JP2002265467A - Optically active thiacalixarene derivative and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a thiacalix[4]arene derivative which has an optically active cage type molecular skeleton and is useful as a sensor, an analysis reagent, an analysis medium, a catalyst ligand, and the like, and to provide a method for producing the same. SOLUTION: A 1,3-alternate type enantiomer is obtained by oxidizing one of the sulfur atoms of the thiacalix[4]arene derivative represented by the general formula 2 (Y is a hydrocarbon group, a halogenated hydrocarbon group, COR<2> or OR<3> ; R<1> , R2<2> and R<3> are each an alkyl) to form the sulfinyl compound, and then optically resolving the obtained optically active thiacalix[4]arene derivative pair.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a thiacalix [4] arene derivative having a novel optically active cage molecular skeleton useful as a sensor, an analysis reagent, an analysis medium, a catalyst ligand and the like, and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Crosslinked alkylphenols having a cage structure have recently been reported to be useful as metal capture agents and substrate specificity sensors. The present inventors have disclosed a high-efficiency production method of a cyclic (cage-type) alkylphenol sulfide having a sulfur cross-linking structure (JP-A-9-2275).
No. 53), which makes it possible to use the above-mentioned functional substance and its sulfonic acid derivative. Further, a method of oxidizing a crosslinked sulfur portion to modify it to a skeleton such as sulfonyl or sulfinyl (Japanese Patent Application No. 10-02789) and the ability of these oxidized products to discriminate metal ions (Tetrahedron Lett., 39, 7559 (199)
8)). However, in recent years, as a sensor or a separation material, identification of an optically active substance has been strongly demanded, and in order to meet this demand, construction of a cage type molecule having optical activity has been urgently required. Cyclodextrin is known as a known optically active cage-type molecule, but its use is limited to foods due to its difficulty in use in an organic solvent environment, which is a characteristic of natural saccharides, and difficulty in selective chemical modification. Was limited to the field.

[0003]

As a method for developing an optically active molecular recognition element, a method of introducing an optically active substituent such as a natural amino acid into the side chain of a cage molecule by chemical modification is generally used. The inventors have also reported an optically active substance using such a method (Chemistry Letters, 1998, 106).
Five). However, this method has a feature that the asymmetric site and the recognition site are adjacent to each other but are not the same, and construction of a recognition site having asymmetry of the cage skeleton itself has been required.

[0004]

Means for Solving the Problems Under such circumstances, the present inventors have conducted intensive research and development and have found that thiacalix [4] arene alkoxy having a specific conformation has a stereoselective partial oxidation reaction. As a result, the present inventors have found that asymmetry based on the configuration of the crosslinked sulfur moiety can be generated, and have completed the present invention. That is, the present invention relates to general formula 1a or general formula 1b

[0005]

Embedded image (Wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, -C
OR ² or —OR ³ , wherein R ¹ is a hydrogen atom or an alkyl group, and R ² and R ³ are alkyl groups). Further, the present invention provides a compound represented by the general formula

[0006]

Embedded image (Wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, -C
OR ² or —OR ³ , wherein R ¹ , R ² and R ³ are alkyl groups), wherein one of the sulfur atoms of the thiacalix [4] arene derivative represented by General formula 1a or general formula 1b, wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, —COR ² or OR ³ , wherein the activated thiacalix [4] arene derivative pair is optically resolved. R ¹ is a hydrogen atom or an alkyl group, and R ² and R ³ are an alkyl group.)
And a method for producing an optically active thiacalix [4] arene derivative represented by the formula:

The present invention also provides an optically active thiacalix [4] arene derivative as described above, wherein sodium perborate is allowed to act in the presence of acetic acid as a method for oxidizing a sulfur atom. 4] A method for producing an arene derivative is provided. Further, in the present invention, in the method for producing an optically active thiacalix [4] arene derivative, the method of optical resolution may be such that the substituent R
^1. A method for producing an optically active thiacalix [4] arene derivative, which comprises introducing an optically active group into ¹ to form a diastereomer pair and then separating the diastereomer pair. Further, the present invention provides the method for producing an optically active thiacalix [4] arene derivative, wherein the optically active substance introduced for optical resolution is 1-menthol. A method for producing a derivative is provided. Hereinafter, the present invention will be described in detail.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The substituent Y in the optically active thiacalix [4] arene derivative represented by the above general formula 1
Is a hydrocarbon, a halogenated hydrocarbon group, —COR ² or —OR ³ . As the hydrocarbon group, C 1-12
Is preferably a saturated or unsaturated hydrocarbon group, specifically,
Alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, methylcyclohexyl, n-octyl, tert-octyl, n-nonyl, vinyl and allyl And phenyl, methylphenyl, toluyl and the like; aromatic groups such as ethylene, propylene and butene; and polymer groups such as acetylene and butadiene. In the general formula 1, a plurality of Ys may be the same or different.
In the general formula 1, R ¹ is a hydrogen atom or an alkyl group. The alkyl group preferably has 1 to 4 carbon atoms, and specific examples are preferably lower alkyl groups such as methyl, ethyl, n-propyl, iso-propyl and tert-butyl. In the general formula 1, a plurality of R ¹ are
They may be the same or different. General formula 1
In the formula, R ² and R ³ are an alkyl group. As the alkyl group for R ² and R ³ , those having 1 to 4 carbon atoms are preferable, and specific examples thereof are preferably lower alkyl groups such as methyl, ethyl, n-propyl, iso-propyl and tert-butyl. In the general formula 1, a plurality of R ² and R ³ may be the same or different.

In the production method of the present invention, the thiacalix [4] arene derivative represented by the general formula 2 as a raw material is a known substance, and Y in the general formula 2 is the same as Y in the general formula 1. R ¹ is an alkyl group and preferably has 1 to 4 carbon atoms, and specific examples are preferably lower alkyl groups such as methyl, ethyl and n-propyl. The method for producing the thiacalix [4] arene derivative represented by the general formula 2 is not particularly limited, but is described in, for example, JP-A-9-2275.
JP 53-175, JP-A-10-175
It can be produced by combining the stereoselective ethoxycarbonylmethylation method described in No. 971. In this synthesis, the orientation of the alkoxy group with respect to the ring, that is, the conformation is different depending on the combination of the base catalyst and the solvent, and the production of the thiacalix [4] arene derivative represented by the general formula 2 which is a raw material of the present invention is performed using By performing the reaction in the coexistence, a favorable result can be obtained. The ethoxycarbonylmethylating agent is preferably a halogenated acetate, and there is no limitation on the type of halogen. Specifically, ethyl iodide acetate, ethyl bromide acetate, ethyl chloride acetate and the like are easily available and preferred.
The amount of the ethoxycarbonylmethylating agent used may be 1 gram equivalent or more, preferably 1 to 5 gram equivalent, more preferably 1 to 3 gram equivalent based on the hydroxyl group contained in the raw material.

As a cesium reagent coexisting with cesium ions, a basic salt such as cesium carbonate, cesium hydride, metal cesium and the like can be used, but hydroxide is not preferred. The amount of the cesium reagent used may be 1 gram equivalent or more based on the hydroxyl group contained in the raw material, preferably 1 to 5 gram equivalent, more preferably 1 to 3 gram equivalent. As a reaction solvent, a ketone solvent such as acetone and methyl ethyl ketone is preferable, and tetrahydrofuran can also be used in the presence of N, N'-dimethylformamide. The amount of solvent used is 5
The reaction can be carried out at a volume of １００100 mL, but in a very small or large amount of a solvent, the reaction progress becomes slow or the economic efficiency is reduced. The reaction temperature is preferably from 0 ° C. to 200 ° C., particularly preferably from 20 ° C. to 100 ° C. Usually, it is convenient to carry out the reaction under atmospheric pressure and heating to reflux utilizing the boiling point of the solvent. The reaction is preferably carried out in an inert gas atmosphere, but this is not essential, and the reaction can be carried out under dry air. Specific examples of the inert gas include nitrogen, argon, helium, and the like. The reaction time may be set while observing the progress of the reaction. When a ketone-based solvent is used, the reaction time is 1 hour to 10 days, usually 2 to 8 days.
Time, when using N, N'-dimethylformamide / tetrahydrofuran solvent, it is usually 1 to 5 hours. The reaction product may be purified by a conventional method such as column chromatography after distilling off the solvent.

Next, a method for introducing an optically active group into the compound represented by the general formula 2 will be described. When R ¹ in the general formula 2 is an alkyl group, that is, when it has an ester group, the ester group is preferably hydrolyzed to a carboxylic acid prior to introduction of the optically active group. The ester group in the general formula 2 can be easily hydrolyzed in the presence of an acid catalyst or a base catalyst and converted into a carboxylic acid. As the acid catalyst, inorganic acids such as dilute hydrochloric acid, dilute sulfuric acid, and dilute nitric acid are preferable, and the amount of the inorganic acid can be 0.01 to 1 gram equivalent based on the ester group to be hydrolyzed. Is 0.05-0.1 gram equivalent. The solvent is preferably a mixed system of water and a lower alcohol such as methanol, ethanol and propanol for the purpose of coexisting the raw material and water, and the coexistence amount of water is 1 to 10 gram equivalent based on the ester group to be hydrolyzed. Possible and preferred amounts are from 1.2 to 5 gram equivalents. The reaction is preferably carried out under continuous stirring. The reaction can be carried out at a temperature of 0 ° C. or higher. Although there is no particular upper limit for the reaction temperature, it is usually preferable to carry out the reaction at a temperature not higher than the boiling point of the solvent used.

As the base catalyst, an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, lithium hydroxide or the like is preferable. The amount of the base catalyst used can be 1 to 10 gram equivalent based on the ester group to be hydrolyzed. And the preferred amount used is 1.2 to 2 gram equivalents. The solvent is methanol, ethanol,
A mixed system of a lower alcohol such as propanol and water is preferable, and the coexisting amount of water can be carried out at 1 to 10 gram equivalent relative to the ester group to be hydrolyzed. It is. The reaction is preferably carried out under continuous stirring. The reaction can be carried out at a temperature of 0 ° C. or higher. Although there is no particular upper limit for the reaction temperature, it is usually preferable to carry out the reaction at a temperature not higher than the boiling point of the solvent used.

The carboxylic acid can be modified by a usual esterification method or the like. If the esterification is carried out using an alcohol having optical activity, for example, 1-menthol, the corresponding optically active substance can be obtained. Compounds having optical activity that can be used for this purpose include, besides 1-menthol, commercially available 1-phenylethanol, 2-phenyl-
Optically active substances such as 1-cyclohexanol and 4-tetradecanol can be used. As a specific method of the esterification, a preferable result can be obtained by contacting with the alcohol in the presence of thionyl chloride in a solvent. As the solvent,
Chlorine solvents such as dichloromethane and chloroform, diethyl ether, tetrahydrofuran (THF), 1,4-
Ether solvents such as dioxane can be used. The amount of thionyl chloride used can be from 1 to 10 gram equivalents per carboxyl group of the raw material, and the preferred amount is from 1.2 to
2 gram equivalents. Further, after an acid chloride is previously formed from the carboxyl group and thionyl chloride, optically active alcohols may be mixed in the presence of a base catalyst. In this case, 100 to 500 gram equivalent of thionyl chloride per carboxyl group is used. After mixing the starting carboxylic acid, excess thionyl chloride is distilled off, and the resulting acid chloride and the optically active alcohol are mixed, whereby the reaction proceeds.

The reaction is preferably carried out under continuous stirring, and the reaction proceeds more smoothly in the presence of a base catalyst. The reaction between the carboxyl group and thionyl chloride is preferably carried out at a temperature from room temperature to a boiling point, and the reaction time is usually 1 to 24 hours. The reaction between the generated acid chloride and the alcohol usually proceeds at 0 ° C. or higher, and may be carried out at a temperature lower than the boiling point of the solvent as necessary. The reaction time is usually 1 to
24 hours. At this stage, an excessive amount of an organic base may be dissolved for the purpose of accelerating the reaction, and pyridines such as pyridine and dimethylaminopyridine, and alkylamines such as diisopropylethylamine can be used. As a method not using thionyl chloride, a method in which heating and refluxing is performed while continuously distilling off water produced by the reaction using a Dean-Stark cooler or the like in the presence of an acid catalyst can be used. Sulfuric acid, p-toluenesulfonic acid and the like can be used as the acid catalyst, and the amount of the acid catalyst is 0.1 to the carboxyl group.
It can be carried out in an amount of from 01 to 1 gram equivalent, and a preferable use amount is from 0.05 to 0.1 gram equivalent. The solvent is preferably toluene, benzene or the like for the purpose of azeotropically removing water.
The reaction time may be appropriately selected, but is usually preferably 1 to 48 hours.

The synthesis of the skeleton of an optically active thiacalix [4] arene derivative is achieved by oxidizing one of the four sulfur atoms in the bridge. An oxidizing agent suitable for the oxidation reaction is sodium perborate. The amount used in the reaction is 0.4 to the total number of sulfur atoms.
0.6 equivalent is preferred, more preferably 0.45 to 0.5
5 equivalents. As the solvent, a halogen-based solvent such as dichloromethane or chloroform, or a protic solvent such as acetic acid, methanol, or ethanol can be used, and these may be used as a mixture. The amount of the solvent used is 5 to 5 g per raw material.
The reaction can be carried out at 200 mL, but in a very small or large amount of solvent, the reaction progress is slowed down or the economic efficiency is reduced. Therefore, the amount is preferably 10 to 100 mL per 1 g of the raw material. The reaction temperature is preferably from 0 to 100 ° C, particularly preferably from 20 to 60 ° C. The reaction time may be set while observing the progress of the reaction, and usually the reaction is completed in 2 hours to 2 days. In the reaction product, a diastereomer pair of a thiacalix [4] arene derivative having an optically active ring is formed together. Therefore, after distilling off the solvent, these are separated and purified by column chromatography or the like to obtain a pure optical product. An active thiacalix [4] arene partial sulfinyl mentoxy derivative is obtained.

From the obtained optically active thiacalix [4] arene alkoxy compound, the optically active group introduced as a carboxylic acid ester can be removed, if necessary. An optically active group can be easily hydrolyzed in the presence of an acid or base catalyst and converted to a carboxylic acid. As the acid catalyst, inorganic acids such as dilute hydrochloric acid, dilute sulfuric acid, and dilute nitric acid are preferable, and the amount of the inorganic acid can be 0.01 to 1 gram equivalent based on the ester group to be hydrolyzed. Is 0.05-0.1 gram equivalent. The solvent is methanol, ethanol,
A mixed system of a lower alcohol such as propanol and water is preferable, and the coexisting amount of water can be carried out at 1 to 10 gram equivalent relative to the ester group to be hydrolyzed. It is. The reaction is preferably carried out under continuous stirring. The reaction can be carried out at a temperature of 0 ° C. or higher. Although there is no particular upper limit for the reaction temperature, it is usually preferable to carry out the reaction at a temperature not higher than the boiling point of the solvent used.

As the base catalyst, an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, lithium hydroxide or the like is preferable. The amount of the base catalyst used can be 1 to 10 gram equivalent based on the ester group to be hydrolyzed. And the preferred amount used is 1.2 to 2 gram equivalents. The solvent is methanol, ethanol,
A mixed system of a lower alcohol such as propanol and water is preferable, and the coexisting amount of water can be carried out at 1 to 10 gram equivalent relative to the ester group to be hydrolyzed. It is. The reaction is preferably carried out under continuous stirring, and the reaction can be carried out at a temperature of 0 ° C. or higher. Although there is no particular upper limit for the reaction temperature, it is usually preferable to carry out the reaction at a temperature not higher than the boiling point of the solvent used. The hydrolyzed carboxylic acid can be converted to another ester by usual esterification. The optically active thiacalix [4] arene derivative of the present invention is useful as a sensor, an analysis reagent, an analysis medium, a catalyst ligand, and the like. Since the compound of the present invention has an asymmetric environment in the ring skeleton itself, unlike a chain molecule having only an asymmetric point, optical resolution, isomer analysis, and asymmetric catalyst preparation by molecular inclusion can be performed. . Specifically, it can be applied to the selective extraction of water-soluble optically active organic molecules and the like.

[0018]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Production Examples, but the present invention is not limited thereto. (Production Example 1) 5,11,17,23-tetra-tert-butyl-2
5,26,27,28-tetrahydroxy-2,8,1
4,20- Tetorachia [1.9.3.1.1 ^3, 7 1
^9,13 1 ^15,19] Okutakosa -1 (25), 3,
5,7 (28), 9, 11, 13 (27), 15, 1
Synthesis of 7,19 (26), 21,23-dodecaene: 4-tert-butylphenol 4 in a glass flask
To 5.2 g, 14.4 g of elemental sulfur, 3.0 g of sodium hydroxide and 7.60 g of tetraethylene glycol dimethyl ether were added, and the mixture was gradually heated to 230 ° C. over 4 hours with stirring under a nitrogen atmosphere, and further 2 hours. Stirred. During this time, water and hydrogen sulfide generated by the reaction were removed. The reaction mixture was cooled to room temperature and ether 500
After adding and dissolving mL, the mixture was hydrolyzed with a 1N aqueous sulfuric acid solution. The separated ether layer was washed with water and dried over magnesium sulfate. The reaction mixture obtained after distilling off ether was further separated by silica gel column chromatography (hexane / chloroform) to obtain a crude product.
This was recrystallized from chloroform / acetone to give colorless and transparent crystals 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrahydroxy-2,8,14,20. -Tetrathia [1.
9.3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,1
3 (27), 15, 17, 19 (26), 21, 23
26.5 g of dodecaene were obtained. Yield was 45%.

(Production Example 2) 5,11,17,23-tetra-tert-butyl-2
5,26,27,28-tetrakis (ethoxycarbonylmethoxy) -2,8,14,20-tetrathia [1.
9.3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,1
3 (27), 15, 17, 19 (26), 21, 23
Synthesis of dodecaene (1,3-alternate type): 5,11,17,23-tetra-t obtained in Production Example 1
tert-butyl-25,26,27,28-tetrahydroxy-2,8,14,20-tetrathia [1.9.
3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,13
(27), 15, 17, 19 (26), and 21,23 dodecaene 10.0 g were put into a glass flask together with 300 mL of acetone, and stirred and suspended with 27.7 g of anhydrous cesium carbonate. At room temperature (about 20 ° C.), 13 mL of ethyl bromoacetate was added dropwise over 1 hour, and the mixture was refluxed for 4 hours under a nitrogen atmosphere. After the completion of the reaction, the mixture was allowed to cool to room temperature, the precipitate was filtered off, and then concentrated to dryness to obtain a white powder. This product was subjected to silica gel column chromatography (benzene / n-hexane) and recrystallization (benzene) to give 5,11,17,23-tetra-
tert-butyl-25,26,27,28-tetrakis (ethoxycarbonylmethoxy) -2,8,14,2
0 Tetorachia ^[1.9.3.1.1 3, 7 ^{1 9, 13}
1 ^15,19 ] octacosa-1 (25), 3,5,7
(28), 9, 11, 13 (27), 15, 17, 19
(26), 11.1 g of white crystals of 21,21-dodecaene (1,3-alternate type) were obtained. The yield was 68%. The physical properties of the obtained crystal are shown below. ^{1 H-NMR (δ, ppm} , CDCl 3) 7.51 (s, 8H, Ar-H), 4.6
0 (s, 8H, OCH ₂ CO), 4.22 (q, J = 7.2Hz, 8H, COOCH ₂ ), 1.
28 (t, J = 7.2Hz, 12H, CH 3), 1.25 (s, 36H, C (CH 3) 3) IR (cm -1, KBr) 2960, 1764, 1734

Example 1 5,11,17,23-Tetra-tert-butyl-2
5,26,27,28-tetrakis (ethoxycarbonylmethoxy) -2,8,14,20-tetrathia [1.
9.3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,1
3 (27), 15, 17, 19 (26), 21, 23
Introduction of an optically active group into dodecaene (1,3-alternate type): 2 provided with a stirrer, an oil bath, a reflux condenser, and a thermometer
The 5,11,1 obtained in Production Example 2 was placed in a 00 mL flask.
7,23-tetra-tert-butyl-25,26,2
7,28-tetrakis (ethoxycarbonylmethoxy)
-2,8,14,20-tetrathia [1.9.3.1.
1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (2
5), 3, 5, 7 (28), 9, 11, 13 (27),
15, 17, 19 (26), 21,23-dodecaene (1,3-alternate type) 10.00 g (9.38 m
mol) and 200 mL of 10% aqueous ethanol, 2.00 g (50 mmol) of sodium hydroxide was added thereto, and the mixture was heated under reflux for 24 hours. After allowing the reaction solution to cool to room temperature, ethanol was distilled off under reduced pressure using a rotary evaporator, and the mixture was neutralized by adding 1 N hydrochloric acid, and 100 mL of dichloromethane was added to dissolve the reaction product. After the solution was washed with water using a separating funnel, anhydrous magnesium sulfate was added to the dichloromethane layer and dried. After filtration, this was concentrated and dried using a rotary evaporator to obtain 8.76 g of a product. The yield was 98%.

5.14 g of the obtained product and 100 mL of thionyl chloride were placed in a 500 mL eggplant-shaped flask equipped with a reflux condenser, and heated under reflux for 5 hours. After the reaction solution was cooled to room temperature, excess thionyl chloride was distilled off using an aspirator, and the solution was heated to 80 ° C. under reduced pressure to obtain a solution.
Dry to dryness for hours. The obtained reaction product was dissolved in 40 mL of dichloromethane under a nitrogen atmosphere, and this was used as solution A. Separately, 6.74 g (43.1 mmol) of l-menthol was placed in a 500 mL eggplant-shaped flask equipped with a dropping funnel.
l), 1.8 mL of pyridine, 2.5 g of 4-dimethylaminopyridine, and 40 mL of dichloromethane were added, and the mixture was ice-cooled under a nitrogen atmosphere. The obtained mixture was taken out of the ice bath to room temperature (20 ° C.), and then heated and refluxed for 24 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, and the solid obtained by drying under reduced pressure was recrystallized (dichloromethane-methanol) to obtain 5,11,
17,23-tetra-tert-butyl-25,26,
27,28-tetrakis (menthoxycarbonylmethoxy) -2,8,14,20-tetrathia [1.9.
1.1 ^3,7 1 ^{9, 13} 1 ^{15, 19]} Okutakosa -1
(25), 3, 5, 7 (28), 9, 11, 13 (2
7), 15, 17, 19 (26), 5.14 g of colorless crystals of 21,23-dodecaene (1,3-alternate type)
I got The yield was 60.9%. The physical properties of the obtained crystal are shown below.

Melting point: 231 ° -233 ° C. IR (KBr, cm ⁻¹ ) 2955 (CH), 1765 (C = O) FAB MS (m / z, 3-nitrobenzyl alcohol): 1505 (M
⁺ +1) ¹ H NMR (CDCl ₃ ): 0.77 to 2.06, 4.77 to 4.83 (m, 20, l
-Menthol), 1.24 (s, 36, But), 4.72 (s, 8, -CH _2- ), 7.
53 (d, 4, J = 2.52, ArH), 7.55 (d, 4, J = 2.49, ArH) Elemental analysis: Calculated value for C ₈₈ H ₁₂₈ O ₁₂ S ₄ : C, 70.
17; H, 8.46; S, 8.52; Found: C, 70.04; H, 8.46; S,
8.54

Example 2 5,11,17,23-Tetra-tert-butyl-2
5,26,27,28-tetrakis (menthoxycarbonylmethoxy) -2,8,14,20-tetrathia
^[1.9.3.1.1 3,7 ^{1 9,13} 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,1
1,13 (27), 15, 17, 19 (26), 21,
Oxidation of 23-dodecaene (1,3-alternate type):
5,11,17,23-tetra-t obtained in Example 1
tert-butyl-25,26,27,28-tetrakis (menthoxycarbonylmethoxy) -2,8,14,2
0 Tetorachia ^[1.9.3.1.1 3, 7 ^{1 9, 13}
1 ^15,19 ] octacosa-1 (25), 3,5,7
(28), 9, 11, 13 (27), 15, 17, 19
(26) 5.21 g (3.28 mmol) of 21,23-dodecaene (1,3-alternate type) and 150 mL of chloroform were put into a 500 mL eggplant-shaped flask equipped with a reflux condenser, and sodium perborate tetrahydrate was added thereto. Japanese 0.
56 g and 240 mL of acetic acid were added, and the mixture was heated under reflux for 24 hours. After cooling the reaction solution to room temperature, it was diluted with 300 mL of distilled water and extracted three times with 200 mL of chloroform.
After the chloroform extract was concentrated under reduced pressure, benzene was added thereto to remove acetic acid by an azeotropic method, and dried under reduced pressure to obtain a crude product. The obtained crude product is purified by silica gel column chromatography (ethyl acetate: hexane = 1: 30), and the obtained diastereomer pair is again subjected to silica gel column chromatography (ethyl acetate: hexane = 1).
1:40) to give each stereoisomer.

Yield Isomer a (MW1522.21) 1.32 g of colorless crystals Yield 26.5% Isomer b (MW1522.21) 1.54 g of colorless crystals Yield 30.8% The physical properties of isomer a and isomer b are shown below. Isomer a Melting point: 215-216 ° C IR (KBr, cm ^-1 ) 2955 (CH), 1763 (C = O), 1055 (S = O) FAB MS (m / z, 3-nitrobenzyl alcohol): 1521 (M
^{+ +1) 1 H NMR (CDCl} 3): 0.78~2.10, 4.73~4.83 (M, 20, l-
Menthol), 1.22 (s, 9, But), 1.25 (s, 9, But), 1.25
(s, 9, But), 1.31 (s, 9, But), 4.55 (d, 1, J = 15.2,-
CH _2- ), 4.56 (d, 1, J = 15.0, -CH _2- ), 4.62 (d, 1, J = 1
5.3, -CH _2- ), 4.77 (s, 2, -CH _2- ), 4.84 (d, 1, J = 15.
3, -CH _2- ), 4.92 (d, 1, J = 15.0, -CH _2- ), 5.00 (d, 1,
J = 15.2, -CH _2- ), 7.39 (d, 1, J = 2.51, ArH), 7.41 (d,
1, J = 2.50, ArH), 7.49 (d, 1, J = 2.51, ArH), 7.53 (d,
1, J = 2.50, ArH), 7.78 (d, 1, J = 2.49, ArH), 7.80 (d,
1, J = 2.65, ArH), 7.83 (d, 1, J = 2.49, ArH), 7.87 (d,
(1, J = 2.65, ArH) Elemental analysis: Calculated value for C ₈₈ H ₁₂₈ O ₁₃ S ₄ : C, 69.
43; H, 8.48; S, 8.43; Found: C, 69.22; H, 8.36; S,
8.49.

Isomer b Melting point: 232-234 ° C. IR (KBr, cm ⁻¹ ) 2957 (CH), 1763 (C = O), 1055 (S = O) FAB MS (m / z, 3-nitrobenzyl alcohol) ): 1521 (M
⁺ +1) ¹ H NMR (CDCl ₃ ): 0.77 to 2.09, 4.72 to 4.86 (m, 20, l-
Menthol), 1.22 (s, 9, But), 1.26 (s, 9, But), 1.26
(s, 9, But), 1.30 (s, 9, But), 4.56 (d, 1, J = 15.0,-
CH _2- ), 4.62 (d, 1, J = 14.9, -CH _2- ), 4.74 (s, 2, J = 1
5.3, -CH _2- ), 4.76 (s, 2, -CH _2- ), 4.78 (d, 1, J = 15.
0, -CH _2- ), 4.85 (d, 1, J = 14.9, -CH _2- ), 4.96 (d, 1,
J = 15.3, -CH _2- ), 7.40 (d, 1, J = 2.54, ArH), 7.44 (d,
1, J = 2.56, ArH), 7.48 (d, 1, J = 2.54, ArH), 7.54 (d,
1, J = 2.56, ArH), 7.73 (d, 1, J = 2.53, ArH), 7.77 (d,
1, J = 2.51, ArH), 7.84 (d, 1, J = 2.53, ArH), 7.94 (d,
1, J = 2.51, ArH) Elementary analysis: Calculated _{for C 88 H 128 O 13 S} 4: C, 69.
43; H, 8.48; S, 8.43; Found: C, 69.13; H, 8.39; S,
8.23.

Example 3 5,11,17,23-Tetra-tert-butyl-2
5,26,27,28-tetrakis (menthoxycarbonylmethoxy) -2,8,14,20-tetrathia
^[1.9.3.1.1 3,7 ^{1 9,13} 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,1
1,13 (27), 15, 17, 19 (26), 21,
Synthesis of Enantiomeric Pairs by Hydrolysis of Partial Sulfinyl Form of 23-Dodecaene (1,3-Alternate Type): 1.05 g (0.69 m) of each of the optically active substances obtained in Example 2
mol) was placed in a 300 mL eggplant-shaped flask equipped with a reflux condenser, and 100 mL of ethanol, 20 mL of water,
5.75 g of sodium hydroxide was added, and the mixture was heated under reflux for 24 hours. After the reaction solution was cooled to room temperature, it was neutralized with 6N hydrochloric acid. The obtained suspension was filtered to collect a solid, which was dissolved in chloroform and washed again with 2N hydrochloric acid. After the chloroform was distilled off, a trace amount of water was removed by a benzene azeotropic method, followed by drying under reduced pressure to obtain 5,11,17,23.
-Tetra-tert-butyl-25,26,27,28
-Tetrakis (carboxylmethoxy) -2,8,1
4,20- Tetorachia [1.9.3.1.1 ^3,7 1
^9,13 1 ^15,19] Okutakosa -1 (25), 3,
5,7 (28), 9, 11, 13 (27), 15, 1
7, 19 (26), 21, 23 dodecaene (1, 3-
0.661 g (99% yield) and 0.628 g (99% yield) of colorless crystals of the enantiomer pair of the (salt type) partial sulfinyl compound were obtained.

Example 4 5,11,17,23-Tetra-tert-butyl-2
5,26,27,28-tetrakis (carboxylmethoxy) -2,8,14,20-tetrathia [1.9.
3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,13
(27), 15, 17, 19 (26), 21,23-Dodecaene (1,3-alternate type) Methyl esterification of a pair of enantiomers of a partial sulfinyl compound: 5,11, obtained in Example 3 17,23-Tetra-tert-butyl-25,26,27,28-tetrakis (carboxylmethoxy) -2,8,14,20-tetrathia [1.
9.3.1.1 ^3,7 1 ^9,13 1 ^15,19] Okutakosa -1 (25), 3,5,7 (28), 9,11,1
3 (27), 15, 17, 19 (26), 21, 23
Dodecaene (1,3-alternate type) enantiomer of a partial sulfinyl form pair each 600 mg (0.62 mmol
l) in dichloromethane 200mL, methanol 100m
Together with L and placed in a 500 mL eggplant-shaped flask equipped with a reflux condenser, 0.5 mL of concentrated hydrochloric acid was added, and the mixture was heated under reflux for 24 hours. After cooling the reaction solution to room temperature, the solvent was distilled off under reduced pressure, and then a trace amount of water was removed by a benzene azeotropic method.
The obtained crude product was subjected to silica gel column chromatography (ethyl acetate: hexane = 1: 3) to give 5,1.
1,17,23-tetra-tert-butyl-25,2
6,27,28-tetrakis (methoxycarbonylmethoxy) -2,8,14,20-tetrathia [1.9.
3.1.1 ^3,7 1 ^9,13 1 ^{1 5,19]} Okutakosa -1 (25), 3,5,7 (28), 9,11,13
400 mg (63% yield) and 358 mg (57% yield) of enantiomeric pairs of (27), 15, 17, 19 (26), 21,23-dodecaene (1,3-alternate type) partial sulfinyl form, respectively ) Got. The physical properties of the obtained isomer a and isomer b are shown below.

Isomer a Melting point: 357-360 ° C. IR (KBr, cm ⁻¹ ) 2955 (CH), 1771 (C = O), 1065 (S = O) ¹ H NMR (CDCl ₃ ): 1.22 (s, 9, t-Bu), 1.25 (s, 9, t-Bu
Bu), 1.27 (s, 9, t-Bu), 1.30 (s, 9, t-Bu), 3.76 (s, 3,
Me), 3.77 (s, 3, Me), 3.79 (s, 3, Me), 3.80 (s, 3, M
e), 4.52 (d, 1, J = 14.7, -CH _2- ), 4.54 (d, 1, J = 13.7,
-CH _2- ), 4.66 (s, 2, -CH _2- ), 4.67 (d, 1, J = 13.7,-
CH _2- ), 4.72 (d, 1, J = 14.3, -CH _2- ), 4.83 (d, 1, J = 1
4.3, -CH _2- ), 4.91 (d, 1, J = 14.7, -CH _2- ), 7.39 (d,
1, J = 2.56, ArH), 7.41 (d, 1, J = 2.55, ArH), 7.47 (d,
1, J = 2.56, ArH), 7.50 (d, 1, J = 2.55, ArH), 7.70 (d,
1, J = 2.52, ArH), 7.71 (d, 1, J = 2.58, ArH), 7.81 (d,
1, J = 2.52, ArH), 7.83 (d, 1, J = 2.58, ArH) [α] ²⁴⁸ _D = -12.0 ° (C = 0.53)

Isomer b Melting point: 357-360 ° C IR (KBr, cm^-1): 2955 (C-H), 1771 (C = O), 1063 (S = O)¹ H NMR: 1.22 (s, 9, t-Bu), 1.25 (s, 9, t-Bu), 1.27
(s, 9, t-Bu), 1.30 (s, 9, t-Bu), 3.76 (s, 3, Me), 3.7
7 (s, 3, Me), 3.79 (s, 3, Me), 3.80 (s, 3, Me), 4.51
(d, 1, J = 14.5, -CH₂-), 4.54 (d, 1, J = 14.0, -CH
₂-), 4.65 (s, 2, -CH ₂-), 4.67 (d, 1, J = 14.0, -CH₂
-), 4.71 (d, 1, J = 14.1, -CH₂-), 4.82 (d, 1, J = 14.1,
-CH₂-), 4.91 (d, 1, J = 14.5, -CH₂-), 7.39 (d, 1, J =
2.51, ArH), 7.40 (d, 1, J = 2.55 ArH), 7.47 (d, 1, J =
2.51, ArH), 7.50 (d, 1, J = 2.55, ArH), 7.69 (d, 1, J =
2.40, ArH), 7.71 (d, 1, J = 2.38, ArH), 7.81 (d, 1, J =
2.40, ArH), 7.83 (d, 1, J = 2.38, ArH) [α]²²⁹ _D= + 12.0 ° (C = 0.39)

[0030]

The thiacalix [4] arene derivative having an optically active cage-type molecular skeleton according to the present invention can be used as a sensor,
It is useful as an analysis reagent, an analysis medium, a catalyst ligand, and the like. Further, according to the production method of the present invention, a thiacalix [4] arene derivative which is a cage molecule having optical activity can be efficiently and easily obtained.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Naoya Morohashi 2-15-5 Shorin, Izumi-ku, Sendai City, Miyagi Prefecture (72) Ryoichiro Naito 5-15 Yayoyama Yayoyama-cho, Taishiro-ku, Sendai City, Miyagi Prefecture 72) Inventor Haruhiko Takeya 1134-2 Gongendo, Satte City, Saitama Prefecture Inside the R & D Center of Kosmo Research Institute Co., Ltd. (72) Inventor Toshihiro Kobori 1134-2 Gongendo, Sate City, Saitama Prefecture F-term in development center (reference) 4H006 AA02 AC83

Claims (5)

[Claims] 1. A compound of the general formula 1a or 1b (Wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, -C
An optically active thiacalix [4] arene derivative represented by the formula: OR ² or —OR ³ , wherein R ¹ is a hydrogen atom or an alkyl group, and R ² and R ³ are alkyl groups. 2. The general formula 2 (Wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, -C
OR ² or —OR ³ , wherein R ¹ , R ² and R ³ are alkyl groups), wherein one of the sulfur atoms of the thiacalix [4] arene derivative represented by General formula 1a or general formula 1b, wherein Y is a hydrocarbon group, a halogenated hydrocarbon group, —COR ² or OR ³ , wherein the activated thiacalix [4] arene derivative pair is optically resolved. R ¹ is a hydrogen atom or an alkyl group, and R ² and R ³ are alkyl groups). 3. A method for oxidizing a sulfur atom, wherein sodium perborate is allowed to act in the presence of acetic acid.
The method for producing the optically active thiacalix [4] arene derivative described above. 4. The optically active method according to claim 3, wherein the optically resolving method is a method of introducing an optically active group into the substituent R ¹ to form a diastereomeric pair and then separating the diastereomer pair. A method for producing a thiacalix [4] arene derivative. 5. The optically active substance introduced for optical resolution is 1
The method for producing an optically active thiacalix [4] arene derivative according to claim 4, wherein the menthol is menthol.