JP2725397B2 - Benzoic acid derivative and method for producing the same - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a benzoic acid derivative useful as an intermediate of an organic electronic material such as a liquid crystal compound.

<Conventional technology> Various compounds have been developed as liquid crystal compounds. However, there are few ferroelectric liquid crystal compounds which are excellent in characteristics such as high-speed response and which become liquid crystals in a low temperature region. The development of the body is not yet sufficient, and there is a demand for the intermediate and an industrially advantageous production method thereof.

<Problems to be Solved by the Invention> The present invention provides an intermediate of a ferroelectric liquid crystal compound which is excellent in the above-mentioned characteristics and becomes a liquid crystal in a low temperature region, and a method for producing the same.

<Means for Solving the Problems> That is, the present invention provides a compound represented by the general formula (I): (Wherein, R represents an optically active alkyl group or alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted with a halogen atom, and n represents an integer of 2 to 6). And its manufacturing method.

Such a novel benzoic acid derivative can be produced through the following four steps.

The first step is the general formula (II) (Wherein, R 'represents a lower alkyl group, and n represents an integer of 2 to 6). (Wherein R ′ and n have the same meanings as described above). The second step is to hydrolyze the ester represented by the general formula (III) to obtain the general formula (IV) (Wherein, n has the same meaning as described above). The third step is to obtain an alcohol represented by the general formula (IV):
Formula (V) RX (V) (wherein, R represents an optically active alkyl group or an alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted with a halogen atom, and X represents a halogen atom or General formula
OSO ₂ R ″, wherein R ″ represents a lower alkyl group or an optionally substituted phenyl group. ) With an alkylating agent represented by the formula (VI) (Wherein, R and n have the same meanings as described above). The fourth step is to oxidize the acetophenones represented by the general formula (VI) and oxidize the acetophenones represented by the general formula (VI). This is the step of obtaining the benzoic acid derivative shown.

 Hereinafter, the production method of the present invention will be described in detail.

For the acetylation in the first step, a usual Friedel-Crafts reaction is applied.

Acetic acid derivatives used for acetylation include acetic acid,
Acetyl chloride, acetyl bromide and the like can be mentioned, and the use amount thereof is not less than 1 mol times and preferably not more than 1 to 3 mol per mol of the benzene derivative (II). As a catalyst used for acetylation, a catalyst used in a normal Friedel-Crafts reaction is used. Examples of such a catalyst include aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, titanium tetrachloride, polyphosphoric acid, and triphosphoric acid. Examples thereof include boron fluoride. These are used in an amount of 0.3 to 3 times the molar amount of the benzene derivative (II).

The reaction temperature is usually −30 to 150 ° C., preferably −10 to 100 ° C.
It is.

 The reaction time is not particularly limited.

From the reaction mixture thus obtained, esters (III) can be obtained by operations such as liquid separation, concentration, distillation, and crystallization.
Is obtained in good yield and can be further purified by column chromatography or the like, if necessary, but can be used as it is in the next step, usually without purification.

The hydrolysis reaction in the second step is usually performed in the presence of water in the presence of an acid or an alkali. Examples of the acid used in the reaction include inorganic acids such as sulfuric acid, phosphoric acid, and hydrochloric acid, and organic acids such as toluenesulfonic acid and methanesulfonic acid. Examples of the alkali include sodium hydroxide, potassium hydroxide, and water. Organic and inorganic bases such as barium oxide, potassium carbonate, sodium carbonate, and 1,8-diazabicyclo [5,4,0] 7-undecene.

The amount of the acid or alkali used is as described below. The acid is preferably used in an amount of 0.02 to 10 moles per 1 mole of the ester (III). In the case of an alkali, it is at least 1 mole or more based on the ester, but preferably 5 mole. It is as follows. These are usually used together with a solvent, and examples of such a solvent include the following.

Water, methanol, ethanol, propanol, acetone, methyl ethyl ketone, chloroform, dichloromethane, toluene, xylene, hexane, heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, aliphatic or aromatic hydrocarbons such as N-methylpyrrolidone, ether, Solvents inert to the reaction, such as alcohols, ketones, amides, halogenated hydrocarbons, and water are used alone or as a mixture, and the amount used is not particularly limited.

The reaction temperature is usually from -30C to 120C, preferably from -20C to 100C.

 The reaction time is not particularly limited.

After completion of the reaction, usual separation means such as extraction, liquid separation,
Alcohol (IV) is obtained in good yield by concentration, recrystallization, etc., which can be further purified by column chromatography or the like if necessary, but can be used as it is without purification in the next step.

The alkylation reaction in the third step is usually performed using an alkylating agent in the presence of a basic substance, and examples of the basic substance include alkyl hydrides such as sodium hydride and potassium hydride, lithium, sodium, and the like. Examples thereof include an alkali metal such as potassium, an alkali metal alcoholate such as sodium ethylate and sodium methylate, an alkali metal carbonate such as sodium carbonate and potassium carbonate, and butyl lithium.

The basic substance is required to be at least 1 equivalent times the alcohol (IV), and the upper limit is not particularly limited, but is preferably 3 equivalent times.

As the alkylating agent (V) used in the above reaction,
Halides such as chlorides, bromides and iodides having an optically active alkyl group or an alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted by a halogen atom, and sulfates such as methanesulfonic acid Ester, ethanesulfonic acid ester, benzenesulfonic acid ester, toluenesulfonic acid ester, etc.).

In the above alkylation reaction, when the substituent R is an optically active alkyl group containing a bromine or iodine atom, sulfates are preferably used as the alkylating agent from the viewpoint of the reaction yield. However, when the substituent R is an optically active alkyl group containing a fluorine atom or a chlorine atom, even if the halide (alkylating agent) is bromide or iodide, it can be used without any problem.

3 carbon atoms which may be substituted by the above halogen atom
Examples of the optically active alkyl group or alkoxyalkyl group of No. 15 to 15 include the following.

1-methylethyl, 1-methylpropyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylbutyl, 1,3
-Dimethylbutyl, 2,3-dimethylbutyl, 1,2,2-trimethylbutyl, 1,2,3-trimethylbutyl, 2,3,3-trimethylbutyl, 1-methylpentyl, 2-methylpentyl, 3- Methylpentyl, 1,2-dimethylpentyl, 1,3
-Dimethylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 1,2,2,3-tetramethylpentyl, 1
-Methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 1,2-dimethylhexyl, 1,3-dimethylhexyl, 1,4-dimethylhexyl,
1-methylheptyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl,
1,3-dimethylheptyl, 1-methyloctyl, 2-methyloctyl, 3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6-methyloctyl, 1,2-
Dimethyloctyl, 1,4-dimethyloctyl, 1-methylnonyl, 2-methylnonyl, 3-methylnonyl, 4-
Methylnonyl, 5-methylnonyl, 6-methylnonyl,
7-methylnonyl, 1,2-dimethylnonyl, 1-methyldecyl, 2-methyldecyl, 3-methyldecyl, 4-methyldecyl, 5-methyldecyl, 6-methyldecyl, 7
-Methyldecyl, 8-methyldecyl, 1-methylundecyl, 9-methylundecyl, 1-methyldodecyl, 10
-Methyldodecyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl, methoxydecyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, ethoxyhexyl, ethoxyheptyl, ethoxy Octyl, ethoxynonyl, ethoxydecyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, propoxyhexyl, propoxyheptyl, propoxyoctyl, propoxynonyl, propoxydecyl,
Butoxyethyl, butoxypropyl, butoxybutyl,
Butoxypentyl, butoxyhexyl, butoxyheptyl, butoxyoctyl, butoxynonyl, butoxydecyl, pentyloxyethyl, pentyloxypropyl,
Pentyloxybutyl, pentyloxypentyl, pentyloxyhexyl, pentyloxyoctyl, pentyloxydecyl, hexyloxyethyl, hexyloxypropyl, hexyloxybutyl, hexyloxypentyl, hexyloxyhexylheptyloxyethyl, heptyloxypropyl, heptyloxybutyl ,
Heptyloxypentyl, octyloxyethyl, octyloxypropyl, decyloxyethyl, decyloxypropyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylheptyl, 2-halopropyl, 3-halo-2-methyl Propyl, 2,3-dihalopropyl, 2-halobutyl, 3-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, 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, 2-haloheptyl, 2-halooctyl (however, halo in the above alkyl group means fluorine, chlorine, bromine or iodine,
Practically, fluorine or chlorine is preferred. ), Etc., these halides or sulfates having an optically active group are derived from the corresponding alcohols, and some of the optically active alcohols are asymmetric metal catalysts for the corresponding ketones, asymmetric reductions by microorganisms or enzymes. Can be easily obtained. Also, some can be derived from optically active amino acids and optically active oxyacids that are naturally occurring or obtained by resolution, such as:

Valine, leucine, isoleucine, phenylalanine, threonine, alosreonine, homoserine, alloisoleucine, tert-leucine, 2-aminobutyric acid, norvaline, norleucine, ornithine, lysine, hydroxylysine, phenylglycine, aspartic acid, glutamic acid, mandelic acid, tropha Acid, 3-hydroxybutyric acid, malic acid, tartaric acid, isopropylmalic acid and the like.

The amount of such an alkylating agent (V) to be used is 1 equivalent or more times the amount of the alcohol (IV), but is usually in the range of 1 to 5 equivalents.

As the reaction solvent, for example, tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chloroform, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, dimethylformamide, aliphatic or aromatic hydrocarbons such as hexane, ketone, ether, Solvents inert to the reaction, such as amides and halogenated hydrocarbons, are used alone or as a mixture, and the amount used is not particularly limited.

Further, a polar solvent such as dimethylsulfoxide, hexamethylphosphorylamide, N-methylpyrrolidone and the like can also be used.

The reaction temperature is usually −50 ° C. to 120 ° C., preferably −30 ° C.
It is in the range of ~ 100 ° C.

After completion of the reaction, usual separation means such as extraction, liquid separation,
Acetophenones [VI] can be obtained by operations such as concentration.

The oxidation reaction in the fourth step is performed by treating the acetophenones (VI) obtained above with an oxidizing agent.

The oxidizing agent used in the above reaction can be used without any particular limitation as long as it can oxidize an acetyl group to a carboxylic acid. Examples of such an oxidizing agent include potassium dichromate, sodium dichromate, and Potassium manganate, sodium permanganate, potassium hypochlorite,
Examples thereof include sodium hypochlorite, potassium hypobromite, and sodium hypobromite.

The amount of the oxidizing agent to be used is required to be at least 1 equivalent equivalent to acetophenones (VI), and the upper limit is not particularly limited, but is preferably 1 to 10 equivalents.

As the solvent used in the above reaction, a solvent which is generally inert to the oxidation reaction is used, and examples of such a solvent include water, dioxane, tetrahydrofuran, N-methylpyrrolidone and the like.

The reaction temperature is usually -20 to 130 ° C, preferably -10 to 100 ° C.
It is in the range of ° C.

After completion of the reaction, the desired benzoic acid derivative (I) can be obtained in good yield by ordinary separation means, operations such as perfusion, acid precipitation, extraction, liquid separation, and concentration. It can also be purified by chromatography, recrystallization and the like.

<Effects of the Invention> The benzoic acid derivative represented by the general formula (I) is useful as an intermediate of an organic electronic material, especially a liquid crystal substance. For example, a novel liquid crystal substance (VI ), Which have very good properties as ferroelectric liquid crystals. Further, the benzoic acid derivative (I) can be industrially advantageously obtained by the production method of the present invention.

(Here, Ar represents a phenylene group, a biphenylene group or a heterocyclic group, and Y represents an alkyl group or an alkoxyl group. R and n have the same meanings as described above.) Further, the benzoic acid derivative (I) ) Can also be used as intermediates for pesticides, medicines and the like.

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

Example 1 In a four-necked flask equipped with a stirrer and a thermometer, 84.0 g (0.63 mol) of aluminum chloride and 400 ml of dichloromethane were charged, and 51.8 g (0.66 mol) of acetyl chloride was required at 10 to 20 ° C for 2 hours. Added. After keeping it at the same temperature for 1 hour,
Β-phenethyl acetate (II-1) 49.2 at 10-25 ° C
g (0.3 mol) was added in 3 hours. After keeping the temperature at 20 to 30 ° C., the mixture was poured into ice water, 100 ml of dichloromethane was added, the organic layer was separated, and washed sequentially with water, 3% aqueous sodium carbonate and water. The organic layer is dried over magnesium sulfate and concentrated under reduced pressure to give 4- (β-acetoxyethyl).
43.0 g (93% yield) of acetophenone (III-1) was obtained.

51.5 g (0.25 mol) of (III-I) obtained above, 20%
65 g of caustic soda and 150 ml of methanol were charged and stirred at room temperature for 4 hours. After the completion of the reaction, the reaction solution was poured into water and extracted with 200 ml of toluene. The organic layer was washed with water and concentrated under reduced pressure to give 40.6 g of 4- (β-hydroxyethyl) acetophenone (IV-1) (99% yield). ) Got. next,
7.88 g (0.048 mol) of (IV-1) obtained above and 80 ml of dimethylformamide were charged and cooled to 0 to 5 ° C.
1.16 g (0.048 mol) of sodium hydride was added, and the mixture was kept at the same temperature for 1 hour and further kept at 20 ° C. for 2 hours. Then, 2S
-Methyl butyl tosylate 12.1 g (0.05 mol)
2 hours at 30 ° C, 30-35 ° C for 30 minutes at the same temperature
For 2 hours. After completion of the reaction, the reaction solution was poured into ice, extracted twice with 60 ml of ethyl acetate, the organic layer was separated, washed with water, concentrated under reduced pressure, and the concentrated residue was purified by column chromatography with toluene to obtain a residue. -{2- (2S-methylbutoxy) ethyl} acetophenone (VI-1) 7.30 g
(65% yield). ▲ [α] ²⁰ _D ▼ + 4.5 ° (c = 1, CH
Cl ₃ ), ▲ n ²⁰ _D ▼ 1.15118 Next, 2.34 g (0.01 mol) of (VI-1) obtained above.
Was added in advance to a mixed solution of 11 g (0.07 mol) of bromine in 16 g of 20% caustic soda water and 30 ml of dioxane, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the reaction solution was poured into ice water, made weakly acidic with 10% sulfuric acid, and ethyl acetate 100 ml.
, The organic layer is separated, further washed with water, concentrated, and the concentrated residue is purified by chromatography with toluene-acetic acid (20: 1) to give 4- {2- (2S-methylbutoxy).
2.1 g of ethyl @ benzoic acid (I-1) (90% yield) was obtained.
▲ [α] ²⁰ _D ▼ + 6.1 ° (c = 1, CHCl ₃ ), melting point 60-62 ° C. Example 2 7.88 g (0.048 mol) of (IV-1) obtained in Example 1 and N-methylpyrrolidone 70 ml was charged, the mixture was cooled to 0 to 5 ° C, 1.16 g (0.048 mol) of sodium hydride was added, and the mixture was kept at the same temperature for 1 hour and further kept at 20 ° C for 2 hours. Next, 17.6 g (0.06 mol) of 1R-methylheptyl tosylate
Was added at 15 to 20 ° C for 2 hours, and the mixture was kept at the same temperature for 1 hour, and then kept at 30 to 35 ° C for 2 hours. After the reaction,
Post-treatment and purification according to Example 1 gave 4-
5.96 g (45% yield) of {2- (1S-methylheptyloxy) ethyl} acetophenone (VI-2) was obtained. ▲ [α]
²⁰ _D ▼ + 3.8 ° (c = 1, CHCl ₃ ), ▲ n ²⁰ _D ▼ 1.5047 Next, 2.76 g (0.01 mol) of (VI-2) obtained above.
Was added at room temperature to a mixture of 16% of 20% aqueous sodium hydroxide, 11 g (0.07 mol) of bromine and 20 ml of dioxane, and the mixture was stirred for 20 hours. After completion of the reaction, 2.56 g (yield 92%) of 4- {β- (1S-methylheptyloxy) ethyl} benzoic acid (I-2) was obtained by post-treatment and purification according to Example 1. . ▲ [α] ²⁰ _D ▼ + 4.9 ° (c = 1, CHCl ₃ ), melting point 41
4343 ° C. Example 3 7.88 g (0.048 mol) of (IV-1) obtained in Example 1 and 80 ml of dimethylformamide were charged and cooled to 0 to 5 ° C. 1.16 g (0.048 mol) of sodium hydride was added, the mixture was kept at the same temperature for 1 hour, and then heated to room temperature. Next, 16.34 g (0.06 mol) of 2S-propoxypropyl tosylate was added dropwise, and the mixture was kept at room temperature for 1 hour and at 25 to 30 ° C. for 3 hours. After completion of the reaction, post-treatment and purification were carried out according to Example 1 to give 4- {2- (2S-propoxypropoxy) ethyl}.
6.98 g (55% yield) of acetophenone (VI-3) was obtained.
▲ [α] ²⁰ _D ▼ + 4.8 ° (c = 1, CHCl ₃ ) 、 ▲ n ²⁰ _D ▼ 1.50
03 Next, 2.64 g (0.01 mol) of (VI-3) obtained above.
Was added at room temperature to a mixture of 16% of 20% aqueous sodium hydroxide, 11 g (0.07 mol) of bromine and 20 ml of dioxane, and the mixture was stirred for 20 hours. After completion of the reaction, post-treatment and purification were carried out in the same manner as in Example 1 to obtain 2.47 g (yield: 93%) of 4- {2- (2S-propoxypropoxy) ethyl} benzoic acid (I-3). ▲ [α] ²⁰ _D ▼ + 6.0 ° (c = 1, CHCl ₃ ), melting point 51
Example 4 44.0 g (0.63 mol) of aluminum chloride and 450 ml of dichloromethane were charged into the same apparatus as in Example 1, and 51.8 g (0.66 mol) of acetyl chloride was added over 2 hours at 10 to 15 ° C. Was. After keeping the temperature for 1 hour at the same temperature, 53.4 g (0.3 mol) of 3-phenylpropyl acetate (II-4) at 10 to 20 ° C.
Was added at 3 hours. After keeping the temperature at 25 ° C. for 4 hours, the reaction solution was poured into ice water, 100 ml of dichloromethane was added, the organic layer was separated, and washed sequentially with water, 3% aqueous sodium carbonate and water. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain 62.4 g (yield 94.5%) of 4- (3-acetoxypropyl) acetophenone (III-4).

55.0 g (0.25 mol) of (III-4) obtained above, 10%
65 g of caustic potash, 20 ml of tetrahydrofuran and 60 mm of methanol were charged and stirred at room temperature for 5 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, tetrahydrofuran and methanol were distilled off, the residue was extracted with toluene, and the organic layer was further washed with water and then concentrated under reduced pressure to give 4-
(3-hydroxypropyl) acetophenone (IV-4)
43.9 g (98.5% yield) was obtained.

Next, 8.54 g (0.048 mol) of (IV-4) obtained above.
And 80 ml of dimethylformamide, cooled to 0 to 5 ° C., and added 1.16 g (0.048 mol) of sodium hydride.
The mixture was kept at the same temperature for 1 hour and further at 25 ° C. for 2 hours. Next, 12.1 g (0.05 mol) of 2S-methylbutyl tosylate was added to 2
Add 3 hours at 0-30 ° C, add 30 minutes at the same temperature
The temperature was kept at 4040 ° C. for 2 hours.

After completion of the reaction, post-treatment and purification according to Example 1 gave 4- {3- (2S-methylbutoxy) propyl}.
8.44 g (yield 71%) of acetophenone (VI-4) was obtained.
▲ [α] ²⁰ _D ▼ + 3.3 (c = 1, CHCl ₃ ), ▲ n ²⁰ _D ▼ 1.5048 Next, 2.48 g (0.01 mol) of (VI-4) obtained above.
In the same manner as in Example 1, 18 ml of 20% caustic soda water and 11 g of bromine (0.0 g
7 mol) and 20 ml of dioxane, and stirred for 24 hours.

Thereafter, by post-treatment and purification according to Example 1, 2.25 g (yield 90.5%) of 4- {3- (2S-methylbutoxy) propyl} benzoic acid (I-4) was obtained. ▲ [α]
²⁰ _D ▼ + 4.6 ° (c = 1, CHCl ₃ ), melting point 49.5-51 ° C. Example 5 8.54 g (0.048 mol) of (IV-4) obtained in Example 3, 10 ml of tetrahydrofuran and 30 ml of dimethylformamide were charged. , Cooled to 0-10 ° C, 1.28 g of sodium hydride
(0.052 mol), and the mixture was kept at the same temperature for 1 hour and further at 20 ° C. for 2 hours.

Next, 17.6 g (0.06 mol) of 1R-methylheptyl tosylate was added at 15 ° C. over 3 hours, and at the same temperature for 1 hour,
The temperature was kept at 30 ° C. for 1 hour. After completion of the reaction, post-treatment and purification were performed according to Example 1 to give 4- {3- (1S-methylheptyloxy) propyl} acetophenone (VI-
5) 6.68 g (48% yield) was obtained.

▲ [α] ²⁰ _D ▼ + 3.1 ° (c = 1, CHCl ₃ ) 、 ▲ n ²⁰ _D ▼ 1.50
20 Next, 2.9 g (0.01 mol) of (VI-5) obtained above.
Was added to a mixed solution of 18 ml of 20% aqueous sodium hydroxide, 11 g (0.07 mol) of bromine and 30 ml of dioxane, and the mixture was stirred for 24 hours.

Thereafter, post-treatment and purification were conducted in the same manner as in Example 1 to obtain 2.66 g of 4- {3- (1S-methylheptyloxy) propyl} benzoic acid (I-5) (yield: 91%). ▲
[Α] ²⁰ _D ▼ + 3.6 ° (c = 1, CHCl ₃ ), melting point 39-40 ° C. Examples 6-11 Except for using sulfate esters shown in Table 1 in place of 1R-methylheptyl tosylate Reaction according to Example 5,
After treatment and purification, the results shown in Table 1 were obtained.

Example 12 As in Example 1, 84.0 g (0.68 mol) of aluminum chloride and 500 ml of dichloroethane were charged, and 51.8 g (0.66 mol) of acetyl chloride was added at 10 to 15 ° C. over 3 hours. After keeping the temperature at the same temperature for 1 hour, 57.6 g (0.3 mol) of 4-phenylbutyl acetate (II-12) was added at 10 to 20 ° C. over 3 hours. After keeping it at 20-25 ℃ for 3 hours, put it in ice water,
Dichloroethane was added and extracted. Thereafter, by post-treatment and purification according to Example 1, 56.2 g of 4- (4-acetoxybutyl) acetophenone (III-12) was obtained (yield: 80).
%).

58.5 g (0.25 mol) of (III-12) obtained above, 20%
75 g of caustic soda and 150 ml of methanol are charged and stirred at room temperature for 5 hours. Thereafter, by post-treatment and purification according to Example 1, 40.8 g of 4- (4-hydroxybutyl) acetophenone (IV-12) was obtained (a yield of 85% was obtained). IV-12) 9.22 g (0.048 mol), 60 ml of dimethylformamide and 15 ml of tetrahydrofuran were charged, cooled to 0 to 5 ° C., added with 1.16 g (0.048 mol) of sodium hydride, and kept at the same temperature for 1 hour. The mixture was further kept at 25 to 30 ° C. for 2 hours, and then 12.1 g (0.05 mol) of 2S-methylbutyl tosylate was added thereto at 15 to 25 ° C. over 3 hours. 30-35
Incubated for 2 hours at ° C.

After completion of the reaction, post-treatment and purification were conducted in the same manner as in Example 1 to obtain 8.94 g (yield 71%) of 4- {4- (2S-methylbutoxy) butyl} acetophenone (VI-12). ▲
[Α] ²⁰ _D ▼ + 1.6 ° (c = 1, CHCl ₃ ), ▲ n ²⁰ _D ▼ 1.5020 Next, 2.62 g (0.01 mol) of (VI-12) obtained above.
In the same manner as in Example 1, 16 g of 20% caustic soda water and 11 g of bromine (0.07
Mol) and 20 ml of dioxane
Stirred for 24 hours. Thereafter, by post-treatment and purification according to Example 1, 2.43 g (yield 92%) of 4- {4- (2S-methylbutoxy) butyl} benzoic acid (I-12) was obtained.
▲ [α] ²⁰ _D ▼ + 2.2 ° (c = 1, CHCl ₃ ) 、 ▲ n ²⁰ _D ▼ 1.50
46 Example 13 9.22 g (0.048 mol) of (IV-12) obtained in Example 12,
80 ml of dimethylformamide was charged, the mixture was cooled to 0 to 5 ° C, 1.16 g (0.048 mol) of sodium hydride was added, the mixture was kept at the same temperature for 1 hour, and then heated to room temperature. Next, 16.34 g (0.06 mol) of 2S-propoxypropyl tosylate was added dropwise, and the mixture was kept at room temperature for 1 hour and then at 25 to 30 ° C for 3 hours. After completion of the reaction, post-treatment and purification were conducted in the same manner as in Example 1 to obtain 8.7 g (yield: 62%) of 4- {4- (2S-propoxypropoxy) butyl} acetophenone (VI-13). ▲ [α] ²⁰ _D ▼ + 4.2 ° (c = 1, CHCl ₃ ) 、 ▲ n ²⁰ _D ▼
1.4990 Next, 2.92 g (0.01 mol) of (VI-13) obtained above.
Was added at room temperature to a mixture of 16% of 20% aqueous sodium hydroxide, 11 g (0.07 mol) of bromine and 20 ml of dioxane, and the mixture was stirred for 20 hours. After completion of the reaction, 2.71 g (yield 92%) of 4- {4- (2S-propoxypropoxy) butyl} benzoic acid (I-13) was obtained by post-treatment and purification according to Example 1.

▲ [α] ²⁰ _D ▼ + 5.2 ° (c = 1, CHCl ₃ ), melting point 39-41 ° C. Example 14 Using 5.44 g (0.036 mol) of 2S-methylbutyl bromide instead of 2S-methylbutyl tosylate An alkylation reaction, a post-treatment, and a purification were carried out in the same manner as in Example 4 to obtain 3.8 g of 4- {3- (2S-methylbutoxy) propyl} acetophenone (VI-4) (64% yield). Was.

2.48 g (0.01 mol) of (VI-4) obtained above was reacted in the same manner as in Example 3 to obtain 4- {3- (2S-methylbutoxy) propyl} benzoic acid (I-4). . 2.26g
(Yield 91%) Reference Example In a four-necked flask, (+)-4- [2- {2 (S)-
[Methylbutoxydiethyl] benzoic acid 1.18 g (5 mmol), 4-decyloxyphenol 1.50 g (6 mmol) and dichloromethane 30 ml were charged, and N, N'-dicyclohexylcarbodiimide 1.13 g (5.5 mmol) and 4
0.1 g of pyrrolidinopyridine was added and the mixture was stirred at 25 to 30 ° C for 24 hours.

After the completion of the reaction, the resulting precipitate was separated and diluted with 200 ml of toluene. The organic layer was formed of water, 5% acetic acid aqueous solution, water, 5% aqueous sodium bicarbonate solution,
After washing in the order of water, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; toluene-ethyl acetate) to give 4- [2- {2 (S) -methylbutoxy} ethyl] benzoic acid 4-decyloxyphenyl ester 2.08
g (89% yield).

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Masayoshi Minai 3-1-198, Kasuga, Konohana-ku, Osaka-shi, Osaka Sumitomo Chemical Industries, Ltd. (72) Inventor Kiyoshi Imamura Kasuga-hi, Konohana-ku, Osaka-shi, Osaka Naka 3-chome No. 98 Sumitomo Chemical Co., Ltd.

Claims (5)

(57) [Claims] 1. The compound of the general formula (I) (Wherein, R represents an optically active alkyl or alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted with a halogen atom, and n represents an integer of 2 to 6). . 2. A compound of the general formula (VI) (Wherein, R and n have the same meanings as described above.) An acetophenone represented by the following formula is oxidized: (Wherein, R and n have the same meanings as described above.) 3. A compound of the general formula (IV) (Wherein, n represents the same meaning as described above) and an alcohol represented by the general formula (V) RX (V) (wherein, R represents the same meaning as described above, and X represents a halogen atom or Wherein R represents a lower alkyl group or a phenyl group which may be substituted.) Wherein R is an alkylating agent represented by the formula: (Wherein, R and n have the same meanings as described above.) An acetophenone represented by the following formula is obtained and oxidized. (Wherein, R and n have the same meanings as described above.) 4. A compound of the general formula (III) (Wherein, n has the same meaning as described above, and R ′ represents a lower alkyl group). (Wherein, n represents the same meaning as described above), and an alcohol represented by the general formula (V) RX (V) (wherein, R and X have the same meanings as described above) ) With an alkylating agent represented by the general formula (VI) (Wherein, R and n have the same meanings as described above.) An acetophenone represented by the following formula is obtained and oxidized. (Wherein, R and n have the same meanings as described above.) 5. A compound of the general formula (II) (Wherein R ′ and n represent the same meanings as described above) by acetylating a benzene derivative represented by the general formula (II)
I) (Wherein R ′ and n have the same meanings as described above), which is hydrolyzed to give an ester represented by the general formula (IV) (Wherein, n represents the same meaning as described above), and an alcohol represented by the general formula (V) RX (V) (wherein, R and X have the same meanings as described above) ) With an alkylating agent represented by the general formula (VI) (Wherein, R and n have the same meanings as described above.) An acetophenone represented by the following formula is obtained and oxidized. (Wherein, R and n have the same meanings as described above.)