RU2841085C1 - Method of producing methionine - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula CH₃XCH₂CH₂C(NH₂)COOH (I) by catalytic conversion of a compound of formula CH₃XCH₂CH₂C(Y)CN (II). In formulas (I) and (II) X is S or Se, and Y is NH₂ or OH. When Y is NH₂, the conversion is carried out in the presence of water and at least one catalyst containing at least titanium dioxide, and when Y is OH, the conversion is carried out in the presence of water, at least one catalyst containing at least titanium dioxide, and NH₃ or ammonium salt.

EFFECT: disclosed method provides an alternative to existing methods, avoids at least one step and leads to methionine or a selenium derivative thereof with high output.

10 cl, 2 tbl, 6 ex

Description

The invention relates to an improvement in the method for producing methionine or its "selenated" analogue (selenomethionine) from precursors of 2-amino-4-methylthiobutyronitrile or 2-hydroxy-4-methylthiobutyronitrile in the case of methionine, or 2-amino-4-methylselenobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile in the case of selenomethionine.

The size of the methionine market no longer needs an introduction, especially in animal feed, and its production methods are still the subject of much development. Selenated methionine derivatives are also of considerable interest in animal nutrition.

The production of methionine can be accomplished by a variety of routes involving various synthesis intermediates, including 2-amino-4-methylthiobutyronitrile (AMTBN), 2-amino-4-methylthiobutyramide (AMTBM), and 2-hydroxy-4-methylthiobutyronitrile (HMTBN).

Document WO01/60790A1 describes the synthesis of methionine from 2-hydroxy-4-methylthiobutyronitrile (HMTBN). When reacted 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 having a certain porosity leads to the formation of ammonium methioninate, from which methionine is isolated.

According to document WO2004/089863A1, a process is known for the preparation of the ammonium salt of HMTBA from the nitrile precursor of HMTBA - HMTBN, according to which HMTBN in an aqueous solution in the presence of a titanium-based catalyst is converted into the ammonium salt of HMTBA in one step. This synthesis also leads to the formation of methionine and HMTBM, and the reported yields of ammonium salts of HMTBA are in the range of 10%. They are too small to consider the possibility of using this process on an industrial scale.

The present invention provides an alternative to existing processes that eliminates at least one step, resulting in methionine or its selenized derivative in high yields.

According to the invention, it has been found that intermediate aminonitrile (AMTBN or its selenated equivalent) and hydroxynitrile (HMTBN or its selenated equivalent) compounds can be converted into methionine (or into selenomethionine) in one step in the presence of water and a catalyst and, if necessary, ammonia or an ammonium salt. The availability and characteristics of this conversion are such that it is possible to scale it up to industrial production of methionine. Compared with known synthesis methods and their improvements, which remain insufficiently useful for modifying traditional industrial methods, the present invention represents a real advance. Significant yields are achieved in a very short time.

Thus, the invention relates to a process for preparing a compound of formula (I),

[Him 1]

CH ₃ XCH ₂ CH ₂ C(NH ₂ )COOH (I)

where X is S or Se,

by catalytic conversion of a compound of formula (II)

[Him 2]

_CH3XCH2CH2C ( _Y )CN(II ₎

where X is S or Se and Y is _NH2 or OH,

wherein when Y is NH ₂ , the conversion is carried out in the presence of water and at least one catalyst containing at least aluminum oxide, titanium dioxide or a mixture thereof, and, if necessary, NH ₃ or an ammonium salt, and

when Y is OH, the conversion is carried out in the presence of water, at least one catalyst containing at least aluminum oxide, titanium dioxide, zirconium dioxide or a mixture thereof, and NH ₃ or ammonium salts.

By the expression "if necessary" in accordance with the present invention it is to be understood that when the process involves a hydroxynitrile precursor, which is a compound of formula (II) in which Y is OH, the presence of NH ₃ or an ammonium salt is necessary; but this is not necessary when the process involves an aminonitrile precursor, which is a compound of formula II in which Y is NH ₂ . However, this definition does not exclude the presence of NH ₃ if the process involves an aminonitrile precursor - this variant is one of the possible embodiments of the invention described below.

The ammonium salt according to the invention includes any salt having the formula (NH ₄ ) _n A, where A is in particular selected from halogens, carbonates, hydrogen carbonates, phosphates, hydrogen phosphates, sulfates, hydrogen sulfates, acetate, citrate, formate, hydroxide, and n is an integer from 1 to 5. By way of illustration, it can be selected from (NH ₄ )H ₂ PO ₄ , (NH ₄ ) ₂ HPO ₄ , (NH ₄ ) ₃ PO ₄ , (NH ₄ ) HSO ₄ , (NH ₄ ) ₂ SO ₄ , (NH ₄ ) HCO ₃ or (NH ₄ ) ₂ CO ₃ .

In the presence of such a catalyst as described above, the compound of formula (II) can be converted directly to methionine, whereas the known methods using an aminonitrile compound or a hydroxynitrile compound require passage through the corresponding aminoamide or hydroxynitrile intermediate, which is then hydrolyzed to methionine, with different conditions being used at each stage.

In the present text, unless otherwise indicated, the expressions "compound (II) wherein Y is _NH2 ", "AMTBN" and "aminonitrile" will be used interchangeably to refer to 2-amino-4-methylthiobutyronitrile and, by analogy, 2-amino-4-methylselenobutyronitrile. Likewise, the expressions "compound (II) wherein Y is OH", "HMTBN" and "hydroxynitrile" refer to 2-hydroxy-4-methylthiobutyronitrile and, by analogy, to 2-hydroxy-4-methylselenobutyronitrile. Compound (II) shall be understood to include all of these designations and, therefore, the two compounds, considered together or separately.

By the expression "directly convertible" it is to be understood that when the process is carried out on an industrial scale, the conversion may be carried out in the same reactor which contains the catalyst, the aqueous mixture, the compound (II) and optionally NH ₃ or ammonium salt, or each of the reactants separately, being fed into the reactor and their mixing being carried out in the reactor.

The term "catalyst" as used herein generally refers to the active phase of the catalyst, without excluding the fact that the catalyst may be doped and/or supported.

By aluminum oxide, titanium dioxide and zirconium dioxide it is meant all polymorphs, where applicable, of aluminum oxide Al ₂ O ₃ , titanium dioxide TiO ₂ and zirconium dioxide ZrO ₂ , respectively, these forms being well known to those skilled in the art. The catalyst may also be a combination of two or even three of aluminum oxide, titanium dioxide and zirconium dioxide. It may also contain any other substance that contributes to its catalytic function.

The features, applications and advantages of the invention are set out below in more detail, taking into account that these features can be considered independently of each other or in combination, regardless of the nature of the combination.

According to the invention, the catalyst comprises or consists of one or more compounds selected from aluminum oxide, titanium dioxide and zirconium dioxide; it/they constitute at least the active phase of the catalyst, and optionally the support. Thus, if the catalyst does not consist entirely of one or more of the said oxides, it may contain any other compound that does not affect the characteristics of the catalyst or even enhances them. In one embodiment of the invention, the catalyst consists of one of the 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. As an illustration, the doping of the catalyst can be performed with one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum and any compound of the above-mentioned elements. The elements K, Cs, Sr, Ba and La are preferred. If the catalyst does not consist exclusively of aluminum oxide, titanium dioxide and/or zirconium dioxide, it can also be supported on any other compounds commonly used and well known to those skilled in the art, and in particular silicon dioxide and silicoaluminates.

According to the invention, all the solid catalysts mentioned above may be in powder form or, preferably, in the form of granules, extrudates, tablets, in the form of a trefoil or any other form allowing their use in a reactor, preferably in a fixed bed reactor or others, or in a batch mode in an open reactor or a reactor under pressure.

Said catalyst preferably has a specific surface area of at least 10 m²/g. Below this limit, the performance of the catalyst drops rapidly, in particular the selectivity towards methionine decreases in favour of the selectivity towards AMBTM or HMTBM according to compound (II) and the conversion of compound (II) decreases. This observation also applies to the selenium equivalent. The upper limit of the specific surface area is not critical in the context of the invention and is limited by commercially available active phases. The values of the specific surface area specified in the present text are determined by the most common method, namely the physical adsorption of nitrogen, and are calculated by the BET (Brunauer-Emmett-Teller) method.

In a preferred embodiment of the process according to the invention, the catalyst is present in a concentration of from 0.1 wt.% to 200 wt.% based on the weight of compound (II), preferably from 0.5 wt.% to 100 wt.% and even more preferably from 1 wt.% to 50 wt.%.

According to the invention, various equipment for carrying out the reaction in a batch or continuous mode can be considered: the solid catalyst, doped or not, can be immobilized in the reactor in the form of grains or extrudates or in any other form or be applied to a metal foam. The reactor associated with this type of catalyst is preferably a fixed tubular or multi-tubular bed operating in a spray or isothermal or adiabatic flooding mode, or an exchange reactor coated with a catalyst.

The conversion of AMTBN or HMTBN in the context of the present invention is preferably carried out at a temperature in the range of 20 °C to 200 °C or even 50 °C to 150 °C, and even more preferably from 80 °C to 110 °C. It has been observed that during the reaction period of about 10 minutes to 3 hours, at a temperature below 20 °C the reaction slows down considerably, and that, starting from 110 °C, the more the temperature increases, the more the selectivity for the dinitrile and the methionine polypeptide increases to the detriment of the selectivity for methionine. In the range from 80 °C to 110 °C, a high selectivity for methionine is observed.

As a rule, AMTBN or HMTBN is in an aqueous solution. It can be prepared for the process or obtained from the reaction medium in which AMTBN or HMTBN, respectively, were obtained. In this case, it is possible that AMTBN or HMTBN is not pure and contains traces or even larger amounts, but remaining insignificant in the sense that they do not adversely affect the conversion of AMTBN or HMTBN according to the invention.

The concentration of AMTBN or HMTBN, depending on the conversion used, can influence the process performance, especially when it is too high. Thus, according to one embodiment of the invention, AMTBN is in aqueous solution at a concentration 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 for AMTBM, dinitrile and even polypeptide, respectively, increases.

When the production of methionine according to the invention includes HMTBN, ammonia should be added to the reaction medium. Ammonia is preferably present in an amount of from 1 equivalent to 50 equivalents relative to HMTBN. Ammonia can be supplied to the medium in any manner, but is preferably supplied as a continuous bubbling.

It has been noted that the presence of ammonia in the AMTBM solution prior to its conversion significantly improves the selectivity to methionine while reducing the selectivity to the dinitrile, which increases over time in the absence of ammonia. The invention therefore includes a preferred embodiment of the process described above, in which AMTBN is placed in the presence of ammonia prior to contact with the catalyst or even during the catalytic conversion in 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 continuous implementation of the process according to the invention and preferably in the presence of ammonia, and even more preferably by bubbling ammonia into the AMTBN solution before its conversion. According to this variant, the process is carried out under a pressure of 1 to 20 bar, preferably 2 to 10 bar. The invention also proposes a device comprising a tank for the AMTBN solution, in which a mixture of ammonia and nitrogen is bubbling. The AMTBN solution is pumped into a stainless steel reactor, which contains a catalyst and which is heated by means of a sleeve to a temperature of 80 to 100 °C. The reaction medium is directed into a gas-liquid separator, from which ammonia is removed, and the liquid from which will be processed to isolate 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 as a white solid is washed, filtered and then dried. This continuous process described for the preparation of methionine from AMTBN is equally applicable to the preparation of methionine from HMTBN, but the supply of ammonia remains necessary.

According to another aspect, a method is proposed for the controlled catalytic conversion of 2-amino-4-methylthiobutyronitrile or 2-amino-4-methylselenobutyronitrile into 2-amino-4-methylthiobutyramide or 2-amino-4-methylselenobutyramide, respectively, wherein said conversion is carried out in the presence of at least one catalyst containing or consisting of aluminum oxide or titanium dioxide.

The invention and its advantages are further illustrated by examples.

Example 1: Production of methionine from AMTBN in the presence of TiO ₂ according to the invention

The AMTBN hydrolysis reaction and the conditions under which it is carried out are described in the diagram below.

[Him 3]

65 g AMTBN were added with 1000 ml _H2O to a 1 liter screw cap vial. The solution was stirred at room temperature with a nitrogen flow (5 ml/min), the solution was introduced into a tubular reactor heated to 100 °C with a flow rate of 0.1 ml/min (contact time 10 min) and containing 4 g _TiO2 (anatase, 150 m2/g, Norpro, ST 61120). The reaction was monitored for 48 hours by proton NMR.

The AMTBN conversion is over 90%, the methionine yield is on average 74% with an average selectivity of 81%, and the dinitrile yield is on average 11% with an average selectivity of 12%.

Example 2: Production of methionine from AMTBN in the presence of TiO ₂ and ammonia according to the invention - Effect of the specific surface area of TiO ₂

The AMTBN hydrolysis reaction and the conditions under which it is carried out are described in the diagram below.

[Him 4]

2.1 _TiO2 (as anatase) with a BET specific area of 90 m²/g

0.4 g _TiO2 (as anatase) (90 m2/g), then 0.1 g AMTBN (98%) were introduced with 2 ml ammonia solution at 28 wt%. The solution was heated at 90 °C for 10 minutes, after which the solution was filtered and analyzed by proton NMR.

The yield of methionine is 93%, AMTBM is 1%, and dinitrile is 6%.

2.2 _TiO2 (as anatase) with a BET specific area of 275 m²/g

0.4 g _TiO2 (as anatase) (275 m2/g), then 0.1 g AMTBN (98%) were introduced with 2 ml ammonia solution at 28 wt%. The solution was heated at 90 °C for 10 minutes, after which the solution was filtered and analyzed by proton NMR.

The yield of methionine is 95%, AMTBM is 1%, and dinitrile is 4%.

Preferred is a _TiO2 catalyst having a BET of at least 90%.

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

This example considers the use of TiO ₂ doped with cesium and strontium, respectively. The doping was performed by impregnating TiO ₂ with cesium hydroxide or strontium hydroxide at a content of 4 wt.% cesium and strontium (non-metallic).

A 0.8 mol/L AMTBN solution is brought into contact with 5 g of any of the doped catalysts for 10 minutes at 100 °C.

The results are presented in Table 1 below.

[Table 1] Alloying AMTBN Conversion Selectivity for methionine Selectivity for AMTBM Selectivity for dinitrile Selectivity for other products Cs 95% 88% 0% 7% 5% Sr 96% 80% 13% 4% 3%

Example 4: Production of methionine from AMTBN in the presence of titanium dioxide and ammonia according to the continuous process according to the invention

The AMTBN hydrolysis reaction and the conditions under which it is carried out are described in the diagram below.

[Him 5]

The catalyst is titanium oxide with a specific surface area of 150 m²/g.

5 g of this catalyst are placed in a reactor in which a 0.1 mol/L aqueous solution of AMTBN is pumped at a flow rate of 0.2 ml/min and an ammonia flow of 10 ml/min. The reaction temperature is 100 °C and the contact time is 6 min.

The results are presented in Table 2 below.

[Table 2] Observation period AMTBN Conversion Selectivity for methionine Selectivity for AMTBM Selectivity for dinitrile Selectivity for other products 1 hour 94% 88% 5% 3% 4% 4 h 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 for other products. The yields of 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.

[Him 6]

13.1 g HMTBN are introduced with 1000 ml _H2O into a 1-liter screw-cap vial. The solution is stirred at room temperature with a nitrogen flow, the solution is introduced into a tubular reactor heated to 160 °C at a flow rate of 0.1 ml/min (contact time 10 min) and containing 4 g _TiO2 (anatase, 150 m2/g, Norpro, ST 61120). The reaction is monitored by HPLC, the yield of methionine 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.

[Him 7]

13.1 g HMTBN are introduced with 1000 ml _H2O into a 1 liter screw cap vial. The solution is stirred at room temperature with ammonia flow at a flow rate of 100 ml/min, the solution is introduced into a tubular reactor heated to 90 °C at a flow rate of 0.1 ml/min (contact time 15 min) and containing 6 g _TiO2 (anatase, 150 m2/g, Norpro, ST 61120). The reaction is monitored by HPLC, the yield of methionine is 80%.

Example 6: Preparation of methionine in the presence of titanium dioxide from HMTBN but without an ammonia source 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.

[Him 8]

13.1 g HMTBN are added with 1000 ml _H2O in a 1 liter screw cap vial. The solution is stirred at room temperature with a nitrogen flow, the solution is introduced into a tubular reactor heated to 160 °C with a flow rate of 0.1 ml/min (contact time 10 min) and containing 4 g _TiO2 (anatase, 150 m2/g, Norpro, ST 61120). The reaction is monitored by HPLC, the yield of HMTBA is 1%, and methionine is 15%.

A comparison of the results of Examples 4-5 according to the invention with the results obtained in the process carried out without ammonia or ammonium salt in Example 6 demonstrates a significant improvement in the characteristics of methionine production in the process according to the invention. The same benefit is observed in the production of selenomethionine.

Claims (19)

1. Method for obtaining a compound of formula I [Him 1] CH ₃ XCH ₂ CH ₂ C(NH ₂ )COOH (I), where X is S or Se, by catalytic conversion of a compound of formula II [Him 2] _CH3XCH2CH2C ( _Y )CN(II ₎ , where X is S or Se and Y is _NH2 or OH, wherein, when Y is NH ₂ , the conversion is carried out in the presence of water and at least one catalyst containing at least titanium dioxide, and when Y is OH, the conversion is carried out in the presence of water, at least one catalyst containing at least titanium dioxide, and NH ₃ or an ammonium salt. 2. The method according to claim 1, wherein a compound of formula II is used, in which Y is OH, and said conversion is carried out in the presence of water, at least one catalyst containing or consisting of at least titanium dioxide, and NH ₃ or an ammonium salt. 3. The method according to claim 1 or 2, wherein said catalyst is doped, preferably it is doped with one or more elements and compounds selected from alkali metals, alkaline earth metals, lanthanum and any compound of the above-mentioned elements, and preferably at least one of K, Cs, Sr, Ba. 4. The method according to any one of claims 1 to 3, wherein said catalyst has a BET specific surface area of at least 10 ^m2 /g. 5. The method according to any one of claims 1 to 4, wherein the catalyst is present in a concentration of from 0.1 to 200 wt.% based on the weight of compound (II), preferably from 0.5 to 100 wt.% and more preferably from 1 to 50 wt.%. 6. The method according to any one of claims 1 to 5, wherein the compound of formula (II) in which Y is NH ₂ is in aqueous solution at a concentration of 0.01 to 10 M, preferably 0.05 to 1 M, and more preferably 0.2 to 0.4 M. 7. The method according to any one of claims 1 to 6, wherein the conversion is carried out at a temperature of from 20 to 200°C, preferably from 50 to 150°C and more preferably from 80 to 110°C. 8. The method according to any one of claims 1 to 7, wherein prior to the conversion the compound of formula (II) in which Y is NH ₂ is placed in the presence of ammonia. 9. The method according to any one of claims 1 to 7, wherein the compound of formula (II) in which Y is OH is placed in the presence of an ammonium salt selected from (NH ₄ )H ₂ PO ₄ , (NH ₄ ) ₂ HPO ₄ , (NH ₄ ) ₃ PO ₄ , (NH ₄ ) HSO ₄ , (NH ₄ ) ₂ SO ₄ , (NH ₄ ) HCO ₃ or (NH ₄ ) ₂ CO ₃ . 10. The method according to any of paragraphs 1-9, which is carried out continuously.