JPH02270838A - Optically active lower alkylcarbonylbenzenes and production thereof - Google Patents

Abstract

NEW MATERIAL:An optically active compound expressed by formula I (R is lower alkyl; n is integer of 1-5; the mark * indicates asymmetric atom). EXAMPLE:(+)- or (-)-4-(3-Hydroxybutyl)acetophenone. USE:An intermediate for agricultural chemical or organic electronic material (e.g. novel ferroelectric liquid crystal substance). PREPARATION:Alcohols expressed by formula II is reacted with a carboxylic acid expressed by the formula R'COOH (R' is lower alkyl) or derivative thereof in the presence of a basic substance or acids to afford a compound expressed by formula III, which is then acylated in a solvent in the presence of a catalyst to give a compound expressed by formula IV. The compound expressed by formula IV is further subjected to asymmetric hydrolysis using an esterase having ability capable of hydrolyzing either one among optically active substances thereof to industrially advantageously provide the optically active compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing a pesticide or an organic electronic material.

<Prior art> Journal of the American Chemical Society (J, A, C, S, ) Volume 98 (1976) 1
Page 967 or European Patent Application No. 21686 describes a compound represented by the following formula (wherein m is 1 or 2).

However, there is no description regarding the use of this compound other than as a pharmaceutical intermediate.

In addition, although various compounds have been developed as liquid crystal compounds, the development of ferroelectric liquid crystal compounds with excellent properties such as high-speed response has not yet been sufficiently developed, and therefore, intermediates of ferroelectric liquid crystal compounds have not been sufficiently developed. development was also insufficient.

<Problems to be Solved by the Invention> The present invention provides optically active lower alkylcarbonylbenzenes useful as intermediates for the above-mentioned ferroelectric liquid crystal compounds, and a method for producing the same.

<Means for Solving the Problems> The present invention is based on the general formula (I) 1, where R represents a lower alkyl group, and n is! It is an integer of ~5. * indicates an asymmetric carbon atom. ) Optically active lower alkylcarbonylbenzenes represented by the following and methods for producing the same.

The above-mentioned optically active lower alkylcarbonylbenzenes have the general formula (1), where R and R' each independently represent a lower alkyl group, and n represents an integer of 1 to 5. ) can be obtained by asymmetric hydrolysis using an esterase capable of hydrolyzing either one of the optically active forms of lower alkylcarbonylbenzenes shown in (a).

In addition, esterase in the present invention means esterase in a broad sense including lipase.

The microorganism that produces the esterase used in this reaction is not particularly limited, and may be any microorganism that produces an esterase capable of asymmetrically hydrolyzing lower alkylcarbonylbenzenes (ID).

Specific examples of such microorganisms include Enterobacter sp., Arthrobacter sp., Brevibacterium sp., Pseudomonas sp., alkaline earth metals, Micrococcus sp., Chromobacterium sp., Microbacterium sp., Corynebacterium sp. , Bacillus, Lactobacillus metall, Trichoderma, Candida, Satucharomyces, Rhodotorula, Cryptococcus, Torulopsis, Vichia, Penicillium, Aspergillus, Rhizopus, Mucor, Aureopacidium, Actino Examples include microorganisms belonging to the genus Mucor, genus Nocardia, genus Streptomyces, genus Hansenula, and genus Achromobacter.

Cultivation of the above-mentioned microorganisms is usually carried out according to conventional methods, and a culture solution can be obtained by performing liquid culture.

For example, sterilized liquid medium [malt extract e yeast extract medium (dissolve peptone 5f, glucose 101, malt extract 8, and yeast extract 3g in 11 water to make pH 6.5) for frequent use of mold and yeast, ζ for bacteria Moss sweetened bouillon medium (dissolve glucose 10y1 peptone 5f, meat extract 51, and NaC489 in water 11 and adjust the pH to 7.2)
] is carried out by inoculating microorganisms and culturing with reciprocating shaking usually at 20 to 40°C for 1 to 3 days, and solid culture may be carried out if necessary.

Furthermore, some of these microbial-derived esterases are commercially available and can be easily obtained. Specific examples of commercially available esterases include the following.

Lipase of the genus Pseudomonas [Lipase P (manufactured by Amano Pharmaceutical's)], lipase of the genus Aspergillus [Lipase A P (manufactured by Amano Pharmaceutical)], lipase of the genus Mucor [
Lipase 84. -AP (Amano Pharmaceutical Co., Ltd.) J, Candida cilinthra, Nose lipase [Lipase MY (Meito Sangyo Co., Ltd.)], alkaline earth metal lipase [Lipase P
],, (Meito Sangyo Co., Ltd.), Achromobacter Lipase 1-Lipase AL (Meito Sangyo Co., Ltd.)], Arthrobacter Lipase [Lipase Joint BSL (Godo Sake Refining Co., Ltd.)], Chromobacterium spp. Lipase (manufactured by Toyo Jozo)
, Rhizopus delemer lipase [Talibase (manufactured by Tanabe Seiyaku)], Rhizopus lipase [Lipase Saiken (manufactured by Tanabe Seiyaku)],
Osaka Bacteriological Research Institute)].

Further, animal/plant esterases can also be used, and specific examples of these esterases include the following.

Steapsin, pancreatin, porcine liver esterase, Wheat Germ esterase.

The esterase used in this reaction is an enzyme obtained from animals, plants, or microorganisms, and its usage forms include purified enzyme, crude enzyme, enzyme-containing material, microorganism culture solution, culture, bacterial cells, and culture They can be used in various forms as needed, such as liquids and processed products, and enzymes and microorganisms can also be used in combination. Or again,
It can also be used as an immobilized enzyme immobilized on a resin or the like, or as an immobilized bacterial cell.

The asymmetric hydrolysis reaction is carried out by vigorously stirring a mixture of lower alkylcarbonylbenzenes (m) and the above-mentioned enzymes or microorganisms, usually in a buffer solution.

As the buffer, commonly used buffers of inorganic acid salts such as sodium phosphate and potassium phosphate, buffers of organic acid salts such as sodium acetate and sodium citrate, etc. The pH is preferably 8 to 11 for a culture solution of a microorganism that is not alkaliphilic or an alkaline esterase, and the pH is preferably 5 to 8 for a culture solution of a microorganism that is not alkalophilic or an alkaline esterase. The concentration of buffer solution is usually 0.
05-2M, preferably 0.05-0.5M.

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

In addition, when a lipase belonging to the genus Pseudomonas or Arthrobacter is used as the lipase in this asymmetric hydrolysis reaction, optically active lower alkylcarbonylbenzenes (I) can be obtained with relatively high optical purity.

Furthermore, during this asymmetric hydrolysis, in addition to the buffer, it is also possible to use organic solvents that are inert to the reaction, such as toluene, chloroform, methyl isobutyl ketone, and dichloromethane. can be done advantageously.

Through this asymmetric hydrolysis reaction, only one of the optically active forms of lower alkylcarbonylbenzenes (rD is hydrolyzed, producing optically active lower alkylcarbonylbenzenes represented by the general formula (■)). On the other hand, the optically active lower alkylcarbonylbenzene, which is the other optically active form of the lower alkylcarbonylbenzenes (11), remains as it is as a hydrolysis residue.

After the completion of such asymmetric hydrolysis reaction, the asymmetric hydrolysis reaction solution is extracted with a solvent such as methyl isobutyl ketone, ethyl acetate, or ethyl ether, and after distilling off the solvent from the organic layer, the concentrated residue is subjected to column chromatography. The optically active lower alkylcarbonylbenzenes (I) which are the asymmetric hydrolysis products and the optically active lower alkylcarbonylbenzenes (lower alkylcarbonylbenzenes ( Among the optically active substances in m, those that were not asymmetrically hydrolyzed can be separated.

The optically active lower alkylcarbonylbenzenes obtained here are further hydrolyzed as necessary, and the optically active lower alkylcarbonylbenzenes (I) obtained earlier are the enantiomers of the optically active lower alkylcarbonylbenzenes. Benzene (I
).

lower alkyl carbonylbenzenes (11+ is - general formula (1); in the formula C, R' represents a lower alkyl group, and n represents an integer of 1 to 5); It can be produced by acylation in the presence of a catalyst.

A normal Friedel-Crafts reaction is applied to this acylation. Acylating agents include acetic acid, acetyl chloride,
Examples include carboxylic acids such as acetyl prochloride, propionic acid, and propionic acid chloride, and the amount of these used must be at least 1 mole relative to the lower alkyl ester (Ifl), and there is no particular restriction on the upper limit. , preferably 8 times the mole or less. The catalyst used in the acylation is a catalyst used in the usual Friedel-Crafts reaction, and examples of such catalysts include aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, titanium tetrachloride, polyphosphoric acid, Examples include boron fluoride. The catalyst is used in an amount of 0.3 to 8 times the lower alkyl ester (ll).

Examples of the solvent include halogenated hydrocarbons that are inert to the reaction, such as dichloromethane and dichloroethane, and the amount used is not particularly limited.

The reaction is usually carried out at -80 to 150°C, preferably from -10 to 1
Perform at oo°C.

The reaction time is not particularly limited.

From the reaction mixture thus obtained, liquid separation, concentration,
Through operations such as distillation and crystallization, lower alkylcarbonylbenzenes (■) can be obtained in good yield, and if necessary, this can be further purified by column chromatography, etc., but it is usually sent unpurified to the fire process. It can be used in

The lower alkyl ester (III) has the general formula (JV)
(In the formula, n represents an integer of 1 to 5.) Alcohols represented by the general formula (V) R' C0O
In the H(V)0 formula, R' represents a lower alkyl group. ) or a derivative thereof.

In such esterification, the acid anhydride or acid halide of lower alkyl carboxylic acid is usually used as the esterifying agent, carboxylic acid or derivative thereof, such as acetic anhydride, propionic anhydride, acetic chloride or bromide, propionic acid chloride. Alternatively, examples include bromide, butyryl chloride or bromide, valeroyl chloride or bromide.

The reaction between alcohols (Un and carboxylic acids or derivatives thereof) is carried out by using a basic substance or acids in the presence or absence of a solvent.

In this reaction, when a solvent is used, examples of the solvent include fatty acids such as tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, pyridine, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, and hexane. Examples include solvents inert to the reaction, such as group or aromatic hydrocarbons, ethers, ketones, organic amines, halogenated hydrocarbons, and aprotic polar solvents, either alone or in mixtures. There is no particular restriction on the amount used.

The amount of carboxylic acid or its derivative used in the reaction is required to be 1 equivalent or more relative to the alcohol (fV), and although the upper limit is not particularly limited, it is preferably 4 equivalent or less.

Examples of the basic substance include organic or inorganic compounds such as dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine, picoline, imidazole, sodium carbonate, sodium methylate, and potassium bicarbonate. The amount used is not particularly limited, but is usually 1 to 5 times the amount of alcohol (PI).

Furthermore, acids such as toluenesulfonic acid, methanesulfonic acid, and sulfuric acid can be used instead of the basic substance. The amount of basic substance or acid used is carboxylic acid or its mm.
It depends on the type of body and the combination of basic substances or acids used, and it is not always possible to specify, but for example, when using an acid halide as a lower alkyl carboxylic acid or its derivative, 1
More than twice the equivalent amount is used.

The reaction temperature is usually -80°C to 100°C, preferably -20°C to 90°C.

The reaction time is not particularly limited, and the end point of the reaction can be the point at which the alcohol (5) disappears from the reaction system.

After the reaction is complete, the lower alkyl esters (■
) can be obtained in good yield, which can be purified by column chromatography etc. if necessary, but can be used unpurified for the next step.

, alcohols (IV) can be obtained, for example, by reducing the corresponding ketone.

The optically active lower alkylcarbonylbenzenes represented by the general formula (I) include (auto- or (→-4-(2-hydroxypropyl)acetophenone), butyl)acetophenone, (→- or (→-4-(4-hydroxypentyl)acetophenone, (+)- or (-1-4-(5-hydroxyhexyl)acetophenone, )- or H-4-(6 -hydroxyheptyl)acetophenone.

<Effects of the Invention> According to the present invention, optically active lower alkylcarbonylbenzenes (■) can be obtained industrially advantageously, and the optically active lower alkylcarbonylbenzenes can be obtained, for example, by the method shown in the following formula. This can lead to a new ferroelectric liquid crystal material (■).

CHs (Here, Ar represents a phenylene group, etc., Y and R
'' each independently represents an alkyl group, etc.) <Examples> The present invention will be explained below with reference to Examples.

Example 1 150 f (1 mol) of 4-phenyl-2-butanol and 50 g of toluene were placed in a fourth flask equipped with a thermometer and a stirring device.
Charge 0 mA and 200 tnt of pyridine, add 1 acetic anhydride
22.4 g (1.2 mol) and 1 g of 4-dimethylaminopyridine were added and reacted for 4 hours while maintaining the temperature at 40-50°C.

After the reaction was completed, the reaction mixture was poured into 500 me of 4N hydrochloric acid, and the organic layer was extracted and separated.
% sodium bicarbonate solution and then water. The obtained organic layer was condensed under reduced pressure to give 2-acetoxy-4-phenylbutane (fJ
J-1) 1.89y (yield 98.5%) was obtained.

Next, add 2 parts of aluminum chloride to 800 parts of anhydrous dichloroethane.
40f (1.8 mol) and acetyl chloride 141ft'1.
8 mol) and stir until almost 1 mm of aluminum chloride is present (approximately 1 hour).

The solution was then cooled to 0-5 °C and obtained above (f
[-1) 178 g (0.9 mol) and dichloroethane 20
07! Add the mixed bath solution dropwise while maintaining the same temperature. After the dropwise addition was completed, the mixture was stirred at the same temperature for 2 hours, and then the reaction mixture was poured into 1 liter of water, extracted, and separated. The organic layer was washed with water, 5% sodium bicarbonate solution, and water in this order, and then the solvent was distilled off under reduced pressure to obtain a yellow oily substance. This was distilled under reduced pressure to give 4-
(8-acetoxybutyl)acetophenone (Rho 1) 1
49.7y (yield 71%) Boiling point 131°C to 134°C
10.8-0.4 yrmH9 was obtained.

100 g of (II-1) obtained here was suspended in 3N phosphate buffer 11, lipase ([Amano PJ) 511 was added, and the suspension was vigorously stirred at 36±2°C for 24 hours. After the reaction is completed, 500 ml of ethyl acetate is added and filtered, followed by extraction and separation. The organic layer obtained is washed with water, and then the solvent is distilled off under reduced pressure. The obtained concentrated residue was purified by column chromatography (eluent: toluene-ethyl acetate) to obtain (-)-4-(8-acetoxybutyl)acetophenone 51. Of (yield 51%) and (-)-4-(8-hydroxybutyl)acetophenone (nee 1-a”) 40
．． Of (yield 48.8%) (Ca]2O--t 2.5
8 (C=1.2, CHCl5), n20=1.5
8141 was obtained.

In addition, 25 g of (-)-4-(8-acetoxybutyl)acetophenone obtained here was dissolved in a bath solution of 100 fnt of methanol and 50 tnt of tetrahydrofuran, and 50 ml of 20% aqueous sodium hydroxide solution was added, and the mixture was heated at 80 to 40°C.
React at C for 6 hours.

After completion of the reaction, the reaction mixture was adjusted to pH 8 with 4N hydrochloric acid, extracted with 300% of toluene, separated into layers, and the organic layer was washed with water and then dried over anhydrous magnesium sulfate. The obtained organic layer was concentrated under reduced pressure to give (+)-4-(8-hydroxybutyl)acetophenone (I-1-b) 20.29
(Yield 98.5%) (CQ':J": -111.
9° (c = 1, CHCh), n20 = 1.58
041 was obtained.

Examples 2 to 8 Esterification, acylation, and asymmetric hydrolysis reactions were carried out in the same manner as in Example 1, except that alcohols shown in Table 1 were used in place of 4-phenyl-2-butanol. −
The results shown in 1 were obtained.

Table-1 (22 completed)

Claims (4)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R represents a lower alkyl group, and n is an integer from 1 to 5. * indicates an asymmetric carbon atom. ) Optically active lower alkylcarbonylbenzenes represented by (2) Lower alkyl carbonyl represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R and R' each independently represent a lower alkyl group, and n represents an integer from 1 to 5.) The method for producing optically active lower alkylcarbonylbenzenes according to claim 1, characterized in that the asymmetric hydrolysis is carried out using an esterase having the ability to hydrolyze any one of the optically active forms of benzenes. . (3) Lower alkyl esters represented by the general formula▲Mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R' represents a lower alkyl group, and n represents an integer from 1 to 5.) is acylated in the presence of a catalyst to form a lower compound represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R represents a lower alkyl group, and R' and n have the same meanings as above.) The method for producing optically active lower alkylcarbonylbenzenes according to claim 2, wherein alkylcarbonylbenzenes are obtained. (4) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, n represents an integer from 1 to 5.) Alcohols represented by the general formula R' The method for producing optically active lower alkylcarbonylbenzenes according to claim 3, wherein lower alkyl esters are obtained by reacting with a carboxylic acid represented by COOH (wherein R' represents a lower alkyl group) or a derivative thereof. .