JP2010208990A - Method of producing sulfone compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an industrially advantageous method of easily producing a highly pure sulfone compound at a high yield using safe reagents. <P>SOLUTION: The method of producing a sulfone compound represented by formula (2): R<SP>1</SP>-SO<SB>2</SB>-R<SP>2</SP>, by oxidizing a sulfide compound by hydrogen peroxide employs niobium carbide as a reaction catalyst. Tantalum carbide used in the reaction can repeatedly be reused by recovering it after the completion of the reaction. In the formula, R<SP>1</SP>and R<SP>2</SP>may be the same or different and each represent an alkyl group that may contain a substituent, an aryl group that may contain a substituent, a heterocyclic group that may contain a substituent, an aralkyl group that may contain a substituent, or an alkenyl group that may contain a substituent, provided that R<SP>1</SP>and R<SP>2</SP>may bind to each other constituting a part of the ring structure. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

The present invention relates to an industrially useful production method for obtaining a sulfone compound by oxidation reaction of a sulfide compound.

The sulfone compounds are extremely useful compounds chemically or biologically, and many examples of synthesis have been reported so far. As a synthesis method thereof, a method by oxidation of a sulfide compound is generally known. Examples of the oxidizing agent used in the oxidation reaction include hydrogen peroxide, peracetic acid, hydroperoxide, peroxodisulfate, permanganate, and sodium perborate (Non-Patent Documents 1 to 4).

Among the oxidizing agents, hydrogen peroxide can be safely stored and can be obtained at a low cost, so it can be said that it is useful for industrial sulfone compound synthesis from sulfide compounds. Furthermore, hydrogen peroxide has high solubility in water and various organic solvents, and becomes water after the reaction. Therefore, hydrogen peroxide is widely used as an oxidizing agent that is highly versatile and suitable from the viewpoint of the environment (non-patent literature). 5, 6).

However, hydrogen peroxide has a weak oxidizing power, and there is a problem that it is difficult to efficiently oxidize depending on the sulfide compound. For this reason, a method using a metal catalyst is known as a method for producing a sulfone compound by reacting a sulfide compound with hydrogen peroxide. Examples of the metal species used as the metal catalyst include vanadium, titanium, molybdenum, tellurium, tungsten, selenium, iron, tantalum, and niobium (Non-Patent Documents 7 to 9 and Patent Document 1).

However, in some methods using these metal catalysts, strong metal toxicity is observed in the metal catalyst itself, which is not always satisfactory from the viewpoint of practical use. Furthermore, since these metal catalysts are generally a reaction in a homogeneous system despite being expensive, it has been extremely difficult to recover and reuse them after the reaction. In addition, some metal catalysts are decomposed during the reaction, which makes it difficult to reuse, and there is room for improvement.

As an example of using niobium having a low toxicity as a metal species as a catalyst, a method for producing an optically active sulfoxide compound by asymmetric oxidation of a sulfide compound has been reported (Patent Document 2). In this method, a salen complex compound having niobium as a central metal is used as a catalyst, and a sulfide compound is asymmetrically oxidized with a urea-hydrogen peroxide adduct to obtain an optically active sulfoxide compound. However, this method is a technique developed for the purpose of obtaining optically active sulfoxide, and has a problem that it is not suitable for an oxidation reaction on an industrial scale because a chiral complex having a complicated structure is used. Moreover, a sulfoxide compound is obtained from a sulfide compound, and cannot be applied to produce a sulfone compound.

In recent years, it has been reported that a sulfoxide compound or a sulfone compound is obtained from a sulfide compound by oxidation with hydrogen peroxide using a toxic tantalum compound as a catalyst. Examples of the tantalum catalyst used include pentavalent tantalum catalysts such as tantalum pentachloride and pentaethoxytantalum (Patent Literature 3, Non-Patent Literature 10). However, in this method, tantalum pentachloride and pentaethoxytantalum are dissolved in the solvent used in the reaction system, and the reaction proceeds in a uniform state. Therefore, there has been a drawback that these tantalum catalysts cannot be recovered and reused after the reaction is completed. Furthermore, tantalum pentachloride and pentaethoxy tantalum are expensive reagents, and are disadvantageous for use on an industrial scale.

Bull. Chem. Soc. Jpn. , 54, 793 (1981). Tetrahedron Lett, 24, 1505 (1983). J. et al. Org. Chem. 45, 3634 (1980). Org. Synth. 64, 157 (1985). J. et al. Chem. Soc. , 1961, 5339. J. et al. Am. Chem. Soc. 71, 2248 (1949). J. et al. Org. Chem. , 28, 1140 (1963). Synthesis, 1978, 299. J. et al. Org. Chem. , 50, 1784 (1985). Tetrahedron Lett, 50, 1180 (2009). JP 2003-300950 A JP 2004-323445 A JP 2008-239490 A

Accordingly, an object of the present invention is to provide a method for producing a corresponding sulfone compound by using a sulfide compound as an oxidizing agent by using a low-toxic and inexpensive reusable oxidation reaction catalyst. An object of the present invention is to provide an industrial production method for efficiently obtaining a sulfone compound.

As a result of intensive studies to solve the above problems, the present inventors have found that a sulfone compound can be efficiently obtained from a sulfide compound by using niobium carbide as an oxidation reaction catalyst. Further, the present inventors have found that this reaction system is completely neutral, and that the present technology can be applied without any problem even if a functional group susceptible to acid or alkali is present in the structure of the reaction substrate.

Niobium carbide is generally used as a raw material for cemented carbide, has a low hardness drop at high temperatures, and is very hard to wear, so it is mainly used for drills, end mills, hobbings, milling machines, lathes, pinion cutters, etc. It is used as a material for cutting tools for metal processing. Therefore, there is no precedent used as a reaction catalyst in organic synthesis reactions in the past. That means that niobium carbide was insoluble in water and organic solvents, and also stable to acids and alkalis, so that it did not have any focus on acting as a reaction catalyst. The inventors have found oxidation catalyst activity of niobium carbide for sulfide compounds, and niobium carbide acts as a catalyst in a heterogeneous state, and can be separated from the reaction mixture and used again as a catalyst after completion of the reaction. A certain fact was found and the present invention was completed.

That is, the present invention has been achieved by the following method.
A sulfone characterized in that niobium carbide is used as a catalyst in a method for producing a sulfone compound represented by the following general formula (2) by oxidizing the sulfide compound represented by the general formula (1) with hydrogen peroxide. Compound manufacturing method.

（一般式（１）において、Ｒ¹及びＲ^２は、同一でも異なっていてもよく、置換基を有していてもよいアルキル基、置換基を有していてもよいアリール基、置換基を有していてもよい複素環基、置換基を有していてもよいアラルキル基及び置換基を有していてもよいアルケニル基を表す。また、Ｒ¹とＲ^２が結合して環構造の一部を形成していてもよい。）

(In General Formula (1), R ¹ and R ² may be the same or different, and may be an alkyl group which may have a substituent, an aryl group which may have a substituent, or a substituent. Represents an optionally substituted heterocyclic group, an optionally substituted aralkyl group and an optionally substituted alkenyl group, wherein R ¹ and R ² are bonded to form a ring structure; It may form part.)

（一般式（２）において、Ｒ¹及びＲ^２は、一般式（１）におけるＲ¹及びＲ^２と同義である。）

(In the general formula (2), R ¹ and ^{R 2} have the same meanings as R ¹ and ^{R 2} in the general formula (1).)

According to the present invention, a sulfone compound can be easily obtained by using non-toxic niobium carbide as a catalyst for an oxidation reaction in an oxidation reaction of a sulfide compound with hydrogen peroxide. Further, after the desired reaction is completed, the used niobium carbide can be recovered and reused, and an industrially advantageous method for producing a sulfone compound with very little waste can be provided.

Hereinafter, the best mode for carrying out the present invention will be described in detail, but the present invention is not limited thereto.

In the present invention, in the sulfide compound used, R ¹ and R ² in the general formula (1) may be the same or different, and may have an alkyl group or a substituent which may have a substituent. An aryl group that may be substituted, a heterocyclic group that may have a substituent, an aralkyl group that may have a substituent, and an alkenyl group that may have a substituent. R ¹ and R ² may be bonded to form part of the ring structure.

In the case where R ¹ and R ² in the general formula (1) are an alkyl group which may have a substituent, specific examples thereof include a linear or branched alkyl group having 1 to 32 carbon atoms. Yes, for example, methyl, ethyl, propyl, isopropyl, n-butyl, s-butyl, t-butyl, n-octyl, tridecyl and the like can be mentioned. These alkyl groups may have a substituent. Specific examples of the substituent include a halogen atom, a cycloalkyl group, an alkenyl group, an aryl group, a heterocyclic group, a cyano group, a hydroxyl group, a nitro group, and an alkoxy group. , Aryloxy group, heterocyclic oxy group, silyloxy group, acyloxy group, alkoxycarbonyloxy group, cycloalkyloxycarbonyloxy group, aryloxycarbonyloxy group, carbamoyloxy group, sulfamoyloxy group, alkanesulfonyloxy group, arene Sulfonyloxy group, acyl group, alkoxycarbonyl group, cycloalkyloxycarbonyl group, aryloxycarbonyl group, carbamoyl group, amino group, anilino group, heterocyclic amino group, carbonamido group, alkoxycarbonylamino group, aryl Alkoxycarbonylamino group, a ureido group, a sulfonamido group, a sulfamoylamino group, and imide group.

In the case where R ¹ and R ² in the general formula (1) are an aryl group which may have a substituent, a specific example thereof is an aryl group having 6 to 32 carbon atoms, for example, a phenyl group , 1-naphthyl group, 2-naphthyl group and the like. These aryl groups may have a substituent, and specific examples of the substituent include the same groups as the substituents of the alkyl group.

When R ¹ and R ² in the general formula (1) are an optionally substituted heterocyclic group, specific examples thereof include a 5- to 8-membered heterocyclic group having 1 to 32 carbon atoms. For example, 2-thienyl group, 2-pyridyl group, 4-pyridyl group, 2-furyl group, 2-pyrimidinyl group, 2-benzothiazolyl group, 2-piperazyl group, 2-piperidyl group, 1-imidazolyl group, 1 -A pyrazolyl group, a morpholino group, a 2-benzimidazolyl group, a benzotriazol-2-yl group and the like can be mentioned. These heterocyclic groups may have a substituent, and specific examples of the substituent include the same groups as the substituents of the alkyl group.

When R ¹ and R ² in the general formula (1) are an aralkyl group which may have a substituent, an alkyl group which may have the substituent and an aryl which may have the substituent Examples thereof include benzyl group, phenylethyl group, phenylbutyl group and the like. These aralkyl groups may have a substituent, and specific examples of the substituent include the same groups as the substituents of the alkyl group.

When R ¹ and R ² in the general formula (1) are alkenyl groups which may have a substituent, specific examples thereof include ethenyl group, 1-propenyl group, 2-propenyl group, 1-methylethenyl group. 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-1-propenyl group, 2-methyl-1-propenyl group, 1-methyl-2-propenyl group, 1-pentenyl group, 2- Examples thereof include linear, branched or cyclic alkenyl groups such as a pentenyl group, a 3-pentenyl group, a 1-hexenyl group, a 1-decenyl group, a 2-cyclopentenyl group, and a 2-cyclohexenyl group. These alkenyl groups may have a substituent, and specific examples of the substituent include the same groups as the substituents of the alkyl group.

In the sulfone compound obtained in the present invention, R ¹ and R ² in the general formula (2) may be the same or different, and may have an alkyl group or a substituent which may have a substituent. An aryl group that may be substituted, a heterocyclic group that may have a substituent, an aralkyl group that may have a substituent, and an alkenyl group that may have a substituent. R ¹ and R ² may be bonded to form a part of the ring structure. As specific examples of the alkyl group, aryl group, heterocyclic group, aralkyl group and alkenyl group, those exemplified for the sulfide compound of the general formula (1) can be mentioned in the same manner. Examples of the good substituent include the same substituents as those mentioned for the sulfide compound of the general formula (1).

The niobium carbide used in the present invention can be used as it is without pretreatment of a commercially available one. The amount of niobium carbide used is preferably in the range of 0.001 to 1.0 equivalent, more preferably in the range of 0.01 to 0.5 equivalent, relative to the sulfide compound as the substrate.

The niobium carbide used for the reaction in the present invention can be separated and recovered from the reaction mixture by an operation such as filtration and reused any number of times. It is a very advantageous point in the present invention that niobium carbide itself is not modified or decomposed by the reaction, is insoluble in most reaction solvents and can be recovered almost completely.

The concentration of the hydrogen peroxide solution used in the present invention is preferably 3 to 50%. However, since the risk of explosion increases as the concentration of hydrogen peroxide increases, it is more preferably in the range of 3 to 35%. Moreover, the usage-amount of hydrogen peroxide has the preferable range of 0.9-30.0 equivalent with respect to the sulfide compound which is a substrate, More preferably, it is the range of 1.0-20.0 equivalent.

The reaction solvent used in the present invention is not particularly limited, but preferred solvents include aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, esters, ketones, nitriles, ethers. , Carboxylic acids, halogen solvents, amide solvents and water. Moreover, the reaction solvent illustrated previously can be used also in the mixed system by arbitrary combinations. Of these, particularly preferred solvents are alcohols and nitriles. Specific examples thereof include methanol, ethanol, 1-propanol, isopropanol, and nitriles as alcohols, and acetonitrile and propionitrile. When these reaction solvents are used, particularly high reaction results can be obtained.

In the present invention, the reaction temperature is not particularly limited, but is preferably in the range of −50 to 120 ° C., particularly preferably in the range of −10 to 80 ° C.

In the present invention, the reaction time varies depending on the structure of the sulfide compound, the amount of niobium carbide used, the amount and concentration of hydrogen peroxide used, the reaction temperature, and the like, and is not particularly limited, but ranges from 1 minute to 60 hours. The range of 5 minutes to 48 hours is particularly preferable.

With the reaction system described above, the corresponding sulfone compound can be obtained from the sulfide compound very efficiently by a method that can be carried out industrially and easily using a simple and safe reagent.

The sulfone compound produced according to the present invention has few by-produced impurities and is easily purified. Of course, the sulfone compound can be removed by distillation from the reaction mixture after the reaction, which can be purified by silica gel column chromatography. It is also possible to separate niobium carbide from the reaction mixture by an operation such as filtration and then distill off the reaction solvent used, and then recrystallize it in a suitable organic solvent or water and take it out. Alternatively, when the sulfone compound is crystallized in the state of the reaction mixture, solid-liquid separation is performed, and then the sulfone compound is dissolved in an appropriate solvent, and then the niobium carbide is separated by an operation such as filtration, and then the appropriate organic It can be replaced with a solvent or water and recrystallized. However, the present invention is not limited to the above-described presence / absence of distillation, presence / absence of recrystallization, presence / absence of solid-liquid separation operation, and apparatus used.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. In addition, the niobium carbide used in the examples is manufactured by Kojundo Chemical Laboratory Co., Ltd. The NMR data was measured using JNM-EX400 (400 MHz) manufactured by JEOL Ltd. Mass spectrum data was measured by the EI method using GCMS-QP1100EX manufactured by Shimadzu Corporation.

Example 1 Synthesis of methylphenylsulfone
At room temperature, 124.0 mg (1.0 mmol) of thioanisole was dissolved in 2 ml of ethanol, 4.2 mg (0.04 mmol) of niobium carbide was added, and 518.5 mg (4.5 mmol) of 30% aqueous hydrogen peroxide was added. In addition, the mixture was heated to 60 ° C. and stirred for 2 hours and 45 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 159.7 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 154.2 mg of methylphenylsulfone in a yield of 98.8%. The appearance was a white solid.
< ¹ > H-NMR (CDCl3) [delta]: 3.06 (3H, s), 7.55-7.59 (3H, m), 7.93-7.95 (2H, m).
MS (m / z): 156 (M ^<+> ).

Example 2 Synthesis of Allylphenylsulfone
At room temperature, 151.2 mg (1.0 mmol) of allyl phenyl sulfide was dissolved in 2 ml of methanol, 4.2 mg (0.04 mmol) of niobium carbide was added, and then 512.4 mg (4.5 mmol) of 30% aqueous hydrogen peroxide. The mixture was heated to 60 ° C. and stirred for 3 hours and 15 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated on a rotary evaporator to obtain 187.2 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 179.2 mg of allylphenylsulfone in a yield of 97.6%. The appearance was a colorless oil.
¹ H-NMR (CDCl 3) δ: 3.80-3.82 (2H, d, J = 7.3 Hz), 5.12-5.34 (2H, dd, J = 17.0, 10.2 Hz) , 5.74-5.83 (1H, m), 7.53-7.57 (3H, m), 7.86-7.89 (2H, m).
MS (m / z): 183 (M ^<+> ).

Example 3 Synthesis of p-methoxyphenylmethylsulfone
At room temperature, 153.9 mg (1.0 mmol) of p-methoxythioanisole was dissolved in 2 ml of ethanol, 4.0 mg (0.04 mmol) of niobium carbide was added, and 514.8 mg (4. 5 mmol) was added, and the mixture was heated to 60 ° C. and stirred for 5 hours. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 186.0 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 182.7 mg of p-methoxyphenylmethylsulfone in a yield of 98.2%. The appearance was a white solid.
¹ H-NMR (CDCl 3) δ: 3.03 (3H, s), 3.89 (3H, s), 7.01-7.04 (2H, dt, J = 8.8 Hz), 7.86- 7.90 (2H, dt, J = 9.0 Hz).
MS (m / z): 186 (M ^<+> ).

Example 4 Synthesis of p-acetylphenylmethylsulfone
At room temperature, 167.1 mg (1.0 mmol) of p- (methylthio) acetophenone was dissolved in 2 ml of ethanol, and 4.1 mg (0.04 mmol) of niobium carbide was added thereto. 0.5 mmol), and the mixture was heated to 60 ° C. and stirred for 22 hours. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 207.4 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 171.3 mg of p-acetylphenylmethylsulfone in a yield of 90.1%. The appearance was a white solid.
¹ H-NMR (CDCl 3) δ: 2.67 (3H, s), 3.08 (3H, s), 8.04-8.06 (2H, d, J = 8.5 Hz), 8.12- 8.14 (2H, d, J = 8.5 Hz).
MS (m / z): 198 (M ^<+> ).

Example 5 Synthesis of benzyl phenyl sulfone
At room temperature, 200.4 mg (1.0 mmol) of benzyl phenyl sulfide was dissolved in 2 ml of ethanol, 4.2 mg (0.04 mmol) of niobium carbide was added, and then 512.1 mg (4.5 mmol) of 30% aqueous hydrogen peroxide. The mixture was heated to 60 ° C. and stirred for 4 hours. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 230.2 mg of a crude product. The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 224.0 mg of benzylphenylsulfone in a yield of 96.0%. The appearance was a white solid.
¹ H-NMR (CDCl3) δ: 4.38 (2H, s), 7.07-7.08 (2H, m), 7.23-7.29 (3H, m), 7.42-7. 46 (2H, m), 7.59-7.64 (3H, m).
MS (m / z): 232 (M ^<+> ).

Example 6 Synthesis of benzylmethylsulfone
At room temperature, 138.1 mg (1.0 mmol) of benzyl methyl sulfide was dissolved in 2 ml of ethanol, 4.1 mg (0.04 mmol) of niobium carbide was added, and then 520.0 mg (4.5 mmol) of 30% aqueous hydrogen peroxide. The mixture was heated to 60 ° C. and stirred for 1 hour and 45 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 174.0 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 169.2 mg of benzylmethylsulfone in a yield of 99.0%. The appearance was a colorless solid.
< ¹ > H-NMR (CDCl3) [delta]: 2.74 (3H, s), 4.24 (2H, s), 7.41-7.45 (5H, m).
MS (m / z): 170 (M ^<+> ).

Example 7 Synthesis of dibenzylsulfone
At room temperature, 215.7 mg (1.0 mmol) of dibenzyl sulfide was dissolved in 2 ml of ethanol, 4.1 mg (0.04 mmol) of niobium carbide was added, and then 521.1 mg (4.5 mmol) of 30% aqueous hydrogen peroxide. The mixture was heated to 60 ° C. and stirred for 1 hour and 45 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated on a rotary evaporator to obtain 265.2 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 240.7 mg of dibenzylsulfone in a yield of 97.6%. The appearance was a white solid.
< ¹ > H-NMR (CDCl3) [delta]: 4.19 (4H, s), 7.37-7.41 ( ¹⁰ H, m).
MS (m / z): 246 (M ^<+> ).

Example 8 Synthesis of diphenylsulfone
At room temperature, 186.0 mg (1.0 mmol) of diphenyl sulfide was dissolved in 2 ml of ethanol, 4.1 mg (0.04 mmol) of niobium carbide was added, and then 511.0 mg (4.5 mmol) of 30% aqueous hydrogen peroxide was added. In addition, the mixture was heated to 60 ° C. and stirred for 6 hours and 30 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 5 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 230.7 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 205.4 mg of diphenylsulfone, yield 94.2%. The appearance was a white solid.
¹ H-NMR (CDCl 3) δ: 7.48-7.58 (6H, m), 7.90-7.94 (4H, m).
MS (m / z): 218 (M ^<+> ).

Example 9 Synthesis of bis (4-methoxyphenyl) sulfone
At room temperature, 246.7 mg (1.0 mmol) of bis (4-methoxyphenyl) sulfide was dissolved in 2 ml of ethanol, 4.1 mg (0.04 mmol) of niobium carbide was added, and then 510.0 mg of 30% aqueous hydrogen peroxide. (4.5 mmol) was added, and the mixture was heated to 60 ° C. and stirred for 4 hours 30 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated on a rotary evaporator to obtain 286.7 mg of a crude product. The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 266.4 mg of bis (4-methoxyphenyl) sulfone in a yield of 95.8%. The appearance was a white solid.
¹ H-NMR (CDCl 3) δ: 3.83 (6H, s), 6.92-6.96 (4H, dt, J = 8.8 Hz), 7.82-7.86 (4H, dt, J = 8.5 Hz).
MS (m / z): 278 (M ^<+> ).

Example 10 Synthesis of methylphenylsulfone
At room temperature, 123.1 mg (1.0 mmol) of thioanisole was dissolved in 6 ml of ethanol, 10.5 mg (0.1 mmol) of niobium carbide was added, and 518.0 mg (4.5 mmol) of 30% hydrogen peroxide solution was added. In addition, the mixture was stirred at room temperature for 1 hour and 40 minutes. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 160.0 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methylphenyl sulfoxide and thioanisole as a raw material were not detected on ¹ H-NMR, and the production rate of methylphenylsulfone was 100%.

Example 11 Synthesis of methylphenylsulfone
The same operation as in Example 10 was carried out except that the niobium carbide was 8.4 mg (0.08 mmol) and the stirring time was 3 hours to obtain 158.5 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methylphenyl sulfoxide and thioanisole as a raw material were not detected on ¹ H-NMR, and the production rate of methylphenylsulfone was 100%.

Example 12 Synthesis of methylphenylsulfone
The same operation as in Example 10 was carried out except that 8.4 mg (0.08 mmol) of niobium carbide, the reaction temperature was 60 ° C., and the stirring time was 2 hours, to obtain 160.1 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methylphenyl sulfoxide and thioanisole as a raw material were not detected on ¹ H-NMR, and the production rate of methylphenylsulfone was 100%.

Example 13 Synthesis of methylphenylsulfone
The same operation as in Example 10 was carried out except that 6.3 mg (0.06 mmol) of niobium carbide was used and the stirring time was 5 hours, to obtain 158.0 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methylphenyl sulfoxide and thioanisole as a raw material were not detected on ¹ H-NMR, and the production rate of methylphenylsulfone was 100%.

Example 14 Synthesis of methylphenylsulfone
The same operation as in Example 10 was carried out except that 6.3 mg (0.06 mmol) of niobium carbide, reaction temperature was 45 ° C., and stirring time was 3 hours, to obtain 158.8 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methyl phenyl sulfoxide: methyl phenyl sulfone = 2: 98 (molar ratio basis). Note that thioanisole as a raw material was not detected on ¹ H-NMR.

Example 15 Synthesis of methylphenylsulfone
The same operation as in Example 10 was carried out except that niobium carbide was 2.1 mg (0.02 mmol), the reaction temperature was 60 ° C., and the stirring time was 7 hours, to obtain 159.1 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. as a result. Methyl phenyl sulfoxide and thioanisole as a raw material were not detected on ¹ H-NMR, and the production rate of methyl phenyl sulfone was 100%.

(Example 16 Synthesis of methylphenylsulfone, separation and recovery of niobium carbide)
At room temperature, 621.0 mg (5.0 mmol) of thioanisole was dissolved in 10 ml of ethanol, 21.0 mg (0.2 mmol) of niobium carbide was added, and then 2580.0 mg (22.5 mmol) of 30% hydrogen peroxide solution was added. In addition, the mixture was heated to 60 ° C. and stirred for 2 hours and 30 minutes. Thereafter, the reaction mixture was filtered through a Kiriyama funnel with filter paper, and niobium carbide was separated on the filter paper. The separated niobium carbide was 21.0 mg (100% recovery rate) when weighed after drying under reduced pressure. The niobium carbide recovered by this series of operations was repeatedly used for the reaction in Example 17 described later.

On the other hand, the reaction mixture after filtering niobium carbide was cooled to room temperature, and 20 ml of a saturated aqueous sodium thiosulfate solution was added. Thereafter, the mixture was extracted 3 times with 15 ml of ethyl acetate. The organic layers were pooled, washed 3 times with 10 ml of water and then 3 times with 10 ml of saturated brine, and then dried over anhydrous magnesium sulfate. Then, ethyl acetate was concentrated with a rotary evaporator to obtain 731.0 mg of a crude product. The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 720.1 mg of methylphenylsulfone in a yield of 92.2%. The appearance was a white solid. ¹ H-NMR spectrum and MS spectrum were completely in agreement with Example 1.

Example 17 Synthesis of methylphenylsulfone by reusing niobium carbide
Using 21.0 mg of niobium carbide recovered in Example 16, the same operation as in Example 16 was repeated three times to obtain methylphenylsulfone. Each acquisition amount and yield were as follows.
Reuse 1st Acquisition amount 696.6mg, Yield 89.2%
Second reuse: Acquired 751.4mg, Yield 96.2%
3rd reuse Acquisition amount 759.2mg Yield 97.2%
In all cases, the ¹ H-NMR spectrum and the MS spectrum completely coincided with the data of Example 1.

(Reference Example 1 Synthesis of methylphenylsulfone, reaction results without using niobium carbide)
At room temperature, 123.1 mg (1.0 mmol) of thioanisole was dissolved in 6 ml of ethanol, and 518.0 mg (4.5 mmol) of 30% aqueous hydrogen peroxide was added, followed by stirring at 60 ° C. for 18 hours. Thereafter, 6 ml of a saturated aqueous sodium thiosulfate solution was added, the aqueous layer and the organic layer were separated, and extracted three times with 3 ml of ethyl acetate. The organic layers were pooled, washed with saturated brine, and dried over anhydrous magnesium sulfate. Ethyl acetate was concentrated by a rotary evaporator to obtain 158.3 mg of a crude product. ¹ H-NMR (CDCl3) of the obtained crude product was measured, and the production ratio was calculated from the proton integral intensity ratio of methylphenylsulfoxide and methylphenylsulfone. As a result, methyl phenyl sulfoxide: methyl phenyl sulfone = 6: 94 (based on molar ratio), and the sulfonation reaction was not completed even after 18 hours of reaction. Note that thioanisole as a raw material was not detected on ¹ H-NMR.

This is an industrially advantageous production method of a sulfone compound that is extremely useful chemically or biologically.

Claims (1)

In a method for producing a sulfone compound represented by the following general formula (2) by oxidizing a sulfide compound represented by the following general formula (1) with hydrogen peroxide, niobium carbide is used as a catalyst. A method for producing a sulfone compound.

(In General Formula (1), R ¹ and R ² may be the same or different, and may be an alkyl group which may have a substituent, an aryl group which may have a substituent, or a substituent. Represents an optionally substituted heterocyclic group, an optionally substituted aralkyl group, an optionally substituted alkenyl group, and R ¹ and R ² are bonded to form a ring structure. It may form part.)

(In the general formula (2), R ¹ and ^{R 2} have the same meanings as R ¹ and ^{R 2} in the general formula (1).)