JP6099133B2 - Method for producing ketol compound - Google Patents

Description

  The present invention relates to a method for producing a ketol compound in which an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group is oxidized under mild conditions to selectively produce a corresponding ketol compound.

  Dihydroxyacetone is a useful compound as a cosmetic or food additive. As a method for producing dihydroxyacetone, a method of producing from glycerol by fermentation using bacteria of the genus Gluconobacter is known. In addition, a method for oxidizing glycerol using a homogeneous catalyst containing expensive palladium is known. Although these methods can produce dihydroxyacetone in high yield, it is difficult to separate reaction products from bacteria and catalysts, and it is difficult to recover and reuse bacteria and catalysts. The problem is that the manufacturing cost increases (Non-Patent Documents 1 and 2).

  As a method for improving the separation between the reaction product and the catalyst, it is conceivable to use a heterogeneous catalyst. Non-patent documents 3 to 5 describe that glycerol is oxidized using a heterogeneous catalyst such as a catalyst obtained by supporting platinum and bismuth on activated carbon or a catalyst obtained by supporting gold or gold and palladium on activated carbon. A process for producing dihydroxyacetone is described. However, the yield of dihydroxyacetone was about 40%. That is, at present, no method has been found for producing dihydroxyacetone selectively and in high yield using a heterogeneous catalyst that can be easily recovered and reused.

J. Ferment. Bioeng. 1994, 78 (5), p351-355 Angew. Chem. Int. Ed. 2010. 49, p9456-9459 Ind. Eng. Chem. Res. 2010, 49, p10876-10882 Appl. Catal., A 1993, 96 (2), p217-228 Appl. Catal., B 2007, 70 (1-4), p637-643

  Accordingly, an object of the present invention is to use a heterogeneous catalyst that can be easily separated and recovered from a reaction product and reused from an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group. Another object of the present invention is to provide a method for selectively producing a corresponding ketol compound in a high yield.

  As a result of intensive investigations by the present inventors to solve the above problems, when a copper catalyst supported on a support is used, an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group is oxidized under a mild condition, and a corresponding ketol is obtained. It was found that the compound can be selectively produced in a high yield, and that the catalyst can be recovered and reused by a simple method such as filtration after the reaction, so that the cost can be reduced. The present invention has been completed based on these findings.

  That is, the present invention provides a method for producing a ketol compound in which a corresponding ketol compound is produced by oxidizing an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group in the presence of a copper catalyst supported on a carrier.

  The present invention also provides the method for producing the ketol compound, wherein the alcohol having at least a primary hydroxyl group and a secondary hydroxyl group is glycerol, and the corresponding ketol compound is dihydroxyacetone.

  The present invention also provides a method for producing the ketol compound, wherein the carrier is boehmite or hydrotalcite.

  The present invention provides a method for producing the above ketol compound using 2,2,6,6-tetramethylpiperidine-N-oxyl and / or benzoquinone together with a copper catalyst.

  The present invention also provides a method for producing the ketol compound, wherein the reaction is carried out in the presence of water and / or nitrile.

  In the present specification, the primary hydroxyl group means that one carbon atom is bonded to the carbon atom to which the hydroxyl group is bonded. A secondary hydroxyl group refers to a group in which two carbon atoms are bonded to a carbon atom to which a hydroxyl group is bonded.

  Since the method for producing a ketol compound of the present invention uses a copper catalyst supported on a carrier, an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group is oxidized under mild conditions to selectively select the corresponding ketol compound. It can be produced in high yield. For example, a large amount of glycerol is produced as a by-product in the production process of biodiesel fuel. When the glycerol is used as a raw material, dihydroxyacetone useful as a cosmetic or food additive can be selectively produced in a high yield. Further, after the reaction, the catalyst and the reaction product can be separated by a simple operation such as filtration, so that the reaction product can be easily purified and the catalyst can be easily recovered and reused. Therefore, the cost can be significantly reduced, and the ketol compound can be provided at a low cost.

[Alcohol having at least a primary hydroxyl group and a secondary hydroxyl group]
The alcohol having at least a primary hydroxyl group and a secondary hydroxyl group of the present invention (hereinafter sometimes referred to as “raw alcohol”) is represented by the following formula (1), for example. In the formula (1), examples of R include an n-valent linear or branched saturated aliphatic hydrocarbon group having 3 to 10 carbon atoms. N is an integer of 2 or more (preferably 2 to 3), for example.
R (OH) _n (1)

  As the raw material alcohol, diols such as 1,2-propanediol and 1,3-butanediol; triols such as glycerol and 1,2,4-butanetriol are preferable, and glycerol is particularly preferable. These can be used alone or in combination of two or more.

[catalyst]
The method for producing a ketol compound of the present invention is characterized by using a copper catalyst supported on a carrier.

  Examples of the carrier include boehmite, hydrotalcite, fluoroapatite, alumina, silica and the like. In the present invention, among them, boehmite or hydrotalcite is preferable and boehmite is particularly preferable in that the corresponding ketol compound can be selectively produced from the raw material alcohol in a high yield.

Boehmite is an alumina monohydrate, represented by AlO (OH) or _{Al 2 O 3 · H 2 O} . Boehmite can be produced, for example, by subjecting alumina trihydrate to heat treatment or hydrothermal treatment in air.

Hydrotalcite is represented by the following formula (2), for example.
[M ^II _1-X M ^III _X (OH) ₂ ] [A ²⁻ _{x / 2} ] · n′H ₂ O (2)
( ^Wherein M ^II is at least one selected from Mg ²⁺ , Fe ²⁺ , Zn ²⁺ , Ca ²⁺ , Li ²⁺ , Ni ²⁺ , Co ²⁺ , Cu ²⁺ , and Mn ^2+. M ^III is at least one trivalent metal selected from Al ³⁺ , Fe ³⁺ , Mn ³⁺ , Ru ³⁺ , x is 0 or more and less than 1 A ²⁻ represents a divalent anion, and n ′ represents an integer of 0 to 30)

As the hydrotalcite in the present invention, a compound represented by Cu ₄ Al ₂ (OH) ₁₂ CO ₃ .n′H ₂ O is particularly preferable. Hydrotalcite is, for example, an aqueous solution of a copper compound such as Cu (NO ₃ ) ₂ , Cu (OAc) ₂ , CuCl ₂ , CuSO ₄ , aluminum nitrate, magnesium nitrate, aluminum chloride, magnesium chloride, aluminum sulfate, magnesium sulfate. one or more aqueous solutions selected from the like, and alkali (e.g., NaOH, Na ₂ basic aqueous solution of CO _3, etc.) was added dropwise at the same time, followed by aging treatment (e.g., 1 at a temperature of 60-80 ° C. It can be produced by a method (simultaneous dropping method) of applying the solution for 5 hours.

Examples of the shape of the carrier include powder, granule, fiber, and molded body. The average pore diameter of the carrier is, for example, about 30 to 120 nm, preferably 50 to 100 nm. The specific surface area of the carrier is, for example, about 100 to 400 m ² / g, preferably 150 to 300 m ² / g.

  Examples of the boehmite include commercial names such as “Boehmite” (manufactured by Wako Pure Chemical Industries, Ltd.), “Boehmite” (manufactured by Daimei Chemical Co., Ltd.), and “boehmite” (manufactured by Aldrich). Goods may be used.

  As hydrotalcite, you may use commercial items, such as brand name "AD500NS" (Tonda Pharmaceutical Co., Ltd. product), for example.

  The aspect of the copper catalyst supported on the carrier is not particularly limited, and examples thereof include a copper simple substance, a copper salt, a copper oxide, a copper hydroxide, or a copper complex. In the present invention, copper (II) salts such as copper nitrate, copper chloride, copper acetate, and copper trifluoromethanesulfonate are particularly preferable.

  The supported amount (metal equivalent amount) of the copper catalyst is, for example, about 0.1 to 10 mmol, preferably 0.5 to 8 mmol, particularly preferably 1 to 5 mmol with respect to 1 g of the support. If the supported amount of the copper catalyst exceeds the above range, the copper catalyst tends to aggregate. On the other hand, if the supported amount of the copper catalyst is less than the above range, sufficient catalytic activity tends to be not obtained.

  As a method for supporting a copper catalyst on a support, the support is contained in a solution (for example, an aqueous solution) in which a copper compound (for example, copper (II) salt such as copper nitrate, copper chloride, copper acetate, copper trifluoromethanesulfonate) is dissolved. It is preferable to carry out by a method (so-called impregnation method) in which the copper compound is impregnated and dried after being soaked. Moreover, it is preferable to control the loading amount by adjusting the concentration of the solution containing the copper compound, the impregnation time on the carrier, the number of impregnation treatments, and the like.

  As temperature at the time of immersing a support | carrier in the solution which melt | dissolves a copper compound, it is about 10-80 degreeC, for example.

  The time for immersing the carrier in the solution dissolving the copper compound is, for example, about 1 to 30 hours, preferably 10 to 24 hours. When the impregnation time is less than the above range, the supported amount of the copper catalyst decreases, and the effect of promoting the oxidation reaction tends to be difficult to obtain.

  The temperature at the time of drying the support | carrier immersed in the solution which melt | dissolves a copper compound is about 30-80 degreeC, for example.

Moreover, after carrying | supporting a copper compound on a support | carrier, you may give a reduction process further. Examples of the reducing agent used for the reduction treatment of the copper compound include borohydride complex compounds such as sodium borohydride (NaBH ₄ ), lithium borohydride (LiBH ₄ ), potassium borohydride (KBH ₄ ), and hydrazine. , Hydrogen (H ₂ ), silane compounds such as dimethylphenylsilane, hydroxy compounds, and the like. Examples of the hydroxy compound include alcohol compounds such as a primary alcohol and a secondary alcohol. The hydroxy compound may be any of monohydric alcohol, dihydric alcohol, polyhydric alcohol (for example, glycerol) and the like.

  The reduction treatment temperature and time are, for example, 0 to 600 ° C. (preferably 0 to 400 ° C.) and about 0.5 to 5 hours (preferably 2 to 4 hours).

  The catalyst (= copper catalyst supported on the carrier) obtained by the above production method may be subjected to a washing treatment (washing with water or an organic solvent), a drying treatment (drying by vacuum drying or the like), and the like.

[Method for producing ketol compound]
The method for producing a ketol compound of the present invention is characterized in that a raw material alcohol is oxidized in the presence of a copper catalyst supported on the carrier to produce a corresponding ketol compound.

  In the present invention, since the copper catalyst supported on the carrier is used, the secondary hydroxyl group of the raw alcohol can be selectively oxidized, and the corresponding ketol compound can be selectively produced. For example, when glycerol is used as the raw alcohol, dihydroxyacetone is used as the corresponding ketol compound, 1,2-propanediol is used as the raw alcohol, acetol is used as the corresponding ketol compound, and 1,3-butanediol is used as the raw alcohol. 1-Hydroxybutan-2-one can be produced as the corresponding ketol compound.

  The usage amount (metal equivalent amount) of the copper catalyst supported on the carrier is, for example, about 0.1 to 50 g, preferably 0.5 to 20 g, particularly preferably 1 to 10 g, per 1 mol of the raw material alcohol. When the amount of the copper catalyst supported on the support is less than the above range, it tends to be difficult to obtain the corresponding ketol compound in high yield.

  For example, molecular oxygen, hydrogen peroxide, peracetic acid, or the like can be used as an oxidizing agent that oxidizes the raw material alcohol. In the present invention, it is preferable to use molecular oxygen (particularly air) because it is inexpensive and easy to handle.

  Examples of the method for supplying molecular oxygen include a method of performing a reaction in an oxygen atmosphere, a method of bubbling oxygen, and the like. In addition, oxygen may be diluted with an inert gas such as nitrogen gas. In the present invention, the reaction is preferably performed in the air. When the reaction is performed in air, the pressure during the reaction is not particularly limited and may be normal pressure or increased pressure, but is preferably 1 to 5 atm.

  In the present invention, it is preferable to use 2,2,6,6-tetramethylpiperidine-N-oxyl (hereinafter sometimes referred to as “TEMPO”) and / or benzoquinone together with the copper catalyst. Since the compound acts as a co-oxidant and can reoxidize the reduced copper catalyst as the reaction proceeds, by using it together with the copper catalyst, the oxidation reaction rate of the raw alcohol is accelerated, and the corresponding ketol compound Can be produced in a more selective and high yield. In the present invention, it is particularly preferable to use TEMPO together with the copper catalyst in terms of excellent raw material conversion efficiency.

  The amount of the compound used is, for example, about 0.05 to 10 mol, preferably 0.5 to 5 mol, particularly preferably 1 to 3 mol, per 1 mol of the raw material alcohol.

  The above reaction is preferably performed in the presence of a solvent. This is because when the reaction is carried out in the absence of a solvent, the raw material alcohol is adsorbed on the copper catalyst supported on the carrier and becomes lumpy and the reaction progress may be inhibited. Examples of the solvent include water; nitriles such as acetonitrile, propionitrile, benzonitrile, butyronitrile; alcohols such as methanol and ethanol; 1,2-dioxane, 1,3-dioxane, 1,4-dioxane, tetrahydrofuran , Tetrahydropyran, diethyl ether, dimethyl ether and the like ethers; acetamide, dimethylacetamide, dimethylformamide, diethylformamide, N-methylpyrrolidone and other amides; ethyl acetate, propyl acetate, butyl acetate and other esters; be able to.

  When the reaction is carried out in the presence of a copper catalyst supported on boehmite, the use of a mixture of water and nitriles (= mixed solvent) as a solvent produces a ketol compound in a selective and excellent yield. It is preferable in that it can be performed. The mixing ratio of the water and the nitrile [the former: the latter (volume ratio)] is, for example, about 1: 1 to 1: 100, preferably 1: 1 to 1:50, and particularly preferably 1: 1 to 1:20. is there. When the mixing ratio is out of the above range, the yield of the ketol compound tends to decrease. Also, when the reaction is carried out in the presence of a copper catalyst supported on hydrotalcite, the use of water as the solvent can prevent the elution of the copper catalyst, and enables selective and excellent yield of ketol. It is preferable at the point which can produce | generate a compound.

  The amount of the solvent used is preferably in the range where the initial concentration of the raw material alcohol is about 1 to 10% by weight, for example, when the reaction is carried out batchwise.

  As reaction temperature, it is about 10-200 degreeC, for example, Preferably it is 30-180 degreeC, Most preferably, it is 40-100 degreeC. The reaction time is, for example, about 1 to 24 hours, preferably 5 to 15 hours.

  The reaction can be carried out by any method such as batch, semi-batch and continuous methods.

  After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, etc., or a separation means combining these.

  According to the method for producing a ketol compound of the present invention, it is possible to selectively produce a corresponding ketol compound in a high yield by converting the raw alcohol at an excellent conversion rate. The conversion rate of the raw alcohol is, for example, 70% or more, preferably 80% or more, particularly preferably 95% or more. The yield of the corresponding ketol compound is, for example, 60% or more, preferably 70% or more, particularly preferably 90% or more.

  Furthermore, in the present invention, since the copper catalyst is supported on the carrier, it can be easily separated from the reaction product by a physical separation technique such as filtration or centrifugation. Therefore, the reaction product can be easily purified, and the separated / recovered catalyst can be reused as it is or after being washed, dried, or the like. The washing treatment can be performed by a method of washing several times (about 2-3 times) with an appropriate solvent (for example, water). Therefore, an expensive catalyst can be repeatedly used, and the production cost of the ketol compound can be greatly reduced.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited by these Examples.

Preparation Example 1 (Preparation of catalyst)
10 g of boehmite (trade name “Boehmite”, manufactured by Wako Pure Chemical Industries, Ltd., average pore diameter: 77 nm, specific surface area: 214 m ² ) in an aqueous copper nitrate solution in which 5 g (20.7 mmol) of copper nitrate was dissolved in 100 mL of water. / G) and stirred at 60 ° C. for 24 hours, water was distilled off with an evaporator, and then dried at 60 ° C. for 12 hours to obtain a copper catalyst-supported boehmite (Cu (II) -AlO (OH)) (Cu ²⁺ : 9% by weight, 1.6 mmol of Cu ²⁺ supported per 1 g of boehmite).

Preparation Example 2 (Preparation of catalyst)
A copper catalyst-supported hydrotalcite (Cu (II) -AlHT) was prepared in the same manner as in Preparation Example 1 except that hydrotalcite (trade name “AD500NS”, manufactured by Tomita Pharmaceutical Co., Ltd.) was used instead of boehmite. (Cu ²⁺ : 9% by weight, 1.6 mmol of Cu ²⁺ supported on 1 g of hydrotalcite) was obtained.

Example 1
Under an air atmosphere (1 atm), glycerol (1.0 mmol) and TEMPO (2.0 mmol) were placed in a flask, and a mixed solvent of 1 mL of water and 3 mL of acetonitrile was added and dissolved.
50 mg (containing Cu ²⁺ : 4.5 mg) of “Cu (II) -AlO (OH)” obtained in Preparation Example 1 was added thereto, and the reaction was performed at 60 ° C. for 12 hours. The progress of the reaction was monitored by TLC (I ₂ color development).
After completion of the reaction, the reaction solution is centrifuged to remove “Cu (II) -AlO (OH)”, and the supernatant is passed through a silica gel column (acetone eluent) to remove TEMPO and concentrated. A light yellow oily reaction product was isolated. The reaction product was subjected to HPLC, ¹ H-NMR, and ¹³ C-NMR analysis. As a result, it was confirmed that it was dihydroxyacetone, the raw material conversion was 100%, and the yield of dihydroxyacetone was 95%.

Example 2
The same procedure as in Example 1 was performed except that 4 mL of water was used instead of the mixed solvent of 1 mL of water and 3 mL of acetonitrile. As a result, dihydroxyacetone was obtained (raw material conversion rate: 73.1%).

Example 3 (referred to as a reference example)
Under an air atmosphere (1 atm), glycerol (1.0 mmol) and benzoquinone (2.0 mmol) were placed in a flask, and 4 mL of a mixed solvent of water was added and dissolved.
To this, 50 mg (containing Cu ²⁺ : 4.5 mg) of “Cu (II) -AlHT” obtained in Preparation Example 2 was added and reacted at room temperature (25 ° C.) for 48 hours. The progress of the reaction was monitored by TLC (I ₂ color development).
After completion of the reaction, the reaction solution is centrifuged to remove “Cu (II) -AlHT”, and the supernatant is passed through a silica gel column (acetone eluent) to remove benzoquinone and concentrated to a pale yellow color. An oily reaction product was isolated. HPLC, ¹ H-NMR, and ¹³ C-NMR analysis of the reaction product confirmed that it was dihydroxyacetone, the raw material conversion was 40%, and the yield of dihydroxyacetone was 32%.

Example 4
The same procedure as in Example 1 was performed except that 1,2-propanediol (1.0 mmol) was used instead of glycerol (1.0 mmol). As a result, acetol was obtained (raw material conversion rate: 100%).

Example 5
The same procedure as in Example 1 was performed except that 1,3-butanediol (1.0 mmol) was used instead of glycerol (1.0 mmol). As a result, 1-hydroxybutan-2-one was obtained (raw material conversion rate: 39.2%).

Comparative Example 1
The same procedure as in Example 1 was performed except that 1,3-propanediol (1.0 mmol) was used instead of glycerol (1.0 mmol). As a result, the reaction did not proceed at all (raw material conversion rate: 0%).

Claims (5)

A method for producing a ketol compound, wherein a corresponding ketol compound is produced by oxidizing an alcohol having at least a primary hydroxyl group and a secondary hydroxyl group as a raw material alcohol in the presence of a copper catalyst supported on boehmite .   The method for producing a ketol compound according to claim 1, wherein the alcohol having at least a primary hydroxyl group and a secondary hydroxyl group is glycerol, and the corresponding ketol compound is dihydroxyacetone. With copper catalyst, 2,2,6,6 tetramethylpiperidine -N- oxyl and / or benzoquinone, ketol compound according to claim 1 or 2, 0.05 to 10 moles relative to 1 mole of the raw material alcohol Manufacturing method. The method for producing a ketol compound according to any one of claims 1 to 3 , wherein the reaction is carried out in the presence of water and / or nitrile. The method for producing a ketol compound according to any one of claims 1 to 3, wherein the reaction is performed in the presence of a mixed solvent of water and nitrile [mixing ratio (the former: the latter, volume ratio) = 1: 1 to 1:20]. .