JPH0446948B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to the production of optically active sulfoxides. That is, the present invention provides a synthetic method that selectively provides D- and L-sulfoxides, which are important as pharmaceuticals such as anti-intestinal ulcer substances, physiologically active substances, and asymmetric synthetic intermediates for synthesizing them.

Conventional techniques and problems It is well known that optically active sulfoxides can be obtained by asymmetric oxidation of prochiral sulfides, but it is one of the rather difficult reactions, and much research has been conducted to date [ J.D.
Morrison, M.S.Mosher (ed.); Asymmetric
Organic Reactions, Prentice-Hall, 1971
Chapter 8].

That is, most of them use optically active peroxides such as (+)-monopersyayonoic acid, but the asymmetric yield is only 10% at most, and optically active peroxides are used. Optically active sulfoxide with high purity cannot be obtained by oxidation. On the other hand, it is also known that highly pure optically active sulfoxides can be obtained by asymmetric oxidation of aromatic sulfides using microorganisms. For example, using Aspergillus niger [BJAutet, DRBoyd, S.Ross.HBHenbest;
J.Chem.Soc., (c) 2371 (1968)] A method was proposed in which the optical yield could reach 70-100% depending on the sulfide, but since it involved handling bacteria, it was not easy for anyone to do. isn't it. Recently, it has also been proposed to obtain optically active sulfoxides with an asymmetric yield of ~80% by oxidizing aromatic sulfides using serum albumin, but this bovine serum albumin is expensive and is not suitable for industrial asymmetric synthesis. is problematic. Furthermore, a method was proposed to obtain an optically active aromatic sulfoxide using an optically inactive peroxide by adding cyclodextrin, which has recently become easy to obtain [AWCzarnik; J.Org.Chem., 49 924- 927
(84)], but the optical yield was as low as ~26%.

As a result of intensive research to solve the above-mentioned problems, the present inventors succeeded in asymmetric oxidation of sulfide using an inexpensive and easily available cyclic oligosaccharide and a normal optically inactive oxidizing agent. It has been found that this can occur in high yield and that sulfoxides with high optical purity can be obtained. The present invention was completed based on this knowledge.

Means for Solving the Problems That is, the present invention includes sulfides in cyclodextrin, causes a contact reaction with an oxidizing agent, and then recovers the sulfoxides generated from the clathrate, thereby producing an optical We succeeded in producing active sulfoxides.

The sulfides used as raw materials in the present invention have the general formula R ¹ SR ² (wherein R ¹ and R ² allow the compound of the formula to exist stably and do not hinder inclusion with cyclodextrin; Any organic residues that do not interfere with the oxidation of the compound may be connected to each other to form a ring.These organic residues include nitro,
cyano, halogen, carboxyl, carbonyl,
Hydroxyl, alkoxy, aryloxy, thiohydroxy, ferrocenyl, silyl, allyloxy, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, allylcarbonyl,
alkyl carboxyl, aryl carboxyl,
Allyl carboxyl, aralkyl carboxyl,
Alkyl, aryl, allyl, alkenyl, alkynyl, aralkyl, aralkenyl, substituted or unsubstituted with groups such as alkoxycarbonyl, aryloxycarbonyl, allyloxycarbonyl, alkoxycarboxyl, aryloxycarboxyl, allyloxycarboxyl, etc.
It is a group such as aralkynyl. However, R ¹ and R ² must not be the same after the oxidation reaction. )
It is expressed as

For example, aliphatic sulfides such as methylpropyl sulfide, ethyl t-butyl sulfide, propyldecyl sulfide, hexyl octyl sulfide; methyl phenyl sulfide, propyl phenyl sulfide, butyl 1-naphthyl sulfide , methyl 9-phenanthryl sulfide,
Aliphatic aromatic sulfides such as ethyl 3-methylphenyl sulfide; aromatic sulfides such as phenyl 2-naphthyl sulfide and phenyl 4-ethyl phenyl sulfide; 2-chloroethyl phenyl sulfide and 6 -Methylnaphthyl-3-
Halogenated sulfides such as bromophenyl sulfide and 3-fluoropropyl-4-chlorophenyl sulfide; 2-nitrohexyl-3-methoxyphenyl sulfide and 3-methylcarbonylpropyl-1-(6-nitro ) Nitrated sulfides such as naphthyl sulfide and 2-arylcarboxylethyl-3-nitrophenyl sulfide; 3-ferrocenylpropylphenyl sulfide and 2-ferrocenyl ethyl-4-silylbutyl sulfide These include ferrocene and silyl-substituted sulfides such as.

The cyclodextrin used in the present invention may be any currently isolated α-, β- or γ-cyclodextrin, or a mixture thereof. In addition, modified or branched cyclodextrins in which appropriate chemical groups are introduced into the side chains of these cyclodextrins, and polycyclodextrins in which cyclodextrins are insolubilized or soluble, do not interfere with inclusion and oxidize compounds within the inclusion. It can be used as long as it does not interfere with the reaction. These include, for example, hexakis-2,6-O-dimethyl-α-cyclodextrin, hexakis-2,6-O-dimethyl-α-cyclodextrin,
2,3,6-O-triethyl-α-cyclodextrin, heptakis-2,6-O-diethyl-β
-Cyclodextrin, heptakis-2, 3, 6
-O-trimethyl-β-cyclodextrin, octakis-2,6-O-dipropyl-γ-cyclodextrin, octakis-2,3,6-O-triethyl-γ-cyclodextrin, hexakis-6-O-nitro- Examples include α-cyclodextrin, heptakis-2, 6-O-dinitro-β-cyclodextrin, and the like. Also, glucose or maltose is present at the 6th position of glucose.
Also included are glucosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, glucosyl-γ-cyclodextrin, maltosyl-γ-cyclodextrin, and the like bound by 6-bonds. Furthermore, insoluble or soluble α-, β-, and γ-polycyclodextrins crosslinked with epichlorohydrin, methacrylamide, or the like may also be used.

It is known that the cyclodextrin and its derivatives used in the present invention form clathrate compounds with various compounds to stabilize the compounds or change their solubility. There are various methods for inclusion, including a kneading method and a solution method.

In the kneading method, water or an inert solvent is added to the cyclodextrins, and approximately
Add 0.1 to 6 times the weight and make a paste. Next, the sulfides to be included are added and thoroughly kneaded.
The kneading time is about 1 to 12 hours, preferably 2 to 8 hours.
The time and kneading temperature may be arbitrary, but room temperature is sufficient. Depending on the type of cyclodextrin derivative, a temperature higher than room temperature may be preferable.
A pickling machine, ball mill, disper mill, emulsifier, etc. are sufficient for kneading. On the other hand, in the solution method, a saturated solution of cyclodextrins in water or an inert solvent is made, and sulfides are added to this.
Stir for 30 minutes to 12 hours, preferably 1 to 4 hours,
The clathrate is obtained as a precipitate.

The resulting clathrate compound can be used as is, but
Drying may be performed by various methods if necessary. There are spray drying methods and vacuum drying methods. The odor unique to each sulfide has disappeared from the powder obtained, but when it is poured into hot water or treated with diethyl ether, the odor of the clathrate is emitted again, and the clathrate is dissolved. When the powder is dissolved in a solvent and H nuclear magnetic resonance is measured, a signal derived from the clathrated compound is observed, so it is clear that the powder contains sulfides.

The oxidizing agent used in the present invention may be any one or two known sulfide oxidizing agents.
Can be used in combination with more than one species. However, depending on the raw material sulfide, its substituent may change depending on the oxidizing agent, so it should be selected as appropriate and necessary. These known oxidizing agents and their characteristics are detailed in Chapters 6 and 8 of New Experimental Chemistry Course 14, edited by the Chemical Society of Japan (February 1971, Maruzen). _For example, hydrogen peroxide, sodium metaperiodate, sodium hypochlorite, _N2O4 , bromine, chromic acid,
Inorganic oxidizing agents such as manganese dioxide, ozone, selenium dioxide, and iodine; organic and inorganic oxidizing agents such as iodosylbenzene, tetra t-butylammonium iodide, t-butyl hypochlorite, and sulfuryl chloride, and hydrous silica gel; performic acid aliphatic peracids substituted or unsubstituted with halogen or nitro groups such as peracetic acid, perpalmitic acid, trichloroperacetic acid, peracetic acid, and their salts with Na, K, etc.; perbenzoic acid and 3-chloroperacetic acid; Benzoic acid, 4-bromopercinnamic acid, monoperphthalic acid, α- and β-pernaphtholic acid, 2-nitro-3-methyl-benzoic acid, etc., substituted or unsubstituted with halogen, nitro, alkyl groups, etc. These include aromatic peracids and their esters.

The obtained cyclodextrin clathrate compound of sulfides is dispersed in various organic solvents, water, or a mixed solvent thereof while blocking light, then an oxidizing agent is added and the mixture is heated at -60°C to 90°C, preferably at -20°C. ℃〜
The reaction is carried out at 50°C for 30 to 300 hours, preferably 2 to 150 hours. The reaction temperature and time should be appropriately selected depending on the stability of the clathrate, the reactivity of the clathrated sulfides, the reactivity of the oxidizing agent, and the stability of the sulfoxides produced. . After the unreacted oxidizing agent remaining after the reaction is appropriately removed, extraction is performed with a suitable solvent such as diethyl ether to obtain the desired optically active sulfoxide from the clathrate.

In addition, to the aqueous solution of the present invention, inorganic salts that do not reduce the reactivity of the oxidizing agent toward sulfides and do not interfere with the stability of the generated sulfoxides can be added alone or in combination of two or more. These inorganic salts include Li, Na, K,
Alkali metals such as Rb, Cs, Be, Mg, Ca,
Metal group of alkaline earth metals such as Sr, Ba, F,
Halogens such as Cl, Br, I, acetic acid, monochloroacetic acid, toluenesulfonic acid, tartaric acid, succinic acid,
Organic acids such as phthalic acid, NO ₂ , NO ₃ and SO ₃ ,
_SO4 , _HSO4 , _N3 , OCN, SCN, _HSO3 , CN,
_CO3 , _{HCO3 , CrO4} , _HPO4 , _SiO3 , _S2O3 , _ClO3
These include salts consisting of combinations of each group of ions, such as.

Furthermore, the solvent used for dispersing the sulfide-cyclodextrin inclusion complex powder of the present invention is one that does not dissolve the inclusion complex powder, stably disperses it, and does not hinder the oxidation of the sulfide. All of them can be used alone or in combination of two or more. For example, alcohols such as methanol and ethanol; saturated aliphatic hydrocarbons such as n-hexane and cyclohexane; halogenated hydrocarbons such as carbon tetrachloride, tetrachlorethylene and trifluoroethylene; Aromatic hydrocarbons and their derivatives; pyridine, quinoline,
These include amines such as dimethylaniline; ethers such as diglyme and anisole; and esters such as acetate. However, these should be selected as appropriate depending on the type of inclusion complex, oxidizing agent, reaction temperature, etc.

Effects of the Present Invention According to the method of the present invention, optically active sulfoxides, which are important as raw materials or synthetic intermediates for various physiologically active substances and pharmaceuticals, can be easily obtained with high purity. This method not only uses a cyclic oligosaccharide that is cheaper and less toxic than conventional optically active catalysts, and is stable and can be used repeatedly.
The product is characterized by high optical purity. Therefore, it is easy to purify the product, there is no problem of toxicity due to the catalyst, and the cost of producing optically active sulfoxides can be significantly lower than in the past.

Examples Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 Put 240g of β-cyclodextrin into water 2,
35 g of n-butylphenyl sulfide was added to the solution obtained by heating to 70°C with stirring and heated at 60°C for 1 hour.
After heating and stirring at 50°C for 2 hours, let it cool to room temperature.
The resulting precipitate was filtered to obtain the clathrate compound. This product was confirmed to be a 1:1 inclusion complex based on the change in the X-ray diffraction pattern obtained by the powder method and the H-NMR spectrum measured after dissolving the powder in deuterated dimethyl sulfoxide.

After exposure to light, this inclusion complex powder was heated to 1°C at 0°C.
The mixture was dispersed in water, 45 g of 40% peracetic acid was added, and the mixture was reacted with stirring for 20 hours. Next, after adding an aqueous sodium thiosulfate solution, the raw material sulfide and the product were extracted with methylene chloride and diethyl ether. The separated organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then separated and purified using methylene chloride on a silica gel column. Yield 96%, concentration in ethanol 2.5g/100ml
The optical rotation measured was [α] _D ²⁵ =+92.2, confirming that it was (R)-n-butylphenyl sulfoxide with an optical purity of 52%. Elemental analysis values (as C ₁₀ H ₁₄ SO): Calculated values C = 65.89, H = 7.74, S = 17.58, O = 8.78% Analysis values C = 66.03, H = 7.66, S = 17.65% Example 2 Example 1 β-cyclodextrin inclusion complex powder of i-butyl phenyl sulfide obtained in the same manner as above was mixed with carbon tetrachloride and n-pentane at a volume ratio of 90:
After dispersing the mixture in a mixed solvent of 10%, a solution of peracetic acid in carbon tetrachloride was added dropwise at -20°C, and the mixture was stirred for 120 hours. Next, an aqueous sodium thiosulfate solution was added to form a homogeneous solution, which was then extracted with methylene chloride and diethyl ether. Thereafter, the same treatment as in Example 1 was carried out to obtain the desired i-butylphenyl sulfoxide in a yield of 60%. Additionally, 38% of unreacted raw material sulfide was recovered. The [α] _D ²⁵ of the produced sulfoxide measured at a concentration of 0.5 g/100 ml in ethanol was +149.9, and it was the (R) form with an optical purity of 64%. Elemental analysis (as C ₁₀ H ₁₄ SO): Calculated values C=65.89, H=7.74, S=17.58, O=8.78% Analytical values C=65.78, H=7.80, S=17.52% Example 3 α-cyclodextrin Put 200g in 1 water
12 g of methyl phenyl sulfide was added to a homogeneous solution heated and stirred at 60°C, heated and stirred for about 1 hour to make it homogeneous, then allowed to cool to 10°C, and the resulting precipitate was filtered to obtain a white powder. . This powder was confirmed to be an inclusion complex with a molar ratio of 1:0.5 in the same manner as in Example 1. After dispersing this inclusion complex powder in carbon tetrachloride, persulfuric acid and t-butyl peroxide were added at -15°C, and the mixture was reacted with stirring for 30 hours. Thereafter, the same treatment as in Example 2 was carried out to obtain the desired methyl phenyl sulfoxide in a yield of 82%. [α] _D ²⁵ measured at a concentration of 1.2 g/100 ml in ethanol is -
It was confirmed to be the (S) form with an optical purity of 36.3 and an optical purity of 24%. Elemental analysis (as C ₇ H ₈ SO): Calculated values C = 59.99, H = 5.75, S = 22.83, O = 11.42% Analytical values C = 59.73, H = 5.70, S = 22.96% Example 4 γ-Cyclodextrin After dispersing the γ-cyclodextrin inclusion complex of i-butyl 1-naphthyl sulfide (molar ratio 1:1) powder obtained in the same manner as in Example 1 or 2 using , Tetra-t-butylammonium iodide was added at 0°C for 5 hours, and peracetic acid was added and stirred for 15 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain the desired i-butyl-1-naphthyl sulfoxide in a yield of 60%. Additionally, 35% of unreacted sulfide was recovered. Concentration of sulfoxide in chloroform 1.0
[α] _D ²⁵ measured in g/100ml is −259.5,
The optical purity analyzed using a Chiral OB column manufactured by Daicel was 67%. Elemental analysis (as C ₁₄ H ₁₆ SO): Calculated values C = 72.39, H = 6.94, S = 13.78, O = 6.89% Analytical values C = 72.47, H = 6.89, S = 13.90% Example 5 Insoluble β- 80℃ to cyclodextrin polymer
After adding enough warm water to swell the mixture, methyl-1-naphthyl sulfide was added and kneaded for 3 hours while heating to 80°C. After cooling, the powder obtained by centrifuging the water was confirmed to be an inclusion complex with a molar ratio of 1:1 based on changes in the infrared absorption spectrum using KBr pellets and analysis similar to Example 1. It was done. Next, this clathrate powder was dispersed in water, and then 3-chloroperbenzoic acid and peracetic acid were added thereto, and the mixture was stirred and reacted at 0 to 5°C for 50 hours. Thereafter, an aqueous solution of sodium thiosulfate was added, followed by filtration. Both the filtrate and the filtrate were thoroughly extracted with methylene chloride and diethyl ether. The organic layer was treated in the same manner as in Example 1 to obtain the desired methyl-
1-Naphthyl sulfoxide was obtained with a yield of 95%. [α] _D ²⁵ measured at a concentration of 1.6g/100ml in ethanol
The value was -353.4, and it was the (S) form with an optical purity of 90%.
Elemental analysis (as C ₁₁ H ₁₀ SO): Calculated values C = 69.46, H = 5.30, S = 16.83, O = 8.41% Analysis values C = 69.31, H = 5.44, S = 16.67% Example 6 2, 3, Add 100 ml of water to 300 g of 6-O-trimethyl-β-cyclodextrin, make a paste at room temperature, and prepare propyl-2-methylphenyl sulfide.
After adding 30 g and kneading for 4 hours, it was heated to 60 to 70°C and centrifugally dehydrated to obtain a powder. In the same manner as in Example 5, it was confirmed that this powder was an inclusion complex with a molar ratio of 1:1. This clathrate powder was dispersed in a saturated potassium chloride aqueous solution, and 30% hydrogen peroxide and peracetic acid aqueous solution were added at 0°C, followed by stirring for 30 hours. After that, the same process as in Example 1 was carried out to obtain the desired propyl-2.
-Methylphenyl sulfoxide was obtained in a yield of 99%.

[α] _D ²⁵ measured at a concentration of 2.1 g/100 ml in dimethyl ketone was −142.7, and the optical purity analyzed using the same chiral column as in Example 4 was 61%.

Calculated values C = 65.89, H = 7.74, S = 17.58, O = 8.78% Analytical values C = 65.63, H = 7.79, S = 17.70% Example 7 Obtained in the same manner as Example 5 using poly γ-cyclodextrin. After dispersing the polyγ-cyclodextrin inclusion complex of methyl-9-phenanthyl sulfide (molar ratio 1:1) powder in water, peroxylic acid and peracetic acid were added and the mixture was heated at 0°C for 25 hours. The reaction was stirred. Thereafter, the same treatment as in Example 1 was carried out to obtain the desired methyl-9-phenanthyl sulfoxide in a yield of 93%. [α] _D ²⁵ measured at a concentration of 2.1 g/100 ml in chloroform was +129.6, and Chiral OB manufactured by Daicel
The optical purity analyzed using a column was 48%. Elemental analysis (as C ₁₅ H ₁₂ SO): Calculated values C = 74.99, H = 5.03, S = 13.32, O = 6.66% Analytical values C = 75.18, H = 5.06, S = 13.20% Example 8 Example 1 and After dispersing the similarly obtained β-cyclodextrin inclusion complex powder of methyl-2-naphthyl sulfide in an aqueous sodium bromide solution, t-butyl hypochlorite and peracetic acid were added to -2
The reaction was stirred at ~0°C for 45 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain the desired methyl-2-naphthyl sulfoxide in a yield of 90%. [α] _D ²⁵ measured at a concentration of 1.8 g/100 ml in chloroform is +
66.4, and was the (R) form with an optical purity of 47%.

Example 9 Poly(α-cyclodextrin) inclusion complex powder of i-propyl methyl sulfide obtained in the same manner as in Example 5 using insoluble poly(α-cyclodextrin) was dispersed in water. After that, the mixture was mixed with hydrogen peroxide and then with peracetic acid, and stirred and reacted at 0°C for 30 hours. After that, the process was carried out in the same manner as in Example 1 to obtain the desired i-propyl methyl sulfide in a yield of 97.
Obtained in %. [α] _D ²⁵ measured at a concentration of 1.1 g/100 ml in ethanol was −11.7.

Elemental analysis (as C ₄ H ₁₀ SO): Calculated values C = 45.27, H = 9.50, S = 30.15, O = 15.08% Analytical values C = 45.38, H = 9.46, S = 30.31% Example 10 Water-soluble poly n-butyl-3- obtained in the same manner as in Example 5 using (β-cyclodextrin)
After dispersing the poly(β-cyclodextrin) inclusion complex powder of methyl phenyl sulfide in water,
Peracetic acid was added dropwise and the reaction was stirred at 0°C for 20 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain the target n-butyl-3-methylphenyl sulfoxide in a yield of 94%. Dimethyl ketone concentration 1.8g/100ml
[α] _D ²⁵ measured in 1 was +83.5, and the optical purity obtained by separate analysis in the same manner as in Example 4 was 50%.

Elemental analysis (C ₁₁ H ₁₆ SO and others): Calculated values C = 67.32, H = 8.22, S = 16.31, O = 8.15% Analytical values C = 67.18, H = 8.26, S = 16.40% Example 11 Example 3 An α-cyclodextrin composite powder of n-propylphenyl sulfide obtained in the same manner as above was dispersed in carbon tetrachloride, peracetic acid was added dropwise at -20°C, and the mixture was reacted with stirring for 120 hours. Thereafter, the same treatment as in Example 3 was carried out to obtain the desired n-propylphenyl sulfoxide in a yield of 58%. [α] _D ²⁵ measured at a concentration of 0.2 g/100 ml in ethanol is +39.2
The optical purity, which was separately analyzed in the same manner as in Example 4, was 42%. Additionally, 40% of unreacted raw material sulfide was recovered.

Elemental analysis (as C ₉ H ₁₂ SO): Calculated values C = 64.27, H = 7.19, S = 19.03, O = 9.51% Analytical values C = 64.43, H = 7.16, S = 18.98% Example 12 Example 4 and Methyl-1-(5
After dispersing the γ-cyclodextrin-encapsulated composite powder of (nitronaphthyl) sulfide in carbon tetrachloride, the mixture was stirred and reacted at -10°C for 100 hours. After that, the desired methyl-1 was processed in the same manner as in Example 3.
-(5-nitronaphthyl)sulfoxide yield 87
[α] _D ²⁵ measured at a concentration of 1.4 g/100 ml in chloroform was −157.

Elemental analysis (as C ₁₁ H ₉ NSO ₃ ): Calculated values C=56.17, H=3.86, N=5.96, S=13.61, O=20.41% Analytical values C=56.03, H=3.90, N=6.01, S= 13.48% Example 13 The β-cyclodextrin inclusion complex powder of i-propylbenzyl sulfide obtained in the same manner as in Example 1 was dispersed in water and treated in the same manner as in Example 1 to obtain the desired sulfoxide. Obtained with a yield of 80%. [α] _D ²⁵ measured at a concentration of 2.1 g/100 ml in ethanol was +41.1, and it was the (S) form with an optical purity of 32%.

In order to characterize the present invention, comparative examples are shown below. That is, the known method of J. Drabowicz and M. Mikolajczyk [Phosphorous and Sulfur, 21 245-
248 (1984)] are shown as Comparative Examples 1 and 2 for comparison.

Comparative Example 1 1 mmol of n-butylphenyl sulfide and 1
After dissolving mmol of β-cyclodextrin in 10 ml of pyridine, a 20-fold molar amount of 30% hydrogen peroxide was added, and the mixture was reacted with stirring for 156 hours. After removing pyridine under reduced pressure, ether was added and β-cyclodextrin was filtered off. Concentrate the ether layer, dissolve the residue in chloroform, wash the solution with an aqueous calcium carbonate solution, dry with anhydrous magnesium sulfate, and add silica gel (70 to 230 mesh) manufactured by Merck & Co.
The product was separated and purified using pentane, hexane, and chloroform to obtain the desired sulfoxide in a yield of 73%.
Furthermore, 19% of the corresponding sulfone was also formed as a by-product. [α] _D ²⁵ measured at a concentration of 5.01g/100ml in ethanol is -
0.30, and was the (S) form with an optical purity of 0.40%. This result shows that compared to Example 1, the chemical yield,
Both optical purity is low, and the steric configuration is reversed.
Unnecessary sulfone was also produced as a by-product.

Comparative Example 2 4 mmol of methyl n-propylsulfide was treated in the same manner as in Comparative Example 1 for 12 hours using 1 mmol of β-cyclodextrin and 10 mmol of 30% hydrogen peroxide solution. The target methyl n-propyl sulfoxide was obtained with a yield of . [α] _D ²⁵ measured at a concentration of 2.50 g/100 ml in ethanol is -
1.20, and was the (R) form with an optical purity of 0.9%.
Although a complete comparison cannot be made since the raw material sulfide is different, it is thought that the chemical yield is at least lower and the optical purity is lower than in Example 9.

Comparative Example 3 Separately obtained n-butylphenyl sulfoxide was prepared using the method of Cramer et al. [F. Cramer, W. Dietsch:
Chem, Ber., 92 378 (1958)] using β-cyclodextrin. β-
[α] _D ²⁵ of recovered sulfoxide from cyclodextrin inclusion complex in ethanol is −1.6
[−1.5 in the report by Drabowicz, Mikolajczyk et al.]
Compared to Example 1, the sign is opposite and the purity is also high.
It is small at 0.9%. Therefore, it is clear that the results of Example 1 are not due to optical resolution.

As described above, it is clear that the present invention is not based on the optical resolution of a racemate as shown in Comparative Example 3, and cannot be achieved by the known homogeneous solution reaction method as shown in Comparative Examples 1 and 2. This method provides optically active sulfoxide with high optical purity in high yield. In addition, the cyclodextrins used can be recycled through filtration and recovery, providing a resource-saving and energy-saving process.

Claims (1)

[Claims] 1 Sulfides having an arbitrary organic residue that does not hinder inclusion with cyclodextrins and do not hinder oxidation reaction, after the sulfides whose oxides can become asymmetric sulfoxides are included in cyclodextrins. A method for producing optically active sulfoxides, which comprises bringing them into dispersion contact with an oxidizing agent.