JPH0751533B2 - Process for producing optically active terphenyl derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention has the general formula (I) (In the formula, X represents a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group having 1 to 15 carbon atoms, and R represents an acetyl group. * Indicates an asymmetric carbon.) Optical activity Terphenyl derivative and its production method.

The optically active terphenyl derivative represented by the above general formula (1) is a novel compound which has been found by the present inventors for the first time and has not been described in any literature. The compound is used as an intermediate for agricultural chemicals or electronic materials, especially liquid crystal compounds. Very useful as a synthetic intermediate.

Such an optically active terphenyl derivative (1) has the general formula (II) (In the formula, X has the same meaning as described above), and dl-4 ″-(1-acetoxyethyl) terphenyls can be produced by reacting esterase with asymmetric hydrolysis.

In this production method, dl-4 ″-(1-acetoxyethyl) terphenyls (II) which is a raw material is, for example, 4 ″ -acetylterphenyl derived from terphenyls (V) as shown in the following formula. By reducing the group (IV) with a reducing agent, for example, a metal hydride such as lithium aluminum hydride, lithium borohydride or sodium borohydride, and then reacting with acetic anhydride or acetyl chloride in the presence of a base. It can be easily synthesized.

Examples of the raw material dl-4 ″-(1-acetoxyethyl) terphenyls include 4- (1-acetoxyethyl) terphenyl and 4 ″-(1-acetoxyethyl)-
4-fluoroterphenyl, 4 ″-(1-acetoxyethyl) -4-chloroterphenyl, 4 ″-(1-acetoxyethyl) -4-bromoterphenyl, 4 ″-(1-
Acetoxyethyl) -4-iodoterphenyl, 4 ″-
(1-acetoxyethyl) -4-methylterphenyl,
4 ″-(1-acetoxyethyl) -4-ethylterphenyl, 4 ″-(1-acetoxyethyl) -4-propylterphenyl, 4 ″-(1-acetoxyethyl) -4-
Butyl terphenyl, 4 ″-(1-acetoxyethyl)
-4-pentylterphenyl, 4 "-(1-acetoxyethyl) -4-hexylterphenyl, 4"-(1-acetoxyethyl) -4-heptylterphenyl, 4 "-
(1-acetoxyethyl) -4-octylterphenyl, 4 ″-(1-acetoxyethyl) -4-nonylterphenyl, 4 ″-(1-acetoxyethyl) -4-decylterphenyl, 4 ″-(1 -Acetoxyethyl) -4
-Undecylterphenyl, 4 "-(1-acetoxyethyl) -4-dodecylterphenyl, 4"-(1-acetoxyethyl) -4-tridecylterphenyl, 4 "-
(1-acetoxyethyl) -4-tetradecylterphenyl, 4 ″-(1-acetoxyethyl) -4-pentadecylterphenyl, 4 ″-(1-acetoxyethyl)-
4-methoxyterphenyl, 4 ″-(1-acetoxyethyl) -4-ethoxyterphenyl, 4 ″-(1-acetoxyethyl) -4-propoxyterphenyl, 4 ″-
(1-acetoxyethyl) -4-butoxyterphenyl, 4 ″-(1-acetoxyethyl) -4-pentyloxyterphenyl, 4 ″-(1-acetoxyethyl)-
4-hexyloxyterphenyl, 4 ″-(1-acetoxyethyl) -4-heptyloxyterphenyl, 4 ″
-(1-acetoxyethyl) -4-octyloxyterphenyl, 4 "-(1-acetoxyethyl) -4-nonyloxyterphenyl, 4"-(1-acetoxyethyl) -4-decyloxyterphenyl, 4 "-(1-acetoxyethyl) -4-undecyloxyterphenyl, 4"-(1-acetoxyethyl) -4-dodecyloxyterphenyl, 4 "-(1-acetoxyethyl)-
4-tridecyloxyterphenyl, 4 ″-(1-acetoxyethyl) -4-tetradecyloxyterphenyl, 4 ″-(1-acetoxyethyl) -4-pentadecyloxyterphenyl and the like are exemplified.

The asymmetric hydrolysis of dl-4 ″-(1-acetoxyethyl) terphenyls (II) is caused by the action of an esterase produced by a microorganism or an esterase derived from animals and plants to produce the raw material dl-4 ″-(1-acetoxyethyl). ) It is carried out by hydrolyzing only one of the optically active terphenyls (II).

The esterase-producing microorganism used in this reaction may be any microorganism that produces an esterase having the ability to asymmetrically hydrolyze the starting material dl-4 ″-(1-acetoxyethyl) terphenyls (II), It is not particularly limited.

The esterase in the present invention means an esterase in a broad sense including lipase.

Specific examples of such microorganisms include, for example, Enterobacter, Arthrobacter, Brevibacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Microbacterium, Corynebacterium, Bacillus genus, Lactobacillus genus, Trichoderma genus, Candida genus, Saccharomyces genus, Rhodotorula genus, Krybtococcus genus, Torulopsis genus, Pichia genus, Penicillium genus, Aspergillus genus,
Examples include microorganisms belonging to Rhizopus, Mucor, Aureopasidium, Actinomucor, Nocardia, Streptomyces, Hansenula, and Achromobacter.

Cultivation of the above-mentioned microorganism is usually carried out by liquid culture according to a conventional method.

For example, sterilized liquid medium [malt extract / yeast extract medium for molds and yeasts (5 g of peptone, 10 g of glucose, 8 g of malt extract, 8 g of yeast extract dissolved in 1 water, pH
6.5), and for bacteria, sweetened broth medium (glucose 10 g, peptone 5 g, meat extract 5 g, Nacl 3 g dissolved in water 1 to pH 7.2)] inoculated with microorganisms, usually 20-40
The culture may be performed by reciprocal shaking culture at ℃ for 1 to 3 days, and if necessary, solid culture may be performed.

Some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include the followings.

Pseudomonas lipase [Lipase P (Amano Pharmaceutical)], Aspergillus lipase [Lipase AP (Amano Pharmaceutical)], Mucor lipase [Lipase M-AP]
(Manufactured by Amano Pharmaceutical Co., Ltd.)], lipase of Candida cylindrasse [lipase MY (manufactured by Meito Sangyo)], lipase of the genus Alcaligenes [lipase PL (manufactured by Meito Sangyo)], lipase of the genus Achromobacter [lipase AL (name) Made by Sugar Industry)],
Arthrobacter lipase (Nippon Kagaku), Chromobacterium lipase (Toyo Brewing), Rhizopus derema lipase [Talipase (Tanabe Seiyaku)], Rhizopus lipase [Lipase Saiken (Osaka Bacterial Research Institute)].

Animal / plant esterases can also be used, and specific esterases thereof include the following.

Steabsin, pancreatin, pig liver esterase, Wheat Germ esterase.

As the esterase used in this reaction, an enzyme obtained from an animal, a plant or a microorganism is used. The usage forms thereof include a purified enzyme, a crude enzyme, an enzyme-containing material, a microbial culture solution, a culture, a bacterium, and a culture medium. It can be used in various forms such as a liquid and a product obtained by treating them as needed, and an enzyme and a microorganism can also be used in combination.

The asymmetric hydrolysis reaction is usually carried out by vigorously stirring the starting material dl-4 ″-(1-acetoxyethyl) terphenyls (II) and the above enzyme or microorganism in a buffer solution.

As the buffer solution, a commonly used buffer solution of an inorganic acid salt such as sodium phosphate or potassium phosphate, a buffer solution of an organic acid salt such as sodium acetate or sodium citrate, etc. is used, and its pH is an alkalophilic bacterium. PH of 8 to 11 for the culture solution and alkaline esterase, and for the culture solution of microorganisms that are not alkalophilic and esterase that does not have alkali tolerance
A pH of 5-8 is preferred. The concentration is usually 0.05 to 2M, preferably
It is in the range of 0.05 to 0.5M.

The reaction temperature is usually 10 to 60 ° C, and the reaction time is generally
10 to 70 hours, but not limited to this.

In this asymmetric hydrolysis reaction, if a water-insoluble solvent such as toluene, chloroform or carbon tetrachloride is allowed to coexist and the reaction is carried out in a two-layer system consisting of an aqueous layer and a water-insoluble solvent, the reaction is extremely easy. proceed.

By such a reaction, one of the optically active substances of the raw material dl-4 ″-(1-acetoxyethyl) terphenyls (II) is hydrolyzed, and R in the general formula (I) is an optically active substance. Terphenyl derivative is produced, while the other optically active terphenyl derivative of the raw material compound, that is, the optically active terphenyl derivative in which the substituent R in the general formula (I) is an acetyl group, remains as a non-hydrolyzate. Consequently, in the method of the present invention, the above two kinds of optically active terphenyl derivatives are simultaneously obtained as a hydrolysis product and a hydrolysis residue.

After the completion of such a hydrolysis reaction, the hydrolysis product and the hydrolysis residue are separated from the reaction solution by subjecting the hydrolysis reaction solution to extraction treatment with a solvent such as methyl isobutyl ketone, ethyl acetate, ethyl ether or chloroform, It is carried out by a method such as distilling off the solvent from the organic layer and then treating it by column chromatography, whereby an optically active terphenyl derivative (hydrolysis product) in which R in the general formula (I) is a hydrogen atom is generally used. An optically active terphenyl derivative (hydrolysis residue) in which R in the formula (I) is an acetyl group can be separated.

The optically active terphenyl derivative in which R in the general formula (I), which is a non-hydrolyzed product, is an acetyl group is chemically hydrolyzed or reduced with a reducing agent such as a metal hydride, if necessary. As a result, an optically active terphenyl derivative in which R in the general formula (I) of the antipode is a hydrogen atom can be obtained.

Examples of the optically active terphenyl derivative represented by the general formula (I) obtained by such a reaction include the following.

4- (1-hydroxyethyl) terphenyl, 4 ″-
(1-hydroxyethyl) -4-fluoroterphenyl, 4 ″-(1-hydroxyethyl) -4-chloroterphenyl, 4 ″-(1-hydroxyethyl) -4-bromoterphenyl, 4 ″-(1 -Hydroxyethyl) -4
-Iodoterphenyl, 4 "-(1-hydroxyethyl) -4-methylterphenyl, 4"-(1-hydroxyethyl) -4-ethylterphenyl, 4 "-(1-hydroxyethyl) -4-propyl Terphenyl, 4 ″-
(1-hydroxyethyl) -4-butylterphenyl,
4 "-(1-hydroxyethyl) -4-pentylterphenyl, 4"-(1-hydroxyethyl) -4-hexylterphenyl, 4 "-(1-hydroxyethyl) -4
-Heptylterphenyl, 4 "-(1-hydroxyethyl) -4-octylterphenyl, 4"-(1-hydroxyethyl) -4-nonylterphenyl, 4 "-(1-
Hydroxyethyl) -4-decylterphenyl, 4 ″-
(1-hydroxyethyl) -4-undecylterphenyl, 4 ″-(1-hydroxyethyl) -4-dodecylterphenyl, 4 ″-(1-hydroxyethyl) -4-tridecyltylphenyl, 4 ″- (1-hydroxyethyl) -4-tetradecylphenyl, 4 ″-(1-hydroxyethyl) -4-pentadecylterphenyl, 4 ″-
(1-hydroxyethyl) -4-methoxyterphenyl, 4 ″-(1-hydroxyethyl) -4-ethoxyterphenyl, 4 ″-(1-hydroxyethyl) -4-propoxyterphenyl, 4 ″-(1 -Hydroxyethyl) -4-butoxyterphenyl, 4 "-(1-hydroxyethyl) -4-pentyloxyterphenyl, 4"
-(1-hydroxyethyl) -4-hexyloxyterphenyl, 4 "-(1-hydroxyethyl) -4-heptyloxyterphenyl, 4"-(1-hydroxyethyl) -4-octyloxyterphenyl, 4 ″-(1-
Hydroxyethyl) -4-nonyloxyterphenyl,
4 "-(1-hydroxyethyl) -4-decyloxyterphenyl, 4"-(1-hydroxyethyl) -4-undecyloxyterphenyl, 4 "-(1-hydroxyethyl) -4-dodecyloxyterl Phenyl, 4 ″-
(1-hydroxyethyl) -4-tridecyloxyterphenyl, 4 ″-(1-hydroxyethyl) -4-tetradecyloxyterphenyl, 4 ″-(1-hydroxyethyl) -4-pentadecyloxyterphenyl , And their acetates.

Thus, according to the method of the present invention, the compound of the general formula (I) can be obtained in high yield.
An optically active terphenyl derivative represented by can be obtained, which can be advantageously used as an intermediate for agricultural chemicals or electronic materials.

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

Reference Example 1 A 4-necked flask was charged with 38.5 g of 4 ″ -acetyl-4-octylterphenyl, 500 ml of ethanol and 5.67 g of sodium borohydride and stirred at 50 ° C. for 2 hours.

After completion of the reaction, ethanol is distilled off under reduced pressure, and toluene is added to the residue for extraction. After washing the organic layer with water, anhydrous magnesium sulfate was added and dried, and the solvent was distilled off to obtain dl-4 ″-(1-hydroxyethyl) -4-octylterphenyl as a white solid.

19.3 g of this white solid is dissolved in 200 ml of dry dichloromethane, 20 ml of pyridine is added thereto, and then a solution of 4.7 g of acetyl chloride in 50 ml of dichloromethane is added dropwise at room temperature.
After about 2 hours, the reaction solution is poured into 200 ml of 3N hydrochloric acid and extracted. The organic layer is washed successively with water and a 7% aqueous sodium hydrogen carbonate solution and then dried over anhydrous magnesium sulfate.

Then, the solvent was distilled off, and the obtained white solid was recrystallized from ethanol to obtain dl-4 ″-(1-acetoxyethyl) -4.
-Octylterphenyl 18.0 g (84% yield) was obtained.

Reference Example 2 Reaction and post-treatment were performed in the same manner as in Reference Example 1 except that 4 ″ -acetyl-4-pentylterphenyl was used instead of 4 ″ -acetyl-4-octylterphenyl, and dl-4 ″
-(1-Acetoxyethyl) -4-pentylterphenyl was obtained.

Example 1 A solution of 6.0 g of dl-4 ″-(1-acetoxyethyl) -4-octylterphenyl in 10 ml of chloroform and 1.0 g of lipase (Amano Pharmaceutical's Lipase “Amano” P) in 0.1 M phosphate buffer (pH 7). ) Add to 300 ml, at 35 ℃ under nitrogen atmosphere
Stir vigorously for 29 hours.

After completion of the reaction, the reaction solution is extracted with ethyl acetate. The extract was concentrated, and the concentrated residue was purified by column chromatography using a mixed solvent of chloroform-ethyl acetate (-)-4 "-.
(1-acetoxyethyl) -4-octylterphenyl
3.2 g (yield 53%) {▲ [α] ²⁵ _D ▼ -73 ° (c = 1, chloroform), 89% ee, m.p122.5-130 ° C) and (+)
-4 ″-(1-hydroxyethyl) -4-octylterphenyl 1.8 g (41% yield) {▲ [α] ²⁵ _D ▼ + 23.6 °
(C = 1, chloroform), 98% ee, m.p 242 ℃ (de
c)} was obtained.

The optical purity was measured by high performance liquid chromatography after using (+)-2-methoxy-2- (trifluoromethyl) phenylacetic acid ester.

Example 2 Except that 6.0 g (16 mmol) of dl-4 "-(1-acetoxyethyl) -4-pentylterphenyl was used instead of dl-4"-(1-acetoxyethyl) -4-octylterphenyl. Reaction and post-treatment were carried out according to Example 1,
(−)-4 ″-(1-acetoxyethyl) -4-pentylterphenyl 3 g (yield 56.7%) {▲ [α] ²⁵ _D ▼ -6
1.8 ° (c = 1, chloroform), 84% ee, m.p110.5-11
5.5 ° C.) and (+)-4 ″-(1-hydroxyethyl) -4-pentylterphenyl 2.4 g (yield 45%) {▲
[Α] ²⁵ _D ▼ + 20.8 ° (c = 1, chloroform), 99.1
% Ee, m.p 240 ° C. (dec)} was obtained.

Claims (1)

[Claims] 1. A general formula (In the formula, X represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 15 carbon atoms or an alkoxyl group.) By allowing esterase to act on dl-4 ″-(1-acetoxyethyl) terphenyls represented by General formula characterized by asymmetric hydrolysis (In the formula, X has the same meaning as described above, R represents an acetyl group, and * represents an asymmetric carbon.) A method for producing an optically active terphenyl derivative represented by