Methods for producing methionine

Abstract

This invention relates to the preparation of compounds of formula I [chemical formula 1] CH3XCH2CH2C(NH) by catalytic conversion of compounds of formula II. 2) COOH(I), where X represents S or Se, [Chemical Formula 2] CH3XCH2CH2C(Y)CN(II), where X represents S or Se, and Y represents NH2 or OH. When Y represents NH2, the conversion is carried out in the presence of water and at least one catalyst, said catalyst comprising at least alumina, titanium dioxide, or a mixture thereof. When Y represents OH, the conversion is carried out in the presence of water, at least one catalyst, and NH3 or an ammonium salt, said catalyst comprising at least alumina, titanium dioxide, zirconium oxide, or a mixture thereof.

Description

Technical Field

[0001] This invention relates to an improvement of a method for producing methionine or its "seleniated" analogue (selenomethionine), the method producing methionine from the precursor 2-amino-4-methylthiobutyronitrile or 2-hydroxy-4-methylthiobutyronitrile, or producing selenomethionine from 2-amino-4-methylthiobutyronitrile or 2-hydroxy-4-methylthiobutyronitrile. Background Technology

[0002] The size of the methionine market is well-established, especially in animal nutrition, where production methods remain a subject of much development. Selenized derivatives of methionine continue to be a major area of ​​interest in animal nutrition.

[0003] Methionine can be prepared by various synthetic intermediates, particularly 2-amino-4-methylthiobutyronitrile (AMTBN), 2-amino-4-methylthiobutyramide (AMTBM), and 2-hydroxy-4-methylthiobutyronitrile (HMTBN).

[0004] Reference WO01 / 60790A1 describes the synthesis of methionine from 2-hydroxy-4-methylthiobutyronitrile (HMTBN). Upon reaction with ammonia, HMTBN is converted to AMTBN, which in turn reacts with acetone in an alkaline medium to form AMTBM. Catalytic hydrolysis of AMTBM in the presence of a titanium compound with a defined porosity yields ammonium methionine, from which methionine is recovered.

[0005] According to document WO2004 / 089863A1, a method for preparing the ammonium salt of HMTBA from the nitrile precursor HMTBN is known. According to this method, HMTBN in aqueous solution is converted to the ammonium salt of HMTBA in a single step in the presence of a titanium-based catalyst. This synthesis also results in the formation of methionine and HMTBM, and the reported yields of the ammonium salt of HMTBA are in the range of 10%. These yields are insufficient to consider the industrial-scale application of this method. Summary of the Invention

[0006] The present invention provides an alternative to existing methods, which eliminates at least one step while producing methionine or its selenized derivatives in high yield.

[0007] According to the present invention, it has been discovered that aminonitrile (AMTBN or its selenized equivalent) and hydroxynitrile (HMTBN or its selenized equivalent) intermediates can be converted to methionine (or selenomethionine) in a single step in the presence of water and a catalyst, and, where appropriate, ammonia or ammonium salts. The accessibility and performance of this conversion enable its industrial production into methionine. This invention represents a true advancement compared to known synthetic methods and their modifications (the benefits of improving conventional industrial methods remain insufficient). Significant yields are achieved in a very short time.

[0008] Therefore, the present invention provides a method for preparing a compound of formula (I) by catalytic conversion of a compound of formula (II).

[0009] [Chemical Formula 1]

[0010] CH3XCH2CH2C(NH2)COOH(I)

[0011] Where X represents S or Se.

[0012] [Chemical Formula 2]

[0013] CH3XCH2CH2C(Y)CN(II)

[0014] Where X represents S or Se, and Y represents NH2 or OH.

[0015] When Y represents NH2, the conversion is carried out in water and at least one catalyst, and, where appropriate, in the presence of NH3 or an ammonium salt, said catalyst comprising at least alumina, titanium dioxide, or a mixture thereof, and

[0016] When Y represents OH, the conversion is carried out in the presence of water, at least one catalyst, and NH3 or an ammonium salt, wherein the catalyst comprises at least alumina, titanium dioxide, zirconium oxide, or a mixture thereof.

[0017] According to the present invention, "where appropriate" should be understood to mean that the presence of NH3 or an ammonium salt is necessary when the method involves a hydroxynitrile precursor (i.e., a compound of formula (II) where Y represents OH), but is unnecessary when the method involves an aminonitrile precursor (i.e., a compound of formula (II) where Y represents NH2). However, this definition does not exclude the presence of NH3 when the method involves an aminonitrile precursor; this variation constitutes a specific embodiment of the invention and will be described later.

[0018] The ammonium salts according to the present invention include those having the chemical formula (NH4). nAny salt of A, wherein A is specifically selected from halogens, carbonates, bicarbonates, phosphates, hydrogen phosphates, sulfates, bisulfates, acetates, citrates, formates, and hydroxides, and n is an integer from 1 to 5. As an example, it can be selected from (NH4)H2PO4, (NH4)2HPO4, (NH4)3PO4, (NH4)HSO4, (NH4)2SO4, (NH4)HCO3, or (NH4)2CO3.

[0019] In the presence of such a catalyst, the compound of formula (II) can be directly converted into methionine, whereas known methods from aminonitrile compounds or hydroxynitrile compounds require passing through the corresponding aminoamide or hydroxynitrile intermediate and then being hydrolyzed into methionine, with each step using different operating conditions.

[0020] In this document, unless otherwise stated, the terms "compound (II) where Y is NH2", "AMTBN", and "aminonitrile" will be used interchangeably to refer to 2-amino-4-methylthiobutyronitrile, and by analogy to 2-amino-4-methylselenobutyronitrile. Similarly, the terms "compound (II) where Y is OH", "HMTBN", and "hydroxynitrile" refer to 2-hydroxy-4-methylthiobutyronitrile, and by analogy to 2-hydroxy-4-methylselenobutyronitrile. Compound (II) should be understood to include all these names, and therefore these two classes of compounds may be considered together or separately.

[0021] The term "direct conversion" should be understood as meaning that when the method is carried out on an industrial scale, the conversion can be carried out in the same reactor containing the catalyst, to which a mixture of water, compound (II) and optional NH3 or ammonium salt is supplied, or each reactant is supplied individually and their mixing is carried out in the reactor.

[0022] The term catalyst is generally used to refer to the active phase of a catalyst, but this does not exclude the fact that catalysts can be doped and / or supported.

[0023] Alumina, titanium dioxide, and zirconium oxide should be understood to refer to all polymorphs of alumina (Al₂O₃), titanium dioxide (TiO₂), and zirconium dioxide (ZrO₂) (where applicable), forms well known to those skilled in the art. The catalyst can also be a combination of two or even three of alumina, titanium dioxide, and zirconium oxide. It may also include any other entities that enhance its catalytic function.

[0024] The features, applications, and advantages of the invention will now be disclosed in more detail. These features can be considered independently of each other or in combination, however the combination may be.

[0025] According to the invention, the catalyst comprises, or is composed of, one or more compounds selected from alumina, titanium dioxide, and zirconium oxide; these compounds at least constitute the active phase of the catalyst and optionally constitute a support. Therefore, if the catalyst is not entirely composed of one or more of the aforementioned oxides, it may contain any other compounds that do not affect or even enhance the catalyst's performance. In variations of the invention, the catalyst is composed of one of the aforementioned oxides.

[0026] The catalyst can be doped and / or supported. It can be doped with any element or compound conventionally used and known to those skilled in the art. As an example, catalyst doping can be carried out by one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum, and any compounds of the aforementioned elements. The elements K, Cs, Sr, Ba, and La are preferred. If the catalyst is not composed solely of alumina, titanium dioxide, and / or zirconium oxide, it can also be supported by any other compound conventionally used and known to those skilled in the art, particularly silica and aluminosilicates.

[0027] According to the present invention, all of the above-mentioned solid catalysts may be in powder form, or preferably in bead, extrusion, tablet, trefoil or other form that allows them to be used in reactors, preferably fixed-bed reactors, or in batch mode in open or pressurized reactors.

[0028] The catalyst advantageously has at least 10m 2 The specific surface area is [value missing] g. Below this limit, the catalyst performance declines rapidly, particularly for compound (II), with decreased selectivity for methionine, reduced selectivity for AMBTM or HMTBM, and decreased conversion of compound (II). This observation applies to selenium equivalents. In the context of this invention, the upper limit of the specific surface area is not critical; the specific surface area is imposed by a commercially available active phase. The specific surface area values ​​shown herein were determined by the most common method, namely nitrogen physical adsorption, and calculated by the BET method.

[0029] In a preferred embodiment of the method of the present invention, the catalyst is present at a mass concentration of 0.1% to 200%, preferably 0.5% to 100%, and even more preferably 1% to 50%, relative to the mass of compound (II).

[0030] According to the invention, various devices can be considered for batch or continuous reactions: the solid catalyst, whether doped or not, can be fixed in the reactor in the form of particles or extrusions or any other form, or loaded on metal foam. Reactors associated with this type of catalyst are preferably tubular or multi-tubular fixed beds operating in a trickle or overflow manner, isothermal or adiabatic, or preferably catalyst-coated exchange reactors.

[0031] The conversion of AMTBN or HMTBN within the scope of this invention is advantageously carried out at temperatures ranging from 20°C to 200°C, even from 50°C to 150°C, and even more preferably from 80°C to 110°C. It has been observed that during the reaction period, ranging from approximately 10 minutes to 3 hours, the reaction slows significantly at temperatures below 20°C, and starting from 110°C, the greater the increase in temperature, the greater the selectivity for dionitriles and methionine peptides, while the selectivity for methionine is unfavorable. High selectivity for methionine can be observed in the range of 80°C to 110°C.

[0032] Typically, AMTBN or HMTBN is in an aqueous solution. This may be prepared for the implementation of this method or derived from the reaction medium that produces AMTBN or HMTBN, respectively. In this case, AMTBN or HMTBN may be impure and may include trace amounts or even larger amounts, but these are still negligible because they do not adversely affect the conversion of AMTBN or HMTBN according to the present invention.

[0033] Depending on the conversion performed, the concentration of AMTBN or HMTBN can affect the performance of the method, especially when the concentration is too high. Therefore, according to a variant of the invention, the concentration of AMTBN in aqueous solution is in the range of 0.01 M to 10 M, preferably 0.05 M to 1 M, and even more preferably 0.2 M to 0.4 M. It has been noted that above 1 M, or even 0.8 M, if the conversion to AMTBN remains high, the selectivity for methionine decreases, while the selectivity for AMTBM, dinitrile, and even peptides increases, respectively.

[0034] When the production of methionine according to the invention involves HMTBN, ammonia should be added to the reaction medium. It is preferably present in an amount of 1 to 50 equivalents relative to the HMTBN in the ammonia. Ammonia can be introduced into the medium by any technique, but advantageously, it is provided in the form of continuous bubbling.

[0035] It has been observed that the presence of ammonia in the AMTBN solution prior to its conversion significantly promotes selectivity for methionine while decreasing selectivity for dionitriles, whereas in the absence of ammonia, selectivity for dionitriles increases over time. Therefore, the present invention relates to an advantageous implementation of the above-described method, wherein AMTBN is contacted with ammonia before being introduced into contact with the catalyst, or even during catalytic conversion within the reactor. Preferably, an inert support gas, such as nitrogen, may be used to introduce ammonia into the AMTBN solution by bubbling.

[0036] The invention also relates to the continuous implementation of the method of the invention, advantageously, prior to its conversion, with ammonia present in the AMTBN solution, or even better, with bubbling of ammonia. According to this variant, the method is carried out at a pressure comprising 1 to 20 bar, preferably 2 to 10 bar. Thus, the invention provides an apparatus comprising bubbling for an AMTBN solution and providing therein a mixture of ammonia and nitrogen. The AMTBN solution is pumped into a stainless steel reactor containing a catalyst and heated to a temperature of 80 to 180°C by a sleeve. The reaction medium is pumped to a gas / liquid separator, from which ammonia is removed, and the liquid is treated from the separator to recover methionine. The solution is then evaporated until a solid is obtained, which is subsequently recrystallized at 60°C in a water / alcohol mixture (1 / 6). The resulting white solid form of methionine is washed, filtered, and then dried. This continuous method for obtaining methionine from AMTBN is also applicable to obtaining methionine from HMTBN, but the supply of ammonia is necessary.

[0037] According to another aspect, a method is provided for the controlled catalytic conversion of 2-amino-4-methylthiobutyronitrile or 2-amino-4-methylselenobutyronitrile to 2-amino-4-methylthiobutyramide or 2-amino-4-methylselenobutyramide, respectively, wherein the conversion is carried out in the presence of at least one catalyst comprising or consisting of alumina or titanium dioxide. Detailed Implementation

[0038] The invention and its advantages are illustrated in the following embodiments.

[0039] Example 1: According to the present invention, methionine was prepared from AMTBN in the presence of TiO2.

[0040] The figure below illustrates the hydrolysis reaction of AMTBN and the conditions under which it proceeds.

[0041] [Chemical Formula 3]

[0042]

[0043] 65 g of AMTBN was introduced into a 1 L screw-cap flask along with 1000 ml of H₂O. The solution was stirred at room temperature with a nitrogen stream (5 ml / min) and injected at a flow rate of 0.1 ml / min (contact time 10 min) into a solution heated to 100 °C containing 4 g of TiO₂ (anatase type, 150 ml). 2 The reaction was carried out in a tubular reactor (Norpro, ST 61120) for over 48 hours, monitored by proton NMR.

[0044] AMTBN conversion was greater than 90%, with an average methionine yield of 74% and an average selectivity of 81%, and an average dinitrile yield of 11% and an average selectivity of 12%.

[0045] Example 2: According to the present invention, the effect of the presence of TiO2 and ammonia on the specific surface area of ​​methionine-TiO2 prepared from AMTBN.

[0046] The figure below illustrates the hydrolysis reaction of AMTBN and the conditions under which it proceeds.

[0047] [Chemical Formula 4]

[0048]

[0049] 2.1BET is 90m 2 / g of TiO2 (anatase form)

[0050] 0.4g TiO2 (anatase form) (90m) 2 0.1 g AMTBN (98%) was introduced together with 2 ml of 28% by weight ammonia solution. The solution was heated at 90 °C for 10 minutes, then filtered and analyzed by proton NMR.

[0051] The yield of methionine was 93%, the yield of AMTBM was 1%, and the yield of dinitrile was 6%.

[0052] 2.2BET is 275m 2 / g of TiO2 (anatase form)

[0053] 0.4g TiO2 (anatase form) (275m) 2 0.1 g of AMTBN (98%) was introduced together with 2 ml of 28% by weight ammonia solution. The solution was heated at 90 °C for 10 minutes, then filtered and analyzed by proton NMR.

[0054] The yield of methionine was 95%, the yield of AMTBM was 1%, and the yield of dinitrile was 4%.

[0055] The preferred catalyst is BET with at least 90% TiO2.

[0056] Example 3: According to the present invention, methionine was prepared from AMTBN in the presence of doped titanium dioxide and ammonia.

[0057] This embodiment covers the use of TiO2 doped with cesium and strontium, respectively. Doping is carried out by impregnating TiO2 with cesium hydroxide or strontium hydroxide, wherein the content of cesium and strontium (nonmetals) is 4% by weight.

[0058] A 0.8 mol / L AMTBN solution was contacted with 5 g of any doped catalyst at 100 °C for 10 minutes.

[0059] The results are shown in Table 1 below.

[0060] [Table 1]

[0061]

[0062] Example 4: Methionine was prepared from AMTBN in the presence of titanium dioxide and ammonia using the continuous method according to the present invention.

[0063] The figure below illustrates the hydrolysis reaction of AMTBN and the conditions under which it proceeds.

[0064] [Chemical Formula 5]

[0065]

[0066] The catalyst has a concentration of 150m 2 / g specific surface area of ​​titanium dioxide.

[0067] 5 g of the catalyst was placed in a reactor in which a 0.1 mol / L AMTBN aqueous solution was circulated at a flow rate of 0.2 ml / min, and ammonia was circulated at a flow rate of 10 ml / min. The reaction temperature was 100 °C, and the contact time was 6 minutes.

[0068] The results are shown in Table 2 below.

[0069] [Table 2]

[0070]

[0071] The system was observed to be stable in terms of conversion and selectivity, exhibiting high selectivity for methionine (90%), high conversion of AMTBN (96%), and low selectivity for other products. The yields of methionine and AMTBN were 86% and 2%, respectively.

[0072] Example 4: According to the present invention, methionine was prepared from HMTBN in the presence of titanium dioxide and diammonium hydrogen phosphate.

[0073] The figure below illustrates the hydrolysis reaction of HMTBN and the conditions under which it proceeds.

[0074] [Chemical Formula 6]

[0075]

[0076] 13.1 g HMTBN was introduced into a 1 L screw-cap flask along with 1000 mL H2O. The solution was stirred with a nitrogen stream at room temperature and injected at a flow rate of 0.1 mL / min (contact time 10 min) into a solution heated to 160 °C containing 4 g TiO2 (anatase type, 150 mL). 2 The reaction was carried out in a tubular reactor (Norpro, ST 61120) with a yield of 47% methionine, as monitored by HPLC.

[0077] Example 5: According to the present invention, methionine was prepared from HMTBN in the presence of titanium dioxide and ammonia.

[0078] The figure below illustrates the hydrolysis reaction of HMTBN and the conditions under which it proceeds.

[0079] [Chemical Formula 7]

[0080]

[0081] 13.1 g HMTBN was introduced into a 1 L screw-cap flask along with 1000 ml H2O. The solution was stirred at room temperature with an ammonia gas flow rate of 100 ml / min, and then injected at a flow rate of 0.1 ml / min (contact time 10 min) into a solution heated to 90 °C containing 6 g TiO2 (anatase type, 150 ml). 2 The reaction was carried out in a tubular reactor (Norpro, ST 61120) with a yield of 80% methionine, as monitored by HPLC.

[0082] Example 6: Preparation of methionine from HMTBN in the presence of titanium dioxide but without an ammonia source, according to existing technology.

[0083] The figure below illustrates the hydrolysis reaction of HMTBN and the conditions under which it proceeds.

[0084] [Chemical Formula 8]

[0085]

[0086] 13.1 g HMTBN was introduced into a 1 L screw-cap flask along with 1000 mL H2O. The solution was stirred with a nitrogen stream at room temperature and injected at a flow rate of 0.1 mL / min (contact time 10 min) into a solution heated to 160 °C containing 4 g TiO2 (anatase type, 150 mL). 2 The reaction was carried out in a tubular reactor (Norpro, ST 61120) with a yield of 1% HMTBA and 15% methionine, as monitored by HPLC.

[0087] Comparison of the results from Examples 4 and 5 according to the present invention with those obtained in Example 6 without ammonia or ammonium salts demonstrates a considerable improvement in methionine production performance in the method of the present invention. The same benefits were observed in the preparation of selenomethionine.

Claims

1. A method for preparing a compound of formula I by catalytic conversion of a compound of formula II. [Chemical Formula 1] CH3XCH2CH2C(NH2)COOH(I) Where X represents S or Se. [Chemical Formula 2] CH3XCH2CH2C(Y)CN(II) Where X represents S or Se, and Y represents NH2 or OH. Its features are, When Y represents NH2, the conversion takes place in the presence of water and at least one catalyst, said catalyst including titanium dioxide, and When Y represents OH, the conversion is carried out in the presence of water, at least one catalyst, and NH3 or an ammonium salt, said catalyst including titanium dioxide.

2. The method according to claim 1, characterized in that... The method involves a compound of chemical formula II, wherein Y represents OH, and the conversion is carried out in the presence of water, at least one catalyst and NH3 or an ammonium salt, wherein the catalyst comprises or is composed of titanium dioxide.

3. The method according to claim 1, characterized in that... The catalyst is doped.

4. The method according to claim 3, characterized in that... The catalyst is doped with one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum, and any compounds of the above elements.

5. The method according to claim 3, characterized in that... The catalyst is doped with one or more elements selected from K, Cs, Sr, and Ba.

6. The method according to claim 1, characterized in that... The catalyst has a BET specific surface area of ​​at least 10 m². 2 / g.

7. The method according to claim 1, characterized in that... The mass concentration of the catalyst is from 0.1% to 200% of the mass of compound (II).

8. The method according to claim 1, characterized in that... The mass concentration of the catalyst is 1% to 50% of the mass of compound (II).

9. The method according to claim 1, characterized in that... Y represents compounds of chemical formula (II) for NH2, which are in the form of aqueous solutions with concentrations ranging from 0.01 M to 10 M.

10. The method according to claim 1, characterized in that... Y represents the chemical formula (II) of NH2 in the form of an aqueous solution with a concentration in the range of 0.2 to 0.4 M.

11. The method according to claim 1, characterized in that... The conversion is carried out at temperatures ranging from 20°C to 200°C.

12. The method according to claim 1, characterized in that... The conversion is carried out at a temperature ranging from 80°C to 110°C.

13. The method according to claim 1, characterized in that, Before the conversion, a compound with chemical formula (II) representing NH2 is brought into contact with ammonia.

14. The method according to claim 1, characterized in that... Contact a compound of chemical formula (II) with Y representing OH with an ammonium salt selected from the following: (NH4)H2PO4, (NH4)2HPO4, (NH4)3PO4, (NH4)HSO4, (NH4)2SO4, (NH4)HCO3 or (NH4)2CO3.

15. The method according to claim 1, characterized in that... The method is performed continuously.

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