JP2687587B2 - Process for producing optically active ether derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Field of Application> The present invention has the general formula (I) useful as a liquid crystal material having excellent responsiveness in image display, for example. (Wherein, X is -COO -, - OCO -, - CH 2 O- or -OC
H ₂ —, A is an alkyl group or an alkoxyl group having 3 to 15 carbon atoms, and R is an alkyl group or an alkyloxyalkyl group which may be substituted with a fluorine, chlorine or bromine atom having 1 to 20 carbon atoms. Represent. l and m represent 1 or 2, respectively. * Indicates that it is an asymmetric carbon. ) Relates to a method for producing an optically active ether derivative.

<Prior Art> European Published Patent No. 0297745 describes a general formula (IV) as a method for producing an optically active ether derivative. (In the formula, A and l have the same meanings as described above.) And a phenol represented by the general formula (V) (In the formula, R ¹ represents an alkyl group or an alkyloxyalkyl group having 1 to 20 carbon atoms, R'represents a hydroxyl group or a halogen atom. M and * have the same meanings as described above.) Reacting with active carboxylic acids or having the general formula (VI) (In the formula, A, R ′ and l have the same meanings as described above.) And a carboxylic acid represented by the general formula (VII) (In the formula, R ¹ , m and * have the same meanings as described above.) And a method for reacting the optically active phenols is described.

However, in this method, when the optically active carboxylic acid (V) or carboxylic acid (VI) as a raw material is a free acid, the reactivity of esterification is slightly low, and dicyclohexylcarbodiimide and imidazoylimidazole are used in addition to the catalyst. However, there is a problem that an esterifying agent such as the above is required, and it cannot be said that the method is industrially satisfactory.

<Problems to be Solved by the Invention> The present invention provides an industrially advantageous method for producing an optically active ether derivative represented by the general formula (I).

<Means for Solving the Problems> The present invention provides a compound represented by the general formula (II): (Wherein, X is -COO -, - OCO -, - CH 2 O- or -OC
H ₂ − and A each represent an alkyl group or an alkoxyl group having 3 to 15 carbon atoms. l and m represent 1 or 2, respectively. * Indicates that it is an asymmetric carbon. ), An optically active alcohol derivative represented by the general formula (III) RY (III) (wherein R is a fluorine or chlorine or bromine atom having 1 to 20 carbon atoms) in the presence of an alkylating auxiliary. the optionally substituted alkyl or alkyloxyalkyl group, Y 'represents respectively groups. wherein R' halogen atoms or -O ₃ SR is lower alkyl group may be a trifluoromethyl group or a substituted It represents a phenyl group.) Is alkylated with an alkylating agent represented by the formula (1).

The optically active alcohol derivative represented by the general formula (II) is, for example, an alkyl acetylbenzoate (having 3 to 15 carbon atoms).
) Phenyl was reduced with sodium borohydride to convert the acetyl group to an α-hydroxyethyl group, and then acetyl chloride / pyridine was used to convert the acetic acid ester to an acetic acid ester, which was then asymmetrically hydrolyzed using the enzyme “lipase”. It can be produced by using an optically active α-hydroxyethyl group.

Examples of the substituent A in the general formula (II) include a linear alkyl group or an alkoxyl group having 3 to 15 carbon atoms.

As the alkylating agent (III), a halide or sulfonate such as chloride, bromide or iodide is used, and as the sulfonate, a lower alkyl sulfonate such as methane sulfonate or ethane sulfonate, trifluoromethyl sulfonate, benzene sulfonate or p-toluene sulfonate, etc. Aryl sulfonate of.

Examples of the substituent R in the general formula (III) include linear or branched alkyl or alkyloxyalkyl groups, and specific examples include the following.

Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxy Butyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl, methoxydecyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, ethoxyhexyl, ethoxyheptyl, ethoxyoctyl, ethoxynonyl, ethoxydecyl, Propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, propoxyhex , Propoxyheptyl, propoxyoctyl, propoxynonyl, propoxydecyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, butoxyhexyl, butoxyheptyl, butoxyoctyl, butoxynonyl, butoxydecyl, pentyloxymethyl, pentyloxy Ethyl, pentyloxypropyl, pentyloxybutyl, pentyloxypentyl, pentyloxyhexyl, pentyloxyoctyl, pentyloxydecyl, hexyloxymethyl, hexyloxyethyl, hexyloxypropyl, hexyloxybutyl,
Hexyloxypentyl, hexyloxyhexyl, hexyloxyoctyl, hexyloxynonyl, hexyloxydecyl, heptyloxymethyl, heptyloxyethyl, heptyloxypropyl, heptyloxybutyl, heptyloxypentyl, octyloxymethyl, octyloxyethyl, octyloxy Propyl,
Decyloxymethyl, decyloxyethyl, decyloxypropyl, 1-methylethyl, 1-methylpropyl,
1-methylbutyl, 1-methylpentyl, 1-methylhexyl, 1-methylheptyl, 1-methyloctyl, 2
-Methylethyl, 2-methylbutyl, 2,3-dimethylbutyl, 2,3,3-trimethylbutyl, 2-methylpentyl, 3-methylpentyl, 2,3-dimethylpentyl, 2,4
-Dimethylpentyl, 2,3,3,4-tetramethylpentyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 2,5-dimethylhexyl, 2-methylheptyl, 2-methyloctyl, 2-methylhexyl Trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylheptyl, 2-haloethyl, 2-halopropyl, 3-
Halopropyl, 3-halo-2-methylpropyl, 2,3-
Dihalopropyl, 2-halobutyl, 3-halobutyl, 4
-Halobutyl, 2,3-dihalobutyl, 2,4-dihalobutyl, 3,4-dihalobutyl, 2-halo-3-methylbutyl, 2-halo-3,3-dimethylbutyl, 2-halopentyl, 3-halopentyl, 4- Halopentyl, 5-halopentyl, 2,4-dihalopentyl, 2,5-dihalopentyl,
2-halo-3-methylpentyl, 2-halo-4-methylpentyl, 2-halo-3-monohalomethyl-4-methylpentyl, 2-halohexyl, 3-halohexyl, 4-
Halohexyl, 5-halohexyl, 6-halohexyl,
2-haloheptyl and 2-halooctyl (however, halo in the above alkyl group represents fluorine, chlorine or bromine).

Here, the branched alkyl or alkyloxyalkyl group may be an optically active group. The alkylating agent (III) having such an optically active group is
It can be produced from the corresponding alcohols by the method described in the literature.

Alkylation is carried out in the presence or absence of solvent.

Examples of the solvent include ether solvents such as tetrahydrofuran and ethyl ether, ketone solvents such as acetone and methyl ethyl ketone, and aliphatic or aromatic hydrocarbon solvents such as hexane, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, and chloroform. Examples thereof include halogenated hydrocarbon solvents such as carbon tetrachloride and the like, or aprotic polar solvents such as dimethylformamide, dimethylsulfoxide and hexamethylphosphoric triamide, which are inert or inert to the reaction, or a mixture thereof. The amount of the solvent used is not particularly limited, but is preferably 1 to 100 times by weight that of the optically active alcohol derivative.

 Alkylation is carried out by the following two methods.

Method in which silver oxide is used as an alkylating aid and the above-mentioned halide is used as an alkylating agent: The amount of the halide used varies depending on the kind of the optically active alcohol derivative (II) and cannot be necessarily specified. It is 1 to 50 equivalent times with respect to the active alcohol derivative (II). Iodide is preferably used as the halide.

Although the amount of silver oxide used cannot be specified as in the above case, it is usually 1 to 10 equivalent times with respect to the optically active alcohol derivative (II).

The alkylation reaction is usually 0 to 150 ° C., preferably 20
It is performed at -100 ° C, and the reaction time is not particularly limited. still,
The reaction time can also be shortened by irradiating ultrasonic waves during the alkylation.

Method using sulfonate or halide as alkylating agent and using basic substance as alkylating aid: The alkylating agent (III) is usually used in an amount of 1 to 4 equivalent times, preferably 1 to 2 equivalent times. When the agent is a halide, iodide is preferably used from the viewpoint of reactivity.

Examples of the basic substance include alkyl metals such as n-butyl lithium and s-butyl lithium, metal hydrides such as sodium hydride, potassium hydride and calcium hydride, sodium hydroxide, potassium hydroxide and calcium hydroxide. Alkali metal or alkaline earth metal hydroxide or sodium carbonate, potassium carbonate, sodium hydrogen carbonate,
A carbonate such as potassium hydrogen carbonate is used.

Alkylation converts these basic substances into the general formula (II)
It can also be carried out by reacting with an optically active alcohol derivative represented by the formula (1) to give an alcoholate, and then reacting the alcoholate with an alkylating agent (III).

The amount of the basic substance used varies depending on the type of the alkylating agent (III) or the optically active alcohol derivative (II) and cannot be specified, but it is usually 1 to 10 relative to the optically active alcohol derivative (II). Equivalent times, preferably 1-3 equivalent times. The alkylation reaction is usually -50 to 15
It is carried out at 0 ° C, preferably 0 to 120 ° C. The reaction time is not particularly limited.

The optically active ether derivative represented by the general formula (I) can be taken out from the reaction mixture obtained by the above-mentioned method and by a usual post-treatment operation such as filtration, extraction, liquid separation, concentration or column chromatography. It is done by adding.

Examples of the optically active ether derivative represented by the general formula (I) include the compounds exemplified below.

4- (1-alkoxyethyl) phenyl 4-alkylbenzyl ether 4- (1-alkoxyethyl) phenyl 4-alkoxybenzyl ether 4- (1-alkoxyethyl) benzyl 4-alkylphenyl ether 4- (1-alkoxyethyl) Benzyl 4-alkoxyphenyl ether 4- (1-alkoxyethyl) phenyl 4'-alkyl-4-biphenylylmethyl ether 4- (1-alkoxyethyl) phenyl 4'-alkoxy-4-biphenylylmethyl ether 4- (1 -Alkoxyethyl) benzyl 4'-alkyl-4-biphenylyl ether 4- (1-alkoxyethyl) benzyl 4'-alkoxy-4-biphenylyl ether 4 '-(1-alkoxyethyl) -4-biphenylyl 4
-Alkylbenzyl ether 4 '-(1-alkoxyethyl) -4-biphenylyl 4
-Alkoxy benzyl ether 4 '-(1-alkoxyethyl) -4-biphenylylmethyl 4-alkylphenyl ether 4'-(1-alkoxyethyl) -4-biphenylylmethyl 4-alkoxyphenyl ether 4- (1 -Alkoxyethyl) phenyl 4-alkylbenzoic acid ester 4- (1-alkoxyethyl) phenyl 4-alkoxybenzoic acid ester 4- (1-alkoxyethyl) benzoic acid 4-alkylphenyl ester 4- (1-alkoxyethyl) benzoic acid Acid 4-alkoxyphenyl ester 4- (1-alkoxyethyl) phenyl 4'-alkyl-4-biphenylylcarboxylic acid ester 4- (1-alkoxyethyl) phenyl 4'-alkoxy-4-biphenylylcarboxylic acid ester 4- (1-alkoxyethyl) cheap Kosan 4'-alkyl-4-biphenylyl ester 4- (1-alkoxyethyl) benzoate 4'-alkoxy-4-biphenylyl ester 4 '(1-alkoxyethyl) -4-biphenylyl 4-
Alkylbenzoic acid ester 4 '-(1-alkoxyethyl) -4-biphenylyl 4
-Alkoxybenzoic acid ester 4 '-(1-alkoxyethyl) -4-biphenylylcarboxylic acid 4-alkylphenyl ester 4'-(1-alkoxyethyl) -4-biphenylylcarboxylic acid 4-alkoxyphenyl ester In, "alkoxy" of alkoxyethyl
Represents an alkyloxyl group or an alkyloxyalkyloxyl group having 1 to 20 carbon atoms which may be substituted with fluorine, chlorine, or bromine.

Further, alkyl or alkoxy in the examples is a linear alkyl group or alkoxyl group having 2 to 15 carbon atoms, and specific examples thereof include ethyl, propyl,
Butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy,
Examples include undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy and the like.

<Effects of the Invention> According to the present invention, the optically active ether derivative represented by the general formula (I) can be industrially advantageously produced.

<Example> Hereinafter, the present invention will be described with reference to examples.

Example 1 (+)-4- (1-hydroxyethyl) benzoic acid 4 ′
-(Octyloxy) -4-biphenylyl ester 8.9g
A mixture of (20 mmol), 1-iodohexane (42.4 g, 0.2 mol), silver oxide (23.2 g, 0.1 mol) and tetrahydrofuran (10 ml) was stirred at 30 ° C. for 2 days in the dark.

To the reaction mixture, 200 ml of toluene was added and filtered, and the obtained filtrate was concentrated under reduced pressure. The obtained concentrated residue is purified by silica gel column chromatography (+)-4.
-(1-Hexyloxyethyl) benzoic acid 4 '-(octyloxy) -4-biphenylyl ester 4.46 g (yield 4
2%).

 Further, it was recrystallized from ethanol.

Instead of the above reaction conditions of stirring at 30 ° C for 2 days, 30 ° C
After stirring for 1 day at 30 ° C., ultrasonic waves were radiated for 6 hours at 30 ° C., and then stirring at the same temperature for 1 day (+)-4- (1-
The yield of hexyloxyethyl) benzoic acid 4 '-(octyloxy) -4-biphenylyl ester was 62%.

Example 2 Instead of 1-iodohexane, 1-iodopropane 3
The reaction and post-treatment were conducted in the same manner as in Example 1 except that 4.0 g was used, and (+)-4- (1-propyloxyethyl) benzoic acid 4 '-(octyloxy) -4-biphenylyl ester 4.40 g ( Yield 45%) was obtained.

Example 3 1-iodooctane 4 instead of 1-iodohexane
Reaction and post-treatment were conducted in the same manner as in Example 1 except that 8.0 g was used, and (+)-4- (1-methoxyethyl) benzoic acid 4 '-(octyloxy) -4-biphenylyl ester.
3.58 g (yield 32%) was obtained.

Examples 4 to 14 Alkylation was carried out according to the method of Example 1 to obtain optically active ether derivatives shown in Table 1. Table 1 shows the phase transition temperature of each optically active ether derivative (I).
It is shown in FIG.

The phase transition temperatures of the optically active ether derivatives obtained in Examples 1 to 3 are also shown in Table 1.

Example 15 (+)-4 '-(1-hydroxyethyl) -4-biphenylcarboxylic acid 4-octyloxyphenyl ester
8.9 g (20 mmol), 1-iodohexane (42.4 g), silver oxide (23.2 g) and dioxane (10 ml) were shielded from light at 2 to 40 ° C and 2 ° C.
Stirred for days.

200 ml of toluene was added to the obtained reaction mixture, and the mixture was filtered. The obtained filtrate was concentrated under reduced pressure. The obtained concentrated residue is purified by silica gel column chromatography to obtain (+)-4 '-(1-hexyloxyethyl) -4-biphenylcarboxylic acid 4-octyloxyphenyl ester (4.67 g, yield 44%). It was

 Further, it was recrystallized from ethanol.

Examples 16 to 20 According to the method of Example 15, the optically active ether derivatives shown in Table 2 were obtained. Table 2 shows the phase transition temperatures of the respective optically active ether derivatives (I).

Example 21 (-)-4- (1-hydroxyethyl) benzoic acid 4
A mixture of 7.40 g (20 mmol) of octyloxyphenyl ester, 28.4 g (0.2 mol) of iodomethane, 23.2 g of silver oxide and 10 ml of tetrahydrofuran at 30 ° C. in the dark.
Stirred for days.

200 ml of toluene was added to the reaction mixture, and the mixture was filtered. The obtained filtrate was concentrated under reduced pressure. The obtained concentrated residue was purified by silica gel column chromatography (eluent: toluene) to give (-)-4- (1-methoxyethyl) benzoic acid 4- (octyloxy) phenyl ester (3.69 g).
(Yield 48%) was obtained.

Example 22 (-)-p- (1-Propyloxyethyl) benzoic acid was reacted and worked up in the same manner as in Example 21 except that 34.0 g of 1-iodopropane was used instead of iodomethane.
3.80 g of 4- (octyloxy) phenyl ester (yield 4
6%).

Examples 23 to 25 Alkylation was carried out according to the method of Example 21 to obtain optically active ether derivatives shown in Table-3. Table 3 shows the degree of light application for each optically active ether derivative (I).

Example 26 (+)-4'-octyloxybiphenylcarboxylic acid 4- (1-hydroxyethyl) phenyl ester 8.9 g
(20 mmol), 28.4 g (0.2 mol) of iodomethane, 23.2 g of silver oxide and 15 ml of tetrahydrofuran in the dark at 30 ° C.
Then, the mixture was stirred for 3 days. 200 ml of toluene was added to the reaction mixture, and the mixture was filtered. The obtained filtrate was concentrated under reduced pressure. The obtained concentrated residue was purified by silica gel column chromatography to obtain (+)-4'-octyloxybiphenylcarboxylic acid 4- (1-methoxyethyl) phenyl ester 4.70 g (yield 51%).

 Further, it was recrystallized from ethanol.

Examples 27 to 42 Alkylation was carried out according to the method of Example 26 to obtain optically active ether derivatives shown in Table-4. Table 1 shows the phase transition temperature of each optically active ether derivative (I).
It is shown in FIG.

Example 43 In place of (+)-4'-octyloxy-4-biphenylcarboxylic acid 4- (1-hydroxyethyl) phenyl ester, (-)-4-octyloxybenzoic acid 4-
(1-hydroxyethyl) phenyl ester 7.40 g (20
(−)-4-octyloxybenzoic acid 4- (4-) octyloxybenzoic acid
(1-Methoxyethyl) phenyl ester was obtained.

Example 44 (+)-4′-octyloxy-4-biphenylcarboxylic acid 4- (1-hydroxyethyl) phenyl ester Instead of (+)-octyloxybenzoic acid 4-
(+)-4-Octyloxy was obtained by reacting and post-treating in the same manner as in Example 26 except that 35 g (0.1 mol) of 1-iodohexadecane was used instead of (1-hydroxyethyl) phenyl ester in place of iodomethane. Benzoic acid 4- (1
-Hexadecyloxyethyl) phenyl ester was obtained.

Example 45 (+)-4- (1-hydroxyethyl) benzoic acid 4 '
Instead of -octyloxy-4-biphenylyl ester, (+)-4- (1-hydroxyethyl) benzyl 4'-octyloxy-4-biphenylyl ether 8.65
The reaction and post-treatment were conducted in the same manner as in Example 1 except that g (0.02 mol) was used, and (+)-4- (1-hexyloxyethyl) benzyl 4′-octyloxy-4-biphenylyl ether 4.44 g (Yield 43%) was obtained. Further, it was recrystallized from ethanol.

Example 46 (+)-4- (1-hydroxyethyl) benzyl 4 '
-Octyloxy-4-biphenylyl ether 4.32 g (1
(0 mmol) is dissolved in 40 ml of anhydrous dimethylformamide, 0.48 g (12 mmol) of 60% sodium hydride is added, and the mixture is stirred at 40 ° C. for 1 hour. Then, 2.79 g (13 mmol) of n-propyl tosylate was added at the same temperature, and the mixture was stirred for 1 hour.

300 ml of water was added to the reaction mixture, and the mixture was extracted with 300 ml of toluene. The obtained organic layer was washed well with water and then concentrated under reduced pressure. The obtained white solid was purified by silica gel column chromatography to obtain (+)-4- (1-propyloxyethyl) benzyl 4'-octyloxy-4-biphenylyl ether 4.18 g (yield 88%). . The results are shown in Table-5.

Examples 47-56 (+)-4- (1-hydroxyethyl) benzyl 4 '
In place of octyloxy-4-biphenylyl ether, the optically active alcohol derivative (II) shown in Table 5 was added to n
The reaction and post-treatment were carried out according to Example 46 except that the alkylating agent (III) shown in Table 5 was used instead of -propyl tosylate to obtain the results shown in Table 5.

Claims (2)

(57) [Claims] 1. A compound of the general formula (II) (Wherein, X is -COO -, - OCO -, - CH 2 O- or -OCH ₂
-And A each represent an alkyl group or an alkoxyl group having 3 to 15 carbon atoms. l and m represent 1 or 2, respectively. However, when X is -CH ₂ O-, l is 2
It is. * Indicates that it is an asymmetric carbon. ) An optically active alcohol derivative represented by the following general formula (III) RY (III) (wherein R is a fluorine, chlorine or bromine atom having 1 to 20 carbon atoms) in the presence of an alkylating auxiliary. in the optionally substituted alkyl group or alkyloxyalkyl group, Y is a halogen atom or -O ₃ S-
Represents each R'group. Here, R'represents a lower alkyl group, a trifluoromethyl group or an optionally substituted phenyl group. ) Is alkylated with an alkylating agent represented by the following general formula (I) (In the formula, A, R, X, 1, m and * have the same meanings as described above.) A method for producing an optically active ether derivative represented by the formula: 2. The method according to claim 1, wherein an alkylating agent in which Y is an iodine atom in the general formula (III) is used, and silver oxide is used as an alkylating auxiliary agent.