Title of Invention

METHOD FOR PRODUCING ALPHA-KETOALDEHYDE COMPOUND [0001]

The present invention relates to a method for producing an a-ketoaldehyde compound, and so on.

Background Art

[0002]

α-ketoaldehyde compounds are known to be used for synthesis of compounds useful in the treatment of diabetes and the like (For example,, see Patent Document 1) .

[0003]

As a method, for producing an α-ketoaldehyde compound, for example, Non-Patent Document 1 describes a method of oxidizing 2-aryl-2-oxoethanol , which is a 2-oxo-primary alcohol compound, in the presence of a catalyst of copper acetate to obtain 2-aryl-2-oxoacetaldehyde, and Patent Document 2 describes a method of oxidizing 4- (methylthio) -2-oxo-l-butanol , which is a 2-oxo-primary alcohol compound, in the presence of a catalyst of copper acetate to obtain 4- (methylthio) -2-oxo-l-butanal . In addition, for example, Non-Patent Document 2 and Patent Document 3 describe a method of gas-phase Oxidizing

2-oxo-l-propanol, which is a 2-oxo-primary alcohol compound, in the presence of a catalyst of phosphomolybdic acid to obtain . methylglyoxal . Citation List

Patent Literature

[0004]

PLT1: JP 2006-501284 A■

PLT2: JP 2008-44929 A (Example 8)- PLT3: JP 2000-336055 A (Example 1)

Non Patent Literature

[0005]

NPLT1: Org. Pro. Res. Dev. , Vol .14 , pp. 1254-1263 (2010) Supplementary Data pp. 14

NPLT2: Bull. Chem. Soc. Jpn., Vol.72, pp. 2143-2148 (1999) Summary of Invention

Technical Problem

[0006]

An object of the present invention is to provide a new method for producing an a-ketoaldehyde compound from a 2-oxo-primary alcohol compound.

Solution to Problem

[0007]

The present inventor has made intensive investigations to accomplish the present invention.

[0008]

Namely, the present invention is as follows. [1] A method for producing an a-ketoaldehyde compound comprising a step of oxidizing a 2-oxo-primary alcohol compound in the presence of platinum, a platinum compound, iron or an iron compound.

[2] The method according to [1] , wherein the step of oxidizing a 2-oxo-primary alcohol compound is carried out in the presence of oxygen.

[3] The method according to [1] or [2], wherein the step of oxidizing a 2-oxo-primary alcohol compound is carried out in the presence of a solvent.

[4] The method according to [3], wherein the solvent is an alcohol.

[5] The method according to any one of [1] to [4], wherein platinum, a platinum compound, iron or an iron compound is supported on a carrier.

^• [6] The method according to [5], wherein the carrier is activated carbon.

[7] The method according to any one of [1] to [6], wherein the 2-oxo-primary alcohol compound is a compound represented by the formula (la) ,

R ^a -C-CH ₂ OH _(1a)

0

wherein R ^a is. a Ci-C6 alkyl group which may have a substituent or a C6-C ₂₀ aryl group which may have a substituent,

and the α-ketoaldehyde compound is a compound represented by the formula (2a) , R ^a —C-CHO

II ^(2a)

o

wherein R ^a is the same as the above,

Advantageous Effects of Invention

[0009]

The present invention can provide a new method for producing an a-ketoaldehyde compound from a 2-oxo-primary alcohol compound. Description of Embodiments

[0010]

Hereinafter, the present invention will be described in detail.

In the present description, the numerical number after "C" in the definition of each substituent indicates the number of carbons in each group.

[0011]

A method for producing an a-ketoaldehyde compound according to the present invention comprises a step of oxidizing a 2-oxo-primary alcohol compound in the presence of platinum, a platinum compound, iron or an iron compound. By oxidizing a 2-oxo-primary alcohol compound in the presence of platinum, a platinum compound, iron or an iron compound, the 2-oxo-primary alcohol compound is converted into an α-ketoaldehyde compound. Hereinafter,- the oxidation of the 2-oxo-primary ^' alcohol compound may be referred to as "the present reaction". [0012]

In the present invention, the 2-oxo-primary alcohol compound can be a 2-oxoethanol which may have a substituent at a second position. Examples of the 2-oxo-primary alcohol compound include a compound represented by the formula (1),

(hereinafter, this may be referred to as a compound (1) ) . The use of the compound (1) as the 2-oxo-primary alcohol compound can produce a compound represented by the formula (2),

R—C—CHO

II ⁽²⁾

o

(hereinafter, this may be referred to as a compound ^' (2) ) as the a-ketoaldehyde compound.

[0013]

In the formulae (1) and (2) , R is a hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a hydrogen atom.

[0014]

Examples of the hydrocarbon group which may have a substituent include an alkyl group which may have a substituent, an alkenyl group which may have a substituent and an aryl group which may have a substituent.

[0015]

In the alkyl group which may have a substituent, examples of the alkyl group include a straight or branched C1-C12 alkyl group such as a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl and decyl group, and a cyclic C3-C12 alkyl group such as a cyclopropyl,

2 , 2-dimethylcyclopropyl, cyclopentyl, cyclohexyl and menthyl group. Examples of the substituent which the alkyl group may have include a group selected from the following Group Gl .

[0016]

<Group Gl>

a C1-C10 alkoxy group which may have a fluorine atom, a C7-C20 aralkyloxy group which may have a C1-C10 alkoxy group, a C7-C20 aralkyloxy group which has a C6-C10 aryloxy group, a C6-C10 aryloxy group which may have a C1-C10 alkoxy group, a C6-C10 aryloxy group which has a C ₆ -Ci ₀ aryloxy group, a C ₂ -Cio acyl. group which may have a C1-C10 alkoxy group, a C1-C10 alkylthio group,

a C2-C10 alkoxycarbonyl group,

a C6-C20 aryl group,

a C5-C20 heteroaryl group,

and

a halogen .atom.

[0017]

Examples of the C1-C10 alkoxy group which may have a fluorine atom in Group Gl include a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy and trifluoromethyloxy group. ^■

[0018]

Examples of the C7-C20 aralkyloxy group which may have a 1-C10 alkoxy group in Group Gl include a benzyloxy, 4-methylbenzyloxy and 4-methoxybenzyloxy group.

[0019]

Examples of the C7-C20 aralkyloxy group which has a C6-C10 aryloxy group in Group Gl include a 3-phenoxybenzyloxy group.

[0020]

Examples of the C6-C10 aryloxy group which may have a C1-C10 alkoxy group in Group Gl include a phenoxy, 2-methylphenoxy, 4-methylphenoxy and 4-methoxyphenoxy group.

[0021]

Examples of the C ^' 6-Cio aryloxy group which has a C6-C10 aryloxy group in Group Gl include a 3-phenoxyphenoxy group.

[0022]

Examples of the C ₂ -Ci ₀ acyl group which may have a C1-C10 alkoxy group in Group Gl include an acetyl, propionyl, benzylcarbonyl , 4-methylbenzylcarbonyl ,

4-methoxybenzylcarbonyl, benzoyl, 2-methylbenzoyl,

4-methylbenzoyl and 4-methoxybenzoyl group.

[0023]

Examples of the C1-C10 alkylthio group in Group Gl include a methylthio, ethylthio and isopropylthio group.

[0024]

Examples of the C ₂ -Ci ₀ alkoxycarbonyl group in Group Gl include a methoxycarbonyl and ethoxycarbonyl group.

[0025]

Examples of the C ₆ -C2o aryl group in Group Gl include a phenyl, 1-naphthyl and 2-naphthyl group..

[0026] Examples of the C ₅ -C ₂ o heteroaryl group in Group- Gl include a 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 3-quinolyl and 4-quinolyl group.

[0027]

Examples of the halogen atom in Group- Gl include a fluorine, chlorine and bromine atom.

[0028]

Examples of the alkyl group which has a group selected from Group Gl include -a chloromethyl , fluoromethyl , trifluoromethyl , methoxymethyl, ethoxymethyl, 1-methoxyethyl, 2-methoxyethyl, methoxycarbonylmethyl , phenylmethyl , 2-pyridylmethyl ,

3-pyridylmethyl ,

1-ethoxycarbonyl-2 , 2-dimethyl-3-cyclopropyl and

2-methylthioethyl group.

[0029]

In the alkenyl group which may have a substituent , examples of the alkenyl group include a straight, branched or cyclic C ₂ -Ci2 alkenyl group such as a vinyl, 1-propenyl, 1-butenyl, 2-methyl-l-propenyl and 1-cyclohexenyl grou . Examples of the- - substituent which the alkenyl group may have include a group selected from the above Group Gl .

[0030] -

Examples of the alkenyl group which has a group selected from Group Gl include a 2-chlorovinyl and

2-trifluoromethylvinyl group.

[0031]

In the aryl group which may have a substituent, examples of the aryl group include a C6-C20 aryl group such as a phenyl, 2-methylphenyl , 4 -methylphenyl , l-naphthyl,- 2-naphthyl and styryl group. Examples of the substituent which the aryl group may have include a group selected from the following Group G2.

[0032]

<Group G2>

a C1-C10 alkoxy group which may have a fluorine atom or a C1-C10 alkoxy group,

a C ₆ -C ₁₀ aryloxy group which may have a C1-C10 alkoxy group, a C ₆ -Cio aryloxy group which has a C ₆ -Cio aryloxy group, a C2-Cio-acyl group which may have a C1-C10 alkoxy group, a Ci-C ₆ alkylenedioxy group,

a nitro group,

and

a halogen atom.

[0033]

Examples of the C1-C10 alkoxy group which may have a fluorine atom or a ^■ C1-C10 alkoxy group in Group G2 include a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, cyclopentyloxy,

fluoromethoxy, trifluoromethoxy, methoxymethoxy,

ethoxymethoxy and methoxyethoxy group.

[0034]

Examples of the C ₆ -Cio aryloxy group which may have a C1-C10 alkoxy group in Group G2 include a phenoxy, 2-methylphenoxy, 4 -methylphenoxy and 4-methoxyphenoxy group.

[0035] Examples of the C ₆ -Cio aryloxy group which has a C6-C10 aryloxy group in Group G2 include a 3-phenoxyphenoxy group.

[0036]

Examples of the C ₂ -Cio acyl group which may have a Ci-Cio alkoxy group in Group G2 include an acetyl, propionyl, benzylcarbonyl , 4-methylbenzylcarbonyl and

4-methoxybenzylcarbonyl group.

[0037]

Examples of the Ci-C ₆ alkylenedioxy group in Group G2 include a methylenedioxy and ethylenedioxy group.

[0038]

Examples of the halogen atom in Group G2 include a fluorine and chlorine atom.

[0039]

Examples of the aryl group which has a group selected from Group G2 include. a 4-chlorophenyl, 4-methoxyphenyl and 3-phenoxyphenyl group.

[0040]

In the heterocyclic group which may have a substituent, examples of the heterocyclic group include a C -C10 heteroaryl group having at least one hetero atom such as a nitrogen, oxygen and sulfur atom, and specific examples thereof include a 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furyl, 3-furyl,

5-methyl-2-furyl and. 2-chloro-3-pyridinyl group.

[0041]

In the formulae (1) and (2) , R is preferably a Ci-C ₆ alkyl group which may have a substituent or a C ₆ -C ₂ o aryl group which may have a substituent.

[0.042]

The 2-oxo-primary alcohol compound is preferably a compound represented by the formula (la),

R ^a -C-CH ₂ OH (la)

O

wherein R ^a is a Ci~C6 alkyl group which may have a substituent or a C ₆ -C ₂ o■ aryl group which may have a substituent,

and the a-ketoaldehyde compound is preferably a compound represented by the formula (2a) ,

R ^a —C-CHO , ₉ _,

o

wherein R ^a is the same as the above.

[0043]

In the Ci-C ₆ alkyl group which may have a substituent represented by R ^a in the formulae (la) and (2a), examples of the Ci-C ₆ alkyl group include a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl and pentyl group. Examples of the substituent which the Ci-C ₆ alkyl group may have include a group selected from the above Group Gl .

[0044]

In the C6-C20 aryl group which may have a substituent represented by R ^a in the formulae (la) and (2a), examples of the C6-C20 aryl group include a phenyl, 2-methylphenyl ,

4-methylphenyl, 1-naphthyl, 2-naphthyl and styryl group. Examples of the substituent which the aryl group may have include a group selected from the above Group G2. [0045]

Specific examples of the 2 -oxo—primary alcohol compound include 2-phenyl-2-oxoethanol ,

2- ( 4-chlorophenyl ) -2-oxoethanol,

2- ( 4-methylphenyl ) -2-oxoethanol,

2- (2-methoxyphenyl) -2-oxoethanol,

2- (2, 5-dimethoxyphenyl ) -2-oxoethanol,

2- ( 3-fluorophenyl ) -2-oxoethanol,

2- (2, 4-dichlorophenyl ) -2-oxoethanol,

2- (1-naphthyl) -2-oxoethanol, 2- (2-pyridyl) -2-oxoethanol, 2-vinyl-2-oxoethanol, 2-oxoethanol, 2-oxo-l-propanol,

2-oxo-l-butanol, 2-oxo-l-pentanol, 2-oxo-l-hexanol ,

'2^oxo-l-heptanol , 2-oxo-l-octanol ,

l-cyclohexyl-2-hydroxyethanone and

4- (methylthio) -2-oxo-l-butanol .

[0046>

These 2-oxo-primary alcohol compounds may be commercially available products or those produced by known methods .

Examples of such known methods include a method of reacting an aldehyde with paraformaldehyde in the presence of a thiazolium salt and a base (for example, JP 2008-44929 A).

[0047]-

Platinum, a platinum compound, iron or an iron compound for use in the present invention is not limited as long as it has oxidation activity, but preferably one in fine particles, more preferably one supported on a carrier. Hereinafter, platinum, a platinum compound, iron or an iron compound which is supported on a carrier may be referred to as a "supported catalyst". Examples of the carrier of the supported catalyst include at least one selected from the group consisting of activated carbon, alumina, silica, zeolite, diatomite and zirconium oxide.. It is preferred for such a carrier to have a larger surface area in terms of enhanced reactivity. Examples of the carrier include preferably activated carbon and zirconium oxide, more preferably activated carbon.

[0048]

The present reaction is carried out in the presence of platinum, a platinum compound, iron or an iron compound. The present invention may.be carried out in the presence of both of platinum and iron. The present invention may be carried out in the presence of both of a platinum compound and iron. The present invention may. be carried out in the presence of both of platinum and an iron compound. The present invention may be carried out in the presence of both of a platinum compound and an iron compound.

[0049]

Examples of the platinum compound include a nitrate, sulfate, . formate, acetate, carbonate, halide, acid halide, hydroxide and oxide of platinum, and a complex of platinum and acetylacetone or the like. The. platinum compound may be a compound with a valence of 0, 2, 4 or 6.

[0050]

Examples of the iron compound include a nitrate, sulfate, formate, acetate, carbonate, halide, acid halide, hydroxide and oxide of iron, and a complex of iron and acetylacetone, carbon - monoxide or the like. The iron compound may be a compound with a valence of 2 or 3.

[0051]

The supported catalyst is preferably one in which platinum, a platinum compound, iron or an iron compound is supported on the above-mentioned carrier.

. [0052]

The supported catalyst may be a commercially available product or may be prepared by using a solution containing platinum nanocolloid, the above-mentioned platinum compound, iron nanocolloid or the above-mentioned iron compound and allowing the■ above-mentioned carrier to support platinum, a platinum compound, iron or an iron compound by a coprecipitation method or an impregnation method, and then subjecting it to calcination. When used, the supported catalyst prepared by calcination may or may not be reduced with hydrogen. The support may be added into the reaction system without previously preparing the supported catalyst , and in such case, preferable support is activated carbon.

[0053]

When the supported catalyst is used, the amount of platinum, a platinum compound,- iron or an iron compound to be supported in the supported catalyst is, f-or example, in the range of 0.01% to 10% by weight, preferably 0.1% to 5% by weight based on the carrier.

[0054] ^■ . The amount of platinum, a platinum compound, iron or an iron compound to be used is preferably in the range of 0.00001 to 0.5 mol based on 1 mol of a 2-oxo-primary alcohol compound. When the supported catalyst is used, the amount of the supported catalyst to be used varies depending on the amount of platinum, a platinum compound, iron or an iron compound to be supported and its type of usage; however, it is in the range of 0.1% to 200% by weight based on a 2-oxo-primary alcohol compound.

[0055]

The present reaction is preferably carried out in the presence of oxygen. The oxygen used in the present reaction may be an oxygen gas, an oxygen gas diluted with an inert, gas such as nitrogen, or oxygen contained in the air. Also, oxygen contained in the air may be diluted with an inert gas such as nitrogen. The amount of oxygen to be used is preferably in the range of 1 to 100 mol based on 1 mol of a 2-oxo-primary alcohol compound .

[0056]

The present reaction is preferably carried out in the presence of a solvent. The solvent is not limited as long as it is inert to the present reaction, and examples thereof include preferably an alcohol or an aromatic solvent, more preferably an alcohol. Examples of the alcohol include an alcohol having 1 to 6 carbon atoms such as methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol , n-pentanol and n-hexanol , preferably methanol and ethanol , more preferably methanol. Examples of the aromatic solvent include toluene,. xylene, chlorobenzene and fluorobenzene . These solvents may be a mixture with a small amount of water or other organic solvents. The amount of the solvent to be used is not limited, but preferably 1 part by weight or more based on 1 part by weight of a 2-oxo-primary alcohol compound in terms of operability and 100 parts by weight or less in terms of practicality.

[0057]

There is no limitation on the order of mixing reaction reagents in the present reaction. As a preferred aspect, there may be provided a method of mixing a 2-oxo-primary alcohol compound, platinum, a platinum compound, iron or an iron compound, and a solvent, and thereafter mixing the obtained mixture with oxygen.

[0058]

The present reaction is carried out under any conditions of reduced pressure, normal pressure or increased pressure, but preferably under normal pressure or increased pressure.

[0059]

The reaction temperature at which the present reaction is carried out varies depending on the amount of platinum, a platinum compound, iron or an iron compound to be used, the amount of oxygen to be used, and the like, but preferably in the range of 0 to 150°C, more preferably 20 to 100°C. When the reaction temperature is lower than 0°C, · the present reaction tends to proceed at a lower rate. When the reaction temperature is higher than 150°C, the present reaction tends to have a lower selectivity . [0060]

The degree of proceeding of the present reaction can be confirmed by analysis means ^" such as gas chromatography, high-performance liquid chromatography, thin-layer

chromatography, nuclear magnetic resonance spectral analysis and infrared absorption spectral analysis.

[0061]

After completion of the present reaction, the obtained reaction mixture is, for example, filtered to remove platinum, a platinum compound, iron or an iron compound from the reaction mixture, _. and then subjected to distillation to remove the solvent, so that an a-ketoaldehyde compound can be extracted.. The extracted α-ketoaldehyde compound can be purified by distillation, column chromatography, crystallization or other purification means.

[0062]

Examples of the thus-obtained a-ketoaldehyde compound include 2-oxo-2-phenylethanal ,

2- OXO-2- ( 4-chlorophenyl ) ethanal,

2- OXO-2- (4-methylphenyl) ethanal,

2- OXO-2- ( 2-methoxyphenyl ) ethanal,

2- OXO-2- (2, 5-dimethoxyphenyl) ethanal,

2-OXO-2- ( 3-fluorophenyl ) ethanal,

2-ΟΧΟ-2- (2, 4-dichlorophenyl) ethanal,

2-OXO-2- (1-naphthyl) ethanal, 2-oxo-2- (2-pyridyl) ethanal, 2-oxo-2-vinylethanal, 2-oxo-l-ethanal , 2-oxo-l-propanal, 2- xo-l-butanal , 2-oxo-l-pentanal, 2-oxo-l-hexanal, 2-oxo-l-heptanal, . 2-oxo-l-octanal , cyclohexylglyoxal and 4- (methylthio) -2-oxo-l-butanal .

Example

[0063]

The present invention will be described in more detail below with reference to Examples.

[0064]

<Example 1>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 100 mg of 1 wt% Pt - 0.1 wt% Fe-supported activated carbon (product manufactured by Evonik Degussa Corporation, water content: 50% by weight) and 3 g of methanol . Then, the reaction tube was pressurized to 2 MPa with air ^" . The obtained mixture was stirred at 60°C for 6 hours. The reaction mixture was cooled to room temperature and allowed to be under normal pressure, by release of the pressure, and then filtered. The obtained . filtrate was analyzed by the gas chromatography internal standard method. The yield of 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 63% . Here, 20% of 4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered.

[0065]

<Example. 2>

Production of 4- (methylthio) -2-oxo-l-butanal : Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 100 mg of 3 wt% Pt - 0.5 wt%- Fe-supported activated carbon (product manufactured by Evonik Degussa Corporation, water content: 50% by weight) and 3 g of methanol. Then, the reaction tube was pressurized to 2 Pa with air . The obtained mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of

4-,(methylthio) -2-oxo-l-butanal was calculated, and it was 62% .

[0066]

<Example 3>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-but ^' anol, 100 mg of 1 wt% Pt-supported activated carbon (product manufactured by N. E. Chemcat Corporation, water content: 50% by weight) and 3 g of methanol.

Then, the reaction tube was pressurized to 2 MPa with air. The obtained mixture was stirred at 60°C for 6 hours. The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of

4- (methylthio) -2-oxo-l-butanal was calculated, and it was 25% . Here, 42% of 4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered.

[0067]

<Example 4>

Production of 2-oxo-2-phenylethanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

2-phenyl-2-oxoethanol, 100 mg of 1 wt% Pt - 0.2 wt% Fe-supported activated carbon, (product manufactured by ^' Evonik Degussa Corporation, water content: 50% by weight) and 3 g of methanol. Then, the reaction tube was pressurized to 2 MPa with air. The obtained mixture was stirred at 60°C for 6 hours. The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield, of 2-oxo-2-phenylethanal was calculated, and it was 91%.

[0068]

<Example 5>

Production of methylglyoxal :

Into. a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of 2-hydroxyacetone, 100 mg of 1 wt% Pt - 0.2 wt% Fe-supported activated carbon (product manufactured by Evonik . Degussa Corporation, water content: 50% by weight) and 3 g of methanol . Then, the reaction tube was pressurized to 2 MPa with air. The obtained, mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of methylglyoxal was calculated, and it was 18%.

[0069]

<Reference Example 1>

Preparation of 0.5 wt% Pt-supported activated carbon:

Into a 500 mL flask equipped with a magnetic rotor were charged 9.0 g of activated carbon and 200 g of acetonitrile, and the mixture was stirred in a nitrogen atmosphere at room temperature. To the obtained slurry was added dropwise, over 2 hours, a solution in which ^{^} 92 mg of the complex

bis (acetylacetonate) platinum (II ) was dissolved in 50 g of acetonitrile, and thereafter the mixture was stirred for 2 hours . The obtained mixture was transferred to an eggplant flask and subjected to distillation to remove acetonitrile with an evaporator, followed by drying under reduced pressure at 60°C for 3 hours. Then, the dried matter was calcined at 300°C for 6 hours to obtain 8.3 g of activated carbon with a platinum compound supported thereon.

[0070]

<Reference Example 2>

Preparation of 0.5 wt% Pt - 0.2 wt% Fe-supported activated carbon:

Into a 500 mL flask equipped with a magnetic, rotor were charged 9.0 g of activated carbon and 200 g of acetonitrile, and the mixture was stirred in a nitrogen atmosphere at room temperature. To the obtained slurry was added dropwise, over 2 hours, a solution in which 92 mg of the complex

bis (acetylacetonate) platinum ( II ) and 100 mg of the complex iron (III) acetylacetonate were dissolved in 50 g of

acetonitrile, and thereafter the mixture was stirred for 2 hours . The obtained mixture was transferred to an eggplant flask and subjected to distillation to remove acetonitrile with an evaporator, followed by drying under reduced pressure at 60°C for 3 hours. Then, the dried matter was calcined at 300°C for 6 hours to obtain 8.5 g of activated carbon with a platinum compound and an iron compound supported thereon.

[0071]

<Reference Example 3>

Preparation of 0.2 wt¾ Pt - 0.3 wt% Fe-supported activated carbon:

Into a 500 mL flask equipped with a magnetic rotor were charged- 9.0 g of activated carbon and 200 g of acetonitrile, and the mixture was stirred in a nitrogen atmosphere at room temperature. To the obtained slurry was added, dropwise, over 2 hours, a solution in which 37 mg of the complex

bis (acetylacetonate) platinum ( II) and 160 mg of the complex iron (III) acetylacetonate were dissolved in 50 g of

acetonitrile, and thereafter the mixture was stirred for 2 hours . The obtained mixture was transferred to an eggplant flask, and subjected to distillation to remove acetonitrile with an evaporator, followed by drying under, reduced pressure at 60°C for 3 hours. Then, the dried matter was calcined at 300°C for 6 hours to obtain 8.5 g of activated carbon with a platinum compound and an iron compound supported thereon.

[0072]

<Reference Example 4>

Preparation of 0.2 wt% Fe-supported activated carbon:

Into a 500 mL flask equipped with a magnetic rotor were charged 9.0 g of activated carbon and 200 g of acetonitrile, and the mixture was stirred in a nitrogen atmosphere at room temperature. To the obtained slurry was added dropwise, over 2 hours, a solution in which 100 mg of the complex iron (III) acetylacetonate was dissolved in 50 g of acetonitrile, and thereafter the mixture was stirred for 2 hours. The obtained mixture was transferred to an eggplant flask and subjected to distillation- to remove acetonitrile with an evaporator,

. followed by drying under reduced pressure at 60°C for 3 hours. ^■ Then, the dried matter was calcined at 300°C for 6 hours to obtain 8.4 g of activated carbon with an iron compound supported thereon .

[0073]

<Example- 6>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-but.anol , 50 mg. of the 0.5 wt%

Pt-supported activated carbon (dried product) prepared in Reference Example 1 and 3 g of methanol. Then, the reaction tube was pressurized to 2 MPa with air. The obtained mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, ^" and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 11%. Here, 71% of

4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered.

[0074]

<Example 7>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 50 mg of the 0.5 wt% Pt - 0.2 wt% Fe-supported activated carbon (dried product) prepared in Reference Example 2 and 3 g of methanol. Then, the reaction - tube was pressurized to 0.5 MPa with air . The obtained mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release οί· the pressure, and then filtered. The obtained ■filtrate was analyzed by the gas chromatography internal standard method. The yield of 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 37%. Here, 36% of

4- (methylthio)- -2-oxo-l-butanol used as the raw material was recovered.

[0075] <Example 8>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 50 mg of the 0.2 wt% Pt - 0.3 wt% Fe-supported activated carbon (dried product) prepared in Reference Example 3 and 3 g of methanol. Then, the reaction tube was pressurized to 0.5 MPa- with air. The obtained mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 59%. Here, 30% of

4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered .

[0076]

<Example 9>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 50 mg of the 0.2 wt%

Fe-supported activated carbon (dried product) prepared in Reference Example 4 and 3 g of methanol. Then, the reaction tube was pressurized to 2 MPa with air. The obtained mixture was stirred at 60°C for 6 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 31%. Here, 1% of

4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered .

[0077]

<Example 10>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor were charged 100 mg of

4- (methylthio) -2-oxo-l-butanol, 50 mg of the 0.2 wt%

Fe-supported activated carbon (dried product) prepared in Reference Example 4 and 3 g of chlorobenzene . Then, the ^■ reaction tube was pressurized to 0.5 MPa with air. The obtained mixture was stirred at 60°C for 6 hours. The- reaction mixture was cooled to room temperature and. allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of

4- (methylthio) -2-oxo-l-butanal was calculated, and it was 7%. Here, 87% of 4- (methylthio) -2-oxo-l-butanol used as the raw material was recovered.

[0078]

<Example 11>

Production of 2-oxo-2-phenylethanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor and a Teflon ^R innertube were charged 100 mg of 2-phenyl-2-oxoetanol, 50 mg of the 0.2 wt% Fe-supported activated carbon (dried product) prepared in Reference Example 4 and 3 g of methanol. Then, the reaction tube was pressurized to 0.5 MPa with air. The obtained mixture- was stirred at 60°C for 6 hours. The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. ^' The yield of 2-oxo-2-phenylethanal was calculated, and it was 89%.

[0079]

<Example 12>

Production of 2-oxo-2-phenylethanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor and a Teflon ^R inner tube were charged 100 mg of 2-phenyl-2-oxoetanol, 5 mg of iron powder (available from Nacalai Tesque, Inc.), 25 mg of activated carbon and 1 g of methanol. Then, the reaction tube was pressurized to 0.5 MPa with air. The obtained mixture was stirred at 100°C for 4 hours .

The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered.. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of 2-oxo-2-phenylethanal was calculated,, and it was 56%.

[0080]

<Example 13> Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor and a Teflon ^R inner tube were charged 100 mg of 4- (methylthio) -2-oxo-l-butanol, 5 mg of iron ( III ) oxide, 20 mg of activated carbon (available from Wako Pure Chemical Industries, Ltd., special grade) and 1 g of methanol. Then, the reaction tube was pressurized to 0.5 MPa with air. The obtained mixture was stirred at 100°C for 5 hours . The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered.

The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of

4- (methylthio) -2-oxo-l-butanal was calculated, and it was 37% . The used 4- (methylthio) -2-oxo-l-butanol as a raw material of which amount was 20% of the used amount thereof was recovered.

[0081]

<Example 14>

Production of 4- (methylthio) -2-oxo-l-butanal :

Into a 50 mL pressure-resistant reaction tube equipped with a magnetic rotor and a Teflon ^R inner tube were charged 100 mg of 4- (methylthio) -2-oxo-l-butanol, 50 mg of iron (II) oxide and 1 g of methanol. Then, the reaction tube was pressurized to 0.5 MPa. with air. The obtained mixture was stirred at 60°C for 8 hours. The reaction mixture was cooled to room temperature and allowed to be under normal pressure by release of the pressure, and then filtered. The obtained filtrate was analyzed by the gas chromatography internal standard method. The yield of- 4- (methylthio) -2-oxo-l-butanal was calculated, and it was 21%. The used 4- (methylthio) -2-oxo-l-butanol as a raw material of which amount was 10% of the used amount thereof was recovered.

Industrial Applicability

[0082]

a-ketoaldehyde compounds are known to be used for synthesis of compounds useful in the treatment of diabetes and the like. The present invention is industrially available as a method for producing an α-ketoaldehyde compound.