Method for producing methionine

Abstract

The present invention relates to a process for preparing a compound of formula I by catalytic conversion of a compound of formula II: [Chemical formula 1] CH3XCH2CH2C(NH2)COOH (I) wherein X represents S or Se; [Chemical formula 2] CH3XCH2CH2C(Y)CN (II) wherein 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 comprising at least alumina, titanium dioxide, or a mixture thereof; when Y represents OH, the conversion is carried out in the presence of water and at least one catalyst comprising at least alumina, titanium dioxide, zirconia, or a mixture thereof, and NH3 or an ammonium salt.

Description

[Technical Field]

[0001] The present invention relates to an improved process for producing methionine or its "selenated" analogue (selenomethionine) from the precursors of methionine, 2-amino-4-methylthiobutyronitrile or 2-hydroxy-4-methylthiobutyronitrile, or from the precursors of selenomethionine, 2-amino-4-methylselenobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile. [Background technology]

[0002] The size of the methionine market is no longer necessary, especially in the field of animal nutrition. Its production methods are still the subject of numerous developments. Selenium derivatives of methionine are also of great interest in animal nutrition.

[0003] The preparation of methionine is carried out by a variety of methods involving various synthetic intermediates, in particular 2-amino-4-methylthiobutyronitrile (AMTBN), 2-amino-4-methylthiobutyramide (AMTBM) and 2-hydroxy-4-methylthiobutyronitrile (HMTBN).

[0004] Document WO 01 / 60790 A1 describes the synthesis of methionine from 2-hydroxy-4-methylthiobutyronitrile (HMTBN). By reaction with ammonia, HMTBN is converted to AMTBN, which is subsequently reacted with acetone in a basic medium to form AMTBM. Catalytic hydrolysis of AMTBM in the presence of a titanium compound of defined porosity gives the ammonium salt of methionine, from which methionine can be recovered.

[0005] According to document WO2004 / 089863A1, a method for preparing the ammonium salt of HMTBA from HMTBN, its nitrile precursor, is known, in which HMTBN in aqueous solution in the presence of a titanium-based catalyst is converted to the ammonium salt of HMTBA in one step. This synthesis also produces methionine and HMTBM, and the reported yield of the ammonium salt of HMTBA is in the range of 10%, which is too low to consider applying this method on an industrial scale. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention provides an alternative to known methods, allowing the omission of at least one step while still providing high yields of methionine or its selenized derivatives. [Means for solving the problem]

[0007] In accordance with the present invention, it has been discovered that amino-nitrile (AMTBN or its selenized equivalent) and hydroxy-nitrile (HMTBN or its selenized equivalent) intermediates can be converted to methionine (or methionine selenide) in one step in the presence of water and a catalyst, and, where appropriate, ammonia or an ammonium salt. The accessibility and performance of this conversion make it possible to consider its application to the industrial production of methionine. Compared with known synthetic methods and their improvements, which are insufficient to modify conventional industrial processes, the present invention represents a real advance. High yields can be obtained in very short times. DETAILED DESCRIPTION OF THE INVENTION

[0008] The present invention provides a process for the preparation of compounds of formula (I) by catalytic conversion of compounds of formula (II). [C1] CH3XCH2CH2C(NH2)COOH (I) Here, X represents S or Se. [Case 2] CH3XCH2CH2C(Y)CN (II) Here, X represents S or Se, and Y represents NH2 or OH.

[0009] when Y represents NH2, the conversion is carried out in the presence of water and at least one catalyst comprising at least alumina, titanium dioxide or a mixture thereof, and, where appropriate, NH3 or an ammonium salt; When Y represents OH, the conversion is carried out in the presence of water and at least one catalyst comprising at least alumina, titanium dioxide, zirconia or mixtures thereof, and NH3 or an ammonium salt.

[0010] In the present invention, "where appropriate" is to be understood as meaning that the presence of NH3 or an ammonium salt is required for processes involving hydroxy-nitrile precursors, which are compounds of formula (II) in which Y represents OH, while they are not required for processes involving amino-nitrile precursors, which are compounds of formula (II) in which Y represents NH2. However, this definition does not exclude the presence of NH3 when the process involves amino-nitrile precursors, and this variant constitutes a particular implementation of the invention as explained below.

[0011] The ammonium salt according to the present invention has the formula (NH4) n Any salt with A, where A is selected in particular from halogen, carbonate, hydrogencarbonate, phosphate, hydrogenphosphate, sulfate, hydrogensulfate, acetate, citrate, formate, hydroxide, and n is an integer from 1 to 5. By way of example, it may be selected from (NH4)H2PO4, (NH4)2HPO4, (NH4)3PO4, (NH4)HSO4, (NH4)2SO4, (NH4)HCO3, or (NH4)2CO3.

[0012] In the presence of such catalysts, the compound of formula (II) can be converted directly to methionine, whereas known methods from amino-nitrile or hydroxy-nitrile compounds require the passage through the corresponding amino-amide or hydroxy-nitrile intermediate, which is then hydrolyzed to methionine. Different operating conditions are used in each step.

[0013] In this document, unless otherwise specified, "Compound (II) where Y is NH," "AMTBN," and "amino-nitrile" are used interchangeably to refer to 2-amino-4-methylthiobutyronitrile, and analogously to 2-amino-4-methylselenobutyronitrile. Similarly, "Compound (II) where Y is OH," "HMTBN," and "hydroxy-nitrile" refer to 2-hydroxy-4-methylthiobutyronitrile, and analogously to 2-hydroxy-4-methylselenobutyronitrile. Compound (II) refers to all of these, and therefore should be understood to refer to these two compounds together or separately.

[0014] By "directly converted" it is to be understood that when the process is carried out on an industrial scale, the conversion takes place in one and the same reactor, which contains the catalyst and to which an aqueous mixture of compound (II) and, optionally, NH or an ammonium salt is fed, or each reactant is fed separately and mixed in the reactor.

[0015] The term catalyst is used generally to refer to the active phase of the catalyst, without excluding the point that the catalyst may be doped and / or supported.

[0016] Alumina, titanium dioxide and zirconia are to be understood as all polymorphs (where applicable) of aluminum oxide Al2O3, titanium dioxide TiO2 and zirconium dioxide ZrO2, respectively, which polymorphs are well known to those skilled in the art. The catalyst may be a combination of two or even three of alumina, titanium dioxide and zirconia. Furthermore, it may contain any other entity that promotes catalytic function.

[0017] The features, areas of application and advantages of the present invention are explained in more detail below. These features may be considered independently of one another or combined in any combination.

[0018] According to the invention, the catalyst comprises or consists of one or more compounds chosen from alumina, titanium dioxide and zirconia, constituting at least the active phase of the catalyst, and optionally a support. In other words, if the catalyst does not consist exclusively of one or more of the oxides mentioned above, it may contain other compounds that do not impair or even enhance the performance of the catalyst. In one variant of the invention, the catalyst consists of one of the oxides mentioned above.

[0019] The catalyst may be doped and / or supported. It may be doped with any element or compound known and conventionally used by those skilled in the art. By way of example, doping of the catalyst may be carried out with one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum and any compounds of the aforementioned elements. The following elements are preferred: K, Cs, Sr, Ba and La. If the catalyst does not consist exclusively of alumina, titanium dioxide and / or zirconia, it may be supported with any other compound known and conventionally used by those skilled in the art, in particular silica and silicoaluminates.

[0020] According to the present invention, all the above solid catalysts may be in the form of powders, preferably beads, extrudates, tablets, trilobes or other forms, and may be used in reactors, preferably fixed bed reactors, or batch reactors, open or pressurized.

[0021] The catalyst is preferably at least 10 m 2 / g. Below this limit, the catalyst performance rapidly decreases. In particular, the selectivity for methionine decreases in favor of AMBTM or HMTBM depending on the compound (II), and the conversion of compound (II) decreases. This is also observed with selenized equivalents. In the context of the present invention, the upper limit of the specific surface area is not critical and is determined by commercially available active phases. The specific surface areas given in this document are calculated by the most common method, i.e., the BET method using the physical adsorption of nitrogen.

[0022] In a preferred embodiment of the present invention, the catalyst is present in a mass concentration of between 0.1% and 200%, preferably between 0.5% and 100%, more preferably between 1% and 50%, relative to the mass of compound (II).

[0023] According to the invention, various batch or continuous reactors are possible for carrying out the reaction. In the reactor, the solid catalyst may be doped or undoped, immobilized in granules, extrudates or other forms, or supported on metal foam. Reactors with this type of catalyst are preferably fixed-tube or multi-tube bed reactors operated in trickle, isothermal or adiabatic flooded mode, or are catalyst-covered exchange reactors.

[0024] The conversion of AMTBN or HMTBN in the context of the present invention is preferably carried out at temperatures ranging from 20° C. to 200° C., further from 50° C. to 150° C., and even more preferably from 80° C. to 110° C. Over reaction times ranging from 10 minutes to 3 hours, it has been observed that at temperatures below 20° C., the reaction slows significantly, and that as the temperature increases, starting at 110° C., the selectivity for dinitriles and polypeptides increases at the expense of the selectivity for methionine. Above the range of 80° C. to 110° C., high selectivity for methionine has been observed.

[0025] Generally, the AMTBN or HMTBN is in an aqueous solution, which may be prepared for carrying out the process or may originate from the reaction medium in which the AMTBN or HMTBN, respectively, was produced. In this case, the AMTBN or HMTBN may not be pure, but may contain trace or even larger amounts, which may be negligible since they do not adversely affect the conversion of AMTBN or HMTBN according to the present invention.

[0026] The concentration of AMTBN or HMTBN may affect the performance of the process, depending on the conversion being carried out, particularly if the concentration is too high. Thus, according to a variant of the invention, AMTBN is present in aqueous solution at a concentration ranging from 0.01 M to 10 M, preferably from 0.05 M to 1 M, and more preferably from 0.2 M to 0.4 M. It is known that above 1 M or even 0.8 M, the selectivity for methionine decreases, while the selectivity for AMTBM, dinitriles, and polypeptides, respectively, increases, provided that the conversion to AMTBN remains dominant.

[0027] When the production of methionine according to the present invention involves HMTBN, ammonia should be added to the reaction medium. Ammonia is preferably present in an amount ranging from 1 to 50 equivalents relative to HMTBN. Ammonia may be introduced into the medium by any means, but is preferably supplied by continuous bubbling.

[0028] It has been observed that the presence of ammonia in the AMTBN solution prior to conversion significantly improves methionine selectivity, while dinitrile selectivity, which increases over time in the absence of ammonia, decreases. Therefore, the present invention relates to an advantageous implementation of the above process in which the AMTBN is placed in the presence of ammonia prior to contact with the catalyst and also during catalytic conversion in the reactor. Preferably, ammonia is introduced into the AMTBN solution by bubbling, optionally with an inert carrier gas such as nitrogen.

[0029] The present invention also relates to the continuous implementation of the process of the present invention in an AMTBN solution, preferably in the presence of ammonia, more preferably under ammonia bubbling, prior to the conversion. According to this variant, the process is carried out under a pressure of 1 to 20 bar, preferably 2 to 10 bar. The present invention therefore provides an apparatus comprising a vessel for the AMTBN solution, through which ammonia and nitrogen are bubbled. The AMTBN solution is pumped into a stainless steel reactor containing a catalyst and heated by a sleeve to a temperature of 80 to 100°C. The reaction medium is drawn into a gas-liquid separator, from which the ammonia is removed, and the liquid is treated to recover methionine. The solution is then evaporated until a solid is obtained, which is then recrystallized in a water / ethanol mixture (1 / 6) at 60°C. The white solid methionine thus obtained is washed, filtered, and dried. The continuous process described for obtaining methionine from AMTBN can also be applied to obtaining methionine from HMTBN, although the supply of ammonia is essential.

[0030] According to another aspect, there is provided a process for the controlled catalytic conversion of 2-amino-4-methylthiobutyronitrile or 2-amino-4-methylselenobutyronitrile, in turn, to 2-amino-4-methylthiobutyramide or 2-amino-4-methylselenobutyronitrile, wherein the conversion is carried out in the presence of at least one catalyst comprising or consisting of alumina or titanium dioxide.

[0031] The invention and its advantages are illustrated by the following examples.

[0032] Example 1: Preparation of methionine from AMTBN in the presence of TiO2 according to the present invention

[0033] The AMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [C3] JPEG0007785786000001.jpg25153

[0034] 65 g of AMTBN was introduced into a 1 liter screw-cap vial along with 1000 ml of HO. The solution was stirred at room temperature under a nitrogen flow (5 ml / min). 4 grams of TiO (anatase, 150 ml) was added at a flow rate of 5 ml / min (contact time 10 min). 2 The solution was injected into a tubular reactor containing 100° C. of 100% ethanol (1 / g, Norpro, ST 61120). The reaction was monitored by proton NMR over a period of 48 hours.

[0035] Conversion of AMTBN was over 90%, methionine yields averaged 74% with an average selectivity of 81%, and dinitrile yields averaged 11% with an average selectivity of 12%.

[0036] Example 2: Preparation of methionine from AMTBN in the presence of TiO and ammonia according to the present invention - Effect of the specific surface area of ​​TiO

[0037] The AMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [C4] TIFF0007785786000002.tif18140

[0038] 2.1 BET is 90m 2 / g of TiO2 (anatase type) 0.4g of TiO2 (anatase type) (90m 2 / g), followed by 0.1 g of AMTBN (98%) together with 2 ml of 28 wt % ammonia solution. After heating the solution at 90° C. for 10 min, the solution was filtered and analyzed by proton NMR.

[0039] The yield of methionine was 93%, the yield of AMTBM was 1%, and the yield of dinitrile was 6%.

[0040] 2.2 BET is 275m 2 / g of TiO2 (anatase type) 0.4g of TiO2 (anatase type) (275m 2 / g), followed by 0.1 g of AMTBN (98%) together with 2 ml of 28 wt % ammonia solution. After heating the solution at 90° C. for 10 min, the solution was filtered and analyzed by proton NMR.

[0041] The yield of methionine was 95%, the yield of AMTBM was 1%, and the yield of dinitrile was 4%.

[0042] A TiO2 catalyst with a BET of at least 90% is preferred.

[0043] Example 3: Preparation of methionine from AMTBN in the presence of doped titanium dioxide and ammonia according to the present invention

[0044] This example deals with the use of TiO2 doped with cesium and strontium, respectively. The doping was achieved by impregnating TiO2 with cesium hydroxide or strontium hydroxide. The cesium and strontium (non-metallic) contents were 4% by weight.

[0045] A 0.8 mol / L AMTBN solution was contacted with 5 g of any one of the doped catalysts at 100° C. for 10 minutes.

[0046] The results are shown in the table below.

[0047] [Table 1]

[0048] Example 4: Preparation of methionine from AMTBN in the presence of titanium dioxide and ammonia by the continuous process of the present invention

[0049] The AMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [5] JPEG0007785786000004.jpg23158

[0050] The catalyst is 150m2 / g specific surface area.

[0051] 5 g of the catalyst was placed in a reactor in which a 0.1 mol / L aqueous AMTBN 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.

[0052] The results are shown in Table 2 below.

[0053] [Table 2]

[0054] The system was stable in terms of conversion and selectivity, with high methionine selectivity (90%), very high AMTBN conversion (96%), and very low selectivity to other products. The yields of methionine and AMTBM were 86% and 2%, respectively.

[0055] Example 4: Preparation of methionine from HMTBN in the presence of titanium dioxide and diammonium hydrogen phosphate according to the present invention

[0056] The HMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [6] JPEG0007785786000006.jpg25149

[0057] 13.1 g of HMTBN was introduced into a 1-liter screw-cap vial with 1000 ml of HO. The solution was stirred at room temperature under a nitrogen flow (5 ml / min). 4 grams of TiO (anatase, 150 ml) was added at a flow rate of 0.1 ml / min (contact time 10 min). 2 The solution was poured into a tubular reactor containing methionine (Met-2000) ...

[0058] Example 5: Preparation of methionine from HMTBN in the presence of titanium dioxide and ammonia according to the present invention

[0059] The HMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [7] JPEG0007785786000007.jpg27154

[0060] 13.1 g of HMTBN was placed in a 1-liter screw-cap vial with 1000 ml of H2O. The solution was stirred at room temperature under a flow of ammonia at a rate of 100 ml / min. 6 grams of TiO2 (anatase, 150 m) was added at a flow rate of 0.1 ml / min (contact time 15 min). 2 The solution was poured into a tubular reactor containing methionine (Met-1000 / g, Norpro, ST 61120) heated to 90° C. The reaction was monitored by HPLC and the yield of methionine was 80%.

[0061] Example 6: Preparation of methionine from HMTBN in the presence of titanium dioxide but without an ammonia source according to the prior art

[0062] The HMTBN hydrolysis reaction and the conditions under which it occurs are shown in the diagram below. [8] JPEG0007785786000008.jpg25160

[0063] 13.1 g of HMTBN was introduced into a 1-liter screw-cap vial with 1000 ml of HO. The solution was stirred at room temperature under a nitrogen purging. 4 grams of TiO (anatase, 150 ml) was added at a flow rate of 0.1 ml / min (contact time 10 min). 2 The solution was poured into a tubular reactor containing 100% HMTBA (HMTBA / g, Norpro, ST 61120) heated to 160° C. The reaction was monitored by HPLC, and the yield of HMTBA was 1% and the yield of methionine was 15%.

[0064] Comparing the results of Examples 4 and 5 of the present invention with those of Example 6, which was carried out using a method without ammonia or ammonium salts, shows that the method of the present invention provides a significant improvement in the performance of methionine production. The same advantage is observed in the production of selenomethionine.

Claims

1. A process for preparing a compound of formula I by catalytic conversion of a compound of formula II, comprising: [Chemical formula 1] CH ３ XCH ２ CH ２ C(NH) ２ )COOH (I) Here, X represents S, [Case 2] CH ３ XCH ２ CH ２ C(Y)CN (II) where X represents S and Y represents NH ２ or OH, Y is NH ２ wherein the conversion is carried out in the presence of water and at least one catalyst comprising at least titanium dioxide; When Y represents OH, the conversion is carried out in the presence of water, at least one catalyst comprising at least titanium dioxide, and NH ３ or an ammonium salt.

2. 10. The method of claim 1, with compounds of formula II in which Y represents OH, The conversion is carried out in a solvent containing water, at least one catalyst comprising or consisting of at least titanium dioxide, and NH ３ or an ammonium salt.

3. In the method of claim 1 or 2, A method for preparing the catalyst, characterized in that the catalyst is doped with one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum and compounds of any of the aforementioned elements.

4. In the method of claim 3, The catalyst is doped with at least one of K, Cs, Sr, and Ba.

5. The method of any one of claims 1 to 4, The catalyst is at least 10 m ２ / g BET specific surface area.

6. The method of any one of claims 1 to 5, The catalyst is present in a mass concentration of 0.1% to 200% relative to the mass of the compound (II).

7. In any one of the methods of claims 1 to 6, The catalyst is present in a mass concentration of 0.5% to 100% relative to the mass of the compound (II).

8. In any one of the methods of claims 1 to 7, The catalyst is present in a mass concentration of 1% to 50% relative to the mass of the compound (II).

9. The method of any one of claims 1 to 8, Y is NH ２ wherein the compound of formula (II) is in an aqueous solution having a concentration ranging from 0.01 M to 10 M.

10. In any one of the methods of claims 1 to 9, A method of preparation characterized in that said compound of formula (II) in which Y represents NH2 is in an aqueous solution having a concentration ranging from 0.05M to 1M.

11. In any one of the methods of claims 1 to 10, A method of preparation characterized in that said compound of formula (II) in which Y represents NH2 is in an aqueous solution having a concentration ranging from 0.05M to 1M.

12. The method of any one of claims 1 to 11, The process is characterized in that the conversion is carried out at a temperature ranging from 20°C to 200°C.

13. The method of any one of claims 1 to 12, The process is characterized in that the conversion is carried out at a temperature ranging from 50°C to 150°C.

14. The method of any one of claims 1 to 13, The process is characterized in that the conversion is carried out at a temperature ranging from 80°C to 110°C.

15. The method of any one of claims 1 to 14, Prior to the conversion, Y is NH ２ a process for preparing the compound of formula (II)

16. The method of any one of claims 1 to 15, The compound of formula (II) in which Y represents OH is (NH ４ ) H ２ P.O. ４ , (NH ４ ) ２ HPO ４ , (NH ４ ) ３ P.O. ４ , (NH ４ ) HSO ４ , (NH ４ ) ２ SO ４ , (NH ４ ) HCO ３ , or (NH ４ ) ２ CO ３ The method for preparing the compound is characterized in that the compound is placed in the presence of an ammonium salt selected from the group consisting of:

17. The method of any one of claims 1 to 16, The preparation method is characterized in that the method is carried out continuously.

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