Process for the preparation of methionine

Abstract

This invention relates to a method for preparing methionine, comprising contacting a solution or suspension containing 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide with water in the presence of a catalyst to obtain a mixture containing methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, average maximum Feret diameter xF 最大,平均 The range is from 3±10% to 40±10% nm, and the average minimum Feret diameter xF 最小,平均 The mean maximum Feret diameter is 2 ± 10% to 30 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

Description

[0001] The present invention relates to a method for preparing methionine in one step using 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide as starting materials.

[0002] Methionine is an essential amino acid and is very important as a feed supplement, especially for poultry. Currently, standard industrial production of methionine uses methanethiol, acrolein, and hydrogen cyanide as starting materials. First, methanethiol is added to the carbon-carbon double bond of acrolein in a Michael addition reaction to give the intermediate 3-(methylthio)propional. This aldehyde then reacts with hydrogen cyanide to give 2-hydroxy-4-(methylthio)butyronitrile, which further reacts with ammonia and carbon dioxide to generate the corresponding hydantoin derivative. Alternatively, the hydantoin derivative can also be obtained by reacting 3-(methylthio)propional with hydrogen cyanide, ammonia, and carbon dioxide. The alkaline hydrolysis of this hydantoin yields an alkali metal salt of methionine. Neutralization with an acid, such as by adding H₂SO₄ or by bubbling carbon dioxide through an aqueous solution containing the alkali metal salt of methionine, yields racemic methionine.

[0003] Alternatively, methionine can also be prepared by hydrolysis of 2-amino-4-(methylthio)butyronitrile or 2-amino-4-(methylthio)butyramide. It is generally accepted that 2-amino-4-(methylthio)butyronitrile, obtained by reacting 2-hydroxy-4-(methylthio)butyronitrile with ammonia or by reacting 3-(methylthio)propionaldehyde with hydrogen cyanide and ammonia, is hydrolyzed via the intermediate 2-amino-4-(methylthio)butyramide to obtain methionine as the desired product. First, the nitrile group of 2-amino-4-(methylthio)butyronitrile is hydrolyzed to an amide group to give 2-amino-4-(methylthio)butyramide. Subsequently, the amide group of 2-amino-4-(methylthio)butyramide is hydrolyzed to a hydroxyl group to give methionine.

[0004] JP S54-46717 discloses a method for preparing amino acids by reacting α-aminonitrile with water in the presence of metallic zinc or zinc oxide. However, the yield of methionine is not satisfactory.

[0005] JP H03-93757 discloses a method for hydrolyzing α-aminonitriles into the corresponding α-amino acids in the presence of a zirconium dioxide-based catalyst. However, the methionine yield is neither satisfactory nor consistent.

[0006] US Patent 6,417,395 B1 discloses the catalytic hydrolysis of 2-amino-4-(meththio)butyronitrile to methionine. However, the catalyst systems used in this document do not exhibit optimal performance in forming the desired product, methionine. Instead, they appear to vary considerably depending on the solvent used in the hydrolysis.

[0007] Published patent application EP 3199519 A1 discloses a method for producing methionine by contacting 2-amino-4-(meththio)butyronitrile and water together in the presence of a cerium-containing oxide catalyst. Specifically, the catalyst used in this method is cerium oxide, such as cerium(III) (Ce₂O₃), cerium(IV) (CeO₂), mixtures thereof, or cerium oxide compounds having these mixed phases, or cerium-containing oxide solid solutions, such as CeO₂-ZrO₂ (cerium oxide-zirconium oxide), CeO₂-Y₂O₃, and CeO₂-La₂O₃. However, the yield of methionine thus obtained is not constant. Instead, the results vary considerably depending on the type, quantity, and source of the CeO₂-based catalyst used, as well as other specific characteristics of the method. Even in examples where methionine is produced in the presence of pure CeO₂, the yield of methionine varies drastically between 60% and 95%. Furthermore, the examples in EP 3199519 A1 do not specify the other components in the resulting mixture of products containing methionine, in particular whether these other components are unconverted starting compounds or byproducts. Therefore, the experimental data in this document cannot draw any conclusions as to whether any type of CeO2-based catalyst is truly suitable for the catalytic hydrolysis of 2-amino-4-(meththio)butyronitrile.

[0008] Therefore, there is a need for an improved method to prepare methionine in one step using 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide as starting materials.

[0009] The problem was found to be solved by using a catalyst containing CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles was 175 to 300 ± 10% m², as measured according to DIN ISO 9277-5 (2003). 2 / g, and the average maximum Feret diameter xF 最大,平均 The range is from 3±10% to 40±10% nm, and the average minimum Feret diameter xF 最小,平均 The mean maximum Feret diameter is 2 ± 10% to 30 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012). Specifically, it was found that one of these parameters was insufficient to characterize the catalyst to obtain the desired conversion and selectivity. In fact, in the preparation of methionine using 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butanamide as starting compounds, a catalyst with a combination of specific parameters within a given range is required to obtain the desired conversion and selectivity.

[0010] Therefore, the object of the present invention is a method for preparing methionine, comprising the step of contacting a solution or suspension containing 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide with water in the presence of a catalyst to obtain a mixture containing methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, average maximum Feret diameter x F最大,平均 The mean minimum Feret diameter is 3 ± 10% to 40 ± 10% nm. F最小,平均 The mean maximum Feret diameter is 2 ± 10% to 30 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0011] In the context of this invention, the terms "maximum Feret diameter" and "minimum Feret diameter" as known from the industrial standard DIN ISO 9276-6 (2012) are used. These are macroscopic shape descriptors reflecting the geometric proportions of particles, such as crystals or particles with a certain degree of crystallinity. In this respect, they represent the distance between two parallel tangents applied to the particle. Specifically, the maximum Feret diameter corresponds to the "length" of the particle, and the minimum Feret diameter corresponds to the "width" of the particle to which the tangents are applied.

[0012] In the context of this invention, the term "average" is used to refer to the arithmetic mean of the parameter in question, also known as the mathematical expectation or average. It is the center value of a set of discrete measurements of the parameter; specifically, it is the sum of the measurements of the parameter divided by the number of measurements.

[0013] In the context of this invention, the term "mixture containing methionine" refers to a mixture containing a catalyst, (where appropriate) unconverted starting compounds (i.e., 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide), and pure methionine, and / or mixed with ammonia released during the contact step as ammonium methionine. After the catalyst is separated from the mixture containing methionine, the term refers to a mixture containing (where appropriate) unconverted starting compounds (i.e., 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide), and pure methionine and / or mixed with ammonia released during the contact step as ammonium methionine.

[0014] In the context of this invention, the term ±10% following a explicitly mentioned value indicates a deviation from the explicitly mentioned value within the range of -10% to +10% and therefore includes all values ​​within that range. The term ±10% also indicates that any deviation from any explicitly mentioned value, with or without the additional 10% range, is also included within the scope of the claimed invention, provided that said deviation also achieves the effect of the claimed invention.

[0015] According to the method of the invention, and more specifically, using a catalyst comprising CeO2-containing particles according to the invention to catalyze the hydrolysis of 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide to a mixture comprising 2-amino-4-(methylthio)butyramide and methionine or methionine, each having higher selectivity than the catalyst of EP 3199519 A1.

[0016] In principle, the method according to the invention places no limitation on the CeO2 content in the catalyst used. Therefore, the catalyst can contain 25% to 100% by weight of CeO2. Every catalytic reaction is generally accompanied by some catalyst loss, also known as catalyst leaching. Depending on the price of the catalytically active component in the catalyst, catalyst loss or leaching more or less affects the economics of the process. Therefore, industrially, it is advantageous to use the catalyst in the smallest possible amount in the catalytic reaction. For example, a catalyst having CeO2-containing particles is mixed with another component that is considered to have no catalytic activity in the method according to the invention. A suitable component in this regard is, for example, ZrO2. It has been found that when a particular catalyst contains only 25% by weight of CeO2 (e.g., using a catalyst containing CeO2 particles, each equivalent of CeO2 is mixed with three equivalents of ZrO2), the method according to the invention has yielded a 95% methionine yield.

[0017] In one embodiment of the method according to the invention, the catalyst contains 25% to 100% CeO2 based on the total weight of the catalyst.

[0018] Nevertheless, in order to obtain the highest possible conversion and methionine yield within a relatively short time, the catalyst according to the invention preferably contains more than 25 wt% CeO2 based on the total weight of the catalyst. Therefore, the catalyst according to the invention preferably contains 25 wt% to 100 wt%, 30 wt% to 100 wt%, 35 wt% to 100 wt%, 40 wt% to 100 wt%, 45 wt% to 100 wt%, 50 wt% to 100 wt%, 55 wt% to 100 wt%, 60 wt% to 100 wt%, 65 wt% to 100 wt%, 70 wt% to 100 wt%, 75 wt% to 100 wt%, 80 wt% to 100 wt%, 85 wt% to 100 wt%, 90 wt% to 100 wt%, or 95 wt% to 100 wt% CeO2, each based on the total weight of the catalyst.

[0019] Generally, like catalysts, CeO2-containing particles are not limited to a specific CeO2 content. Specifically, it has been found that CeO2-containing particles with different CeO2 contents yield comparable results in the method according to the invention. In particular, CeO2-containing particles having 50% to 100% by weight of CeO2, with the remainder being one or more metals or metal oxides other than cerium or cerium oxide (such as ZrO2), produce particularly good results in the method according to the invention. Therefore, catalysts suitable for the method according to the invention include those containing CeO2, (CeO2... 0.5 -(ZrO2) 0.5 (CeO2) 0.7 -(ZrO2) 0.3 , and / or (CeO2) 0.8 -(ZrO2) 0.2 Or pure CeO2 particles.

[0020] In one embodiment of the method according to the invention, the CeO2-containing particles contain 50% to 100% by weight of CeO2.

[0021] Specifically, the CeO2-containing particles contain 50 wt%, 70 wt%, 80 wt%, or 100 wt% CeO2.

[0022] Experiments show that the BET surface area of ​​CeO2-containing particles is between 200 and 280 m². 2The catalyst according to the invention, within the range of / g, yields methionine with up to 100% selectivity and up to 100% overall selectivity for the formation of methionine and 2-amino-4-(methylthio)butyronitrile in the catalytic hydrolysis of 2-amino-4-(methylthio)butyronitrile (T = 75 °C, t = 120 min, 4 g catalyst (0.35 equivalent) and 10 g 2-amino-4-(methylthio)butyronitrile).

[0023] In one embodiment of the method according to the invention, the BET surface area of ​​the CeO2-containing particles, measured according to DIN ISO 9277-5 (2003), is 200 ± 10% to 280 ± 10% m². 2 / g. In a further preferred embodiment, the BET surface area of ​​the CeO2-containing particles, measured according to DIN ISO 9277-5 (2003), is 225 ± 10% to 265 ± 10% m². 2 / g.

[0024] It was also found that the catalyst according to the invention, containing fairly dense CeO2-containing particles, was more beneficial for high methionine yield and high methionine selectivity than the catalyst containing spherical CeO2-containing particles. A suitable parameter for distinguishing between spherical and dense CeO2-containing particles is the so-called aspect ratio. This parameter describes the proportion of each side of the particle; specifically, it describes the ratio x of the minimum Feret diameter to the maximum Feret diameter according to DIN ISO 9276-6 (2012). F最小 / x F最大 In the context of this invention, an average aspect ratio is preferred because CeO2-containing particles already have an average minimum Feret diameter x F最小,平均 and average maximum Feret diameter x F最大,平均 Description. Therefore, the average aspect ratio can be expressed as x F最小,平均 / x F最大,平均 Spherical particles have similar Feret diameters and therefore have an aspect ratio very close to 1 (average). Perfectly spherical particles have an aspect ratio of 1 (average). In contrast, the CeO2-containing particles of the catalyst used in the method according to the invention have an average aspect ratio of less than 1, and therefore their Feret diameters are not uniform.

[0025] In another embodiment of the method according to the invention, the average minimum Feret diameter of the CeO2-containing particles is always less than the average maximum Feret diameter of the particles.

[0026] Preferably, the average minimum Feret diameter x of the CeO2-containing particles is... F最小,平均The value is 3 ± 10% to 10 ± 10% nm. More preferably, the average maximum Feret diameter x of the CeO2-containing particles is... F最大,平均 It ranges from 4 ± 10% to 10 ± 10% nm. Specifically, the average minimum Feret diameter x of CeO2-containing particles... F最小,平均 The mean maximum Feret diameter is 3 ± 10% to 10 ± 10% nm. F最大,平均 It ranges from 4±10% to 10±10% nm.

[0027] In one embodiment of the method according to the invention, the BET surface area of ​​the CeO2-containing particles, measured according to DIN ISO 9277-5 (2003), is 175 to 300 ± 10% m². 2 / g, average minimum Feret diameter x F最小,平均 The mean maximum Feret diameter is 3 ± 10% to 10 ± 10% nm. F最大,平均 The mean maximum Feret diameter is 4 ± 10% to 10 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0028] In a preferred embodiment of the method according to the invention, the BET surface area of ​​the CeO2-containing particles, measured according to DIN ISO 9277-5 (2003), is 225 ± 10% to 265 ± 10% m². 2 / g, average minimum Feret diameter x F最小,平均 The mean maximum Feret diameter is 3 ± 10% to 10 ± 10% nm. F最大,平均 The mean maximum Feret diameter is 4 ± 10% to 10 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0029] Compared to fairly dense CeO2-containing particles, CeO2-containing particles with an average aspect ratio greater than 0.75 as measured according to DIN ISO 9276-6 (2012) were found to exhibit lower methionine yields and lower methionine selectivity. Specifically, catalysts containing CeO2-containing particles with an average aspect ratio of 0.55 ± 10% to 0.80 ± 10%, particularly 0.6 ± 10% to 0.8 ± 10%, were found to exhibit exceptionally high methionine yields and high methionine selectivity.

[0030] In another embodiment of the method according to the invention, the average aspect ratio x of the CeO2-containing particles is measured according to DIN ISO 9276-6 (2012). F最小,平均 / x F最大,平均 It ranged from 0.55±10% to 0.80±10%.

[0031] According to the present invention, the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m², as measured according to DIN ISO 9277-5 (2003). 2 / g, average maximum Feret diameter x F最大,平均 The range is from 3 ± 10% to 40 ± 10% nm, and the average minimum Feret diameter x F最小,平均 The mean maximum Feret diameter is 2 ± 10% to 30 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012). Based on the definition of Feret diameter, their values ​​can vary considerably. Furthermore, Feret diameter is not a diameter in the strict sense, but rather reflects the geometric proportions of particles, such as crystals or particles with a certain degree of crystallinity. Therefore, the size of primary particles cannot be described solely based on Feret diameter. The so-called equivalent circle diameter x A This is a suitable measure for describing the primary particle size of CeO2-containing particles in the catalyst according to the present invention. In the context of this invention, the term "equivalent circle diameter" as known from the industrial standard DIN ISO 9276-6 (2012) is used. Generally, the equivalent circle diameter corresponds to the diameter of a circle having the same projected area as the particle in question. The equivalent circle diameter is calculated using the following formula.

[0032]

[0033] Where A is in nm 2 The projected area of ​​the particles in question is given and measured according to DIN ISO 9276-6 (2012). Typically, the projected area of ​​the particles in question is obtained by graphical analysis of high-resolution transmission electron microscopy (HR-TEM) images of a meaningful number (at least 100, preferably at least 200, 300, 400 or 500) particles using image analysis software. In the context of this invention, the average equivalent circle diameter x is used. AIt can describe the general mean primary particle size of all CeO2-containing particles analyzed. The CeO2-containing particles in the catalyst of the present invention are characterized by the average equivalent circle diameter x, measured according to DIN ISO 9276-6 (2012). A The values ​​are 3±10% to 30±10% nm, preferably 4±10% to 30±10%, 10±10% to 30±10% nm, or 4±10% to 20±10%. In contrast, the CeO2-containing particles in catalyst #4 (purchased from Wako, see Table 1 in the Experimental Section) have an equivalent circular diameter of about 48 nm, and are therefore larger and bulkier than the catalyst according to the invention.

[0034] In one embodiment of the method according to the invention, the average equivalent circular diameter x of the CeO2-containing particles is measured according to DIN ISO 9276-6 (2012). A,平均 The value ranged from 3±10% to 30±10% nm.

[0035] Further analysis of the catalyst used in the method according to the invention showed that, in CeO2-containing particles, a lattice plane distance of 0.24±10% to 0.32±10% nm, preferably 0.28±10% to 0.32±10% nm, is beneficial for high methionine yield and high methionine selectivity.

[0036] In another embodiment of the method according to the invention, the CeO2-containing particles have a crystal plane distance of 0.24±10% to 0.32±10% nm.

[0037] Particles with a facet spacing of 0.24 ± 10% to 0.32 ± 10% nm have a (111) surface, which is necessary for the presence of octahedral particles. This finding is consistent with HR-TEM images of highly effective and selective catalysts according to the method of the invention, which contain octahedral particles containing CeO2. The catalyst according to the invention, containing CeO2-containing particles, with a facet spacing of 0.24 ± 10% to 0.32 ± 10% nm, catalyzes the hydrolysis of 2-amino-4-(methylthio)butyronitrile to methionine in at least 99% yield. In contrast, a catalyst not according to the invention containing CeO2-containing particles with a facet spacing of 0.40 nm (see Comparative Catalyst #3 in Example 3.3) yields only 35% methionine. In fact, the closer the average aspect ratio of the CeO2-containing particles is to 0.71, the closer they are to an octahedral shape. Perfect octahedral particles have an aspect ratio of 0.71. Therefore, the presence of CeO2-containing octahedral particles also aligns with the fact that effective catalysts contain CeO2-containing particles with an average aspect ratio of 0.55±10% to 0.80±10%, particularly 0.6±10% to 0.8±10%.

[0038] In another embodiment of the method according to the invention, the CeO2-containing particles comprise octahedral particles.

[0039] Catalysts containing CeO2-containing particles (which are spherical and have fairly soft edges) were found to have low yields and selectivity for the formation of methionine. In contrast, the effective catalyst in the method according to the invention contains CeO2-containing particles with a fairly crystalline appearance, i.e., a crystallinity of at least 50%. Specifically, the effective catalyst can be distinguished from the less effective catalyst by the clear and identifiable geometric appearance of its CeO2-containing particles, which have sharp edges, corners, and regions. In contrast, the CeO2-containing particles of the less effective catalyst have round or smooth corners and edges, which cannot be clearly specified as a particular geometric appearance.

[0040] In another embodiment of the method according to the invention, the CeO2-containing particles have a crystallinity of at least 50%.

[0041] Preferably, the CeO2-containing particles have a crystallinity of 50-100%, 50-95%, or 55-90%.

[0042] In principle, the method according to the invention is not limited in terms of the temperature at which the contact step is performed. Therefore, the contact step can be carried out at any temperature at which the starting compound 2-amino-4-(methylthio)butyronitrile is thermally stable. Specifically, in the method according to the invention, no byproducts were detected in the mixture containing methionine obtained from the hydrolysis of 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide at a temperature of up to 90°C. For example, the contact step can be carried out at temperatures of 20°C-90°C, 30°C-90°C, 40°C-90°C, 50°C-90°C, 60°C-90°C, 70°C-90°C, or 80°C-90°C. For example, the method according to the invention has completely converted the starting material 2-amino-4-(methylthio)butyronitrile at a lower temperature of 75°C for a reaction time of 2 hours using 4 g (0.35 equivalents) of catalyst and 10 g of starting compound, and obtained a methionine yield between 99% and 100%. In contrast, when 2-amino-4-(meththio)butyronitrile is hydrolyzed to methionine at 105°C, 4% methionine sulfoxide is formed, i.e., oxidized methionine, as an undesirable byproduct.

[0043] In one embodiment, the contact step of the method according to the invention is carried out at a temperature of up to 90°C using a solution or suspension containing 2-amino-4-(methylthio)butyronitrile. Preferably, the contact step of the method according to the invention is carried out at a temperature of 50°C to 90°C using a solution or suspension containing 2-amino-4-(methylthio)butyronitrile.

[0044] The method according to the invention aims to achieve the highest possible yield of methionine. However, it is possible that the starting material, particularly 2-amino-4-(methylthio)butyronitrile, is not completely converted to methionine or the conversion is not to the desired extent. Here, the remainder is particularly 2-amino-4-(methylthio)butyramide. Because said 2-amino-4-(methylthio)butyramide is an intermediate and a suitable starting material in the method according to the invention, it is preferable to feed the mixture containing methionine from the (first) contact step into a further contact step of the method according to the invention. Here, in the presence of a specific catalyst according to the invention, the solution or suspension containing 2-amino-4-(methylthio)butyramide is contacted with water to maximize the conversion to methionine.

[0045] In one embodiment of the method according to the invention, the mixture containing methionine obtained from the contact step is fed into at least one further contact step.

[0046] Therefore, the method according to the present invention preferably includes the following steps:

[0047] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% nm to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012), and

[0048] ii) Feed the mixture containing methionine obtained in step i) into at least one further contact step.

[0049] To achieve complete conversion of the unconverted portion of the starting compound, the second or further contacting step is preferably carried out at a higher temperature relative to the temperature in the first contacting step. The increased temperature relative to the temperature in the preceding (i.e., the first) contacting step, compared to the preceding contacting step (i.e., the first contacting step), does not lead to the formation of any measurable byproducts. Therefore, the second or further contacting step can be carried out at temperatures exceeding 90°C. For example, the second or further contacting step can be carried out at temperatures of 70°C to 140°C, 80°C to 130°C, 90°C to 120°C, or 100°C to 110°C.

[0050] In another embodiment of the method according to the invention, at least one further contact step is performed in a temperature range of 70°C to 140°C.

[0051] The method according to the invention can be carried out in a solution or suspension containing 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide in a concentration range preferably from 1 wt% to 30 wt%, 3 wt% to 25 wt%, 6 wt% to 24 wt%, or 6 wt% to 20 wt%.

[0052] In one embodiment of the method according to the invention, the contact step is carried out with a solution or suspension containing 1 to 30% by weight of 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide.

[0053] The method according to the invention does not limit the specific shape or size of the catalyst containing CeO2-containing particles. In the simplest case, the catalyst is a powder obtained from the production of CeO2-containing particles. However, when using a catalyst composed of fine particles in a catalytic reaction, the fine powdered catalyst must be separated from the mixture containing methionine. A suitable separation step in the context of this invention must meet the requirements of efficiency and applicability in a continuous process. The most common technique for separating particles from a liquid medium is so-called dead-end filtration. However, this type of filtration is unsuitable for use in a completely continuous process or for separating particles smaller than 10 μm in diameter from a liquid medium in large-scale applications. This problem has been solved by using continuous cross-flow filtration. Cross-flow filtration, also known as tangential flow filtration, is a filtration technique in which a suspension containing initial methionine and CeO2 is passed tangentially along the surface of a filter. The pressure differential of the filter drives components smaller than the pore size through the filter (permeate). Components larger than the pore size are trapped and pass through the membrane surface, flowing back to the feed reservoir (residue).

[0054] In a further embodiment, the method according to the invention further includes the step of separating the catalyst from the mixture containing methionine obtained in step i) and / or ii) by continuous cross-flow filtration.

[0055] Therefore, the method according to the present invention preferably includes the following steps:

[0056] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0057] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step, and

[0058] iii) Separate the catalyst from the mixture containing methionine in step i) and / or step ii) by continuous cross-flow filtration.

[0059] Optionally or additionally, the method according to the invention therefore preferably includes the following steps:

[0060] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0061] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step.

[0062] iii) Separate the catalyst from the mixture containing methionine in steps i) and / or ii) by continuous cross-flow filtration, and

[0063] ii') Optionally, repeat steps i) and iii), or steps i) through iii).

[0064] In principle, polymer or ceramic membranes can be used to separate CeO2-containing particles. However, small CeO2-containing particles are abrasive when flowing through the membrane. Ceramic membranes made of (but not limited to) TiO2, ZrO2, or Al2O3 and supported on (but not limited to) TiO2, ZrO2, or Al2O3 have proven resistant to abrasive CeO2-containing particles and are therefore preferred in cross-flow filtration for separating catalysts containing CeO2-containing particles from mixtures containing methionine. When the catalyst according to the method of the invention consists of CeO2-containing particles themselves (e.g., in the form of fine powder), the catalyst particles have an equivalent circular diameter x of 10 to 30 nm, similar to the CeO2-containing particles. A Therefore, the pore size of the membrane used in cross-flow filtration must be carefully selected to retain catalyst particles. Simultaneously, the membrane used for filtration must allow methionine formed during the reaction to permeate through the membrane. The nominal molecular weight cutoff (NMWC) is the molecular weight of the largest molecule that can pass through the membrane and is a suitable parameter characterizing this property of membranes ranging from 1 to 150 kD (kilodaltons = 1000 g / mol), where 150 kD roughly corresponds to a pore size of about 20 nm. Therefore, these ultrafiltration membranes with NMWMC values ​​of 1 to 150 kD can be used to effectively separate CeO2-containing particles in the permeate from the methionine-containing product solution in the permeate. Filtration with a membrane pore size less than 100 nm is also called ultrafiltration, and filtration with a membrane pore size of 100 nm or larger is also called microfiltration. In the context of this invention, microfiltration membranes with pore sizes from 100 nm to 1 μm can also be used because the formation of aggregates and agglomerates of CeO2-containing catalyst particles results in practically larger diameters of aggregates and agglomerates ranging from 100 nm to several μm. However, microfiltration membranes cannot retain all CeO2-containing catalyst particles as effectively as ultrafiltration membranes. In this case, a second filtration must be performed on the permeate from the first filtration. Therefore, it is preferred that the continuous cross-flow filtration is ultrafiltration. More preferably, the continuous cross-flow filtration is performed using a membrane, preferably a ceramic membrane, with a nominal molecular weight cutoff of 1 to 150 kD and / or a pore size of 20-50 nm.

[0065] The desired product, methionine, can be separated from the resulting permeate solution, for example, by crystallization or recrystallization. As described above, the permeate solution or suspension containing the catalyst comprising CeO2 particles can be returned to a second or any further contact step as described above. For example, the permeate can be returned to a first reactor or a downstream reactor for further contact steps. If the permeate is sent to a downstream reactor, the downstream reactor is also equipped with a membrane as described above for separating the catalyst from the product solution.

[0066] Independently, regardless of whether the method according to the invention begins with 2-amino-4-(methylthio)butyramide or 2-amino-4-(methylthio)butyronitrile, it is always accompanied by the release of ammonia. In the first step of the hydrolysis of 2-amino-4-(methylthio)butyronitrile, the cyanide group is converted into an amide group, which is in principle achieved by adding water to the carbon-nitrogen triple bond of the cyanide group. Subsequently, in the hydrolysis of the 2-amino-4-(methylthio)butyronitrile thus obtained, the amide group is converted into the corresponding carboxylic acid group upon the release of ammonia. Therefore, the hydrolysis of one equivalent of 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyronitrile is always accompanied by the release of one equivalent of ammonia. Furthermore, the starting material 2-amino-4-(methylthio)butyronitrile already contains ammonia, especially when it is prepared according to US 2012 / 215021 A1 by reacting 3-(methylthio)propionaldehyde with hydrogen cyanide in the presence of ammonia as a base. Even when a base other than ammonia is used in this preparation process, 2-amino-4-(methylthio)butyronitrile still contains ammonia. This is because the hydrogen cyanide used to prepare 2-amino-4-(methylthio)butyronitrile usually still contains unreacted ammonia, regardless of whether it is prepared independently according to the Andrussow process or the BMA process (also known as the Degussa process). Therefore, any 2-amino-4-(methylthio)butyronitrile used for hydrolysis to methionine, as well as the hydrolysis intermediate 2-amino-4-(methylthio)butyramide and the final hydrolysis product methionine, always contain ammonia. However, the presence of ammonia in mixtures containing methionine inevitably leads to the formation of ammonium salts of methionine. Therefore, neutral methionine or ammonia-free methionine cannot be obtained using the method according to EP 3199519 A1. Conversely, contact between 2-amino-4-(meththio)butyronitrile and / or 2-amino-4-(meththio)butyramide and water always yields a mixture containing methionine with ammonium methionine as the major product, and therefore, the resulting methionine-containing product must be crystallized to obtain neutral methionine, i.e., methionine without ammonia. Preferably, crystallization is carried out directly from an aqueous solution of the aqueous ammonium methionine obtained from the contact step. Alternatively, the methionine-containing product, i.e., containing ammonium methionine as the major product, can also be precipitated from said solution, subsequently separated from the solution, redissolved in a suitable solvent, preferably in water, and recrystallized from the resulting second solution. In the context of this invention, the second solution is also referred to as a mixture containing methionine.

[0067] In another embodiment, the method according to the invention further includes a step of crystallizing or recrystallizing methionine from a mixture containing methionine obtained by at least one contact step.

[0068] Therefore, the method according to the present invention preferably includes the following steps:

[0069] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0070] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step.

[0071] iii) Separate the catalyst from the mixture containing methionine in steps i) and / or ii) by continuous cross-flow filtration, and

[0072] iv) Crystallize or recrystallize methionine from the mixture containing methionine obtained in step iii).

[0073] Optionally or additionally, the method according to the invention therefore preferably includes the following steps:

[0074] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0075] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step.

[0076] iii) Separate the catalyst from the mixture containing methionine in step i) and / or step ii) by continuous cross-flow filtration.

[0077] ii') Optionally, repeat steps i) and iii), or steps i) to iii), and

[0078] iv) When at least one step ii'), crystallize or recrystallize methionine from the mixture containing methionine obtained by the final separation step iii).

[0079] According to the technical teachings of EP 3199519 A1, 2-amino-4-(methylthio)butyronitrile is prepared by contacting 3-(methylthio)propionaldehyde, hydrogen cyanide, and ammonia with each other; therefore, the starting material used to prepare methionine also contains ammonia. Thus, it is not surprising that almost all examples in this document use an aqueous solution of 2-amino-4-(methylthio)butyronitrile that still contains ammonia. Only Example 5 of this document uses deaminated 2-amino-4-(methylthio)butyronitrile. Compared with other examples, the methionine yield obtained in this example is only 80%, which is significantly lower than the other examples in EP 3199519 A1. Based on these results, it should be expected that the presence of a base such as ammonia is beneficial for obtaining high yields when preparing methionine by hydrolysis of 2-amino-4-(methylthio)butyronitrile. However, it has been found that high methionine yields can also be obtained with reduced ammonium methionine formation during the hydrolysis of 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide. This effect is achieved because at least one contact step of the method according to the invention is accompanied by vacuum distillation or steam stripping of the reaction solution or suspension to remove at least partially ammonia from the reaction solution or suspension. Performing the contact step of the method according to the invention under reduced pressure allows the reaction solution or suspension to relax, resulting in the release of ammonia from the solution or suspension. By steam stripping, the ammonia contained in the reaction solution or suspension is carried away from the solution or suspension and removed from the reaction system.

[0080] In another embodiment of the method according to the invention, at least one contact step is accompanied by vacuum distillation or steam stripping of the reaction solution or suspension.

[0081] Therefore, the method according to the present invention preferably includes the following steps:

[0082] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0083] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step.

[0084] iii) Separate the catalyst from the mixture containing methionine in steps i) and / or ii) by continuous cross-flow filtration, and

[0085] iv) Crystallize or recrystallize methionine from the mixture obtained in step iii).

[0086] At least one of steps ii) to iv) is accompanied by vacuum distillation or steam stripping of the reaction solution or suspension.

[0087] Optionally or additionally, the method according to the invention therefore preferably includes the following steps:

[0088] i) In the presence of a catalyst, a solution or suspension comprising 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide is first contacted with water to obtain a mixture comprising methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, or 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012).

[0089] ii) Optionally, the mixture containing methionine obtained in step i) is fed into at least one further contact step.

[0090] iii) Separate the catalyst from the mixture containing methionine in step i) and / or step ii) by continuous cross-flow filtration.

[0091] ii') Optionally, repeat steps i) and iii), or steps i) to iii), and

[0092] iv) When step ii') is performed at least once, crystallize or recrystallize methionine from the mixture containing methionine obtained by the final separation step iii).

[0093] At least one of steps ii) to iv) is accompanied by vacuum distillation or steam stripping of the reaction solution or suspension.

[0094] Preferably, if steps ii) and iii), steps ii) and iv), steps iii) and iv), or all steps ii) to iv) are performed independently once or repeatedly, the reaction solution or suspension is accompanied by vacuum distillation or steam stripping.

[0095] The ammonia thus removed from the reaction solution or suspension can be used in an upstream reaction step of the method according to the invention to convert 2-hydroxy-4-(methylthio)butyronitrile to 2-amino-4-(methylthio)butyronitrile.

[0096] The catalyst used in the method according to the invention is not limited in its preparation, provided that the preparation provides CeO2-containing particles contained in the catalyst, said CeO2-containing particles having the technical characteristics according to the invention, particularly a BET surface area of ​​175 to 300 ± 10% m² as measured according to DIN ISO 9277-5 (2003). 2 / g, preferably 200±10% to 280±10%m 2 / g, 225±10% to 265±10%m 2 / g, average maximum Feret diameter x F最大,平均 The mean value is 3±10% to 40±10% nm, preferably 4±10% to 10±10% nm, and the mean minimum Feret diameter x F最小,平均 The average maximum Feret diameter is 2±10% to 30±10% nm, preferably 3±10% nm to 10±10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012). For example, they can be prepared according to Example 1 of the published patent application EP1 506 940.

[0097] The invention is further described with reference to the following figures and embodiments. Example:

[0098] 1. Analytical Methods

[0099] 1.1 HPLC-chromatographic analysis

[0100] Chromatographic analysis of 2-hydroxy-4-(methylthio)butyronitrile (MMP-CN), 2-amino-4-(methylthio)butyronitrile (MMP-AN), 2-amino-4-(methylthio)butyramide (Met-amide), 3-(methylthio)propionaldehyde (MMP), and methionine (Met) was performed using an HPLC system from JASCO or Agilent equipped with an RP-18 column (250 x 4.6 mm; 5 μm) and subsequent UV detection at 210 nm. The eluent consisted of a mixture of 3.3 g H₃PO₄, 6.8 g CH₃CN, and 89.9 g H₂O at a flow rate of 1 mL / min. 10 μL of each sample solution (50 mg of sample in 25 mL H₂O) was injected into the eluent for analysis. Calibration was performed beforehand by injecting appropriate standard stock solutions of the analytes and subsequently comparing the peak areas with external standards, as is common in organic chemical synthesis.

[0101] 1.2BET surface area:

[0102] The BET surface area A is determined by the physical adsorption of nitrogen on a solid surface and by calculating the amount of adsorbed gas corresponding to the monolayer on the surface according to the Brunauer-Emmett-Teller (BET) method. BET Prior to measurement, the sample (0.2–0.9 g) was degassed under vacuum at 150 °C for 20 minutes. The determination was then performed at liquid nitrogen temperature (77 K). The amount of adsorbed gas was measured using a TriStar 3000 Miromertrics instrument via a three-point static volume measurement. This method is generally described in DIN ISO 9277-5 (2003) and applied accordingly.

[0103] 1.3 X-ray powder diffraction and crystallinity:

[0104] X-ray powder diffraction (XRPD) is a non-destructive analytical technique for determining the crystalline phase in solid samples. XRPD measurements, including the determination of crystallinity, are performed as follows. 0.5–2.0 g of material are analyzed using the following parameters in a Cubix 3 Pharma X-ray powder diffractometer from PANalytical:

[0105] X-ray tube: LFF-Cu X-ray tube, Cu Kα, λ=0.1542nm

[0106] Generator settings: 40mA, 40kV

[0107] Detector: X'Celerator

[0108] Rotation: Yes / 1 revolution / second

[0109] 2θ range: 5°-100°

[0110] Step size (°2θ): 0.017°

[0111] Time per step: 40 seconds

[0112] The results were evaluated using the current version of PANalytical HighScore Plus software and the latest version of the ICDD database with a crystalline reference phase. The crystallinity of the material was determined using the constant background method implemented in the HighScore Plus PANalytical software. This method is based on the following equation:

[0113]

[0114] in

[0115] A is the integral area below the crystal reflection.

[0116] B represents the area of ​​the amorphous background, and is the integrated area between the crystal reflection and the instrument background line.

[0117] C is the integral area below the instrument background line caused by air scattering of X-rays, fluorescence radiation, and other instrument factors.

[0118] The integrated area A in the X-ray diffraction pattern is determined by laying down a background line that separates the crystal reflections from the apparent amorphous background. The instrument background line (constant background) and therefore the integrated area C are determined by measuring CeO2 NIST-certified reference material with 100% crystallinity. The integrated area B in the measurement sample is determined by establishing an amorphous background and applying a constant instrument background defined in the CeO2 NIST-certified reference material.

[0119] 1.4 High-resolution transmission electron microscopy (HR-TEM):

[0120] A Jeol 2010F field emission transmission electron microscope was operated at an accelerating voltage of 200 keV. The system was calibrated, qualityed, and stabilized using Magical no. 641 standard (Norrox Scientific Ltd., Beaver Pond, Ontario, Canada). High-resolution transmission electron microscopy (HR-TEM) was used to determine the distances between crystal planes.

[0121] Samples were prepared by manually dispersing 10 mg of powder in 2 mL of chloroform or 2 mL of a 2:1 isopropanol / water mixture in a clean test tube. The dispersion was stirred for 3 minutes using a UP100H ultrasonic probe (Hielscher), which was inserted to a depth of 1 cm from the bottom of the test tube. During this time, the test tube was also placed in a Sonorex Super RK102H ultrasonic bath (Bandelin, 240 W peak energy input). An HR-TEM support coated with porous carbon foil was used as the support (CF200-Cu carbon film on a 200-mesh copper grid; manufacturer: Electron Microscopy Sciences, Hatfield, PA). 10 μL of the dispersion was transferred onto the carbon foil using a Transferpette.

[0122] For point analysis of nanoparticles, a 30mm aperture is used. 2 Energy-dispersive X-ray nanodot analysis was performed using a Noran SiLi detector and a Noran System Six instrument.

[0123] To determine the maximum Feret diameter x of the nanoparticles F最大 Minimum Feret diameter x F最小 Aspect Ratio x F最小 / x F最大 Projected area A and equivalent circle diameter x A Statistical evaluation was performed by manually selecting 500 particles from the sample in the HR-TEM analysis and evaluating them according to DIN ISO 9276-6 (2012) using the I-TEM software from Soft Imaging Systems (SIS) in Münster, Germany. The obtained values ​​were used to calculate the corresponding mean x. F最大,平均 x F最小,平均 x F最小,平均 / x F最大,平均 A 平均 and x A,平均 .

[0124] 2. Preparation of the catalyst according to the present invention

[0125] The catalysts according to the invention are not limited in their preparation, provided that the procedures used for their preparation provide catalysts having the characteristics according to the invention. In this case, catalysts #1 and #2 according to the invention were purchased from Treibacher Industrie AG.

[0126] The Brunauer-Emmett-Teller (BET) surface area A of different catalyst powders was analyzed using high-resolution transmission electron microscopy (HR-TEM) and subsequent pattern analysis of 500 particles. BET Crystallinity and their average maximum Feret diameter x F最大,平均 Minimum Feret diameter x F最小,平均 Average aspect ratio x F最小,平均 / x F最大,平均 Crystal plane distance and average equivalent circle diameter x A,平均 Catalysts #3 and #4 were purchased from Wako Pure Chemicals Ltd., catalyst #5 from Kanto Chemical Co., Inc., and catalyst #6 from Daiichi Kigenso Kagaku Kogyo Co., Ltd., and the same parameters as the catalysts according to the present invention were analyzed.

[0127] Table 1: Summary of tested catalysts ( 1 (Comparative example).

[0128]

[0129] 3. Synthesis Example:

[0130] 3.1 Synthesis of 2-amino-4-(methylthio)butyronitrile starting from 2-hydroxy-4-(methylthio)butyronitrile

[0131] 10.1 g of 2-hydroxy-4-(methylthio)butyronitrile (MMP-CN; 90 wt%, 69.3 mmol, 1 molar equivalent in water) was mixed with 26.0 g of NH3 (32 wt%, 7 molar equivalent, 48.8 mmol in water) in a glass reactor and then sealed. The slightly beige, turbid emulsion containing 25 wt% MMP-CN was stirred and heated to 50 °C for 30 min in a preheated hot water bath. Analysis of the resulting pale yellow solution by HPLC confirmed 100% conversion of MMP-CN and 98.8% selectivity for 2-amino-4-(methylthio)butyronitrile (MMP-AN; 67.2 mmol) and 2-amino-4-(methylthio)butyramide (Met-amide; 1.2 mmol).

[0132] 3.2 The obtained 2-amino-4-(methylthio)butyronitrile was directly converted into a mixture containing 2-amino-4-(methylthio)butyramide and methionine.

[0133] To the reaction solution obtained according to Example 3.1, which contained 8.75 g MMP-AN (67.2 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH3 (419 mmol, 6 molar equivalents), and 19.9 g water, 36.2 g water (MMP-AN concentration 12 wt%) and 1.0 g (5.8 mmol, 0.09 molar equivalents) of CeO2-containing catalysts #1 to #2 from Table 2 were added. The glass reactor was resealed and heated to 60°C for 30 minutes with stirring. Subsequently, the reaction solution was rapidly cooled to room temperature and analyzed by HPLC. Furthermore, the reaction was also carried out in the presence of ZrO2 (catalyst #7) and in the absence of any catalyst. The results regarding the conversion of MMP-AN, selectivity for methionine (Met), combined selectivity for Met-amide and Met, Met:Met-amide ratio, yield of Met, and combined yield of Met-amide and Met are listed in Table 2.

[0134] Table 2: Summary of Results of Example 3.2 1 (Comparative example, X = conversion rate, Y = yield, S = selectivity)

[0135]

[0136] 3.3 The obtained 2-amino-4-(meththio)butyronitrile was directly and completely converted into methionine.

[0137] The reaction solution obtained according to Example 3.1, containing 8.76 g MMP-AN (67.3 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH3 (419 mmol, 6 molar equivalents), and 19.9 g water, was transferred to a stainless steel autoclave reactor. An additional 36.2 g of water (MMP-AN concentration 12 wt%) and 4.0 g (23 mmol, 0.35 molar equivalents) of CeO2-containing catalysts #1 to #4 and catalyst 6 according to Table 3 were added. The reactor was sealed and heated to 75°C for 120 minutes with stirring using a heating block heater. Subsequently, the reaction solution was rapidly cooled to room temperature and analyzed by HPLC. The results regarding the conversion of MMP-AN, selectivity for methionine (Met), combined selectivity for Met-amide and Met, Met:Met-amide ratio, yield of Met, and combined yield of Met-amide and Met are listed in Table 3.

[0138] Table 3: Summary of Results of Example 3.3 1 Comparative example, 2 Met-amide not detected, X = conversion, Y = yield, S = selectivity)

[0139]

[0140] 3.4 The obtained 2-amino-4-(methylthio)butyronitrile was directly converted into a mixture containing 2-amino-4-(methylthio)butyramide and methionine at different initial concentrations of the obtained 2-amino-4-(methylthio)butyronitrile.

[0141] To the reaction solution obtained according to Example 3.1, comprising 8.75 g MMP-AN (67.2 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH3 (419 mmol, 6 molar equivalents), and 19.9 g water, 0 g, 36.2 g, or 110 g of water (MMP-AN concentration 24 wt%, 12 wt%, or 6 wt%) and 0.5 g of catalyst #1 (2.9 mmol, 0.04 molar equivalents) according to Table 1 were added. The glass reactor was resealed and heated to 60 °C for 30 minutes with stirring. Subsequently, the reaction solution was rapidly cooled to room temperature and analyzed by HPLC. The results regarding the conversion of MMP-AN, selectivity for methionine (Met), combined selectivity for Met-amide and Met, Met:Met-amide ratio, yield of Met, and combined yield of Met-amide and Met are listed in Table 4.

[0142] Table 4: Summary of results from Example 3.4, C = concentration, X = conversion, Y = yield, S = selectivity

[0143]

[0144] 3.5 The obtained solution containing 2-amino-4-(meththio)butyramide and methionine was reacted completely to methionine at an elevated temperature.

[0145] The reaction solution obtained according to Example 3.2 using catalyst #1 from Table 2 was transferred to a stainless steel autoclave reactor and heated to 120°C for 120 minutes with stirring and a heating block heater. The reaction solution was then rapidly cooled to room temperature. HPLC analysis of the solution showed a 98% Met-amide conversion and a 91% selectivity for Met, which equates to a 91% Met yield.

[0146] 3.6 The catalyst is separated from the mixture containing methionine by continuous cross-flow filtration.

[0147] A mixture containing 3 wt% Met and 1 wt% methionine-containing catalyst #1 according to Table 1 was pumped through an Al2O3 channel (support), which was covered by an Al2O3 membrane with a pore size of 50 nm, or by a ZrO2 membrane with a nominal molecular weight cutoff (NMWC) of 150 or 25 kD. In each case, the permeate was analyzed by HPLC and showed that Met successfully and unimpededly passed through the membrane at an ideal Met concentration of 3%, compared to the mixture containing the starting methionine. In each case, particle size distribution analysis by laser diffraction and dynamic light scattering of the permeate solution indicated that the catalyst was completely retained in the permeate and did not pass through the membrane.

Claims

1. A method for preparing methionine, comprising contacting a solution or suspension containing 2-amino-4-(methylthio)butyronitrile and / or 2-amino-4-(methylthio)butyramide with water in the presence of a catalyst to obtain a mixture containing methionine, wherein the catalyst comprises CeO2-containing particles, wherein the BET surface area of ​​the CeO2-containing particles is 232 m² as measured according to DIN ISO 9277-5 (2003). 2 / g to 264 m 2 / g, average maximum Feret diameter x F最大,平均 The range is from 3 ± 10% to 40 ± 10% nm, and the average minimum Feret diameter x F最小,平均 The mean maximum Feret diameter is 2 ± 10% to 30 ± 10% nm. F最大,平均 and average minimum Feret diameter x F最小,平均 Both were measured according to DIN ISO 9276-6 (2012). Based on the total weight of the catalyst, the catalyst contains 100% by weight of CeO2.

2. The method according to claim 1, wherein the average minimum Feret diameter x of the CeO2-containing particles F最小,平均 Always smaller than the average maximum Feret diameter x of the particles F最大,平均 .

3. The method according to claim 1 or 2, wherein the average aspect ratio x of the CeO2-containing particles is measured according to DIN ISO 9276-6 (2012). F最小,平均 / x F最大, 最小 The percentage ranged from 0.55±10% to 0.80±10%.

4. The method according to claim 1 or 2, wherein the crystal plane distance of the CeO2-containing particles is 0.24 ± 10% to 0.32 ± 10% nm.

5. The method according to claim 1 or 2, wherein the CeO2-containing particles comprise octahedral particles.

6. The method according to claim 1 or 2, wherein the average equivalent circle diameter x of the CeO2-containing particles is measured according to DIN ISO 9276-6 (2012). A,平均 The range is 3 ± 10% to 30 ± 10% nm.

7. The method according to claim 1 or 2, wherein the crystallinity of the CeO2-containing particles is at least 50%.

8. The method according to claim 1 or 2, wherein the contacting step is performed at a temperature of up to 90°C using a solution or suspension containing 2-amino-4-(methylthio)butyronitrile.

9. The method according to claim 1 or 2, wherein the mixture containing methionine obtained from the contact step is fed into at least one further contact step.

10. The method of claim 9, wherein the at least one further contact step is performed in a temperature range of 70°C to 140°C.

11. The method of claim 1 or 2, wherein the method further comprises the step of separating the catalyst from the mixture containing methionine by continuous cross-flow filtration.

12. The method according to claim 1 or 2, wherein the at least one contacting step is accompanied by vacuum distillation or steam stripping of the reaction solution or suspension.

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