer separation, the aqueous layer was extracted with 300 ml of methylene chloride, the organic layers were combined, dried over sodium sulfate, and methylene chloride was distilled off. The residue was distilled under reduced pressure to obtain the title (2R, 3S) -3-fluoro-2-nonanol.

Boiling point (51-53 ℃ / 0.8mmHg) Yield 9.1g proton NMRδ (ppm) 0.87 (3H, t, J = 5Hz, CH 3) 1.10 (3H, d, J = 6Hz, CH (OH) C
H ₃ ) 1.2−2.0 (10H, m, CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CHF) 2.9 (1H, d,
J = 5Hz, OH) 3.1-4.2 (1H, m, CH (OH)) 3.1-4.9 (1H, d
q, CHF) ▲ [α] ²⁵ _D ▼ = −23.4 ° (c = 2.0, EtOH) Elemental analysis C ₉ H ₂₉ FO CHF Theoretical value 66.63 11.80 10.71 Measurement value 65.70 11.73 10.64 There are several stereoisomers. The compound obtained in this example was derivatized with (S) -α-acetoxypropanoic acid chloride and analyzed by gas chromatography (PEG-20M, df = 0.3 μm, 0.25 mm × 25 m). Isomeric ratio is (2R, 3S) 89.3%
(2S, 3R) 2.3% (2R, 3R) 4.7% (2S, 3S) 3.7%.

(F) -2 0.1 g (0.6 mmol) of (S) -2-fluorooctanal obtained in the above (e) was dissolved in 2 ml of ether, and 0.17 g (0.7%) of methyltitanium triisopropoxide was added at -78 ° C in an argon atmosphere. mmol) was added. Then -50 ° C
After stirring for 1 hour, the mixture was poured into ice water. After extraction with ether, the ether layer was dried over sodium sulfate. The ether was distilled off to give (2R, 3S) -3-fluoro-2
0.9 g of nonanol was obtained. Analysis by gas chromatography indicated a diastereomeric excess of 67% de.

Example 2 10.3 g (63.5 mmol) of (2R, 3S) -3-fluoro-2-nonanol obtained in Example 1 (f) -1 and 12.0 ml (146 mmol) of pyridine were dissolved in 50 ml of methylene chloride.
To this, 7.0 ml (90 mmol) of methanesulfonic acid chloride was added to 3
It was added dropwise over 0 minutes. After stirring overnight, the reaction mixture was poured into 2N hydrochloric acid. After separation, the aqueous layer was extracted with 150 ml of methylene chloride, the organic layers were combined, and the organic layer was washed with an aqueous sodium hydrogen carbonate solution and then with a saturated saline solution, dried over sodium sulfate, concentrated, and concentrated to give methanesulfone. Acid ester
16.6 g were obtained. This was stirred with 23.7 g (241 mmol) of potassium acetate and 5.0 g (19.1 mmol) of 18-crown-6-ether at 100 ° C. for 15 hours in 300 ml of dimethyl sulfoxide. The reaction mixture was poured into ice water and extracted with ether. This ether layer is washed with 2% sodium bicarbonate, 2%
% Hydrochloric acid and then with a saturated saline solution. After the ether layer was dried over sodium sulfate, the ether was distilled off to obtain 12.8 g of acetic ester. This is added to 1N hydrochloric acid methanol 200
The mixture was dissolved in ml and stirred at 40 ° C. for 3 hours. Then, the mixture was neutralized with sodium hydrogen carbonate, ether was added, and the precipitated salt was removed. The residue was dissolved in ether, washed with saturated saline, and dried over sodium sulfate.
After the ether was distilled off, the residue was distilled under reduced pressure to obtain the title (2S, 3S) -3-fluoro-2-nonanol.

Boiling point (41-45 ° C./0.7 mmHg) Yield 6.9 g Proton NMR δ (ppm) 0.89 (3H, t, J = 6 Hz, CH ₃ ) 1.19 (3H, dd, J = 6.1 Hz, CH (O
_{H) CH 3) 1.2-2.0 (10H} , m, CH 2 CH 2 CH 2 CH 2 CH 2 CHF) 2.04
(1H, dd, J = 4,3Hz, OH) 3.4-4.2 (1H, m, CH (OH)) 3.4
−4.6 (1H, dq, J = 63, 6 Hz, CHF) ［[α] ²⁵ _D ＝ −18.6 ° (c = 1.8, EtOH) This compound has four types of stereoisomers. The compound obtained in this example was derivatized with (S) -α-acetoxypropanoic acid chloride and analyzed by gas chromatography (PEG-20M, df = 0.3 μm, 0.25 mm × 25 m). Isomer abundance ratio is (2R, 3S) 6.1%
(2S, 3R) 3.7% (2R, 3R) 0.5% (2S, 3S) 89.7%.

Example 3 In Example 1 (f) -1, 2.0 g of (1S, 2R) -N, N-dibutylnorefedrin was used instead of 2.0 g of (1R, 2S) -N, N-dibutylnorefedrin, (S) -2
-Racemic 2 instead of 12.6 g of fluorooctanal
Example 1 uses 12.6 g of fluorooctanal, and
(F) By operating in the same manner as -1, (2S) -3-fluoro-
2-Nonanol was synthesized.

Boiling point (48-49.5 ° C./0.5 mmHg) Yield 8.6 g Proton NMR δ (ppm) 0.89 (3H, t, J = 6 Hz, CH ₃ ) 1.1 (1 H, d, J = 6 Hz, CH (OH) CH
_{3) 1.2-2.0 (10H, m,} CH 2 CH 2 CH 2 CH 2 CH 2 CHF) 2.5 (1H, s, O
H) 3.3-4.2 (1H, m, CH (OH)) 3.3-4.9 (1H, dq, CHF) ▲ [α] ²⁵ _D ▼ = + 1.91 ° (c = 2, EtOH) There are four stereoisomers. The compound obtained in this example was derivatized with (S) -α-acetoxypropanoic acid chloride and analyzed by gas chromatography (PEG-20M, df = 0.3 μm, 0.25 mm × 25 m). Isomers abundance ratio is (2R, 3S) 15.0%
(2S, 3R) 49.4% (2R, 3R) 1.9% (2S, 3S) 33.7%.

Usage example 1 In a reaction tube, (2S) -3-fluoro-2-tosyloxynonanol 1 synthesized from (2S) -3-fluoro-2-nonanol obtained in Example 3 and tosylate chloride.
3.6 g, 4.8 g of 2-fluorophenol, 12 sodium carbonate
g and 100 ml of cyclohexanone were charged and heated and stirred at 140 ° C. for 15 hours. The reaction solution was poured into dilute hydrochloric acid, extracted with ether, washed with water, dried over sodium sulfate, and the residue obtained by distilling off the solvent was subjected to silica gel column chromatography using hexane / benzene = 1/1 as an eluent. Purify by graph and recrystallize with acetone to give (1R) -2- (1-methyl-2-fluorooctyl) oxyfluorobenzene
5.89 g were obtained. The above-mentioned purification is purification only by silica gel column chromatography.

Yield 53.5% HPLC 94.5% In the reaction tube, the (1R) -2- (1-methyl-2-fluorooctyl) oxyfluorobenzene obtained in (a) was added.
5.89 g and chloroform 20 ml were charged, and while stirring at room temperature, Br ₂
4 g was added dropwise over 30 minutes. The reaction solution was poured into a dilute aqueous sodium hydroxide solution, the chloroform layer was washed with brine, the solvent was distilled off, and the residue [(1R) -3-fluoro-4
-(1-Methyl-2-fluorooctyl) oxybromobenzene] 6.70 g was obtained.

Yield 87% HPLC 96.0% Under a nitrogen stream, were charged Mg0.27GI ₂ small amounts to the reaction solution, to which 2-fluoro-4-bromo-4'was poured an appropriate amount of THF20ml solution octyloxy Biff enyl 3.56 g, warmed. After the start of the reaction, the remaining THF solution was added dropwise under reflux and stirring. After the addition, the mixture was stirred and refluxed for 2 hours to prepare a Grignard reagent. In a separate container, 0.03 g of Cl ₂ Pd (PPh ₃ ) ₂ and ₂ ml of THF were charged, and 1 m of (iso-C ₄ H ₉ ) ₂ AlH / hexane was added under a nitrogen stream.
l, and (1R) -3- obtained in the above (b).
Fluoro-4- (1-methyl-2-fluorooctyl)
A solution of 2.10 g of oxybromobenzene in 15 ml of THF was added, and 50-
The mixture was heated to 55 ° C., and the Grignard reagent prepared above was added dropwise thereto, followed by aging at the same temperature for 2 hours. The reaction solution was poured into dilute hydrochloric acid, extracted with benzene, washed with water, dried over sodium sulfate, and the solvent was distilled off. The residue was purified by chromatography,
Further, by recrystallization with a mixed solvent of methanol / acetone, 1.36 g of (1R) -3,3'-difluoro-4- (1-methyl-2-fluorooctyl) oxy-4 ″ -octyloxy-p-terphenyl was obtained. The purity of the product was 99.6% by HPLC.
Mass analysis showed a molecular ion peak at 554,
From the raw materials used, it was confirmed that the obtained substance was the specified substance. This is the METTLER HOT stage
The results of observing the phase change under a polarizing microscope equipped with FP-82 are shown below.

Usage Example 2 Polyvinyl alcohol (PVA) was applied to the surface, and a rubbing treatment was performed on the surface to produce a liquid crystal cell having a cell thickness of 3 μm and a transparent electrode having been subjected to a parallel alignment treatment. The compound obtained in the above was sealed and gradually cooled from an isotropic liquid to an SmC ^* phase to prepare a liquid crystal device. This liquid crystal device was scissored on two polarizing plates, a rectangular wave of ± 25 V, 200 Hz was applied, and the response time was determined from the change in the transparent intensity.
It was 193 µsec at ° C. In addition, 205μsec at 45 ° C
And the temperature dependency was good.

The present invention is considered to be difficult to synthesize using natural products or amino acids as starting materials. It is possible to provide an optically active fluoroalcohol having an alkyl group of various lengths, and further, as shown in a usage example, was synthesized using the optically active fluoroalcohol according to the present invention (1R)- 3,3'-Difluoro-4- (1-methyloxy-2-fluorooctyl) oxy-4 "-octyloxy-p-terphenyl shows a chiral smectic phase at 53.1-71.6 ° C, and shows the response time and its Since the compound has good temperature dependency, it is clear that the optically active fluoroalcohol according to the present invention is extremely useful as a synthetic intermediate for ferroelectric liquid crystals.

────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Tsuneori Fujii 1-7-1, Inari, Soka City, Saitama Prefecture Kanto Chemical Co., Ltd. Central Research Laboratory Co., Ltd. (56) References Am. Chem. Soc. , Vol. 102, no. 9, p. 3115-3120 (1980) Am. Chem. Soc. , Vol. 103, no. 13, p. 3800-3806 (1981) Tetrahedron, Vol. 44, No. 10, p. 2875-2881 (1988) Tetrahedron Letters, Vol. 30, No. 8, p. 967-970 (1989) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 31/38 CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. The following general formula (Wherein R ¹ is an alkyl group having 3 to 12 carbon atoms,
R ² represents an alkyl group having 1 or 2 carbon atoms. An asymmetric carbon atom). 2. The optically active fluoroalcohol according to claim 1, wherein R ² is a methyl group. 3. The following general formula: (Wherein, R ¹ is an alkyl group having 3 to 12 carbon atoms)
Wherein, in the presence or absence of a catalyst, an organometallic reagent which can be used as an alkylating agent is added to the fluoroaldehyde represented by the general formula (1): (Wherein R ¹ is an alkyl group having 3 to 12 carbon atoms,
R ² represents an alkyl group having 1 or 2 carbon atoms. Asymmetric carbon atom). 4. The method according to claim 3, wherein an optically active fluoroaldehyde is used as the fluoroaldehyde, and an organometallic reagent usable as an alkylating agent is added to the optically active fluoroaldehyde in the absence of a catalyst. A method for producing an optically active fluoroalcohol. 5. The method according to claim 3, wherein an optically active amino alcohol is used as the catalyst, and a dialkyl zinc reagent is used as the organometallic reagent.