JP2885255B2 - Optically active alcohol and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel optically active alcohol having a trifluoromethyl group on an asymmetric carbon and an alkoxy group at a terminal, and a process for producing the same.

[0002]

2. Description of the Related Art Optically active substances have hitherto been used in the fields of pharmaceuticals and agricultural chemicals, but have recently attracted attention as functional materials such as ferroelectric liquid crystals and organic nonlinear materials. For example, in the field of organic nonlinear materials, it is desirable that an asymmetric center exists in a molecule in order for the organic material to produce a second-order nonlinear optical effect [for example, Yamaguchi, Nakano, Fueno; Chemistry, Vol. No., p. 757 (1987)]. In the field of ferroelectric liquid crystals, it is essential that the liquid crystal molecules be optically active in order for the liquid crystal to exhibit ferroelectricity [for example, Jono and Fukuda;
No., p. 568 (1989)]. Conventionally, in such a field, optically active substances such as 2-butanol, 2-octanol, 2-methyl-1-butanol and amino acid derivatives have been used as optically active sources. However, when such an optically active substance is used, the properties of the obtained material are limited, and it is desired to find a new optically active substance.

Recently, in the field of ferroelectric liquid crystals, CF ₃ C * H (OH) in which fluorine is substituted on asymmetric carbon as an optically active source.
CH ₂ COOC ₂ H ₅ , CF ₃ C * H (OH) CH ₂ CH ₂ OC ₂ H ₅ , CF ₃ C * H (OH) CH ₂ C
H ₂ CH ₂ OC ₂ H ₅ , CF ₃ C * H (OH) CH ₂ CH ₂ CH ₂ CH ₂ OC ₂ H ₅ , CF ₃ C * H (O
Attempts to produce ferroelectric liquid crystals using alcohols such as H) C ₆ H ₁₃ , CF ₃ C * H (OH) C ₈ H ₁₇ , C ₂ F ₅ C * H (OH) C ₈ H ₁₇ have been made. It has been actively performed (for example, JP-A-64-3154, JP-A-1-316339, JP-A-1-316267,
JP-A-1-316372, JP-A-2-225434
And JP-A-2-229128. ). All of the ferroelectric liquid crystals produced using these alcohols have a large spontaneous polarization and a relatively fast response speed because a fluorine atom having a high electronegativity is substituted on the asymmetric carbon. Furthermore, CF ₃ C * H (OH) C ₆ H ₁₃ , CF ₃ C * H (OH) C ₈
It has been recognized that liquid crystals produced using H ₁₇ , C ₂ F ₅ C * H (OH) C ₈ H ₁₇ etc. are likely to give ferroelectric liquid crystals having an antiferroelectric phase. Is attracting attention as a very characteristic alcohol. Ferroelectric liquid crystals having an antiferroelectric phase have been discovered very recently [(AD
L. Chandani, E. Gorecka, Y. Ouchi, H. Takezoe, A. Furukawa:
Jpn. Appl. Phys., 28, (1989)] Alignment is easier than conventional ferroelectric liquid crystals, alignment self-healing ability, high contrast ratio, clear DC threshold It has attracted great attention because of its various advantages.

[0004]

An alcohol having a structure in which a fluorine atom is substituted on an asymmetric carbon in a molecule (hereinafter, sometimes abbreviated as a fluorine-substituted alcohol) is a ferroelectric substance having an antiferroelectric phase. Has attracted attention as a raw material for producing a ferroelectric liquid crystal (hereinafter sometimes abbreviated as an antiferroelectric liquid crystal), but the antiferroelectric liquid crystal obtained using the above-mentioned known fluorine-substituted alcohol is There is still a demand for a fluorine-substituted alcohol that is not sufficient in terms of response speed, practical temperature range, and the like, and that provides a liquid crystal with even better performance. Further, as a method for producing the optically active alcohol of the present invention, an alcohol similar to the present invention is used as shown below.
Although it is conceivable to produce according to the production method of F ₃ C * H (OH) (CH ₂ ) ₄ OC ₂ H ₅ , this method is an extremely complicated method, and it is desired to develop a more efficient production method. It is.

[0005]

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The present invention has been made in view of the above situation, and has a trifluoromethyl group on an asymmetric carbon atom which can be used for producing a liquid crystal material having excellent performance, and has an alkoxy terminal at the terminal. It is intended to provide a novel optically active alcohol having a group and a simple method for producing the same.

[0007]

SUMMARY OF THE INVENTION The present invention provides a novel optically active alcohol represented by the general formula (I), wherein, in the general formula (I), for example, m is 4 or less. To

[0008]

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(In the above formula, m represents an integer of 5 or more, n represents an integer of 1 or more, and C * represents an asymmetric carbon atom.) As shown in, for example, JP-A-64-3154. When such a liquid crystal compound is produced, the liquid crystal compound does not have an antiferroelectric phase, whereas when the optically active alcohol of the present invention is used, a liquid crystal compound having an antiferroelectric phase can be obtained. The optically active alcohol of the present invention is particularly useful as a raw material for producing such an antiferroelectric liquid crystal. In the present invention, after protecting the hydroxyl group of the optically active ethyl 4,4,4-trifluoro-3-hydroxybutanoate, the ester moiety is reduced, and the obtained alcohol is converted to a sulfonic acid ester. After substitution with an alkylalkoxy group, any of m and n in the general formula (I) where m is 5 or more and n is 1 or more in the general formula (I), which has been difficult by the conventional method, by removing the protected hydroxyl group first. Based on the fact that the present inventors have found that the optically active alcohol can be produced very easily, the present invention provides a new method for producing the optically active alcohol of the present invention. That is, the method for producing an optically active alcohol of the present invention comprises:
(1) The following general formula (I-1),

[0010]

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(In the above formula, W represents a hydroxyl-protecting group, Y represents a sulfonyl group, and C * represents an asymmetric carbon atom.)
The sulfonate represented by the following general formula (I-
2),

[0012]

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(Wherein m represents an integer of 5 or more and n represents an integer of 1 or more), and reacted with a Grignard reagent represented by the following general formula (I-3):

[0014]

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(Wherein W, n and C * have the same meanings as described above, and m represents an integer of 5 or more). Formula (I-
3) A process for producing an optically active alcohol represented by the following general formula (I), wherein the hydroxyl group protecting group (W) of the ether compound is eliminated.

[0016]

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(In the above formula, m represents an integer of 5 or more and n represents an integer of 1 or more. C * represents an asymmetric carbon atom.) Also, the sulfonic acid represented by the above general formula (I-1) The ester is (a) a compound represented by the following general formula (I-4):

[0018]

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(In the above formula, A represents lower alkyl, W represents a hydroxyl-protecting group, and C * represents an asymmetric carbon atom.) Optical activity 4,4,4-trifluoro-3 -Reduction of hydroxybutanoic acid ester to the following general formula (I-
5),

[0020]

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(Wherein W and C * have the same meanings as described above),
(B) It is produced by reacting this alcohol with a sulfonating agent. Next, the method for producing the optically active alcohol of the present invention will be described more specifically by the following reaction formula.

[0022]

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Further description will be given according to the above reaction formula. (1) First, protection of the hydroxyl group of ethyl 4,4,4-trifluoro-3-hydroxybutanoate can be easily carried out according to a known method. As the protecting agent, any of known protecting agents such as dihydropyran (DHP) and benzyl chloride can be used. Next, the ester portion is reduced, which can also be reduced by a known reduction method using lithium aluminum hydride or the like. Since the produced alcohol is a relatively unstable compound, it is used immediately in the next step without purification. The production of the sulfonic acid ester of the alcohol obtained by reduction is also easily carried out according to a known method using p-toluenesulfonyl chloride (TsCl). (2) The Grignard reagent as another raw material is obtained by brominating an alkoxy alcohol by a general bromination method and then converting the alkoxy alcohol into a Grignard reagent in a nitrogen stream by a known method. (3) Then, the sulfonate obtained in (1) <
A coupling reaction is performed between 1> and the Grignard reagent <2> obtained in (2) to obtain the optically active alcohol of the present invention. In this reaction, it is particularly important to control the reaction temperature.
At a temperature below ℃, the progress of the reaction is slow. On the other hand, a temperature of -5 ° C or more is not preferable because side reactions increase. The optimum temperature is a narrow range around −10 ° C. and the temperature is ±
It is preferred to keep it within 2 ° C. In this coupling reaction, cuprous iodide is used as a catalyst, and it is used in an amount of from 1 mol to 0.5 mol, preferably from 0 mol to 1 mol of the sulfonic acid ester as a reaction raw material. 0.2 to 0.35 mol. As a method of adding cuprous iodide, it is desirable to add it little by little over the entire reaction time. The reaction is carried out for 5 to 25 hours, preferably 8 to 14 hours. In addition, 4,4,4-trifluoro-3- one of the raw materials used in the present invention.
Ethyl hydroxybutanoate has an R-form by reduction of ethyl 4,4,4-trifluoroacetoacetate with baker's yeast, and an R, S-form by asymmetric hydrogenation using a ruthenium-optically active phosphine complex as a catalyst. Any of them can be easily manufactured (Japanese Patent Application Laid-Open No. 63-3108).
No. 47). The alkoxy alcohol, which is a raw material of the Grignard reagent used in the present invention, can be easily produced from a diol as a raw material by a known method according to the following reaction formula.

[0024]

The novel optically active alcohol having a trifluoromethyl group on the asymmetric carbon and an alkoxy group at the terminal of the present invention is useful as a raw material for producing ferroelectric liquid crystals, pharmaceuticals, agricultural chemicals and other functional materials. Things.

[0025]

Next, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

Example 1 Production of R-(+)-1,1,1-trifluoro-7-ethoxy-2-heptanol [In the general formula (I), m =
5, when n = 2] (1) Protection of hydroxyl group of ethyl 4,4,4-trifluoro-3-hydroxybutanoate with dihydropyran R-(+)-4,4,4-trifluoro-3- 33.4 g of ethyl hydroxybutanoate and 22.6 of dihydropyran
7 ml of concentrated hydrochloric acid was added dropwise to the mixture (g) while stirring under ice cooling. After completion of the dropwise addition, stirring was continued at room temperature for another 5 hours. The reaction mixture was poured into ice water, neutralized with sodium hydrogen carbonate, and extracted with methylene chloride. After drying, the solvent is distilled off and 6 mmHg
The desired product 4,4,4-trifluoro-3 was distilled under reduced pressure.
-Ethyl tetrahydropyranyloxybutanoate (1)
Was obtained (41.3 g, yield 85%).

(2) Reduction of ethyl 4,4,4-trifluoro-3-tetrahydropyranyloxybutanoate with lithium aluminum hydride 50 ml of an ether solution of 30.1 g of ethyl trifluoro-3-tetrahydropyranyloxybutanoate (1) was added dropwise over 1.5 hours. 3 more
After refluxing for 0 minutes, a mixed solution of 8 g of water and 50 ml of tetrahydrofuran was added dropwise under ice cooling, and the solid was filtered off and extracted with ether. After drying, ether was distilled off and 28.1 g of 4,
4,4-Trifluoro-3-tetrahydropyranyloxybutanol (2) was obtained with a purity of 65%. Since (2) was relatively unstable to heat and acid, it was used in the next step only after drying with molecular sieve 4A in pyridine without purification.

(3) Sulfonic acid esterification of 4,4,4-trifluoro-3-tetrahydropyranyloxy-butanol 50 ml of a 28.1 g pyridine solution of compound (2) (purity 65%) was brought to -10 ° C. After cooling, 23.3 g of p-toluenesulfonyl chloride was added and the mixture was stirred for 1.5 hours. Thereafter, pyridine was distilled off under reduced pressure at room temperature, and methylene chloride was added to the precipitated solid to dissolve it. The methylene chloride solution was then washed with a saturated aqueous solution of ammonium acetate. After drying, methylene chloride was removed at room temperature, and low-boiling substances were removed under reduced pressure. Then, the sulfonate ester (3) having a purity of 83% was purified by a silica gel column using benzene as a solvent.
Was obtained from ethyl 4,4,4-trifluoro-3-tetrahydropyranyloxybutanoate (1) in a yield of 35%.

(4) Production of 3-ethoxy-1-bromopropane 14.5 g of phosphorus tribromide was slowly added dropwise to 16.8 g of 3-ethoxy-1-propanol. 90mmH after 30 minutes
g, distillation under reduced pressure at 150 ° C., methylene chloride was added to the distillate, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate. After drying, the solvent was distilled off under reduced pressure, and 3-ethoxy-1- with a purity of 94% was obtained.
14.8 g (55% yield) of bromopropane (4) was obtained.

(5) Production of 1,1,1-trifluoro-7-ethoxy-2-tetrahydropyranyloxyheptane 10 ml of tetrahydrofuran was added to 1.5 g of magnesium pieces under a nitrogen atmosphere, and a small amount of iodine was added to remove magnesium. After activation, a solution of 9.4 g of compound (4) in 20 ml of tetrahydrofuran was added dropwise at room temperature to prepare a Grignard reagent in the system. The solution was cooled to −10 ° C., and the sulfonate (3) was slowly added dropwise. In addition, 1 g of copper iodide as a catalyst was added 14 times at a rate of almost once every hour. After the reaction for about 14 hours, the reaction mixture was poured into 100 g of an aqueous solution of 4.4 g of ammonium acetate, and extracted with hexane and ether. After drying, the solvent is distilled off and ether 50 ml
Was added dropwise to a suspension of lithium aluminum hydride in ether, and the mixture was refluxed for 1 hour. After cooling, water was added under ice cooling to decompose excess lithium aluminum hydride, and the solid was filtered off and extracted with hexane and ether. After drying, the solvent was distilled off and the residue was distilled under reduced pressure to obtain 4.5 g of the target product (5) with a purity of 70% (yield 54%).

(6) Production of 1,1,1-trifluoro-7-ethoxy-2-heptanol To a solution of 4.5 g of compound (5) in 10 ml of methanol was added 1 ml of concentrated hydrochloric acid, and the mixture was allowed to stand overnight. This solution was poured into a saturated aqueous solution of sodium hydrogen carbonate and extracted with hexane and ether. After drying, the solvent was distilled off to obtain 2.2 g of the final target compound with a purity of 86%. Yield 72%, [α] D ²⁸ = + 12 °
_{(C = 1.5, CHCl 3)} . 1,1,1 which is the final target
N of trifluoro-7-ethoxy-2-heptanol
The MR spectrum is shown in FIG.

(7) The following liquid crystal compound was produced using the optically active alcohol obtained in (6), and its phase sequence was measured.

[0033]

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The phase sequence was as follows: (Here, SCA * indicates an antiferroelectric chiral smectic C phase, SA indicates a smectic A phase, and SX indicates an unidentified smectic phase.) On the other hand, a similar known antiferroelectric liquid crystal is used. The following compound,

[0035]

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The phase sequence of this compound was as follows: (Here, SC * indicates a chiral smectic C phase.) It can be seen that the temperature range of the SCA * phase is further lower. Therefore, when considering a blend of liquid crystal compounds, the liquid crystal compound obtained by using the optically active alcohol of the present invention can be used very advantageously for expanding the temperature range below room temperature.

Example 2 Production of R-(+)-1,1,1-trifluoro-9-ethoxy-2-nonanol [In the general formula (I), m =
7, n = 2]

(1) (1), (2),
4,4,4-trifluoro-3 exactly as in (3)
-A sulfonate of tetrahydropyranyloxy-butanol was prepared.

(2) 1,1,1-trifluoro-9-
Production of ethoxy-2-tetrahydropyranyloxynonane Except that 5-ethoxy-1-bromopentane was used instead of 3-ethoxy-1-bromopropane in (5) of Example 1, (5) of Example 1 Just like 1,
1,1-trifluoro-9-ethoxy-2-tetrahydropyranyloxynonane was prepared. Yield 65%.

(3) 1,1,1-trifluoro-9-
Production of ethoxy-2-nonanol 1,1,1-trifluoro- in Example (6)
Exactly the same as (6) of Example 1 except that 1,1,1-trifluoro-9-ethoxy-2-tetrahydropyranyloxynonane was used instead of 7-ethoxy-2-tetrahydropyranyloxyheptane. 1,1,1-
Trifluoro-9-ethoxy-2-nonanol was prepared. Purity 89%, Yield 87%, [α] D ²⁶ = + 11 °
(C = 1.2, CHCl ₃ ). Note that the N
FIG. 2 shows the MR spectrum.

[0041]

[Brief description of the drawings]

FIG. 1 shows 1,1,1-trifluoro- of Example 1.
It is a figure which shows the NMR spectrum of 7-ethoxy-2-heptanol.

FIG. 2 shows 1,1,1-trifluoro- of Example 2.
It is a figure which shows the NMR spectrum of 9-ethoxy-2-nonanol.

Claims (3)

(57) [Claims] 1. A compound of the general formula (I) (In the above formula, m represents an integer of 5 or more, n represents an integer of 1 or more, and C * represents an asymmetric carbon atom.) (1) The following general formula (I-1): (W represents a hydroxyl-protecting group, Y represents a sulfonyl group, and C * represents an asymmetric carbon atom.) The sulfonate represented by the following general formula (I-2): Chemical formula 3] (In the above formula, m represents an integer of 5 or more, and n represents an integer of 1 or more), and reacted with a Grignard reagent represented by the following general formula (I-3): (Wherein W, n and C * have the same meaning as described above,
m represents an integer of 5 or more. ) Is obtained, and then (2) the hydroxyl group protecting group (W) of the ether compound of the above general formula (I-3) is eliminated. The method for producing the optically active alcohol represented. Embedded image (In the above formula, m represents an integer of 5 or more and n represents an integer of 1 or more. C * represents an asymmetric carbon atom.) 3. The sulfonate represented by the general formula (I-1) includes: (a) the following general formula (I-4): (In the above formula, A represents lower alkyl, W represents a hydroxyl-protecting group, and C * represents an asymmetric carbon atom.) An optically active 4,4,4-trifluoro-3-hydroxybutane represented by the following formula: The acid ester is reduced to give the following general formula (I-5): (In the above formula, W and C * have the same meaning as described above.)
3. The method for producing an optically active alcohol according to claim 2, wherein the alcohol is represented by the following formula: and then (b) reacting the alcohol with a sulfonating agent.