Methionine manufacturing process

Abstract

The invention relates to the preparation of a compound of formula I, where X represents S or Se, by catalytic conversion of a compound of formula II where X represents S or Se and Y represents NH2 or OH, said conversion being carried out in the presence of water, at least one catalyst comprising or consisting of at least one of alumina, titanium dioxide and zirconia, and, where appropriate, NH3 or an ammonium salt.

Description

Description Title of the invention: Process for manufacturing methionine

[0001] | The invention relates to an improvement of a process for manufacturing methionine or its selenium analogue (selenomethionine), from the precursors 2-amino-4-methylthiobutyronitrile or 2-hydroxy-4-methylthiobutyronitrile for the me- thionine, or 2-amino-4-methylselenobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile for selenomethionine.

[0002] The size of the methionine market is well established, particularly in Animal nutrition, and its manufacturing processes, are still the subject of much research. developments. Selenite derivatives of methionine are also constituents of major interest in animal nutrition.

[0003] — The preparation of methionine can be carried out by various processes involving various intermediate synthesis methods, and in particular the 2-amino-4-methylthiobutyronitrile (AMTBN), 2-amino-4-methylthiobutyramide (AMTBM) and 2-hydroxy-4-methylthiobutyronitrile (HMTBN).

[0004] — Document WO0O1 / 60790A1 describes a synthesis of methionine from the 2-Hydroxy-4-methylthiobutyronitrile (HMTBN). By reaction with ammonia, HMTBN is transformed into AMTBN which, in turn, is reacted with acetone into A basic medium is used to form AMTBM. A catalytic hydrolysis of AMTBM, in the presence of a titanium compound with a specific porosity leads to the me- ammonium thionate from which methionine is recovered.

[0005] A process for manufacturing salt is known according to document WO2004 / 089863A1 ammonium of HMTBA from the nitrile precursor of HMTBA, HMTBN, according to which HMTBN in aqueous solution, placed in the presence of a catalyst based on titanium is converted in a single step to the ammonium salt of HMTBA. This synthesis also leads to the formation of methionine and HMTBM, and yields The levels reported in ammonium scl of HMTBA are on the order of 10%. They are too in- sufficient to consider applying this process on an industrial scale.

[0006] The present invention provides an alternative to existing processes allowing to to bypass at least one step, while still leading to methionine or its derivative selenized, in high yields.

[0007] It has been discovered according to the invention that amino-nitrile intermediates (AMTBN or its selenium equivalent) and hydroxynitrile (HMTBN or its selenium equivalent) could be converted into methionine (or selenomethionine) in a single step, in the presence of water and a catalyst and, where applicable, ammonia or a salt of ammonium. The accessibility and performance of this conversion are such that its Adapting methionine production to an industrial scale is conceivable. Compared to Compared to known synthesis processes and their improvements, which remain insufficiently beneficial to justify modifying conventional industrial processes, the present invention represents a genuine advance. Significant yields are obtained in very short times. Thus, the invention provides a method for preparing a compound of formula (I), [Chem 1] CH,XCH,CH,C(NH,)COOH (I) where X represents S or Se, by catalytic conversion of a compound of formula (IT) [Chem 2] CH,XCH,CH,C(Y)CN (ID where X represents S or Se and Ÿ represents NH, or OH, said conversion being carried out in the presence of water, at least one catalyst comprising or consisting of at least one of alumina, titanium dioxide and zirconia, and, where appropriate, NH; or an ammonium salt. The expression "where applicable" is meant according to the invention that, when the process involves the hydroxynitrile precursor, which is the compound of formula (II) in which Y represents OH, the presence of NH₄⁺, or an ammonium salt, is necessary, whereas it is not necessary when the process involves the aminonitrile precursor, which is the compound of formula II in which Y represents NH₄⁺. This definition does not, however, exclude the presence of NH₄⁺ when the process involves the aminonitrile precursor, this variant constituting a particular embodiment of the invention, described later. An ammonium salt according to the invention comprises any salt corresponding to the formula (NH4)HPO4, where A is selected in particular from among the halogens, carbonates, hydrogen carbonates, phosphates, hydrogen phosphates, sulfates, hydrogen sulfates, acetate, citrate, formate, hydroxide, and n is an integer ranging from 1 to 5. By way of illustration, it may be selected from (NH4)HPO4, (NH2)HPO4, (NH4)PO4, (NH4)HSO4, (NH5)5SO4, (NH2)HCO3, or (NH4)CO4 In the presence of such a catalyst as above, the compound of formula (II) can be directly transformed into methionine, whereas the processes known from the amino-nitrile compound or the hydroxy-nitrile compound require passing through the corresponding amino-amide or hydroxy-nitrile intermediate, which is then hydrolyzed into methionine, each of the steps employing different operating conditions. In this text, unless otherwise specified, the terms "compound (IT) where Y is NH;", "AMTBN" and "amino-nitrile" will be used interchangeably to refer to 2-amino-4-methylthiobutyronitrile, and by analogy, the 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. By compound (II), we mean all these denominations and therefore these two compounds, taken together or separately. By "transformed directly", we must understand that, when the process is carried out on an industrial scale, the transformation can be conducted in a single reactor which includes the catalyst, the reactor being fed with a mixture of water, compound (II) and optionally NH, or ammonium salt, or by each of the reactants separately, their mixing being carried out in the reactor. The term catalyst as used generally refers to the active phase of the catalyst, without excluding the fact that the catalyst may be doped and / or supported. Alumina, titanium dioxide, and zirconia are understood to mean all polymorphs, where applicable, of aluminum oxide (AlsO3), titanium dioxide (TiO2), and zirconium dioxide (ZrO2), respectively, these forms being well known to those skilled in the art. The catalyst may also be a combination of two or even three alumina, titanium dioxide, and zirconia. It may also include any other entity that promotes its catalytic function. The features, applications and advantages of the invention are set out in more detail below, it being understood that these features can be considered independently of each other, or in combination, whatever the combination. According to the invention, the catalyst comprises or consists of one or more compounds selected from alumina, titanium dioxide, and zirconia; it / they constitute at least the active phase of the catalyst, optionally the support. Thus, if the catalyst is not entirely composed of one or more of said oxides, it may comprise any other compound that does not affect the performance of the catalyst, or may even enhance it. In one embodiment of the invention, the catalyst consists of one of said oxides. The catalyst can be doped and / or supported. It can be doped with any element or compound commonly used and well known to those skilled in the art. By way of illustration, the catalyst can be doped with one or more elements and compounds chosen from among the alkali metals, alkaline earth metals, lanthanum, and any compound of the aforementioned elements. The following elements are preferred: potassium (K), cervin (Cs), sr (Sr), ba (Ba), and laminar (La). If the catalyst does not consist solely of alumina, titanium dioxide, and / or zirconia, it can also be supported by any other compound commonly used and well known to those skilled in the art, and in particular silica and silicoaluminates. According to the invention, all the solid catalysts mentioned above can be in powder form or preferably in the form of beads, extruded, tablet, trilobe or any other form allowing them to be used in a reactor, preferably a fixed bed reactor or others or in batch mode in an open or pressurized reactor. The catalyst advantageously has a specific surface area of ​​at least 10 m² / g. Below this limit, the catalyst's performance drops rapidly, notably with a decline in methionine selectivity in favor of AMBTM or HMTBM selectivity, depending on the compound (II), and a decrease in the conversion of the compound (ID). This observation applies to the selenium equivalent. The upper limit of the specific surface area is not critical within the scope of the invention, as it is dictated by commercially available active phases. The specific surface area values ​​indicated herein are determined by the most common method, namely nitrogen physisorption, and calculated using the BET method. In a preferred embodiment of the process of the invention, the catalyst is present in a mass concentration of 0.1% to 200% relative to the mass of the compound (ID), preferably from 0.5% to 100% and even better from 1% to 50%. According to the invention, different equipment can be used to carry out the reaction in batch or continuous mode: the solid catalyst, doped or undoped, can be immobilized in a reactor in the form of grains or extrudates or any other form, or supported on a metallic foam. The reactor associated with this type of catalyst is preferably a fixed tubular or multitubular bed, operated in isothermal or adiabatic trickling or submerged mode, or a catalyst-coated heat exchanger reactor. The conversion of AMTBN or HMTBN within the framework of the invention is advantageously carried out at temperatures ranging from 20°C to 200°C, or even from 50°C to 150°C, and better still from 80°C to 110°C. It has been observed, over a reaction period ranging from approximately 10 minutes to 3 hours, that at temperatures below 20°C, the reaction is significantly slowed, and that from 110°C onwards, the higher the temperature, the greater the selectivity for dinitrile and methionine polypeptide at the expense of that for methionine. In the range of 80°C to 110°C, the selectivity for methionine is observed to be high. AMTEBN or HMTBN is generally in aqueous solution. This solution may have been prepared for the implementation of the process, or may originate from a reaction medium in which the AMTBN or HMTBN was produced, respectively. In this case, the AMTBN or HMTBN may not be pure and may contain traces, or even larger quantities, but these remain negligible as they do not adversely affect the conversion of the AMTBN or HMTBN according to the invention. The concentration of AMTBN or HMTBN, depending on the transformation implemented, can influence the performance of the process, particularly when it is too high. Thus, according to one embodiment of the invention, AMTBN is in aqueous solution at a concentration ranging from 0.01 M to 10 M, preferably of 0.05 M to 1 M, and even better from 0.2 M to 0.4 M. It has been noted that beyond | M, or even 0.8 M, if the conversion to AMTBN remains strong, the selectivity in methionine decreases while that in AMTBM, in dinitrile and even in polypeptide, respectively, increases. When the manufacture of methionine according to the invention involves HMTBN, ammonia should be added to the reaction medium. Preferably, it is present in a concentration ranging from 1 to 50 equivalents relative to the HMTBN ammonia. The ammonia can be added to the medium by any technique, but advantageously, it is supplied by continuous bubbling. It has been observed that the presence of ammonia in the AMTBM solution prior to its conversion significantly improves methionine selectivity while decreasing dinitrile selectivity, which increases over time in the absence of ammonia. The invention thus relates to an advantageous implementation of the process described above, in which the AMTBN is exposed to ammonia before contact with the catalyst, or even during the catalytic conversion within the reactor. Preferably, ammonia is introduced into the AMTBN solution by bubbling, possibly using an inert carrier gas such as nitrogen. The invention also relates to the implementation of the process of the invention continuously, advantageously in the presence of ammonia, and even more preferably with ammonia bubbling, in the AMTBN solution, prior to its conversion. According to this embodiment, the process is conducted under a pressure of 1 to 20 bar, preferably 2 and 10 bar. Thus, the invention provides a device comprising a tank for the AMTBN solution in which a mixture of ammonia and nitrogen is bubbling. The AMTBN solution is pumped to a stainless steel reactor containing the catalyst, which is heated by means of a sleeve to a temperature of 80 to 100°C. The reaction mixture is drawn off to a gas / liquid separator from which the ammonia is removed and from which the liquid is treated to recover the methionine. The solution is then evaporated until a solid is obtained, then the solid is recrystallized in a water / ethanol mixture (1 / 6) at 60°C.The methionine thus obtained in the form of a white solid is washed, filtered, and then dried. This continuous process described for obtaining methionine from AMTBN applies identically to obtaining methionine from HMTBN, although the addition of ammonia is essential. In another aspect, a controlled catalytic transformation process of 2-amino-4-methylthiobutyronitrile or of 2-amino-4-methylselenobutyronitrile to 2-amino-4-methylthiobutyramide or 2-amino-4-methylselenobutyramide, respectively, said conversion is carried out in the presence of at least one catalyst comprising or consisting of alumina, titanium dioxide and zirconia. The invention and its advantages are illustrated in the following examples. Example 1: Preparation of methionine from AMTBN in the presence of TiO₂, according to the invention The hydrolysis reaction of AMTEBN and the conditions under which it is carried out are described in the diagram below. [Chem.3] 49 Ti0.9 Ace + H20 + N, same BC 0ù NH, EE valteaïn 1D0°C NH, 5 moist sms os mimi mature s 74% In a 1-liter screw-top bottle, 65 g of AMTBN are introduced with 1000 ml of H₂O. The solution is stirred at room temperature with a nitrogen flow (5 ml / min). The solution is then injected into a tubular reactor heated to 100°C at a flow rate of 0.1 ml / min (contact time 10 minutes) containing 4 grams of TiO₂ (Anatasc, 150 m³ / g, Norpro, ST 61120). The reaction is monitored for 48 hours by proton NMR. The conversion of AMTBN is greater than 90%, the methionine yield averages 74% with an average selectivity of 81%, and the dinitrile yield averages 11% with an average selectivity of 12%. Example 2: Preparation of methionine from AMTBN in the presence of TiO₂ and ammonia, according to the invention — Influence of the specific surface area of ​​TiO₂; The hydrolysis reaction of AMTBN and the conditions under which it is carried out are described in the diagram below. [Chem.4] , NH, (28% wt} 2m 90°, 10 min CN S. UV, (30 ï 0.49 Ti02 s 2 9 Pt VE BA = NH S oH 90°, 10 ei qe M NH, A 0.19 2.1 TiO₂, (as anatase) with a BET of 90 m7 / g In a 10 mL bottle, 0.4 g of TiO₂ (as anatase) (90 µm / g) and then 0.1 g of AMTBN (98%) were introduced with 2 mL of a 28% wt. ammonia solution. The solution was heated to 90°C for 10 minutes, after which it was filtered and analyzed by proton NMR. The yields are 93% for methionine, 1% for AMTBM and 6% for dinitrile. 2.2 TiO₂, (as anatase) with a BET of 275 mμ / g In a 10 mL bottle, 0.4 g of TiO₂ (as anatase) (275 µm / g) and then 0.1 g of AMTBN (98%) were introduced with 2 mL of a 28% wt. ammonia solution. The solution was heated to 90°C for 10 minutes, after which it was filtered and analyzed by proton NMR. The yields are 95% for methionine, 1% for AMTBM and 4% for dinitrile. A TiO catalyst with a BET of at least 90% is preferred. Example 3: Preparation of methionine from AMTBN, in the presence of doped titanium dioxide and ammonia, according to the invention This example involves the use of TiO₂ doped with cesium and strontium, respectively. The doping was carried out by an impregnation method of TiO₂ with cesium hydroxide or strontium hydroxide, with a content of 4% by mass of cesium and strontium (non-metallic). A 0.8 mol / L AMTBN solution is contacted with 5 g of either of the doped catalysts for 10 minutes at a temperature of 100°C. The results are presented in Table 1 below. [Table 1] [Doping Conversion | Selectivity | Selectivity | Selectivity | Selectivity of AMTBN | in Met in AMTBM jen dinitrile | in other Cs 95% 88% [0% 7% 5% = 96% 80% [13% = = Example 4: Preparation of methionine from AMTBN in the presence of titanium dioxide and ammonia according to a continuous process of the invention. The hydrolysis reaction of AMTBN and the conditions under which it is carried out are described in the diagram below. [Chem.5] 5g, THO, s. CN hu s CESSE ttes …- CONK, LS COH NH; 10 mLimin 106°C "4 € en 81morL The catalyst is a titanium oxide with a specific surface area of ​​150 m² / g. Five grams of this catalyst are placed in the reactor where a 0.1 mol / L aqueous solution of AMTBN is circulated at a flow rate of 0.2 mL / min, and an ammonia flow rate of 10 mL / min. The reaction temperature is 100°C and the contact time is 6 minutes. The results are presented in Table 2 below. [Tables 2] Conversion Time | Selectivity | Selectivity | Selectivity | Selectivity followed by AMTBN | to Met to AMTBM to dinitrile | to others 1h 94% 88% 5% 3% 4% 4h 96% 90% 2% 4% 4% The system is observed to be stable in conversion and selectivity, with high selectivity for methionine (90%), very high conversion of AMTBN (96%), and low selectivity towards other products. The yields for methionine and AMTBM are 86% and 2%, respectively. Example 4: Preparation of methionine from HMTBN, in the presence of titanium dioxide and diammonium hydrogen phosphate, according to the invention. The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below. [Chem.6] 49102 £ 8 N DSSOLUS LA 4 (NH HPO me SLT 08 ÔH 2 160°C NH, Hu 1 1, 16076 NH, 0.4 mob. 209 0.4 malin Yield: 475 In a 1-liter screw-top bottle, 13.1 g of HMTBN are introduced with 1000 ml of H₂O. The solution is stirred at room temperature with a nitrogen flow. The solution is then injected into a tubular reactor heated to 160°C at a flow rate of 0.1 ml / min (contact time 10 minutes) and containing 4 grams of TiO₂ (anatase, 150 m³ / g, Norpro, ST 61120). The reaction is monitored by HPLC; the methionine yield is 47%. Example 5: Preparation of methionine from HMTBN, in the presence of titanium dioxide and ammonia, according to the invention The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below. [Chem.7] 8970; 9 PÉL0A0N LH ORNH D AS 08 OH 0 sec NH, OH 10 ac 0.1 mL / min 0.1 mL / min In a 1-liter screw-top bottle, 13.1 g of HMTBN were introduced with 1000 mL of H₂O. The solution was stirred at room temperature with an ammonia flow rate of 100 mL / min. The solution was then injected into a tubular reactor heated to 90°C at a flow rate of 0.1 mL / min (contact time 15 minutes) and containing 6 grams of TiO₂ (anatase, 150 mL / g, Norpro, ST 61120). The reaction was monitored by HPLC. The yield in 80% methionine. Example 6: Preparation of methionine in the presence of titanium dioxide, from HMTBN but without a source of ammonia, according to the prior art. The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below. [Chem.8] + 03 —meeeeeeceereeeeeeennnce it 160°G 49 Ti0, LA 9 8. CN EN 8 À ' vi +5 —— OH + - nas oH ÔH , 16016 OH NH, 0.1 mph eo A0 + OH Yield: 1% 0.1 LS word yield: 1% yield: 15% In a 1-liter screw-top bottle, 13.1 g of HMTBN were introduced with 1000 mL of H₂O. The solution was stirred at room temperature with a nitrogen flow. It was then injected into a tubular reactor heated to 160°C at a flow rate of 0.1 mL / min (contact time 10 minutes) and containing 4 grams of TiO₂ (anatase, 150 mO₂ / g, Norpro, ST 61120). The reaction was monitored by HPLC. The yield of HMTBA was 1% and of methionine 15%. Comparing the results of Examples 4 and 5 according to the invention with those obtained in a process conducted without ammonia or ammonium salt in Example 6 demonstrates a considerable improvement in the performance of methionine production in a process of the invention. The same benefit is observed in the production of selenomethionine.

Claims

Demands

1. Process for preparing a compound of formula I, [Chem 1] CH,XCH,CH,C(NH,)COOH (D where X represents S or Se, by catalytic conversion of a compound of formula II [Chem 2] CH,XCH,CH,C(Y)CN (ID where X represents S or Se and Ÿ represents NH, or OH, characterized in that said conversion is carried out in the presence of water, of at least one catalyst comprising at least one of the alumina, of the titanium dioxide and zirconia, and, where applicable, NH3, or a salt ammonium.

2. The method according to claim 1, characterized in that it involves the compound of formula II in which Y represents OH and said The conversion is carried out in the presence of water and at least one catalyst. comprising or consisting of at least one of alumina, dioxide titanium and zirconia, and NH; or an ammonium se!

3. A method according to claim 1 or 2, characterized in that said ca- the talyzer is doped, preferably it is doped with one or more of the elements and compounds selected from the alkali metals, the metals alkaline earth metals, lanthanum and any compound of the aforementioned elements, and of preference at least one of K, Cs, Sr, Ba.

4. A method according to any one of claims 1 to 3, characterized in that said catalyst has a specific surface area BET of at least 10 m? / g.

5. A method according to any one of claims 1 to 4, characterized in the catalyst is present in a mass concentration of 0.1% to 200% relative to the mass of compound (II), preferably from 0.5% to 100% and even better, from 1% to 50%.

6. A method according to any one of claims | to 5, characterized in the compound of formula (IT) with Y representing NH, is in solution aqueous in a concentration ranging from 0.01 M to 10 M, preferably of 0.05M to 1M, and even better from 0.2 to 0.4M.

7. A method according to any one of claims 1 to 6, characterized in that the conversion is carried out at a temperature ranging from 20°C to 200°C, preferably from 50°C to 150°C, and even better from 80°C to 110°C.

8. A method according to any one of claims 1 to 7, characterized in that, before conversion, the compound of formula (II) with Ÿ re- containing NH; is placed in the presence of ammonia.

9. A method according to any one of claims 1 to 7, characterized in the compound of formula (II) with Y representing OH, is put in presence of an ammonium salt chosen from (NH₄)HPO₄, (NH₄)HPO₄, (NH2)3PO, (NH3)HSO, (NH4)HCO3, (NA)HCO3, or (NA)CO3;

10. A method according to any one of claims 1 to 9, characterized in which is conducted continuously.