Method for producing tetrahydrofuran-2-carboxylic acid

Abstract

The present invention provides an industrially applicable method for producing tetrahydrofuran-2-carboxylic acid, which is important as a pharmaceutical raw material, etc. The method for producing tetrahydrofuran-2-carboxylic acid of the present invention is to add a base in an amount of 0 to 0.5 times the molar amount of furan-2-carboxylic acid 1 mole in the presence of a palladium-carbon catalyst, and to carry out a catalytic hydrogenation reaction of furan-2-carboxylic acid and hydrogen at 100° C. or less in an aqueous solvent, thereby producing tetrahydrofuran-2-carboxylic acid.

Description

Technical Field

[0001] The present invention relates to a method for producing tetrahydrofuran-2-carboxylic acid which is important as a raw material for a pharmaceutical intermediate or the like. Background Art

[0002] Tetrahydrofuran-2-carboxylic acid is known as a compound useful in industries such as medicine. As a method for producing tetrahydrofuran-2-carboxylic acid, for example:

[0003] (1) A method for producing tetrahydrofuran-2-carboxylic acid by subjecting furan-2-carboxylic acid to a catalytic hydrogenation reaction in water to which sodium hydroxide has been added in the presence of Raney nickel (see Patent Documents 1 and 2);

[0004] (2) A method for producing tetrahydrofuran-2-carboxylic acid by catalytically hydrogenating furan-2-carboxylic acid in a mixed solvent of water and ethyl acetate in the presence of ruthenium nanoparticles and polyEPG-β-CD (see Non-Patent Document 1);

[0005] (3) By loading on γ-Al 2 O 3 A method for producing tetrahydrofuran-2-carboxylic acid by subjecting furan-2-carboxylic acid to a catalytic hydrogenation reaction in the presence of palladium or palladium-nickel on an aqueous solution of 4,4-dihydrofuran-2-carboxylic acid (see Non-Patent Documents 2 and 3).

[0006] In addition, as a method for producing 2-methoxycarbonylfuran which is an analog of furan-2-carboxylic acid, for example, the following is known:

[0007] (4) By pre-storing hydrogen in a hydrogen storage alloy CaNi 5 A method for producing 2-methoxycarbonyltetrahydrofuran by subjecting 2-methoxycarbonylfuran to a catalytic hydrogenation reaction in the presence of (see Patent Document 3) and the like.

[0008] However, in the method (1) of producing tetrahydrofuran-2-carboxylic acid by catalytically hydrogenating furan-2-carboxylic acid in water to which sodium hydroxide has been added in the presence of Raney nickel, Raney nickel is used, which may easily ignite when dried. Furthermore, considering the need for high pressure (80 kg / cm 2 The industrial production method has problems such as the need for a neutralization step in the post-processing when isolating the product due to the use of sodium hydroxide as an additive, which makes the process complicated.

[0009] In addition, in the above-mentioned method (2) of producing tetrahydrofuran-2-carboxylic acid by catalytically hydrogenating furan-2-carboxylic acid in a mixed solvent of water and ethyl acetate in the presence of ruthenium nanoparticles and polyEPG-β-CD, since special and expensive ruthenium nanoparticles and polyEPG-β-CD are used as catalysts and a water / ethyl acetate mixed solvent is used as a solvent in an amount of 90 times the weight of the substrate, it is not an industrially advantageous production method.

[0010] Furthermore, for the above (3), by loading the γ-Al 2 O 3 A method for producing tetrahydrofuran-2-carboxylic acid by catalytically hydrogenating furan-2-carboxylic acid in the presence of palladium or palladium-nickel on an aluminum oxide substrate is not an industrially advantageous production method because, when the aluminum oxide-supported metal catalyst used is prepared by an impregnation method, chloride ions present in the system during the preparation process are firmly bonded to the metal, and the presence of the chloride ions affects the catalytic hydrogenation reaction, and because high pressure (above 1 MPa) and high temperature (above 150° C.) are required.

[0011] In addition, in the above (4), by storing hydrogen in the hydrogen storage alloy CaNi 5 A method for producing 2-methoxycarbonyltetrahydrofuran by catalytic hydrogenation of 2-methoxycarbonylfuran in the presence of 5 Since high temperature (150° C.) conditions are required as a catalyst, this is industrially problematic.

[0012] Prior art literature

[0013] Patent Literature

[0014] Patent Document 1: U.S. Patent No. 3342838

[0015] Patent Document 2: Japanese Patent Application Laid-Open No. 03-188072

[0016] Patent Document 3: Japanese Patent Application Laid-Open No. 06-056702

[0017] Non-patent literature

[0018] Non-patent literature 1: Catalysis Science & Technology, 2017, 75982-5992

[0019] Non-patent document 2: Molecular Catalysis, 2005, 19(6), 436-439

[0020] Non-patent document 3: Molecular Catalysis, 2005, 19(2), 131-135 Summary of the invention

[0021] Problems to be solved by the invention

[0022] An object of the present invention is to provide an industrially applicable method for producing tetrahydrofuran-2-carboxylic acid which is important as a pharmaceutical raw material and the like.

[0023] Means of solving the problem

[0024] In order to solve the above-mentioned problems, the inventors have repeatedly conducted intensive studies and found the present invention as a result. That is, the present invention is a method for producing tetrahydrofuran-2-carboxylic acid, wherein a base is added in an amount of 0 to 0.5 times by mole relative to 1 mole of furan-2-carboxylic acid in the presence of a palladium-carbon catalyst, and furan-2-carboxylic acid and hydrogen are subjected to a catalytic hydrogenation reaction at 100° C. or less in an aqueous solvent, thereby producing tetrahydrofuran-2-carboxylic acid.

[0025] Effects of the Invention

[0026] When tetrahydrofuran-2-carboxylic acid is used as a pharmaceutical raw material, high purity is strongly required. According to the present invention, high-purity tetrahydrofuran-2-carboxylic acid can be produced by an industrially applicable method.

[0027] In the method for producing tetrahydrofuran-2-carboxylic acid of the present invention, a catalytic hydrogenation reaction is carried out without using a base such as sodium hydroxide as an additive, or only using a very small amount of a base such as sodium hydroxide. Therefore, there is no need to add a neutralization step in the post-treatment after the reaction is completed, and tetrahydrofuran-2-carboxylic acid can be produced by a simple operation. DETAILED DESCRIPTION

[0028] Hereinafter, the present invention will be described in detail.

[0029] The present invention performs a catalytic hydrogenation reaction on furan-2-carboxylic acid in the presence of a palladium-carbon catalyst in an aqueous solvent by adding a base in an amount of 0 to 0.5 times by mole relative to 1 mole of furan-2-carboxylic acid.

[0030] The catalytic hydrogenation reaction is carried out in an aqueous solvent. The aqueous solvent refers to water or a mixed solvent containing water. As a mixed solvent containing water, various solvents can be used as components other than water. For example, N,N-dimethylformamide, acetonitrile and other aprotic polar solvents, alcohol solvents such as methanol, ethanol, isopropanol, ether solvents such as tetrahydrofuran, ester solvents such as ethyl acetate, etc., which have high solubility in furan-2-carboxylic acid, can be cited. The aqueous solvent is preferably water. The solubility of furan-2-carboxylic acid in water is 12 g at 40°C relative to 100 g of water, and 160 g at 70°C relative to 100 g of water. In the method for producing tetrahydrofuran-2-carboxylic acid of the present invention, the catalytic hydrogenation reaction will proceed even if furan-2-carboxylic acid is not completely dissolved in water. The amount of aqueous solvent used is preferably 0.5 to 5 times by weight, more preferably 0.5 to 3 times by weight, and further preferably 1 to 2 times by weight relative to furan-2-carboxylic acid. The less the amount of water used, the easier it is to separate the reactant tetrahydrofuran-2-carboxylic acid, and the higher the productivity.

[0031] In the present invention, 0 to 0.5 mole times of a base is added to furan-2-carboxylic acid in an aqueous solvent in the presence of a palladium-carbon catalyst relative to 1 mole of furan-2-carboxylic acid. The amount of the base used is preferably 0 to 0.2 mole times, more preferably 0 to 0.1 mole times, relative to 1 mole of furan-2-carboxylic acid.

[0032] A base such as sodium hydroxide may be optionally added or not. If more than 0.5 mole times of the base is added relative to 1 mole of furan-2-carboxylic acid, the furan-2-carboxylic acid dissolves in water as a salt, but the catalytic hydrogenation reaction slows down significantly. In addition, a neutralization step needs to be added in the post-treatment after the reaction is completed, so the productivity is reduced.

[0033] In the present invention, a palladium carbon catalyst is used. The palladium carbon catalyst formed by palladium supported on carbon is preferred because the surface area of ​​palladium is high and the catalyst activity decreases less over time. For the palladium carbon catalyst, separation and recovery can be carried out by precipitating or filtering the palladium carbon catalyst from the reaction solution. In the manufacture method of the present invention, the palladium carbon catalyst recovered is preferably used again.

[0034] The amount of the palladium carbon catalyst used in the production method of the present invention is preferably 0.0001 to 0.0025 times by weight, more preferably 0.0002 to 0.00125 times by weight, and further preferably 0.0002 to 0.001 times by weight relative to furan-2-carboxylic acid, in terms of metal conversion. In the case of using 0.0001 to 0.0025 times by weight relative to the raw material furan-2-carboxylic acid in terms of metal conversion, the catalytic hydrogenation reaction can be completed in a few hours at a pressure of 1 MPa or less, which allows the first type of pressure vessel, which is a relatively simple device, to be used for pressurized reaction. On the other hand, in the case of more than 0.0025 times by weight in terms of metal conversion, it is economically undesirable as a production process because a large amount of high-priced metals are used.

[0035] In the present invention, the temperature of the catalytic hydrogenation reaction is 100°C or less. When the reaction temperature is 100°C or less, the reaction is fast and the purity of tetrahydrofuran-2-carboxylic acid can be improved. The reaction temperature is preferably 40 to 100°C, more preferably 50 to 70°C.

[0036] In the present invention, it is preferred to replace the reaction vessel with hydrogen before carrying out the catalytic hydrogenation reaction. The hydrogen pressure is preferably 0.8 MPa or less. When the hydrogen pressure is high, the reaction time can be shortened, but sometimes it is difficult to control the reaction temperature due to the heat of reaction, and impurities increase, and the purity of tetrahydrofuran-2-carboxylic acid decreases. On the other hand, if the hydrogen pressure is low, the reaction time becomes long, so the hydrogen pressure is more preferably 0.2 to 0.8 MPa, and more preferably 0.3 to 0.6 MPa.

[0037] After the catalytic hydrogenation reaction is completed, the palladium carbon catalyst used is separated by filtration, and then water is distilled off under reduced pressure, thereby obtaining the target product, tetrahydrofuran-2-carboxylic acid.

[0038] By the manufacturing method of tetrahydrofuran-2-carboxylic acid of the present invention, it is possible to manufacture tetrahydrofuran-2-carboxylic acid having a chemical purity of 99.0 area % or more. Furthermore, in the manufacturing method of tetrahydrofuran-2-carboxylic acid of the present invention, it is preferred that it is possible to manufacture tetrahydrofuran-2-carboxylic acid having a chemical purity of 99.3 area % or more. The chemical purity (area %) of tetrahydrofuran-2-carboxylic acid can be measured by gas chromatography (GC) analysis as described in the following examples.

[0039] Example

[0040] Hereinafter, the present invention will be described by way of examples.

[0041] The chemical purity (area %) in Examples and Comparative Examples was measured by the method shown below.

[0042] <Chemical Purity Analysis Method>

[0043] Gas chromatography (GC) analysis conditions

[0044]

[0045] Example 1

[0046] In a 30mL SUS pressure-resistant reaction vessel with a thermometer and a stirrer, 1.12g (0.01 mol) of furan-2-carboxylic acid was added, followed by 1.68g of water (1.5 times by weight relative to furan-2-carboxylic acid) and 0.01g of 5% palladium carbon (50% wet product) as a catalyst (0.01 times by weight relative to furan-2-carboxylic acid). After replacing the reaction vessel with hydrogen, the pressure was increased to 0.4MPa, and then the hydrogen pressure was adjusted to 0.2-0.4MPa until the reaction was completed. After pressurization, the reaction vessel was heated in a water bath and the internal temperature was adjusted to around 60°C. It took 6 hours before the absorption of hydrogen was completed. After the reaction was completed, it was aged for 2 hours at a hydrogen pressure of 0.4MPa and around 60°C. Then, the catalyst was filtered out after returning to normal pressure at around 20°C, and the aqueous solution obtained thereafter contained 1.16g of tetrahydrofuran-2-carboxylic acid (chemical purity 99.9 area%, yield 100 mol%).

[0047] As 5% palladium carbon (50% wet product), 5% Pd carbon powder (water-containing product) STD type manufactured by NECHEMCAT Co., Ltd. was used. The quality standard of Pd carbon powder (water-containing product) STD type is that the noble metal content (dry basis) is 5.00±0.05% and the water content is 55.00±5.00%.

[0048] Example 2

[0049] In a 3500L SUS pressure-resistant reaction tank equipped with a thermometer and a stirrer, 500kg (4.46 kmol) of furan-2-carboxylic acid is added, followed by 500kg of water (1.0 times by weight relative to furan-2-carboxylic acid), and 5kg (0.01 times by weight relative to furan-2-carboxylic acid) of 5% palladium carbon (50% wet product) as a catalyst. The reaction tank replaced with nitrogen is pressurized with hydrogen until the pressure in the system reaches 0.4MPa, and then the hydrogen pressure is adjusted to about 0.4MPa until the reaction is completed. The 5% palladium carbon (50% wet product) is the same palladium carbon as in Example 1. After pressurization, the reaction vessel is heated in a water bath, and the internal temperature is adjusted to about 60°C. It takes 6 hours before the absorption of hydrogen is completed. After the reaction is completed, the system is aged for 2 hours at a hydrogen pressure of 0.4MPa and about 60°C. Then, after returning to normal pressure at around 20°C, the catalyst was filtered off, and the aqueous solution obtained contained 511 kg of tetrahydrofuran-2-carboxylic acid (chemical purity 99.3 area %, yield 99 mol %).

[0050] Example 3

[0051] The same operation as in Example 1 was performed except that 0.04 g of sodium hydroxide (0.1 molar times relative to furan-2-carboxylic acid) was added as an additive. After returning to normal pressure at around 20° C., the catalyst was filtered off, and the aqueous solution obtained contained 1.16 g of tetrahydrofuran-2-carboxylic acid (chemical purity 99.8 area %, yield 100 mole %).

[0052] Comparative Example 1

[0053] 5.6 g of water (5.0 times by weight relative to furan-2-carboxylic acid) and 0.06 g of 5% ruthenium carbon (50% wet product) as a catalyst (0.05 times by weight relative to furan-2-carboxylic acid) were added, and the same operation as in Example 1 was performed except that the reaction time including the aging time was set to 6 hours. The formation of tetrahydrofuran-2-carboxylic acid due to the change in reaction conditions was compared and studied. The results are shown in Table 1.

[0054] Comparative Example 2

[0055] 5.6 g of water (5.0 times by weight relative to furan-2-carboxylic acid) and 0.06 g of 5% platinum carbon (50% wet product) as a catalyst (0.05 times by weight relative to furan-2-carboxylic acid) were added, and the same operation as in Example 1 was performed except that the reaction time including the aging time was set to 4 hours. The formation of tetrahydrofuran-2-carboxylic acid due to the change in reaction conditions was compared and studied. The results are shown in Table 1.

[0056] Comparative Example 3

[0057] 5.6 g of water (5.0 times by weight relative to furan-2-carboxylic acid) and 0.4 g of sodium hydroxide (1.0 times by mole relative to furan-2-carboxylic acid) as an additive were added, the internal temperature was adjusted to about 100° C., and the reaction time including the aging time was set to 27 hours. The same operation as in Example 1 was performed. The formation of tetrahydrofuran-2-carboxylic acid due to the change in reaction conditions was compared and examined. The results are shown in Table 1.

[0058] Comparative Example 4

[0059] The same operation as in Example 1 was performed except that 5.6 g of water (5.0 times by weight relative to furan-2-carboxylic acid) was added and the internal temperature was adjusted to approximately 160° C. The formation of tetrahydrofuran-2-carboxylic acid due to the changes in reaction conditions was compared and examined. The results are shown in Table 1.

[0060]

Claims

1. A method for producing tetrahydrofuran-2-carboxylic acid, comprising adding a base in an amount of 0 to 0.5 mole times relative to 1 mole of furan-2-carboxylic acid in the presence of a palladium-carbon catalyst, and subjecting furan-2-carboxylic acid and hydrogen to a catalytic hydrogenation reaction in an aqueous solvent at a temperature below 100° C. and a hydrogen pressure below 0.8 MPa, thereby producing tetrahydrofuran-2-carboxylic acid, wherein the amount of the aqueous solvent used is 0.5 to 3 times by weight relative to the furan-2-carboxylic acid.

2. The method for producing tetrahydrofuran-2-carboxylic acid according to claim 1, wherein the amount of the palladium-carbon catalyst used is 0.0001 to 0.0025 times by weight relative to furan-2-carboxylic acid in terms of metal.

3. The method for producing tetrahydrofuran-2-carboxylic acid according to claim 1 or 2, wherein tetrahydrofuran-2-carboxylic acid having a chemical purity of 99.0 area % or more is produced.

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