JP2536577B2 - Optically active benzene derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a compound represented by the general formula (I): (In the formula, R represents an alkyl group which may contain an allogen atom having 1 to 20 carbon atoms, and n is 1 or 2. * represents an asymmetric carbon.) The present invention relates to a benzene derivative and a method for producing the same.

<Prior Art> The optically active benzene derivative represented by the general formula (I) is a novel compound that has not been described in any literature, and it has been known not only about its production method but also its usefulness as a compound. Not not.

<Problems to be Solved by the Invention> The optically active benzene derivative represented by the general formula (I) is useful as an intermediate for medicines, agricultural chemicals, etc., but particularly as an intermediate for organic electronic materials, especially novel liquid crystal compounds. Very useful.

For example, the optically active benzene derivative can be led to a novel liquid crystal compound by a method represented by the following formula, and the compound has very excellent properties as a ferroelectric liquid crystal.

<Means for Solving the Problems> The present invention is not limited to such a medical or agricultural chemical intermediate,
The present invention provides an optically active benzene derivative represented by the above general formula (I), which is a novel compound useful as an organic electronic material, particularly as an intermediate of a liquid crystal compound.

The optically active benzene derivative represented by the general formula (I) has a general formula (II) (In the formula, n and * have the same meanings as described above) and an optically active alcohol compound represented by the general formula (II
I) R-COOH (III) (wherein R has the same meaning as described above), and easily produced in good yield by reacting with an acid anhydride or acid halide of an aliphatic carboxylic acid. You can

The optically active alcohol compound (I
I) can be produced, for example, by the reaction exemplified below.

(Wherein R ′ and R ″ are lower alkyl groups) In this method, for example, an acetyl derivative as a starting material is reduced with a reducing agent such as sodium borohydride or lithium aluminum hydride to give an alcohol derivative. Then, this is acylated with an acid anhydride or acid halide of a lower aliphatic carboxylic acid such as acetyl chloride or acetic anhydride to obtain an ester compound, and the esterified product is asymmetrically hydrolyzed with an enzyme to give a carboxylic acid. It is carried out by hydrolyzing the acid ester.

As the other raw material in the method of the present invention, an acid anhydride or an acid halide of an aliphatic carboxylic acid (III) (for example, acid chloride, acid bromide) is used. Examples of the aliphatic carboxylic acid include acetic acid and propion Acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid,
Tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, isolacic acid, 2-methylbutanoic acid, 2,3-dimethylbutanoic acid, 2,3,3-trimethylbutanoic acid, 2-methylpentanoic acid, 3-methylpentanoic acid, 2,
3-dimethylpentanoic acid, 2,4-dimethylpentanoic acid, 2,
3,3,4-tetramethylpentanoic acid, 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 2,
5-dimethylhexanoic acid, 2-methylheptanoic acid, 2-
Methyl octanoic acid, 2-trihalomethyl pentanoic acid, 2
-Trihalomethylhexanoic acid, 2-trihalomethylheptanoic acid, 2-halopropanoic acid, 3-halo-2-methylpropanoic acid, 2,3-dihalopropanoic acid, 2-halobutanoic acid, 3-halobutanoic acid, 2, 3-dihalobutanoic acid, 2,4-dihalobutanoic acid, 3,4-dihalobutanoic acid, 2-halo-3-
Methylbutanoic acid, 2-halo-3,3-dimethylbutanoic acid,
2-halopentanoic acid, 3-halopentanoic acid, 4-halopentanoic acid, 2,4-dihalopentanoic acid, 2,5-dihalopentanoic acid, 2-halo-3-methylpentanoic acid, 2-halo-4
-Methylpentanoic acid, 2-halo-3-monohalomethyl-
4-methylpentanoic acid, 2-halohexanoic acid, 3-halohexanoic acid, 4-halohexanoic acid, 5-halohexanoic acid, 2-haloheptanoic acid, 2-halooctanoic acid (however, halo in the above compound means fluorine, chlorine, bromine or Which represents iodine) and the like, and of these compounds, when the secondary carbon is an asymmetric carbon, it may be an optically active carboxylic acid.

Among these aliphatic carboxylic acids, some of the above-mentioned optically active carboxylic acids can be obtained by oxidation of the corresponding alcohol and reductive deamination of amino acids. Some can be derived from optically active amino acids and optically active oxyacids that occur naturally or are obtained by resolution, such as:

Alaline, valine, leucine, isoleucine, phenylalanine, serine, threonine, arosreonine, homoserine, alloisoleucine, tert-leucine, 2-aminobutyric acid, ilvaline, norleucine, ornithine, lysine, hydroxylysine, phenylglycine, trifluoroalanine, asparagine. Acid, glutamic acid, lactic acid,
Mandelic acid, tropic acid, 8-hydroxybutyric acid, malic acid, tartaric acid, isopropylmalic acid, etc.

The reaction of such an optically active alcohol compound (II) with an acid anhydride or acid halide of an aliphatic carboxylic acid (III) is usually carried out in the presence or absence of a solvent, generally in the presence of a catalyst. .

When a solvent is used in this reaction, examples of the solvent include an aliphatic or aromatic solvent such as tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, and hexane. Solvents such as hydrocarbons, ethers, halogenated hydrocarbons and the like which are inert to the reaction may be used alone or as a mixture. The amount used can be used without particular limitation.

The amount of the acid anhydride or acid halide of the aliphatic carboxylic acid used in the reaction needs to be 1 equivalent or more with respect to the optically active alcohol compound, and the upper limit is not particularly limited, but it is preferably 4 equivalents.

Examples of the catalyst include dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine,
Picoline, collidine, imidazole, sodium carbonate,
Examples thereof include organic or inorganic basic substances such as sodium methylate and potassium hydrogen carbonate. Further, an organic acid or an inorganic acid such as toluenesulfonic acid, methanesulfonic acid or sulfuric acid may be used as a catalyst.

When using such a catalyst, for example, when an acid halide of an aliphatic carboxylic acid is used as a raw material, pyridine and triethylamine are particularly preferably used.

The amount of the catalyst used varies depending on the type of the acid anhydride or acid halide of the aliphatic carboxylic acid and the combination of the catalyst used, and is not necessarily specified.For example, when an acid halide is used, the amount of the acid halide is It is 1 equivalent or more.

The reaction temperature is usually -30 ° C to 100 ° C, preferably -25 ° C to 80 ° C.

The reaction time is not particularly limited, and the time when the optically active alcohol compound as the raw material disappears can be regarded as the end point of the reaction.

After completion of the reaction, usual separation means such as extraction, liquid separation,
The desired optically active benzene derivative represented by the general formula (I) can be isolated from the reaction mixture by concentration, distillation and the like, and may be purified by column chromatography or the like if necessary.

<Effect of the Invention> According to the method of the present invention, an optically active benzene derivative (I), which is a novel compound, can be obtained at a high yield. It can be used not only as an intermediate but also as an intermediate of an organic electronic material such as a liquid crystal compound.

<Examples> Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited to these Examples.

Reference Example 1 0.3 M phosphate buffer (pH 7.
0) 500 ml was charged, and after adding 22.2 g of methyl dl-4- (1-acetoxyethyl) benzoate, 4.0 g of lipase (Amano P, manufactured by Amano Pharmaceutical Co., Ltd.) and 4 ml of chloroform,
Stir vigorously for 24 hours at 38 ± 2 ° C under nitrogen stream. After completion of the reaction, the reaction mixture was extracted twice with 300 ml of ethyl acetate, the obtained organic layer was concentrated, and the concentrated residue was separated and purified by silica gel column chromatography (eluent: toluene-ethyl acetate). (+)-4-
Methyl (1-hydroxyethyl) benzoate 8.5 g [Yield 47
%, ▲ [α] ²⁰ _D ▼ + 46 ° (c = 1, chloroform)]
And 10.5 g of methyl (-)-4- (1-acetoxyethyl) benzoate [yield 47%, ▲ [α] ²⁰ _D ▼ -96 ° (c = 1, chloroform)] were obtained.

8 g of methyl (+)-4- (1-hydroxyethyl) benzoate obtained here was dissolved in 80 ml of tetrahydrofuran, and 40 ml of 20% aqueous sodium hydroxide solution was added thereto, and the mixture was stirred at room temperature for 5 minutes.
Stir vigorously for hours.

After completion of the reaction, the reaction solution is adjusted to pH 3 with 4N hydrochloric acid and then extracted with 200 ml of ether three times. The organic layer was washed with saturated brine and then concentrated under reduced pressure to obtain (+) as a concentrated residue.
6.72 g of 4- (1-hydroxyethyl) benzoic acid (yield 9
1%) [▲ [α] ²⁵ _D ▼ + 39.0 ° (c = 1, methanol), melting point 155-156 ° C].

With respect to the previously obtained methyl (−)-4- (1-acetoxyethyl) benzoate, hydrolysis reaction and post-treatment were performed in the same manner as above, and 5.52 g of (−)-4- (1-hydroxyethyl) benzoic acid (Yield 92%) [▲ [α] ²⁵ _D ▼ -35.6 ° (c =
1, methanol)] was obtained.

Reference Example 2 15.6 g of ethyl dl-4- (1-acetoxyethyl) -4'-biphenylcarboxylate was used instead of methyl dl-4- (1-acetoxyethyl) benzoate, 500 ml of 0.3 M phosphate buffer, Asymmetric hydrolysis reaction and post treatment were carried out in the same manner as in Reference Example 1 except that 6.4 g of lipase and 5 ml of chloroform were used, and then (+)-4- (1-hydroxyethyl)-
Ethyl 4'-biphenylcarboxylate 6.4 g [▲ [α] ²⁵ _D
▼ + 36 ° (c = 1, chloroform), melting point 75 ° C] and ethyl (-)-4- (1-acetoxyethyl) -4'-biphenylcarboxylate 7.4 g [▲ [α] ²⁵ _D ▼ -87 ° ( c
= 1, chloroform), melting point 46-47 ° C.].

(+)-4- (1-hydroxyethyl) -obtained here
6.0 g of ethyl 4'-biphenylcarboxylate is added to a mixture of 60 ml of 20% aqueous sodium hydroxide solution and 60 ml of methanol, and the mixture is stirred at room temperature for 6 hours.

After the reaction is completed, 50 ml of water is added to the reaction solution and the pH is adjusted to 3 with 3N hydrochloric acid. The resulting precipitate is removed, washed with water and (+)-4-
5.04 g (yield 94%) of (1-hydroxyethyl) -4'-biphenylcarboxylic acid was obtained as a white solid.

▲ [α] ²⁵ _D ▼ + 44 ° (c = 0.4, dimethylformamide) Melting point 222-223 ° C (decomposition) (−)-4- (1-acetoxyethyl) -4′-biphenylcarboxylate Ethylate 6.0 g Hydrolysis reaction and post treatment were carried out in the same manner as in (-)-4- (1-hydroxyethyl) -4'-biphenylcarboxylic acid 4.44 g.
(95% yield).

[Α] ²⁵ _D ▼ −38 ° (c = 1, dimethylformamide) Example 1 (−)-4- (1-hydroxyethyl) benzoic acid 0.83
0.56 g of butyryl chloride is added to a mixed solution of g, 5 ml of pyridine and 5 ml of toluene at 10 to 15 ° C. over 1 hour. Then, the mixture is stirred at room temperature for 2 hours. After the reaction,
The reaction solution is poured into 25 ml of 5% hydrochloric acid aqueous solution and extracted with 30 ml of toluene. The organic layer is washed with water and then concentrated under reduced pressure.
The concentrated residue was purified by column chromatography using a mixed solution of toluene: acetic acid = 20: 1 to obtain 1.12 g (yield 95%) of (−)-4- (1-butyryloxyethyl) benzoic acid.

▲ [α] ²⁵ _D ▼ -91.3 ° (c = 1, chloroform) ▲ n ²⁵ _D ▼ 1.5134 Examples 2 to 6 Examples except that the aliphatic carboxylic acids shown in Table 1 were used instead of butyryl chloride. Reaction and post-treatment were carried out according to 1, and the results shown in Table 1 were obtained.

Example 7 (+)-4- (1-hydroxyethyl) benzoic acid 0.83
g, hexanoic anhydride 1.12 g, toluene 30 ml and pyridine
Mix 5 ml and react at 40-50 ° C for 5 hours. After completion of the reaction, the reaction solution is washed with 1% hydrochloric acid water, further washed twice with water, and then concentrated under reduced pressure. Thereafter, post-treatment was carried out in the same manner as in Example 1 to obtain 1.35 g (yield 96.5%) of (+)-4- (1-hexanoyloxyethyl) benzoic acid.

▲ [α] ²⁵ _D ▼ + 68.5 ° (c = 1, chloroform) ▲ n ²⁵ _D ▼ 1.4856 Example 8 0.88 g of 2S, 3S-2-chloro-3-methylpentanoic acid chloride was used instead of hexanoic anhydride. Use the reaction temperature of 20
The reaction and post-treatment were carried out in the same manner as in Example 7 except that the reaction time was -25 ° C and the reaction time was 3 hours. Then, (+)-4- (2S, 3S-2-
Chloro-3-methylpentanoyloxyethyl) benzoic acid (1.38 g, yield 92.5%) was obtained.

▲ [α] ²⁵ _D ▼ + 64.8 ° (c = 1, chloroform) ▲ n ²⁵ _D ▼ 1.5132 Example 9 (-)-4- (1-hydroxyethyl) -4'-biphenylcarboxylic acid 1.21 g, pyridine Hexanoic acid chloride 1.72 was added to a mixed solution consisting of 15 ml and 25 ml of dichloromethane.
g at 15-25 ° C over 2 hours. Then, the mixture is stirred at room temperature for 3 hours.

After completion of the reaction, the reaction solution is poured into 60 ml of 10% hydrochloric acid water and extracted with 50 ml of dichloromethane. The organic layer was washed with water, concentrated under reduced pressure, and the concentrated residue was purified by column chromatography using a toluene: acetic acid = 15: 1 mixture solution to obtain (−)-4- (1-hexanoyloxyethyl) -4′-. Biphenylcarboxylic acid (1.58 g, yield 93%) was obtained.

▲ [α] ²⁵ _D ▼ -59 ° (c = 1, chloroform) Melting point 130 ° C Example 10 (+)-4- (1-hydroxyethyl) -4'-biphenylcarboxylic acid 1.21 g, pyridine 20 ml, dichloromethane 30 ml And 0.87 g of butanoic acid anhydride are mixed, and 40-50 ° C.
React for 6 hours. After completion of the reaction, the reaction solution is washed with 5% hydrochloric acid water, further washed with water, and then concentrated under reduced pressure. Thereafter, post-treatment was carried out in the same manner as in Example 9 to obtain (+)-4- (1-butanoyloxyethyl) -4'-biphenylcarboxylic acid.
1.49 g (96% yield) was obtained.

▲ [α] ²⁵ _D ▼ + 82.6 ° (c = 1, chloroform) Melting point 165 ° C. Examples 11 to 13 In Example 9 except that the aliphatic carboxylic acids shown in Table 2 were used in place of hexanoic acid chloride. The reaction and post-treatment were carried out in the same manner, and the results shown in Table 2 were obtained.

Claims (2)

(57) [Claims] 1. A general formula (In the formula, R represents an alkyl group having 1 to 20 carbon atoms and optionally containing a halogen atom, and n is 1 or 2. * indicates an asymmetric carbon) Benzene derivative. 2. General formula (In the formula, n is 1 or 2, and * indicates an asymmetric carbon), and an optically active alcohol compound represented by the general formula R-COOH (wherein R is a halogen having 1 to 20 carbon atoms). A general formula characterized by reacting an acid anhydride or an acid halide of an aliphatic carboxylic acid represented by (Wherein R, n and * have the same meanings as described above).