JP2727675B2 - Novel optically active phenol derivative and its production method - Google Patents

Description

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

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

<Problems to be Solved by the Invention> The present invention provides a novel optically active phenol derivative which becomes a ferroelectric liquid crystal in a low temperature region and is useful as an intermediate of a ferroelectric liquid crystal compound excellent in the above-mentioned properties, and a method for producing the same. The present invention also provides an intermediate of the optically active phenol derivative 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 an alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted by a halogen atom, and n represents an integer of 1 to 6). The present invention provides a derivative (hereinafter, referred to as the compound of the present invention), a production method thereof, and an intermediate.

The compound of the present invention has the general formula (VII) (Wherein, R ′ represents a lower alkyl group, and n represents an integer of 1 to 6).
I) (Wherein, R ′ and n have the same meanings as described above), and then hydrolyzed to obtain an ester represented by the general formula (V) (Wherein, n has the same meaning as described above), and the alcohol is represented by the following general formula (IV): R—X (IV) (where R is substituted with a halogen atom) Represents an optically active alkyl group or an alkoxyalkyl group having 3 to 15 carbon atoms, and X represents a halogen atom or a general formula -OSO ₂
Represents R ", wherein R" represents a lower alkyl group or an optionally substituted phenyl group. ) To react with an alkylating agent represented by the general formula (III) (Wherein R and n have the same meanings as described above), and the acetophenones are subjected to Bayer-Villiger oxidation to give a compound represented by the general formula (II): (Wherein, R and n have the same meanings as described above), and the compound of the present invention can be obtained by further hydrolysis.

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

For the acetylation which is the first step of the production method of the present invention, a usual Friedel-Crafts reaction is applied. Examples of the acetylating agent include acetic acid derivatives such as acetic acid, acetyl chloride and acetyl bromide. The amount of these used is 1 mol or more, preferably 1 to 8 mol, per 1 mol of the benzene derivative (VII). . As the catalyst used for acetylation, a catalyst used for a normal Friedel-Crafts reaction can be used. Examples of such a catalyst include aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, titanium tetrachloride,
Examples thereof include polyphosphoric acid and boron trifluoride. The amount of these used is based on 1 mole of the benzene derivative (VII).
0.3 mol to 8 mol.

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

 The reaction time is not particularly limited.

From the reaction mixture thus obtained, the above-mentioned esters (VI) can be obtained in a high yield by ordinary operations such as liquid separation, concentration, distillation, and crystallization. Although it can be purified, it can be usually used as it is in the next step.

The hydrolysis of the ester (VI) in the second step is carried out in the presence of water, usually 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 organic and inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium 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 mol to 10 mol per 1 mol of the ester (VI), and in the case of an alkali, at least 1 mol, preferably 1 mol or more, per 1 mol of the ester (VI). 1 to 5 mol. Of course, you can use more than this. The reaction is usually performed in the presence of a solvent, and examples of such a solvent include the following.

Methanol, ethanol, propanol, acetone,
Methyl ethyl ketone, chloroform, dichloromethane,
Inert in reactions of aliphatic or aromatic hydrocarbons such as toluene, xylene, hexane, heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, N-methylpyrrolidone, ethers, alcohols, ketones, amides and halogenated hydrocarbons These solvents are used alone or as a mixture, and the amount used is not particularly limited.

The reaction temperature is usually −30 ° C. to 120 ° C., preferably −20 ° C. to 100 ° C.

The reaction time is not particularly limited. After completion of the reaction, the above alcohols (V) can be obtained in good yield by ordinary separation means, for example, extraction, liquid separation, concentration, recrystallization, etc., which can be further purified by column chromatography or the like if necessary. Can be used as it is without purification in the next step.

The alkylation reaction in the eighth step is performed by reacting the alcohol (V) with an alkylating agent represented by the general formula (IV).

The reaction is usually performed in the presence of a basic substance. Examples of the basic substance include alkali metal hydrides such as sodium hydride and potassium hydride, alkali metals such as lithium, sodium, and potassium; sodium ethylate; Examples thereof include alkali metal alcoholates such as methylate, alkali metal carbonates such as sodium carbonate and potassium carbonate, and butyl lithium.

Such a basic substance is required to be at least 1 equivalent times the alcohols (V), and the upper limit is not particularly limited, but is preferably 3 equivalent times.

Examples of the alkylating agent used in the above reaction include chlorides, bromides, 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 as exemplified below. Halides or sulfates such as methanesulfonic acid ester, ethanesulfonic acid ester, benzenesulfonic acid ester, toluenesulfonic acid ester, etc.
Is raised.

3 carbon atoms which may be substituted by the above halogen atom
Examples of the optically active alkyl group or alkoxyalkyl group of Nos. 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, Ethoxyoctyl, 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, hexyloxyhexyl, heptyloxyethyl, heptyloxypropyl, heptyloxy Butyl,
Heptyloxypentyl, octyloxyethyl, octyloxypropyl, decyloxyethyl, decyloxypropyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylbutyl, 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.).

In the case where the substituent R in the general formula (IV) is an optically active alkyl group containing a bromine or iodine atom, in general, sulfates are preferably used as the alkylating agent from the viewpoint of reaction yield.

However, when the substituent R is an optically active alkyl group containing a fluorine or chlorine atom, even if the alkylating agent is bromide or iodide, it can be used without any problem.

Further, halides (chloride, bromide or iodide) or sulfates having these optically active groups are derived from the corresponding optically active alcohols,
Certain of the optically active alcohols are readily obtained by asymmetric reduction of the corresponding ketone with asymmetric metal catalysts, microorganisms or enzymes. Others can be derived from optically active amino acids and optically active oxyacids as described below, which are either naturally occurring or obtained by resolution.

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, ispropyl malic acid and the like.

The amount of the above-mentioned alkylating agent (IV) to be used is 1 equivalent or more equivalent to the alcohol (V), but is usually in the range of 1 to 5 equivalent.

As the reaction solvent, for example, aliphatic or aromatic hydrocarbons such as tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chloroform, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, dimethylformamide, hexane, ether, halogenated A solvent inert to a reaction such as a hydrocarbon is used alone or as a mixture, and the amount of the solvent 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 (III) can be obtained by operations such as concentration.

The Bayer-Villiger oxidation reaction in the fourth step is performed by treating the acetophenones (III) with an oxidizing agent.

Examples of such an oxidizing agent include peracids such as peracetic acid, formic acid, methachloroperbenzoic acid, and perbenzoic acid. Such a peracid can be generated, for example, from the corresponding acid and hydrogen peroxide, and Bayer-Villiger oxidation can be performed while synthesizing the peracid in the reaction system.

The amount of peracid to be used is usually at least 1 equivalent times the acetophenones represented by the general formula (III), which is a raw material, and the upper limit is not particularly limited, but is preferably 5 equivalent times.

As the solvent used in the above reaction, usually, a solvent inert to the oxidation reaction is used. Examples of such a solvent include water or dioxane, tetrahydrofuran, N-methylpyrrolidone, di-n-butyl ether, ether,
Ethyl acetate, n-propyl acetate, dichloromethane, dichloroethane, chloroform, chlorobenzene, benzene, toluene, xylene, hexane, ether such as cyclohexane, ketone, ester, halogenated hydrocarbon,
Inert solvents, such as aromatic or aliphatic hydrocarbons, are used alone or as a mixture.

The reaction temperature is usually in the range of -10C to 100C, or preferably in the range of 0C to 90C.

In this way, phenyl esters (II) are obtained, but these phenyl esters are new compounds which have not been described in the literature as far as the present inventors know.

The hydrolysis reaction in the fifth step is performed using an acid or an alkali in the presence of water.

Examples of the acid used for 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 organic and inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, 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. For acids, phenyl esters (II) 1
The mole is preferably used in an amount of 0.02 to 10 times the mole, and in the case of an alkali, it is at least 2 times the mole, preferably 2 to 10 times the mole of the phenyl ester (II). Of course, you can use more than this. These are usually used together with a solvent, and examples of such a solvent include the following.

Methanol, ethanol, propanol, acetone,
Methyl ethyl ketone, chloroform, dichloromethane,
Inert in reactions of aliphatic or aromatic hydrocarbons such as toluene, xylene, hexane, heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, N-methylpyrrolidone, ethers, alcohols, ketones, amides and halogenated hydrocarbons These solvents 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, the compound of the present invention can be obtained in a high yield by usual separation means, for example, operations such as acid precipitation, extraction, liquid separation, and concentration, and if necessary, purified by column chromatography, recrystallization, or the like. Can also.

<Effect of the Invention> The compound of the present invention can be led to a novel liquid crystal compound (VIII) by, for example, a method shown by the following formula, and this compound has very excellent properties as a ferroelectric liquid crystal. I have. Further, the compound of the present invention can be industrially advantageously obtained by the production method of the present invention.

(Here, Ar represents a phenylene group, a biphenylene group, a heterocyclic group, or the like, Y represents an alkyl group, an alkoxyl group, or the like. R and n represent the same meaning as described above.) It can also be used as an intermediate for pharmaceuticals 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 (VII-1) at 10-25 ° C
2 g (0.3 mol) were added in 3 hours. After keeping the temperature at 20-30 ° C, the mixture was poured into ice water, 100 ml of dichloromethane was added, and the organic layer was separated. The organic layer was sequentially washed with water, 3% aqueous sodium carbonate and water, dried over magnesium sulfate, and concentrated under reduced pressure to give 43.0 g of 4- (β-acetoxyethyl) acetophenone (VI-1) (yield). 93%).

51.5 g (0.25 mol) of (VI-1) obtained above, 20%
65 g of caustic soda and 150 ml of methanol were charged and stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was poured into water and extracted with 200 ml of toluene. After liquid separation, the organic layer was washed with water and concentrated under reduced pressure to obtain 40.6 g (99% yield) of 4- (β-hydroxyethyl) acetophenone (V-1).

Next, 7.88 g (0.048 mol) of (V-1) obtained above.
And 80 ml of dimethylformamide, cooled to 0 to 5 ° C., and added 1.16 g (0.048 mol) of sodium hydride.
It was kept at the same temperature for 1 hour and further kept at 20 ° C. for 2 hours.
Next, 12.1 g (0.05 mol) of 2S-methylbutyl tosylate
Was added at 15 to 25 ° C for 2 hours, and the mixture was kept at the same temperature for 30 minutes, and then kept at 30 to 35 ° C for 2 hours. After the reaction,
The reaction solution was poured into ice, extracted 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 give 4- {2- (2S-
Methylbutoxy) ethyl acetophenone (III-1)
7.30 g (65% yield) were obtained.

Next, 2.34 g (0.01 mol) of (III-1) obtained above, 3.44 g (0.02 mol) of metachloroperbenzoic acid and 20 ml of dichloromethane were charged, and reacted at 20 to 30 ° C. for 24 hours. The point at which the raw material (III-1) was not detected was regarded as the reaction end point.

After the reaction, the reaction solution was washed with 3% sodium carbonate, further washed with water and concentrated. The concentrated residue was purified by column chromatography with toluene to give 4- {2- (2S-methylbutoxy) ethyl} phenylacetate (II-1) 2.
25 g (90% yield) were obtained.

Next, 1.25 g (5 mmol) of (II-1) obtained above, 1.5 g (7.5 mmol) of 20% sodium hydroxide, and 5 ml of methanol were charged and stirred at room temperature for 4 hours. After completion of the reaction, methanol was distilled off, the mixture was made weakly acidic with 2N-hydrochloric acid aqueous solution, extracted with 20 ml of ethyl acetate, and the organic layer was washed with water and concentrated under reduced pressure. The concentrated residue is purified by chromatography with toluene: ethyl acetate = 5: 1 to give 4- {2- (2S-methylbutoxy).
0.92 g (96% yield) of ethyl diphenol (I-1) was obtained.

Example 2 7.88 g (0.048 mol) of (V-1) obtained in Example 1 and 70 ml of N-methylpyrrolidone were charged, cooled to 0 to 5 ° C, and 1.16 g (0.048 mol) of sodium hydride was added. It 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 to 15 to 20 ° C over 2 hours, kept at the same temperature for 1 hour, and then kept at 30 to 35 ° C for 2 hours. After completion of the reaction, post-treatment and purification were carried out according to Example 1 to give 4-
5.96 g (45% yield) of {2- (1S-methylheptyloxy) ethyl} acetophenone (III-2) was obtained.

Next, 2.76 g (0.01 mol) of (III-2) obtained above, 4.3 g (0.025 mol) of metachloroperbenzoic acid and 20 ml of dichloroethane were charged and reacted at 20 to 30 ° C. for 20 hours. After completion of the reaction, the reaction solution was washed with 3% sodium carbonate. Thereafter, post-treatment and purification were carried out according to Example 1, and 4
2.69 g (yield 92%) of-{2- (1S-methylheptyloxy) ethyl} phenyl acetate (II-2) was obtained.

Next, 1.46 g (5 mmol) of (II-2) obtained above, 2.1 g (7.5 mmol) of 20% potassium hydroxide, 3 ml of methanol and 1 ml of tetrahydrofuran were stirred at 30 ° C. for 4 hours. After the completion of the reaction, methanol and tetrahydrofuran were distilled off, and the residue was made weakly acidic with 2N aqueous hydrochloric acid.

Thereafter, by post-treatment and purification according to Example 1, 4- {2- (1S-methylheptyloxy) ethyl} was obtained.
1.20 g (95.5% yield) of phenol (I-2) was obtained.

Example 3 7.88 g (0.048 mol) of (V-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 were added,
After keeping at the same temperature for 1 hour, the temperature was raised to room temperature. to this,
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 kept at 25 to 30 ° C. for 3 hours. After completion of the reaction, 6.98 g of 4- {2- (2S-propoxypropoxy) ethyl} acetophenone (III-3) was obtained by post-treatment and purification according to Example 1.
%).

Next, 2.64 g (0.01 mol) of (III-3) obtained above, 4.3 g (0.025 mol) of methachloroperbenzoic acid and
20 ml of 1,2-dichloroethane was charged and stirred at 20 to 30 ° C. for 15 hours. After completion of the reaction, 2.61 g (93% yield) of 4- {2- (2S-propoxypropoxy) ethyl} phenylacetate (II-3) was obtained by post-treatment and purification according to Example 1.

Next, 1.40 g (5 mmol) of (II-3) obtained above, 2.1 g (7.5 mmol) of 20% potassium hydroxide and 5 ml of methanol were charged, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, methanol was distilled off, and the mixture was worked up and purified according to Example 1 to give 1.17 g of 4- {2- (2-propoxypropoxy) ethyl} phenol (I-3) (yield: 98). %).

Example 4 The same apparatus as in Example 1 was charged with 84.0 g (0.63 mol) of aluminum chloride and 450 ml of dichloromethane, and 51.8 g (0.66 mol) of acetyl chloride was added over 2 hours at 10 to 15 ° C. After keeping at the same temperature for 1 hour, 53.4 g (0.3 mol) of 3-phenylpropyl acetate (VII-4) at 10 to 20 ° C.
Was added over 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, and the organic layer was separated. The organic layer was washed successively with water, 3% aqueous sodium carbonate and water, dried over magnesium sulfate, and concentrated under reduced pressure to give 4- (3-acetoxypropyl).
62.4 g (94.5% yield) of acetophenone (VI-4) was obtained.

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

Next, 8.54 g (0.048 mol) of (V-4) obtained above and 80 ml of dimethylformamide were charged, the mixture was cooled to 0 to 5 ° C, and 1.16 g (0.048 mol) of sodium hydride was added. The mixture was kept warm and further kept at 25 ° C. for 2 hours.

Next, 12.1 g (0.05 mol) of 2S-methylbutyl tosylate
Was added at 20 to 30 ° C for 3 hours, and the mixture was kept at the same temperature for 30 minutes and then kept at 30 to 40 ° C for 2 hours. After the reaction,
By post-treatment and purification according to Example 1, 4-
8.44 g (71% yield) of {3- (2S-methylbutoxy) propyl} acetophenone (III-4) was obtained.

Next, 2.48 g (0.01 mol) of (III-4) obtained above.
And 1.14 g of 60% peracetic acid in a solution of 20 ml of propyl ether
Was added at 20 ° C for 2 hours, and the mixture was stirred at 20 to 30 ° C for 15 hours. After completion of the reaction, the reaction solution was washed with water, 2% sodium carbonate,
Washed sequentially with water, 2% aqueous hydrochloric acid and water. Hereinafter, Example 1
By post-treatment and purification according to
2.44 g (92.5% yield) of (2S-methylbutoxy) propyl diphenylacetate (II-4) was obtained.

Next, 1.32 g (5 mmol) of (II-4) obtained above, 2 g (0.01 mol) of 20% sodium hydroxide, and 0.1 g of tetrabutylammonium bromide were charged and stirred at 30 ° C. for 10 hours. After completion of the reaction, the mixture was made weakly acidic with 2N-hydrochloric acid aqueous solution and extracted with 20 ml of ethyl acetate. Hereinafter, according to Example 1,
Post-treatment and purification yielded 1.06 g of 4- {3- (2S-methylbutoxy) propyl} phenol (I-4) (yield 95.5%).

Example 5 8.54 g (0.048 mol) of (V-4) obtained in Example 4,
20 ml of tetrahydrofuran and 60 dimethylformamide
ml, cool to 0-10 ° C and add sodium hydride 1.28
g (0.052 mol), and keep at the same temperature for 1 hour.
Incubated for 2 hours at ° C.

Next, 17.06 g (0.06 mol) of 1R-methylheptyl tosylate was added at 15 ° C. over 3 hours. After keeping the temperature 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 carried out according to Example 1 to give 4-
6.68 g (48% yield) of {3- (1S-methylheptyloxy) propyl} acetophenone (III-5) was obtained.

Next, 2.9 g (0.01 mol) of (III-5) obtained above, 4.3 g (0.025 mol) of metachloroperbenzoic acid and 15 ml of dichloromethane were charged and reacted at 20 to 30 ° C. for 24 hours. After completion of the reaction, the reaction solution was washed with 3% sodium hydroxide and water in that order, and the organic layer was concentrated and purified by column chromatography to give 4- {3- (1S-methylheptyloxy) propyl} acetate ( II-4) 2.83 g
(92.4% yield).

1.53 g (5 mmol) of (II-5) obtained above, 20
% Caustic soda 3g (0.015 mol) and methanol 5ml 20
Stirred at 3030 ° C. for 5 hours. After completion of the reaction, methanol was distilled off, and the residue was made weakly acidic with 2N-hydrochloric acid solution.
After extraction with 20 ml, the organic layer was washed with water and concentrated under reduced pressure. The concentrated residue was purified by column chromatography with toluene: ethyl acetate = 5: 1 to give 4- {3- (1S-methylheptyloxy) propyl} phenol (I-5) 1.27.
g (96.5% yield).

Examples 6 to 11 The reaction was performed in the same manner as in Example 5, except that the sulfates shown in Table 1 were used instead of 1R-methylheptyl tosylate.
After treatment and purification, the results shown in Table 1 were obtained.

Example 12 In the same manner as in Example 1, 84.0 g (0.63 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 at the same temperature for 1 hour, add 57.6 g (0.3 mol) of 4-phenylbutyl acetate (VII-12) at 10 to 20 ° C for 3 hours, keep at 20 to 25 ° C for 3 hours, and then add ice water Open,
Dichloroethane was added and extracted. Thereafter, by post-treatment and purification according to Example 1, 59.0 g of 4- (4-acetoxybutyl) acetophenone (VI-12) was obtained (yield: 84).
%).

58.5 g (0.25 mol) of (VI-12) obtained above, 20%
75 g of caustic soda and 150 ml of methanol were charged and stirred at room temperature for 5 hours. Thereafter, post-treatment and purification were carried out in the same manner as in Example 1 to obtain 40.8 g (yield: 85%) of 4- (4-hydroxybutyl) acetophenone (V-12).

9.22 g (0.048 mol) of (V-12) obtained above, 60 ml of dimethylformamide and 15 ml of tetrahydrofuran were charged, cooled to 0 to 5 ° C., and 1.16 g of sodium hydride was added.
(0.048 mol), and the mixture was 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 at 15 to 25 ° C for 3 hours. It was kept at 35 ° C. for 2 hours. After completion of the reaction, post-treatment and purification were conducted in the same manner as in Example 1 to obtain 8.94 g of 4- {4- (2S-methylbutoxy) butyl} acetatephenone (III-12) (yield: 71).
%).

2.62 g (0.01 mol) of (III-12) obtained above, 3.44 g (0.02 mol) of methachloroperbenzoic acid and ethyl acetate 1
2 ml was charged and reacted at 25 to 35 ° C for 20 hours. After completion of the reaction, the reaction solution was washed with 3% sodium carbonate and water sequentially,
The organic layer was concentrated and purified by column chromatography to obtain 2.52 g of 4- {4- (2S-methylbutoxy) butyl} phenylacetate (II-12) (yield 90.5%).
%).

Next, 1.39 g (5 mmol) of (II-12) obtained above, 3 g (0.015 mol) of 20% caustic soda and 3 ml of methanol were charged and stirred at 25 to 30 ° C. for 5 hours. Less than,
By post-treatment and purification according to Example 1, 4-
{4- (2S-methylbutoxy) butyl} phenol (I
-12) 1.13 g (95.5% yield) was obtained.

Example 13 9.22 g (0.048 mol) of (V-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 carried out in the same manner as in Example 1 to obtain 8.7 g of 4- {4- (2S-propoxypropoxy) butyl} acetophenone (III-13) (yield: 62%).

Next, 2.92 g (0.01 mol) of (III-13) obtained above, 4.3 g (0.025 mol) of methachloroperbenzoic acid and
20 ml of 1,2-dichloroethane was charged and stirred at 20 to 30 ° C. for 20 hours. After completion of the reaction, post-treatment and purification were conducted in the same manner as in Example 1 to obtain 2.84 g of 4- {4- (2S-propoxypropoxy) butyl} phenyl acetate (II-13) (yield: 92%).

Next, 1.54 g (5 mmol) of (II-13) obtained above, 3 g (0.015 mol) of 20% sodium hydroxide, and 5 ml of methanol were stirred at room temperature for 3 hours. Thereafter, post-treatment and purification were carried out according to Example 1 to give 4- {4- (2S-propoxypropoxy) butyl} phenol (I-13) 1.
38 g (98% yield) were obtained.

Example 14 An alkylation reaction, post-treatment, and purification were carried out in the same manner as in Example 4 except that 10.88 g (0.072 mol) of 2S-methylbutyl bromide was used instead of 2S-methylbutyl tosylate to give 4- ｛. 7.62 g (64% yield) of 3- (2S-methylbutoxy) propyl @acetophenone (III-4) was obtained.

By subjecting 2.48 g (0.01 mol) of (III-4) obtained above to an oxidation reaction according to Example 4, 4- {3-
2.46 g (98% yield) of (2S-methylbutoxy) propyl diphenylacetate (II-4) was obtained.

Further, by subjecting 1.32 g (5 mmol) of (II-4) obtained above to a hydrolysis reaction in the same manner as in Example 3,
1.06 g (yield 95.3%) of 4- {3- (2S-methylbutoxy) propylphenol (I-4) was obtained.

Reference example In a four-necked flask equipped with a stirrer and thermometer (+)
1.04 g (5 mmol) of -4- [2- {2 (s) -methylbutoxy} ethyl] phenol, 1.67 g (6 mmol) of 4-decyloxybenzoic acid and 30 ml of anhydrous dichloromethane are charged, and N, N'-dicyclohexylcarbodiimide is added. 1.22g
(6 mmol) and 0.1 g of 4-pyrrolidinopyridine were added, and the mixture was stirred at room temperature for 24 hours.

After the completion of the reaction, the resulting precipitate was separated and diluted with 200 ml of toluene.
After washing with 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-decyloxybenzoic acid 4- [2
2.10 g (yield 90%) of-{2 (s) -methylbutoxy} ethyl] phenyl ester was obtained.

Continued on the front page (72) Inventor Masayoshi Minami 3-1-1, Kasuganaka, Konohana-ku, Osaka-shi, Sumitomo Chemical Co., Ltd. (72) Inventor Kiyoshi Imamura 3-chome, Kasuganaka, Konohana-ku, Osaka-shi, Osaka No. 1 No. 98 Sumitomo Chemical Co., Ltd. (56) References JP-A-2-131451 (JP, A)

Claims (7)

(57) [Claims] 1. The compound of the general formula (I) (Wherein, R represents an optically active alkyl group or an alkoxyalkyl group having 3 to 15 carbon atoms which may be substituted by a halogen atom, and n represents an integer of 1 to 6). Derivatives. 2. A compound of the general formula (II) (Wherein R and n have the same meanings as described above). A process for producing an optically active phenol derivative represented by the general formula (I), comprising hydrolyzing a phenyl ester represented by the following formula: 3. A compound of the general formula (III) (Wherein, R and n have the same meanings as described above.) A Bayer-Villiger oxidation of an acetophenone represented by the following formula is obtained to obtain a phenyl ester represented by the general formula (II) and hydrolyze it. General formula (I)
A method for producing an optically active phenol derivative represented by the formula: 4. The formula (V) (In the formula, n represents the same meaning as described above.) An alcohol represented by the general formula (IV) RX (IV) (wherein, R has the same meaning as described above, and X is a halogen atom Or a general formula -OSO ₂ R ", wherein R" represents a lower alkyl group or a phenyl group which may be substituted.) And reacted with an alkylating agent represented by the general formula (III). Acetophenones, which are subjected to Bayer-Villiger oxidation to obtain phenyl esters of the general formula (II), which are hydrolyzed to obtain an optically active phenol of the general formula (I) Method for producing derivatives. 5. A compound of the general formula (VI) (Wherein, n has the same meaning as described above, and R ′ represents a lower alkyl group.) An alcohol represented by the general formula (V) is hydrolyzed to obtain an alcohol represented by the general formula (V). Reaction with an alkylating agent represented by the general formula (IV) gives an acetophenone represented by the general formula (III), which is subjected to Bayer-Villiger oxidation to obtain a phenyl ester represented by the general formula (II). And a method for producing an optically active phenol derivative represented by the general formula (I), which is hydrolyzed. 6. A compound of the general formula (VII) (Wherein R ′ and n represent a lower alkyl group.) The benzene derivative represented by the general formula (V)
The ester represented by I) is obtained, and this is hydrolyzed,
An alcohol represented by the general formula (V) is obtained, and is reacted with an alkylating agent represented by the general formula (IV) to obtain an acetophenone represented by the general formula (III). A method for producing an optically active phenol derivative represented by the general formula (I), wherein a phenyl ester represented by the general formula (II) is obtained and hydrolyzed. 7. A phenyl ester represented by the general formula (II).