JPH02311440A - Production of optically active ether derivative - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as a liquid crystal material, etc., having excellent image-display response without using catalysts, etc., at a low cost by using an optically active alcohol derivative as a raw material and alkylating the raw material with an alkylating agent in the presence of an alkylation assistant. CONSTITUTION:The objective compound of formula III can be produced by alkylating an optically active alcohol derivative of formula I (X is COO, OCO, CH2O or OCH2; A is 3 to 15C alkyl or alkoxy; (l) and (m) are 1 or 2; *represents asymmetric carbon) with an alkylating agent of formula II (R is 1 to 20C alkyl or alkoxyalkyl which may be substituted with F, Cl or Br; Y is halogen or O2SR'; R' is lower alkyl, trifluoromethyl or phenyl) in the presence of an alkylation assistant such as silver oxide. The compound of formula II is a halide (e.g. chloride, bromide or iodide) or a sulfonate.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention is directed to the general formula (1) (wherein, X bar COO-1-0CO-, -CI,O-
or -0CR2-, A is an alkyl group or alkoxyl group having 3 to 15 carbon atoms, and R is an alkyl group or alkyloxyalkyl group having 1 to 20 carbon atoms, which may be substituted with fluorine, chlorine, or bromine. Represent each. ! and m each represent 1 or 2.

* indicates an asymmetric carbon. ) relates to a method for producing an optically active ether derivative.

<Prior Art> European Patent Publication No. 0297745 describes a method for producing optically active ether derivatives using phenols represented by the general formula (wherein A and l have the same meanings as above) and a method for producing an optically active ether derivative. (V) (wherein, R1
represents an alkyl group or an alkyloxyalkyl group having 1 to 20 carbon atoms, and Ro represents a hydroxyl group or a halogen atom, respectively. m and *marks have the same meanings as above.

) or the general formula (Vl) (wherein A, R' and β have the same meanings as above).

) and the general formula (■) (where R',
m and *marks have the same meanings as above. ) A method for reacting optically active phenols shown in the following is described.

However, in this method, when the raw material optically active carboxylic acids (V) or carboxylic acids (VI>) is a free acid, the reactivity of esterification is somewhat low, and in addition to the catalyst, dicyclohexylcarbodiimide, imidazo There are problems such as the need for an esterifying agent such as ylimidazole, and this method cannot necessarily be said to be industrially satisfactory.

<Problems to be Solved by the Invention> The present invention provides an industrially advantageous method for producing an optically active ether derivative represented by the general formula (I>).

<Means for solving the problem> The present invention is based on the general formula (n) Hs (where x barcoo-1-0CO-, -Cl120
- or -0CR2-, and A represents an alkyl group or an alkoxyl group having 3 to 15 carbon atoms, respectively. ! and m each represent 1 or 2. * indicates an asymmetric carbon. ) An optically active alcohol derivative represented by the general formula (III) RY (I) (wherein R is a fluorine, chlorine or bromine atom having 1 to 20 carbon atoms) in the presence of an alkylation auxiliary agent. Y represents an optionally substituted alkyl group or alkyloxyalkyl group, and Y represents a halogen atom or a 103SR' group, respectively. Here, Ro represents a lower alkyl group, a trifluoromethyl group, or an optionally substituted phenyl group. This is a method for producing an optically active ether derivative represented by the above general formula 1), which is characterized in that the optically active ether derivative is alkylated with an alkylating agent represented by the following formula.

The optically active alcohol derivative represented by the general formula (n) can be obtained, for example, by reducing an acetylbenzoate alkyl (having 3 to 15 carbon atoms) phenyl with borohydride. After that, it can be produced by converting it into an acetate ester with acetyl chloride/pyridine, and then asymmetrically hydrolyzing this acetate ester using an enzyme "lipase" to form an optically active α-hydroxyethyl group.

In the general formula (n), the substituent A includes, for example, a straight-chain alkyl group or alkoxyl group having 3 to 15 carbon atoms.

As the alkylating agent (I [I), a halide or sulfonate such as chloride, bromide or iodide is used, and the sulfonate is lower alkyl sulfonate such as methanesulfonate or ethanesulfonate, trifluoromethylsulfonate, benzenesulfonate or p-toluene. Examples include aryl sulfonates such as sulfonates.

In the general formula (nl), examples of the substituent R include straight or branched alkyl or alkyloxyalkyl groups, and specific examples include the following.

Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, methoxymethyl, methoxyethyl,
Methoxypropyl, methoxyethyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl, methoxydecyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, ethoxyhexyl, ethoxyhbutyl, ethoxyoctyl, ethoxy Nonyl, ethoxydecyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, propoxyhexyl, propoxyheptyl, propoxyoctyl, propoxynonyl, propoxydecyl, butoxymethinopebutoxyethyl, butquinpropyl, butoxybutyl, but Quinpentyl, butoxyhexyl,
Butoxyheptyl, butoxyoctyl, butoxynonyl, butoxydecyl, pentyloxymethyl, pentyloxyethyl, heptyloxypropyl, pentyloxybutyl, pentyloxypentyl, pentyloxyhexyl, pentyloxyoctyl, pentyloxydecyl, hexyloxymethyl, hexyloxy Ethyl, hexyloxyethyl, hexyloxyethyl, hexyloxypentyl, hexyloxyethyl, hexyloxyoctyl, hexyloxynonyl, hexyloxydecyl, heptyloxymethyl, heptyloxyethyl, heptyloxypropyl, heptyloxybutyl, heptyloxypentyl, Octyloxymethyl, octyloxyethyl, octyloxypropyl, decyloxymethyl, decyloxyethyl, decyloxypropyl, ■
-Methylethyl, 1-methylproyl, 1-methylbutyl, 1-methylpentyl, 1-methylhexyl, 1-methylheptyl, 1-methyloctyl, 2-methylethyl, 2-methylbutyl, 2.3-dimethylbutyl, 2. 3
．． 3-trimethylbutyl, 2-methylpentyl, 3-methylpentyl, 2.3-'; Methylpentyl, 2.4
-dimethylpentyl, 2,3,3.4-tetramethylpentyl, 2-methylhexyl, 3-methylhexyl, 4
-Methylhexyl, 2.5-dimethylhexyl, 2-methylhebutyl, 2-methyloctyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-)dihalomethylheptyl, 2-haloethyl, 2-haloflovir, 3-halopropyl, 3-halo 2-methylpropyl,
2.3-'; halopropyl, 2-herobutyl, 3-halobutyl, 4-halobutyl, 2.3-dihalobutyl, 2.
4-dihalobutyl, 3.4-dihalobutyl, 2-halo 3-methylbutyl, 2 to halo 3. 3-'; methylbutyl, 2-halopen-f-l, 3-halopentyl, 4
-halopentyl, 5-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-halohexyl5
/% halohexyl, 6-halohexyl, 2-haloheptyl, 2-halooctyl (however, halo in the above alkyl group is
fluorine, chlorine or bromine).

Here, the branched alkyl or alkyloxyalkyl group may be an optically active group. In addition, the alkylating agent (I[[) having such an optically active group is
It can be produced from the corresponding alcohol by methods described in the literature.

Alkylation is carried out in the presence or absence of a solvent.

Examples of the solvent include ether solvents such as tetrahydrofuran and ethyl ether, ketone solvents such as acetone and methyl ethyl ketone, aliphatic or aromatic hydrocarbon solvents such as hexane, toluene, and benzene, or chlorobenzene, dichloromethane, dichloroethane, and chloroform. , halogenated hydrocarbon solvents such as carbon tetrachloride, and aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, and the like, and solvents inert to the reaction may be used alone or in mixtures. The amount of the solvent used is not particularly limited, but is preferably 1 to 100 times the weight of the optically active alcohol derivative.

Alkylation is carried out by two methods shown below.

■ A method using silver oxide as an alkylation auxiliary agent and the above-mentioned halide as an alkylating agent;
) and cannot necessarily be specified, but it is usually 1 to 1 for the optically active alcohol derivative (I[).
It is 50 times the equivalent. Iodide is preferably used as the halide.

Although the amount of silver oxide used cannot necessarily be specified as mentioned above, it is usually 1 liter for the optically active alcohol derivative (■).
-10 times the allowance.

The alkylation reaction is usually carried out at 0 to 150°C, preferably at 2°C.
The reaction is carried out at a temperature of 0 to 100°C, and the reaction time is not particularly limited.

Incidentally, the reaction time can also be shortened by irradiating ultrasonic waves during alkylation.

■ A method using a sulfonate or halide as an alkylating agent and a basic substance as an alkylation auxiliary agent: The alkylating agent (lT[) is usually used 1 to 4 times the equivalent, preferably 1 to 2 times the equivalent of the alkylating agent. When the alkylating agent is a halide, iodide is preferably used from the viewpoint of reactivity.

Basic substances include alkyl metals such as n-butyllithium and S-butyllithium, metal hydrides such as sodium hydride, potassium hydride, and calcium hydride, IJium hydroxide, potassium hydroxide, and hydroxide. Hydroxides of alkali metals such as calcium or alkaline earth metals, or carbonates such as thorium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. are used.

Alkylation is carried out by reacting the basic substance e with an optically active alcohol derivative represented by general formula (n) to form an alcoholade, and then reacting the alcoholade with an alkylating agent (III). You can also do it.

The usage of the basic substance varies depending on the type of the alkylating agent (III) or the optically active alcohol derivative (n), and cannot necessarily be specified, but it is usually 1 to 10% of the optically active alcohol derivative (n). The amount is equivalent to 1 to 3 times the amount of the pot, preferably 1 to 3 times.

The alkylation reaction is usually carried out at -50 to 150°C, preferably at 0 to 120°C. The reaction time is not particularly limited.

The optically active ether derivative represented by general formula (I) can be extracted from the reaction mixture obtained by the above methods (1) and (2), for example, by filtration, extraction, liquid separation, etc. This is carried out by adding conventional post-treatment operations such as IIwi or column chromatography.

Examples of the optically active ether derivative represented by the general formula (I) include the following compounds.

4-(1-Alkoxyethyl)phenyl 4-alkylbenzyl ether 4-(1-alkoxyethyl)phenyl 4-alkoxybenzyl ether 4-(1-alkoxyethyl)benzyl 4-alkyl phenyl ether 4-(1-alkoxyethyl ) Benzyl 4-alkoxyphenyl ether 4- (1-alkoxyethyl) phenyl 4'-alkyl-4-biphenylyl methyl ether 4-(1-alkoxyethyl) phenyl 4'-alkoxy-4-biphenylyl methyl ether 4-( 1-Alkoxyethyl)benzyl 4'-alkyl-4-biphenylyl ether 4-(1-alkoxyethyl)benzyl 4'-alkoxy-4-biphenylyl ether 4' -(1-alkoxyethyl)-4-biphenylyl 4- Alkylbenzyl ether 4' -(1-alkoxyethyl)-4-biphenylyl 4-alkoxyphenyl ether 4' -(1-alkoxyethyl)-4-biphenylylmethyl 4-alkylphenyl ether 4' -(1-alkoxyethyl) -4
-biphenylylmethyl 4-alkoxyphenyl ether 4- (1-alkoxyethyl)phenyl 4-alkylbenzoate 4-(1-'alkoxyethyl)phenyl 4-alkoxybenzoate 4-(1-alkoxyethyl)benzoic acid 4-Alkylphenyl ester 4-(l-alkoxyethyl)benzoic acid 4-alkoxyphenyl ester 4-(1-alkoxyethyl)phenyl 4'-alkyl-4-biphenylylcarboxylic acid ester 4-(1-alkoxyethyl)phenyl 4'-Alkoxy-4-biphenylylcarboxylic acid ester 4-(1-alkoxyethyl)benzoic acid 4'-alkyl-4-biphenylyl ester 4-(1-alkoxyethyl)benzoic acid, 1HfF acid 4'-alkoxy- 4-biphenylyl ester 4' (1-alkoxyethyl)-4-biphenylyl 4-alkylbenzoate 4' -(1-alkoxyethyl)-4-biphenylyl 4-alkoxybenzoate 4' -(1-alkoxyethyl )-4-biphenylylcarboxylic acid 4-alkylphenyl ester 4'-(1-alkoxyethyl)
-4-biphenylylcarboxylic acid 4-alkoxyphenyl ester In the above examples, "alkoxy" of alkoxyethyl is an alkyloxyl group or alkyloxy which has 1 to 20 carbon atoms and may be substituted with fluorine, chlorine, or bromine. Indicates an alkyloxyl group.

In addition, the alkyl or alkoxy in the examples is a linear alkyl group or alkoxyl group having 2 to 15 carbon atoms, and specific examples thereof include ethyl, propyl,
Butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodenle, tridecyl, tetradecyl, pentadecyl, ethoxy, propoxy, butquin, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyl oxine,
Examples include undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy and the like.

<Effects of the Invention> According to the present invention, the optically active ether derivative represented by the general formula (1) can be produced with industrial advantage.

<Example> The present invention will be explained below with reference to Examples.

Example 1 (+)-4-(1-hydroxyethyl)benzoic acid 4'-
(Octyloxy)-4-biphenylyl ester 8.9
g (20 mmol), 1-iodohexane 42.4 g (
0.2 mol), 23.2 g (0.1 mol) of silver oxide and 10 mj of tetrahydrofuran! A mixture of 30
Stirred at ℃ for 2 days.

200 g of toluene was added to the reaction mixture, filtered, and the resulting filtrate was concentrated under reduced pressure. The obtained III residue was purified by silica gel column chromatography to obtain (+)-
4-(1-hexyloxyethyl)benzoic acid 4'-(octyloxy)-4-biphenylyl ester 4.46g
(yield 42%).

Furthermore, it was recrystallized from ethanol.

Light intensity [α] 8'+38.4° (c = 1.(:H
CI,).

Instead of the above reaction condition of stirring at 30°C for 2 days,
After stirring at ℃ for 1 day, irradiating with ultrasonic waves at 30℃ for 6 hours, and further stirring at the same temperature for 1 day, (+)-4-(
The yield of 1-hexyloxyethyl)benzoic acid 4'-(octyloxy)-4-biphenylyl ester was 62%.

Example 2 1-iodopropane 34 instead of 1-iodohexane
．． The reaction and post-treatment were carried out in the same manner as in Example 1, except that 4.40 g of (+)-4-(1-propyloxyethyl)benzoic acid 4'-(octyloxy)-4-biphenylyl ester ( A yield of 45% was obtained.

Ca'3 o'+ 41.6° (c = 1.CHC
I-).

Example 3 1-iodooctane 48 instead of 1-iodohexane
．． 3.58 g (yield) of (+)-4-(1-methoxyethyl)benzoic acid 4'-(octyloxy)-4-biphenylylester was obtained by the same reaction and post-treatment as in Example 1 except that 0 g of 32%).

Cal:'+46.5' (c=1.CH
Cl+).

Examples 4 to 14 Alkylation was performed according to the method of Example 1 to obtain optically active ether derivatives shown in Table 1. Table 1 shows the phase transition temperature for each optically active ether derivative (I).
Shown below.

The phase transition temperatures of the optically active ether derivatives obtained in Examples 1 to 3 are also shown in Table 1.

(The following is a blank space) Example 15 (+)-4'-(14 droxyethyl)-4-biphenylcarboxylic acid 4-octyloxyphenyl ester 8
．． 9 g (20 mmol), l-iodohexane 42.4
g, 23.2 g of silver oxide, and 10 d of dioxane were stirred at 40 to 50° C. for 2 days in the dark.

20 (fml) of toluene was added to the resulting reaction mixture,
Filtered. The resulting filtrate was concentrated under reduced pressure.

The obtained concentrated residue was purified by silica gel column chromatography to obtain (+)-4'-(1-hexyloxyethyl)-4-biphenylcarboxylic acid 4-octyloxyphenyl ester 4.67 g (yield 44%) I got it.

Furthermore, it was recrystallized from ethanol.

Light intensity [α) g0+ 38.4° (c = 1.C
HCl5).

Examples 16 to 20 According to the method of Example 15, optically active ether derivatives shown in Table 2 were obtained. Table 2 shows the phase transition temperature of each optically active ether derivative (I).

Example 21 (-)-4-(1-hydroquinethyl)benzooctaic acid 4-
7.40 g (20 mmol) of octyloxyphenyl ester, 28.4 g (0.2 mol) of iodomethane, 23.2 g of silver oxide and 10 mI of tetrahydrofuran! The mixture was stirred at 30° C. for 3 days in the dark.

200ml of toluene was added to the reaction mixture and filtered. The resulting filtrate was concentrated under reduced pressure. The obtained concentrated residue was purified by silica gel column chromatography (eluent: toluene) to obtain (-)-4-(l-methoxyethyl)benzoic acid 4-(octyloxy)phenyl ester 3.69
g (yield 48%) was obtained.

Light intensity [α] 2° - 57,8° (c = 1.CII
CL).

Example 22 34.0 g of 1-iodopropane instead of iodomethane
The reaction and post-treatment were carried out in the same manner as in Example 21 except that (-'')-p-(1-propyloxyethyl)benzoic acid 4-(octyloxy)phenyl ester 3.8
0 g (yield 46%) was obtained.

Optical rotation [α] 8° - 48,8° (c = 1.CHC
l3).

Examples 23 to 25 Alkylation was performed according to the method of Example 21 to obtain optically active ether derivatives shown in Table 3.

Table 3 shows the optical rotation of each optically active ether derivative (I).

Example 26 (+)-4'-octyloxybiphenylcarboxylic acid
4-(1-hydroxyethyl)phenyl ester 8.9
g (20 mmol), iodomethane 28.4 g (0,2
mole), 23.2 g of silver oxide and 1 mol of tetrahydrofuran
5- was stirred at 30° C. for 3 days in the dark. Toluene 20 (ILI!) was added to the reaction mixture and filtered. The obtained filtrate was concentrated under reduced pressure. The obtained concentrated residue was purified by silica gel column chromatography to obtain (+)-4'
-Octyloxybiphenylcarboxylic acid 4-(1-methoxyethyl)phenyl ester 4.70 g (yield f
i51%) was obtained.

Furthermore, it was recrystallized from ethanol.

Optical rotation (αl M'+ 50.1° (c = 1.C
HCl5).

Examples 27 to 42 Alkylation was performed according to the method of Example 26 to obtain optically active ether derivatives shown in Table 4.

Table 4 shows the phase transition temperature for each optically active ether derivative N).

Example 43 (−)-4-octyloxybenzoic acid 4-(
1-hydroxyethyl) phenyl ester 7.40g (
(-)-4-octyloxybenzoic acid 4-(1-methoxyethyl)phenyl ester was obtained by carrying out the reaction and post-treatment in the same manner as in Example 26, except that 20 mmol) was used.

Optical rotation [α] Mo-57,5' (c = 1.C
HCIa).

Example 44 (+)-4'-octyloxy-4-biphenylcarboxylic acid 4-(1-hydroxyethyl)phenyl ester was replaced with (+)-octyloxybenzoic acid 4-(1
(10)-4-octyloxy Benzoic acid 4-
(1-hexadecyloxyethyl)phenyl ester was obtained.

Optical rotation [α] +35.9° (C = 1.CHCl
,).

(Left below) Example 45 (+) -4-(1-hydroxyethyl)benzoic acid 4'
-octyloxy-4-biphenylyl ester, (+)-4-(1-hydroxyethyl)benzyl 4'
-Octyloxy-4-biphenylylether 8.65
(+)-4-(1-hexyloxyethyl)hensyl 4'-octyloxy-4-
4.44 g (yield 43%) of biphenylyl ether was obtained. Furthermore, it was recrystallized from ethanol.

[α] 8°+ 36.8° (C= 1.CHC!,)
.

Example 46 (+)-4-(1-hydroxyethyl)benzyl 4'-
Octyloxy-4-biphenylene IJ ether 4.3
2 g (10 mmol) of anhydrous dimethylformamide 40
- dissolved in 60% sodium hydride 0.48g (12
Mi! J mol) and stirred at 40°C for 1 hour. Thereafter, 2.79 g (13 mmol) of n-propyl tosylate was added at the same temperature and stirred for 1 hour.

300 mj of water in the reaction mixture! Add 30 toluene
0m! Extracted with. The obtained organic layer was thoroughly washed with water and then concentrated under reduced pressure. The obtained white solid was purified by silica gel column chromatography to obtain (+)-4-(1-
Propyloxyethyl)benzyl 4'-octyloxy-4-biphenylylether 4.18g (yield 88%)
I got it. The results are shown in Table-5.

Examples 47-56 (+)-4-(1-hydroxyethyl)benzyl 4'-
Instead of octyloxy-4-biphenylylether,
The optically active alcohol derivative (II) in Table 5 was converted into n-
In place of propyl tosylate, the alkylating agent (
The reaction and post-treatment were carried out in the same manner as in Example 46, except that II[) was used, and the results shown in Table 5 were obtained.

(Margin below)

Claims (2)

[Claims] (1) The following general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, X is -COO-, -OCO-, -CH_2O-
or -OCH_2-, and A represents an alkyl group or an alkoxyl group having 3 to 15 carbon atoms, respectively. l and m each represent 1 or 2. * indicates an asymmetric carbon. ) An optically active alcohol derivative represented by the following general formula (III)RY(III) in the presence of an alkylation aid (wherein R is a fluorine, chlorine, or bromine atom having 1 to 20 carbon atoms) Y represents a halogen atom or an -O_3SR' group, respectively. Here, R' is a lower alkyl group, a trifluoromethyl group, or an optionally substituted phenyl group. The following general formula (I) is characterized by being alkylated with an alkylating agent represented by , m and * have the same meanings as above.) A method for producing an optically active ether derivative. (2) The method according to claim 1, characterized in that an alkylating agent in the general formula (III) in which Y is an iodine atom is used, and silver oxide is used as an alkylation auxiliary agent.