JP2000080073A - Sulfone derivative and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a sulfone derivative useful as an intermediate for synthesizing compounds used in the fields of medicines, foods and feed additives, such as canthaxanthin compounds, by oxidizing a sulfone compound derived from geraniol as an inexpensive raw material, etc. SOLUTION: A sulfone derivative of formula I [Ar is an aryl; X is H, a halogen or a hydroxy group; Y is an oxo group or a hydroxy group; Q is H or a group of formula II (R1, R2 are each H or a hydroxyl group-protecting group). The sulfone derivative of formula I (X is H; Y is an oxo group; Q is H), namely a ketosulfone compound of formula IV, is obtained, for example, by reacting a sulfone compound of formula III with an oxidizing agent based on a group 6 or 7 metal in the periodic table (preferably a chromium or manganese oxide or its salt). The sulfone derivative of formula I is useful as an intermediate for synthesizing canthaxanthin derivatives or astaxanthin derivatives, and the utilization of the sulfone derivative of formula I in the fields of medicines, foods and feed additives can thereby be expected.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a sulfone derivative useful in the fields of medicine, food and feed additives, and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, as a method for producing canthaxanthin derivatives and astaxanthin derivatives, C13 ketones (β
-Ionone) as a key intermediate has been used to enrich the side chain and via vitamin A and β-carotene (Pure Appl. Chem. (1991), 63 (1), 35-44). . However, the synthesis of β-ionone goes through a multi-step process and is a very expensive raw material on the market.

[0003]

SUMMARY OF THE INVENTION The present invention provides an industrial advantage by oxidizing a sulfone derivative which is a key intermediate of a canthaxanthin derivative or an astaxanthin derivative with sulfones derived from geraniol or linalool which are inexpensive raw materials. It is an object of the present invention to provide a production method which can be obtained at the same time.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have reached the present invention. That is, the present invention provides a compound represented by the general formula (1): (Wherein, Ar represents an aryl group which may have a substituent, X represents a hydrogen atom, a halogen atom or a hydroxyl group, Y represents an oxo group (＝ O) or a hydroxyl group,
Q is a hydrogen atom or the following group (Wherein, R ¹ and R ² represent a hydrogen atom or a protecting group for a hydroxyl group). ) And a method for producing the same.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. Ar of the sulfone derivative represented by the general formula (1)
Represents an aryl group which may have a substituent. Examples of the aryl group include a phenyl group and a naphthyl group. Examples of the substituent include a C1 to C5 alkyl group and a C1 to C5
Alkoxy group, halogen, nitro group and the like.
Specifically, phenyl, naphthyl, o-tolyl, m-tolyl, p-tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-toluene Bromophenyl, m-bromophenyl, p-bromophenyl, o-iodophenyl, m-iodophenyl, p-iodophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-nitrophenyl,
m-nitrophenyl, p-nitrophenyl and the like.

Further, R ¹ and R ² of the sulfone derivative represented by the general formula (1) represent a hydrogen atom or a protecting group for a hydroxyl group, and the compounds represented by the general formulas (4), (5) and (9) R ³ and R ^{4 in the above} represent a hydroxyl-protecting group. Specific examples of the hydroxyl-protecting group include acyl groups such as acetyl, pivaloyl, benzoyl and p-nitrobenzoyl, silyl groups such as trimethylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl, tetrahydropyranyl, methoxymethyl, Methoxyethoxymethyl, alkoxymethyl group such as 1-ethoxymethyl, benzyl group,
p-methoxybenzyl group, t-butyl group, trityl group,
Examples thereof include a 2,2,2-trichloroethoxycarbonyl group and an allyloxycarbonyl group.

In the general formula (1), a compound wherein X is a hydrogen atom and Y is an oxo group, that is, a compound of the general formula (3) (Wherein, Ar represents an aryl group which may have a substituent), and a general formula (5) (Wherein, Ar represents the same meaning as described above, and R ³ and R ⁴
Represents a hydroxyl-protecting group. The ketosulfone derivative represented by the general formula (2) Wherein Ar represents the same meaning as described above, or a general formula (4) (Wherein, Ar represents the same meaning as described above, and R ³ and R ⁴
Represents a hydroxyl-protecting group. ) And a metal-based oxidizing agent belonging to Group 6 or Group 7 of the periodic table.

The oxidizing agent of Group 6 or 7 of the Periodic Table used in the above reaction includes oxides of chromium or manganese and salts thereof. Specifically, pyridinium chlorochromate, pyridinium dichromate, dioxide Manganese, potassium permanganate, tris (acetonylacetic acid) manganese (III) and the like can be mentioned. The amount of the oxidizing agent to be used is usually about 1 to 10 mol times, preferably about 1 to 3 mol times, relative to the sulfones (2) or the sulfone derivative (4).

In the above reaction, an organic solvent is usually used. Examples of such a solvent include aprotic polar solvents such as N, N-dimethylformamide, dimethylsulfoxide, N, N-dimethylacetamide and hexamethylphosphoric triamide. Solvents, ether solvents such as 1,4-dioxane and tetrahydrofuran, hydrocarbon solvents such as n-hexane, cyclohexane, n-pentane, n-heptane, toluene and xylene, chloroform, dichloromethane, 1,2-dichloroethane, mono Chlorobenzene, o
And halogen-based solvents such as dichlorobenzene.

The reaction temperature is usually in the range from 0 ° C. to the boiling point of the solvent used. The reaction time varies depending on the type of the oxidizing agent used in the reaction and the reaction temperature, but is usually in the range of about 1 hour to 24 hours. After the reaction, the ketosulfones (3) or the ketosulfone derivative (5) can be obtained by a usual post-treatment operation. Further, if necessary, it can be purified by silica gel chromatography.

A compound of the general formula (1) wherein X and Q are hydrogen atoms and Y is a hydroxyl group, that is, a compound of the general formula (6) Wherein Ar represents the same meaning as described above. The hydroxysulfone derivative represented by the general formula (2) is obtained by reacting a sulfone represented by the general formula (2) with a metal oxidizing agent belonging to Group 16 of the periodic table. be able to.

The metal oxidizing agent belonging to Group 16 of the periodic table used in the above reaction includes selenium oxide and the like.
Specific examples include selenium dioxide. The amount of the metal oxidizing agent to be used is usually 1 to the sulfones (2).
The molar ratio is about 10 to 10 times, preferably about 1 to 3 times.

In the above reaction, an organic solvent is usually used, and such a solvent may be an aprotic polar solvent such as N, N-dimethylformamide, dimethylsulfoxide, N, N-dimethylacetamide, hexamethylphosphoric triamide and the like. Solvents, ether solvents such as 1,4-dioxane and tetrahydrofuran, hydrocarbon solvents such as n-hexane, cyclohexane, n-pentane, n-heptane, toluene and xylene, chloroform, dichloromethane, 1,2-dichloroethane, mono Chlorobenzene, o
And halogen-based solvents such as dichlorobenzene.

The reaction temperature is usually in the range from 0 ° C. to the boiling point of the solvent used. The reaction time varies depending on the type of the oxidizing agent used in the reaction and the reaction temperature, but is usually in the range of about 1 hour to 24 hours. After the reaction, the hydroxysulfone derivative (6) can be obtained by performing ordinary post-treatment operations. Further, if necessary, it can be purified by silica gel chromatography.

In the general formula (1), a compound wherein X is a halogen atom, Y is an oxo group and Q is a hydrogen atom, that is, a compound of the general formula (7) (In the formula, Ar and Hal represent the same meaning as described above.)
Can be obtained by reacting a sulfone represented by the general formula (2) with a halogen-based oxidizing agent.

Examples of the halogen-based oxidizing agent used in the above reaction include N-halide succinimide, specifically, N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide. And the like. The amount of the halogen-based oxidizing agent to be used is generally about 1 to 10 mol times, preferably 1 to 10 times, based on the sulfones (2).
It is about 3 mole times.

In the above reaction, usually, an organic solvent is used. Examples of such a solvent include chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenzene and o.
-A halogenated solvent such as dichlorobenzene, methanol,
Alcoholic solvents such as ethanol and isopropyl alcohol; aprotic polar solvents such as N, N-dimethylformamide, dimethylsulfoxide, N, N-dimethylacetamide and hexamethylphosphoric triamide; n
And hydrocarbon solvents such as -hexane, cyclohexane, n-pentane, n-heptane, toluene, and xylene.

The reaction temperature is usually in the range from -30 ° C to the boiling point of the solvent used. The reaction time varies depending on the type of the halogen-based oxidizing agent used in the reaction and the reaction temperature, but is usually in the range of about 1 hour to 24 hours.
After the reaction, an ordinary post-treatment operation can be performed to obtain the α-haloketosulfone derivative (7). If necessary, it can be purified by silica gel chromatography.

In the general formula (1), a compound wherein X is a hydroxyl group, Y is an oxo group and Q is a hydrogen atom, that is, a compound of the general formula (8) (In the formula, Ar represents the same meaning as described above.) The α-hydroxyketosulfone derivative represented by the general formula (7) is combined with an alkali metal or alkaline earth metal water. It can be obtained by reacting with an oxide.

Examples of the alkali metal or alkaline earth metal hydroxide used in the above reaction include sodium hydroxide, magnesium hydroxide, potassium hydroxide, magnesium hydroxide and the like. The amount of use is usually about 1 to 10 mol times, preferably about 1 to 3 mol times with respect to the α-haloketosulfone derivative (7).

In the above reaction, an organic solvent is usually used, and such solvents include chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenzene, and the like.
Halogen solvents such as o-dichlorobenzene, alcohol solvents such as methanol, ethanol, and isopropyl alcohol; aprotic solvents such as N, N-dimethylformamide, dimethylsulfoxide, N, N-dimethylacetamide, and hexamethylphosphoric triamide Polar solvents and the like.

The reaction temperature is usually in the range from 0 ° C. to the boiling point of the solvent used. The reaction time varies depending on the kind of the alkali metal or alkaline earth metal hydroxide used in the reaction and the reaction temperature, but is usually from 1 hour to 2 hours.
The range is about 4 hours. After the reaction, α-hydroxyketosulfone derivative (8) can be obtained by ordinary post-treatment operation. If necessary, it can be purified by silica gel chromatography or the like.

Formula (10) (In the formula, Ar represents an aryl group which may have a substituent, and R ¹ and R ² represent a hydrogen atom or a protecting group for a hydroxyl group.) The ketosulfone derivative represented by the general formula (3) And a general formula (9) (In the formula, Hal represents a halogen atom, and R ³ and R ⁴ each represent a hydroxyl-protecting group.) The compound can be obtained by reacting the compound with a halohydrin derivative represented by the formula:

Hal of the halohydrin derivative (9) includes a halogen atom such as a chlorine atom, a bromine atom and an iodine atom.

The base used in the above reaction includes alkyl lithium, Grignard reagent, alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal hydride, alkaline earth metal hydride, alkali metal hydride. Alkoxides, alkoxides of alkaline earth metals and the like, specifically, n-butyllithium, s-butyllithium, t-butyllithium, ethylmagnesium bromide, ethylmagnesium chloride, sodium hydroxide, potassium hydroxide, Examples thereof include sodium hydride, potassium hydride, sodium methoxide, potassium methoxide, sodium t-butoxide, potassium t-butoxide and the like. The amount of the base to be used is usually 0.1 to the ketosulfone represented by the general formula (3).
It is about 1 to 2 mol times.

In the above reaction, it may be preferable to use a phase transfer catalyst in order to accelerate the reaction. Such phase transfer catalysts include quaternary ammonium salts, quaternary phosphonium salts, and sulfonium salts. Examples of the quaternary ammonium salt include an ammonium halide having an alkyl group and / or an aralkyl group having 1 to 24 carbon atoms, such as tetramethylammonium chloride, tetraethylammonium chloride, tetrapropylammonium chloride, tetrabutylammonium chloride, Tetrapentyl ammonium chloride, tetrahexylammonium chloride, tetraheptyl ammonium chloride, tetraoctylammonium chloride, tetrahexadecyl ammonium chloride, tetraoctadecyl ammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, 1-methyl chloride Pyridinium, 1-hexadecylpyridinium chloride, dimethylpyridinium chloride, trimethylcyclyl Propylammonium, tetramethylammonium bromide, tetraethylammonium bromide, tetrapropylammonium bromide, tetrabutylammonium bromide, tetrapentylammonium bromide, tetrahexylammonium bromide, tetraheptylammonium bromide, tetraoctylammonium bromide, Tetrahexadecyl ammonium bromide, tetraoctadecyl ammonium bromide, benzyltrimethylammonium bromide, benzyltriethylammonium bromide, benzyltributylammonium bromide, 1-methylpyridinium bromide, 1 bromide
-Hexadecylpyridinium, dimethylpyridinium bromide, trimethylcyclopropylammonium bromide, tetramethylammonium iodide, tetrabutylammonium iodide, tetraoctylammonium iodide, t-butylethyldimethylammonium iodide, tetradecyltrimethylammonium iodide , Hexadecyltrimethylammonium iodide, octadecyltrimethylammonium iodide,
Benzyltrimethylammonium iodide, benzyltriethylammonium iodide, benzyltributylammonium iodide and the like.

The quaternary phosphonium salts include, for example, tributylmethylphosphonium chloride, triethylmethylphosphonium chloride, methyltriphenoxyphosphonium chloride, butyltriphenylphosphonium chloride, tetrabutylphosphonium chloride, benzyltriphenylphosphonium chloride, hexadecyltrimethylphosphonium chloride , Hexadecyltributylphosphonium chloride, hexadecyldimethylethylphosphonium chloride, tetraphenylphosphonium chloride, tributylmethylphosphonium bromide, triethylmethylphosphonium bromide, methyltriphenoxyphosphonium bromide, butyltriphenylphosphonium bromide, tetrabutylphosphonium bromide , Benzyltriphenylphosphonium bromide, hexadecyltrimethylphosphonium bromide, odor Hexadecyltributylphosphonium, hexadecyldimethylethylphosphonium bromide, tetraphenylphosphonium bromide, tributylmethylphosphonium iodide, triethylmethylphosphonium iodide, methyltriphenoxyphosphonium iodide, butyltriphenylphosphonium iodide, tetrabutylphosphonium iodide Benzyltriphenylphosphonium iodide, hexadecyltrimethylphosphonium iodide and the like.

Examples of the sulfonium salt include dibutylmethylsulfonium chloride, trimethylsulfonium chloride, triethylsulfonium chloride, dibutylmethylsulfonium bromide, trimethylsulfonium bromide, triethylsulfonium bromide, dibutylmethylsulfonium iodide, trimethylsulfonium iodide, And triethylsulfonium iodide. Among them, quaternary ammonium salts are preferable, and ammonium halides having an alkyl group and / or an aryl group having 1 to 24 carbon atoms are more preferable. The amount of the phase transfer catalyst used is
It is usually about 0.01 to 0.2 mol times, preferably about 0.02 to 0.1 mol times, relative to the ketosulfones (3).

In the above reaction, an organic solvent is usually used, and examples of such a solvent include diethyl ether, 1,4-
Ether solvents such as dioxane, tetrahydrofuran and anisole; hydrocarbon solvents such as n-hexane, cyclohexane, n-pentane, n-heptane, toluene and xylene; or N, N-dimethylformamide, dimethylsulfoxide, N, N- Aprotic polar solvents such as dimethylacetamide and hexamethylphosphoric triamide.

The reaction temperature is usually in the range of -78 ° C to the boiling point of the solvent used. The reaction time varies depending on the base used in the reaction, the type of catalyst and the reaction temperature, but is usually in the range of about 0.5 to 24 hours. After the reaction, the ketosulfone derivative (10) can be obtained by performing ordinary post-treatment operations. If necessary, it can be purified by silica gel chromatography.

The halohydrin derivative (9) may be either an E or Z geometric isomer or a mixture thereof. Further, it may be a racemic body or an optically active body. It is described in Japanese Patent No. 2558275 that sulfones (2) can be easily synthesized from linalool via a halide compound, and a halohydrin derivative (9) can be synthesized from geraniol. The sulfone derivative (4) can be easily synthesized by reacting the sulfones (2) with the halohydrin derivative (9) in the presence of a base.

[0032]

The sulfone derivative of the present invention is useful in the field of pharmaceuticals, foods and feed additives, for example, as an intermediate for canthaxanthins and astaxanthins.

[0033]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.

Example 1 0.5 g (1.71 mmol) of sulfone (I)
l) was dissolved in dimethyl sulfoxide (10 ml), and a solution of pyridinium chlorochromate (1.13 g, 5.13 mmol) in dimethyl sulfoxide (10 ml) was slowly added dropwise at room temperature. After stirring at the same temperature for 3 hours, the temperature was raised to 50 ° C., and the mixture was stirred for 6 hours. After cooling, ether was added to the reaction solution, which was filtered, washed with water and extracted with ether. A crude product was obtained from the organic layer by distilling off the solvent. The obtained crude product was purified by silica gel column chromatography to obtain the desired product ketosulfone (II) in a yield of 39%. ^{1 H-NMR δ (CDCl3)} 1.23 (6H, s), 1.79 (3H, s), 1.90 (2H, t, J = 6Hz), 2.48 (3H,
s), 2.55 (2H, t, J = 6Hz), 4.13 (2H, s), 7.33 (2H, d, J = 8Hz),
7.81 (2H, d, J = 8Hz) ¹³ C-NMR δ (CDCl3) 13.1, 21.4, 26.9, 34.5, 35.2, 37.3, 58.8, 127.1, 1
29.4, 137.6, 138.1, 146.0, 150.1, 198.2

(Example 2) 1.0 g (3.42 mmo) of sulfone (I)
l) was dissolved in 20 ml of dioxane, and 0.57 g (5.1%) of selenium dioxide was dissolved.
3 mmol) was added. The reaction solution was heated to 80 ° C. and stirred for 1.5 hours. After the reaction, the solid content was filtered, and the solvent was distilled off to obtain a mixture of ketosulfone (II) and hydroxysulfone (III). The obtained crude product was purified by silica gel column chromatography to obtain the desired ketosulfone (II) at a yield of 29% with hydroxysulfone (II).
I) was obtained in 59% yield. Hydroxysulfone (III) ¹ H-NMR δ (CDCl 3) 1.00 (3H, s), 1.05 (3H, s), 1.39-1.42 (1H, m), 1.65-1.98
(3H, m), 1.82 (3H, s), 2.44 (3H, s), 3.30 (1H, d, J = 8Hz),
3.98 (3H, m), 7.33 (2H, d, J = 8Hz), 7.81 (2H, d, J = 8Hz) ¹³ C-NMR δ (CDCl3) 18.5, 21.4, 27.2, 27.7, 27.9, 28.0, 34.5, 57.8, 6
9.6, 127.1, 129.4, 138.1, 140.1, 144.2

Example 3 1.0 g (3.42 mmo) of sulfone (I)
l) is dissolved in 5 ml of chloroform and 5 ml of methanol,
0.61 g (3.42 mmol) of N-bromosuccinimide was added.
After stirring at room temperature for 18 hours, the disappearance of the raw materials was confirmed by TLC, and the solvent was distilled off to obtain a crude product. The obtained crude product was purified by silica gel column chromatography to obtain α-bromoketosulfone (IV) as a target substance at a yield of 37%.
I got it. ^{1 H-NMR δ (CDCl3)} 1.27 (3H, s), 1.30 (3H, s), 1.89 (3H, s), 2.35-2.47 (2H,
m), 2.47 (3H, s), 4.08 (1H, d, J = 12Hz), 4.19 (1H, d, J = 12H
z), 4.92 (1H, dd, J = 12Hz, J = 9Hz), 7.39 (2H, d, J = 8Hz), 7.8
1 (2H, d, J = 8Hz) ¹³ C-NMR δ (CDCl3) 14.5, 21.4, 26.9, 27.9, 38.5, 48.7, 48.9, 58.8, 12
7.8, 129.4, 136.9, 138.1, 146.1, 150.2, 190.8

Example 4 α-bromoketosulfone (I
V) 0.09 g (0.234 mmol) was dissolved in 3 ml of dimethylformamide, and 0.055 g of a 20% aqueous sodium hydroxide solution was further added.
(0.281 mmol) was added dropwise. After stirring at room temperature for 5 hours, water was poured into the reaction solution, and the mixture was extracted with ether. Further, the organic layer was sequentially washed with an aqueous ammonium chloride solution and a saline solution. The organic layer was dehydrated with anhydrous magnesium sulfate, and the solvent was distilled off to obtain a crude product. The obtained crude product was purified by silica gel column chromatography to obtain the desired product α-hydroxyketosulfone (V) in a yield of 77%.

(Example 5) 0.7 g of sulfone (VI) was placed in a flask.
(1.28 mmol) was dissolved in 25 ml of dimethyl sulfoxide, 0.83 g (3.86 mmol) of pyridinium chlorochromate was added, and the mixture was stirred at 50 ° C. for 10 hours. After the reaction, the reaction solution was filtered, washed well with ether, and the filtrate was washed with water and extracted with ether. The organic layer was dehydrated with anhydrous magnesium sulfate, and the solvent was distilled off to obtain a crude product. The obtained crude product was purified by silica gel column chromatography, and ketosulfone (VII) was isolated as a pale yellow oil in a yield of 41%. ¹ H-NMR δ (CDCl ₃ ) 0.88-1.27 (6H, m), 1.39 (3H, s), 1.70 (3H, s), 1.61-1.87
(4H, m), 1.90-2.39 (2H, m), 2.00 (3H, s), 2.01 (3H, s),
2.03 (3H, s), 2.44 (3H, s), 2.66-3.11 (2H, m), 3.95-4.12
(1H, m), 4.53 (2H, d, J = 7Hz), 5.10 (1Hx40 / 100, d, J = 9Hz),
5.20 (1Hx60 / 100, d, J = 9Hz), 5.34 (1H, br), 5.45-5.60 (1
H, br), 7.33 (2H, d, J = 8Hz), 7.76 (2H, d, J = 8Hz) ¹³ C-NMR δ (CDCl ₃ ) 15.1, 16.0, 16,1, 16.6, 18.8, 20.8, 20.9 , 21.4, 2
8.2, 29.0, 35.5, 40.5, 40.8, 44.6, 60.8, 65.3, 65.
5, 65.7, 68.3, 68.5, 68.8, 121.9, 127.1, 128.3, 12
9.4, 130.5, 130.6, 136.2, 137.1, 137.6, 137.7, 13
8.4, 143.9, 144.0,169.8, 170.0, 170.7, 198.1

Example 6 Sulfon (II) 0.5 was added to a flask.
3 g (1.8 mmol) and 20 ml of THF are charged and dissolved.
Cooled to 60 ° C. At the same temperature, 1.13 ml (1.8 mmol) of a hexane solution of n-butyllithium was slowly added dropwise, and 3
Incubated for hours. Then, 0.3 g of halohydrin derivative (VIII)
(0.9 mmol) of a THF solution (5 ml) was added dropwise over 1 hour.
After stirring at the same temperature for 3 hours, TLC confirmed that one of the raw materials had disappeared, and the reaction mass was poured into a saturated aqueous ammonium chloride solution and extracted with ether. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain a crude product.
The obtained crude product was purified by silica gel column chromatography, and ketosulfone (VII) was isolated as a pale yellow oil in a yield of 49%.

[0040] The structural formulas of the compounds used in the examples are shown above.

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Claims (14)

[Claims] 1. The general formula (1) (Wherein, Ar represents an aryl group which may have a substituent, X represents a hydrogen atom, a halogen atom or a hydroxyl group, Y represents an oxo group (＝ O) or a hydroxyl group,
Q is a hydrogen atom or the following group (Wherein, R ¹ and R ² represent a hydrogen atom or a protecting group for a hydroxyl group). ). 2. The general formula (2) Wherein Ar represents the same meaning as described above, and a sulfonate represented by the general formula (3) characterized by reacting with a metal-based oxidizing agent belonging to Group 6 or 7 of the periodic table. (Wherein, Ar represents the same meaning as described above). 3. The formula (4) (Wherein, Ar represents the same meaning as described above, and R ³ and R ⁴
Represents a hydroxyl-protecting group. Wherein the sulfone derivative of the formula (5) is reacted with a metal-based oxidizing agent of Group 6 or 7 of the Periodic Table. (Wherein, Ar, R ³ and R ⁴ have the same meanings as described above). 4. The method according to claim 2, wherein the metal oxidizing agent of Group 6 or 7 of the periodic table is an oxide of chromium or manganese or a salt thereof. 5. A compound of the general formula (6), wherein the sulfone represented by the general formula (2) is reacted with an oxidizing agent of Group 16 of the periodic table. (Wherein, Ar represents the same meaning as described above). 6. The method according to claim 5, wherein the metal oxidizing agent belonging to Group 16 of the periodic table is an oxide of selenium. 7. A compound represented by the general formula (7), wherein the sulfone represented by the general formula (2) is reacted with a halogen-based oxidizing agent. (In the formula, Ar represents the same meaning as described above, and Hal represents a halogen atom.) A method for producing an α-haloketosulfone derivative represented by the following formula: 8. The method according to claim 7, wherein the halogen-based oxidizing agent is N-halide succinimide. 9. A compound of the general formula (8) characterized by reacting the α-haloketosulfone derivative represented by the general formula (7) with a hydroxide of an alkali metal or an alkaline earth metal. (In the formula, Ar represents the same meaning as described above.) A method for producing an α-hydroxyketosulfone derivative represented by the formula: 10. The ketosulfone represented by the general formula (3) and the general formula (9) (Wherein Hal represents a halogen atom, R ³ and R ⁴ each represent a hydroxyl-protecting group), and reacted with a halohydrin derivative represented by the following general formula (10): (Wherein, Ar, R ¹ and R ² have the same meanings as described above). 11. The base is alkyl lithium, Grignard reagent, alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal hydride, alkaline earth metal hydride, alkali metal alkoxide or alkaline earth. The production method according to claim 10, which is an alkoxide of a class of metals. 12. The method according to claim 10, wherein a phase transfer catalyst is present. 13. The method according to claim 12, wherein the phase transfer catalyst is a quaternary ammonium salt. 14. A quaternary ammonium salt having 1 to 2 carbon atoms.
The production method according to claim 13, which is an ammonium halide having an alkyl group and / or an aralkyl group of No. 4.