WO2023067061A1

WO2023067061A1 - Precursors for the preparation of dl-methionine and dlld-methionylmethionine

Info

Publication number: WO2023067061A1
Application number: PCT/EP2022/079209
Authority: WO
Inventors: Thomas HÄUSSNER; Sascha Braune; Hans-Albrecht Hasseberg
Original assignee: Evonik Operations GmbH
Current assignee: Evonik Operations GmbH
Priority date: 2021-10-20
Filing date: 2022-10-20
Publication date: 2023-04-27
Anticipated expiration: 2024-04-20

Abstract

The invention provides the chemical compound of formula (II), a composition comprising methionine hydantoin, DKP (I), Hyd-Met (II), BMU (III), optionally methionylmethionine and water, and also the use thereof for the optionally simultaneous production of methionylmethionine and methionine, and also corresponding production processes.

Description

PRECURSORS FOR THE PREPARATION OF DL-METHIONINE AND DLLD-METHIONYLMETHIONINE

Field of the invention

The present invention relates to methionine derivatives suitable for use in a process for producing methionylmethionine in conjunction with the production of DL-methionine.

Background of the invention

WO2010043558 A1 discloses a process for producing methionylmethionine (Met- Met), the homologous dipeptide of DL-methionine, which finds increasing use primarily as a high-value methionine source for the feeding of fish and crustaceans kept in aquacultures. Its two stereocentres (two asymmetric carbon atoms) mean that the product is present in the form of two diastereomers, DLLD-Met-Met and DDLL-Met-Met, i.e. in the form of two configurationally isomeric enantiomer pairs, both of which can be utilized by animals particularly readily.

WO2010043558 A1 describes various synthetic possibilities for producing Met-Met. However, what all synthetic options have in common is that Met-Met is synthesized via the homologous cyclic dipeptide of methionine, methionine diketopiperazine (I, Met-DKP or DKP).

Unfortunately, the highest DKP yields of 78% and 69% are respectively achieved with the starting materials N-carbamoylmethioninamide and N-carbamoylmethionine, which are not currently available on an industrial scale. When using other starting substances that are available on an industrial scale, for example methionine hydantoin (cf. Scheme 1), the best-case yield that has been reported is 64% (example 7). This means that at least 30% of the sulfur-containing starting substances after isolation of the DKP are present in a chemically modified form that is no longer utilizable and must be disposed of, which is a burden on resources and the environment.

Scheme 1 :

Object

The object underlying the invention was therefore that of providing a process for producing methionylmethionine that minimizes the amount of sulfur-containing starting substances or by- products that after isolation of the DKP needs to be disposed of and is accordingly lost. Byproducts - where unavoidable - should be usefully recycled. There was also a desire to find further suitable precursors for methionine products over and above the methionine product precursors already known, such as methionine hydantoin, and to make it possible to use them for the production of methionine products. The methionine products thus obtained, such as Met-Met or methionine itself, should be produced in high yield and purity and should also have handling and safety properties that are at least as good, but ideally better, than those of the existing product.

Description of the invention

The stated object is achieved according to the invention by using a suitable process stream from a methionine production facility as starting material for the synthesis of DKP. This process stream contains as the principal component methionine hydantoin formed by the reaction of 3- methylmercaptopropionaldehyde (MMP), carbon dioxide and ammonia. Adjustment of the pH with an aqueous potassium-based base to a pH of 8.0-9.0 and heating to temperatures of 170-180°C results in the formation of DKP accompanied by the release of carbon dioxide and ammonia. The extremely low solubility of DKP means that it can be readily separated from the residual secondary components by crystallization, initiated by lowering the temperature. The isolated yield of DKP is in this process step about 30%.

The secondary components remaining in the DKP mother liquor (= DKP-containing mother liquor) after the solid/liquid separation comprise, besides small proportions of residual DKP, mainly three components, these being DL-methionine itself, the homologous dipeptide of methionine Met- Met, and a previously unknown condensation product II of methionine and hydantoin (Hyd-Met):

(II).

A further secondary component that was also found in the mother liquor is bismethionylurea III (BMU), which is previously known from the literature, e.g. from EP1457486 A1 :

Both on a laboratory scale and on an industrial scale, it has been found that not only Met-Met, but also Hyd-Met and BMU can be quantitatively cleaved to methionine and thus surprisingly completely converted into methionine by being fed into the existing methionine process.

It has in addition been shown that other secondary components formed in the DKP process also do not have an adverse effect on the methionine process, so that the whole DKP mother liquor can be directly utilized in the methionine process without any relevant disadvantage. This is rather surprising because plant operators have made the experience that due to the existence of several recycling steps within the methionine process slight changes of compositions of any process solution may result in adverse effects on any other process step due to the interdependencies of all process steps. Thus, for example a considerable number of patent applications have been published in the last decades concerning the problem how to control the Met-Met content in the hydrolysate or in the mother liquor of crystallization in order to provide methionine of a good crystalline form, especially to avoid scaly crystals which are extremely fragile, difficult to separate from liquids and have low bulk density, e,g. according to EP1457486 A1 [0002] and the state of the art cited herein. Because the already existing several internal recycling steps are even sometimes critical to the performance of the whole process a recycling of an external product stream from a different process was even more expected to result in adverse effects which destroy the overall good performance of a methionine process and/or the quality of the end product.

Through the novel combination of the DKP process/Met-Met process with the methionine process it is in addition possible to recycle the carbon dioxide and ammonia gases released in the DKP synthesis back to the synthesis of the starting material methionine hydantoin. Thus, through the combination of the DKP process/Met-Met process and the methionine process, the starting substances MMP and hydrocyanic acid are without additional emissions converted almost quantitatively into methionine and Met-DKP, the precursor of Met-Met.

The present invention thus makes possible a process for the concomitant production of methionine and methionylmethionine that cuts waste volumes to a minimum, thereby conserving the environment and resources to a large degree.

The present invention accordingly provides the novel chemical compound of formula II (Hyd-Met)

and also a composition comprising Hyd-Met (II) and water and a composition comprising methionine hydantoin, DKP (I), Hyd-Met (II), BMU (III),

optionally methionylmethionine and water, which can in each case according to the invention also be used to obtain DKP, Met-Met and also methionine. This composition is obtained by combining the corresponding DKP mother liquor from the Met-Met process with the Met hydantoin solution from the methionine process (cf. Figurel).

Preference here is given to compositions comprising 0.1 % to 40% by weight of methionine hydantoin, 0.1% to 5% by weight of DKP, 0.1% to 20% by weight of Hyd-Met, 0.1% to (maximum) 2% by weight of BMU, optionally 0.1% to 5% by weight of methionylmethionine and water. The according to the invention useful compositions can be generated in these ratios on account of the throughput volumes specified by production and the concentration ratios required for DKP separation and can be further employed directly in the methionine process without further processing as surprisingly found by the inventors, which represents a major technical, economic and even ecological advantage.

The object formulated above is therefore achieved by various component aspects of the invention, namely through the use of compound II (Hyd-Met) for the production of DL-methionine (cf. example 8), through the use of the compound corresponding to formula III (BMU) forthe production of DL- methionine (cf. example 11), and through the use of the aqueous composition comprising methionine hydantoin, DKP (I), Hyd-Met (II), BMU (III) and any proportions of methionylmethionine or DL-methionine already present forthe production of DL-methionine (cf. examples 5 and 6 and Figure 1 , j), since the use according to the invention of the recited products recycles them usefully, increases the overall yield of methionine and methionylmethionine in a combined overall process, and in doing so cuts residual waste volumes to a minimum, thereby conserving the environment and resources to a substantial degree.

The above mentioned compounds II and III can be produced in house by the chemical processes described hereinbelow and subsequently used as starting substance for further conversion into DKP, Met-Met or else methionine. The procedure of choice is however to recycle those process solutions in which these products occur as by-products of the processes mentioned, and to do this such that methionine in particular, but optionally also DKP or Met-Met, is formed therefrom.

The invention thus also provides a process for producing the compound of formula II (Hyd-Met), characterized in that methionine hydantoin is reacted in the presence of base, with the release of 1 mol. equiv. (molar equivalent) of NH3 (cf. example 7).

Preference here is given to using 0.1-1 mol. equiv. of base based on the total amount of methionine equivalent. Compound II can however also be isolated in an advantageous manner from the alkaline DKP mother liquor as a process solution of a process for producing Met-Met via DKP that is particularly suitable for this purpose (cf. example 7 and Figure 1). Hyd-Met is separating out as an organic layer after acidifying the alkaline DKP mother liquor to pH 1 to 3, preferably pH 2 by addition of mineral acid. Herein the DKP mother liquor has been typically obtained from a filtration step in which DKP is isolated from a DKP containing reaction liquid which has been previously obtained by the reaction of an alkali base, e.g. sodium hydroxide or potassium hydroxide with methionine hydantoin at higher temperature e.g. 195 to 205 °C for a reaction time of typically 1 to 2 hours.

As known from EP1457486 A1 BMU is convertible to DL-methionine. Thus BMU can be used as an alternative starting material or intermediate for the industrial production of DL-methionine.

Therefore, there was a demand for a synthesis of said alternative starting material. The inventors surprisingly found that new compound II (Hyd-Met) can be reacted to form BMU.

Thus, the invention additionally provides a process for producing the compound of formula III (BMU-Met), characterized in that the compound of formula II (Hyd-Met) undergoes alkaline hydrolysis to the alkali metal salt of compound I and that this is converted by reaction with appropriate amounts of mineral acid, preferably hydrochloric acid, sulfuric acid or phosphoric acid, into the free acid of formula (III) (cf. example 10 and Figure 1).

The invention further provides, in addition, a process for producing the above mentioned composition, characterized in that 3-methylthiopropionaldehyde is reacted with HCN, NH3 and CO2 in the presence of at least 20% to 80% by weight, preferably with 50% to 70% by weight, of water, based on the total amount of 3-methylthiopropionaldehyde, HCN, NH3, CO2 and water used, at a temperature of 90 to 220°C, preferably at 95 to 150°C, to give an aqueous methionine hydantoin solution and that this is then combined with a DKP mother liquor comprising methionine diketopiperazine, Hyd-Met (II), BMU (III), Met-Met and Met that originates from the separation of DKP in a process for producing Met-Met from DKP (cf. Figure 1).

The invention also provides the associated processes for producing Met-Met and methionine, that is to say a process for producing DL-methionine by hydrolysis of a compound of formula II (Hyd- Met) to the alkali metal salt of DL-methionine and subsequent neutralization with acid to methionine. In this process, the hydrolysis is preferably carried out at temperatures of 160-180°C and with min. 1 mol. equiv. (preferably 1 - 5 mol. equiv., most preferably 1.2-5 mol. equiv.) of base in order to ensure rapid and/or complete conversion.

Herein also described is an associated process for producing DL-methionine by hydrolysis of a compound of formula III (BMU) at temperatures of 100-180°C and with min. 2 mol. equiv. to 3 mol. equiv., preferably 2.2-2.8 mol. equiv., of base to form the alkali metal salt of DL-methionine and subsequent neutralization with acid (cf. example 11 and Figure 1 j. to I.). A further embodiment of the invention is lastly a process for producing DL-methionine by alkaline hydrolysis of the above mentioned composition to the alkali metal salt of methionine and subsequent neutralization with acid to DL-methionine (cf. examples 5 and 6 and Figure 1).

The invention also provides a process for producing DL-methionine and methionine diketopiperazine (DKP), characterized in that a DKP-containing mother liquor is concomitantly hydrolysed in the step of alkaline hydrolysis of methionine hydantoin to the alkali metal salt of methionine of a methionine production process, wherein the DKP-containing mother liquor originates from a process for producing DKP starting from a precursor product comprising methionine hydantoin, said process comprising the process steps formation of DKP, crystallization of DKP and separation of DKP from the associated DKP mother liquor.

The alkali metal salt of methionine initially obtained is then neutralized with acid to methionine. The acid used can for example be carbonic acid, sulfuric acid or hydrochloric acid.

The separated DKP undergoes alkaline hydrolysis to the alkali metal salt of Met-Met and this is then neutralized with acid to Met-Met.

Lastly, the invention also provides an overall process for the (concomitant) production of methionylmethionine and DL-methionine, characterized in that (cf. sequence of the steps in the flowchart in Figure 1) a. an aqueous solution comprising methionine hydantoin together with alkali metal base is reacted to form methionine diketopiperazine (DKP, I), b. the DKP from a. is brought to crystallization by concentrating or cooling the reaction solution from a., c. the crystallized DKP from b. is separated from the DKP mother liquor, d. the DKP separated off in c. is mixed into water and the mixture brought, by addition of appropriate amounts of alkali, to a pH of 10 to 14, preferably 13, measured using a pH electrode at 20°C, and is hydrolysed at a temperature of 90 to 150°C with a residence time of 30 to 180 min to give a corresponding aqueous solution or suspension of the alkali metal salt of methionylmethionine, e. the pH of the solution or suspension from d., measured using a pH electrode at 20°C, is lowered, by mixing with appropriate amounts of mineral acid solution, to a pH of 4 to 6, preferably to 4.5 to 5.5, more preferably to 4.8 to 5.2, f. evaporation of water and/or cooling is/are used to produce a suspension consisting of a solids fraction that mainly comprises methionylmethionine, and residual amounts of a methionylmethionine-containing mother liquor, g. the solids fraction from f. is separated from the mother liquor and h. this is washed and/or dried, affording (highly pure) methionylmethionine, and i. the methionylmethionine-containing mother liquor from g. undergoes a cyclization reaction giving rise to an aqueous solution or suspension comprising methionine diketopiperazine, which is then recycled to step b., and j. the DKP mother liquor from c. comprising methionine diketopiperazine, Hyd-Met (II), BMU (III), Met-Met and Met is combined with a methionine hydantoin solution and k. the composition formed in j. is subjected to an alkaline hydrolysis to the alkali metal methioninate, preferably in the corresponding hydrolysis part of a methionine production facility, l. the alkali metal methioninate from k. is neutralized with acid, giving rise to a methionine suspension, m. the methionine from the suspension in I. is isolated, washed and dried.

The composition obtained in j. is preferably formed by combining the DKP mother liquor from c. and the methionine hydantoin solution from the methionine process in a weight ratio of from 1 :1 to 1 :1000, preferably from 1 :3 to 1 :100, more preferably from 1 :5 to 1 :20. Stable, continuous operation, and thus the high robustness, of the combination according to the invention of the two subprocesses into the overall process has been demonstrated here, even with long-term operation, and affords the two end products DL-methionine and Met-Met in very good product quality, which is likewise greatly advantageous.

Furthermore, the broad scope for variation in the weight ratios of the process solutions to be combined - the DKP mother liquor from c. and the methionine hydantoin solution from the methionine process - means there is also a relatively broad scope for variation in the amounts of DL-methionine and Met-Met that can be concomitantly produced. The surprisingly high flexibility of the overall process of the invention thus makes it possible to vary the amounts of methionine and Met-Met produced according to market demand, which is of high economic value.

The aqueous solution comprising methionine hydantoin mentioned in a. can essentially be prepared according to the details for the production of a methionine hydantoin solution provided in EP 780370 A2 in Figure 1.

Steps k. to m. correspond to the hydantoin hydrolysis process section described in EP 780370 A2 in Figures 2 + 3, but relating to the methionine hydantoin solution only, and the hydrolysis conditions specified therein can likewise be employed in the overall process claimed here.

Description of the figures:

Figure 1 shows a scheme for the methionine/methionylmethionine process.

The scheme comprises the following steps (List of reference numerals):

Forming an aqueous solution comprising methionine hydantoin a. reacting to form DKP starting from the preceding methionine hydantoin solution with the aid of an alkali metal hydroxide (MOH), b. crystallizing of the DKP from a., c. separating the crystallized DKP from b. from the DKP mother liquor, d. hydrolysing the separated DKP from c. with the aid of an alkali metal hydroxide (MOH) to the alkali metal methioninate (M-Met-Met), e. acidifying the hydrolysate from d. by addition of acid, with the release of methionylmethionine and f. precipitating of the methionylmethionine (Met-Met), g. separating the precipitated Met-Met from f. from the Met-Met mother liquor, h. washing and/or drying the methionylmethionine from g., hi . bagging of the Met-Met, i. reacting the methionylmethionine in the Met-Met mother liquor from g. to give DKP and recycling to step c., j. combining the DKP mother liquor from c. comprising methionine diketopiperazine (I), Hyd- Met (II), BMU (III), Met-Met and Met with a methionine hydantoin solution to form a composition, k. subjecting to alkaline hydrolysis the composition from j. comprising methionine hydantoin, Hyd-Met, bismethionylurea, DKP and methionylmethionine to form the alkali metal methioninate in the hydrolysis part of a methionine production facility, l. neutralizing the alkali metal methioninate from k. with acid, giving rise to a methionine suspension, m. isolating, washing and drying of the methionine from I., ml . bagging of the methionine.

Figure 2 shows a DKP synthesis reactor/hydrolysis reactor, wherein the reference numerals have the meanings stated in the table below.

Examples

Methods used

1. High-performance liquid chromatography (HPLC)

Chromatographic investigations (MMP cyanohydrin, MMP, methionine, methionine amide, methionine hydantoin, methionine hydantoin amide, methionine hydantoin acid, Met-Met) were carried out using an HPLC from Jasco on a suitable RP column with subsequent UV detection at 210 nm. The mobile phase used was acetonitrile-water acidified with phosphoric acid. 10 pl of the respective sample solution was injected at a flow rate of 1 ml/min. The system was calibrated beforehand by injecting suitable calibration solutions of appropriate reference compounds from the methionine/Met-Met process, with evaluation by peak area comparison using the external standard method. The procedure of the standard method is known to those skilled in the art.

Note: The term “equivalent” (equiv.) used occasionally throughout the text means molar equivalents (also mol. equiv.).

Example 1 : Preparation of methionine hydantoin solution according to EP780370 A2 (not part of the invention)

First of all, methionine hydantoin solution for further use in the examples was prepared from MMP, HCN and ammonia according to EP 780370 A2, examples 1-4, page 9, line 54 to page 10, line 4).

Example 2: Preparation of methionine DKP from methionine hydantoin solution according to WO2010/043558 A1

In analogous manner to WO2010/043558 A1 , example 7, an intermediate methionine hydantoin solution was first of all prepared from MMP, HCN and (NH^CCh and reacted further for 6 h at 160°C to form DKP and this product obtained in the form of a solid precipitate was filtered off from the DKP mother liquor and the two products provided for further examples. Isolated yield of DKP 64%.

Examples 3-6: Hydrolysis experiments with and without DKP filtrate (DKP mother liquor)

In the DKP synthesis reactor/hydrolysis reactor shown in Figure 2, DKP filtrates in pure form or in mixtures with hydantoin solution underwent hydrolysis under conditions similar to those in the hydrolysis column (HC) of a methionine production facility as described in EP780370 A2, example 6 (HR ~ 2; p = 9 bara, T = 178°C).

The following reactions were carried out:

Example 3 (comparative): Technical hydantoin solution was reacted with working solution (pH > 12, see below), which corresponds to the operating mode of a pure methionine process without recycling of the DKP mother liquor (cf. Figure 1 , left part of flowchart).

Example 4: Exclusively DKP filtrate was reacted with working solution.

Example 5: A mixture of w = 95% hydantoin solution and w = 5% DKP filtrate was reacted (w = parts by weight). Example 6: A mixture of approx, w = 75% hydantoin solution and w = 25% DKP filtrate was reacted.

The working solution here is a strongly alkaline aqueous solution of mainly KHCO3 and K2CO3 having a pH of > 12, which is obtained in the concentration of the mother liquor from the methionine crude crystallization and is, after replenishing lost proportions of hydroxide equivalents in the form of pure KOH, recycled to the methionine process as hydrolysis agent in accordance with EP 780370 A2 example 7.

The mixtures in examples 5 and 6 are particularly suitable as an input stream composition for a methionine/Met-Met via DKP production process according to the invention.

Examples3 to 6 were executed in the DKP synthesis reactor (Figure 2) according to the details in Table 1 in a procedure whereby a hydantoin reservoir connected to the reactor via pipe conduit 1 was initially manually filled with hydantoin solution and/or DKP filtrate (= DKP mother liquor in Figure 1). The reactor was initially charged with the calculated amount of working solution (cf. Table 1) from a corresponding reservoir vessel via pipe conduit 2 and this was heated to min. 160°C. Steam was then introduced and, on reaching steady state, the hydantoin solution or the DKP filtrate or the corresponding mixture of the two was transferred to the reactor from the reservoir and reacted accordingly therein (Tab. 1). The composition primarily generated here corresponds to the above aqueous composition (cf. also Figure 1 j.), comprising Met hydantoin, DKP (I), Hyd-Met (II), BMU (III) and proportions of methionylmethionine and DL-methionine already present.

Table 1 : Overview of the set parameters for examples 4 to 6 with DKP filtrate in a comparison with example 3 without DKP filtrate (corresponding to pure methionine process)

The hydrolysis ratio shown in Table 1 was defined beforehand and the respective mass of working solution to be used calculated. Because of the varying concentrations of the solutions used (methionine hydantoin solution and DKP filtrate), the concentrations of the reaction solutions (compositions) for the hydrolysis were likewise of varying strength.

Table 2: Chemical compositions of hydrolysed solutions (examples 4-6) in a comparison with methionine process solution (example 3)

As shown in Table 2 (lower part), the compositions of the various methionine derivatives show good comparability with one another. In examples 3, 5 and 6, the methionine contents are between w(Met) = 78.2% and 79.4%. These values are comparable with the corresponding process solutions of approx. w(Met) = 78.5% obtained when executing an industrial methionine process according to EP 780370 A2, example 6, which means that full compatibility is advantageously achieved here. Only example 4 deviates therefrom, since this does not employ any hydantoin solution, but instead uses for the hydrolysis exclusively the DKP filtrate of different concentration.

The relatively high proportion of Met-Met in all four examples is attributable to the batchwise operating mode, which experience has shown favours dimerization by comparison with continuous hydrolysis, for example in the column as described in EP 780370 A2. However, since the examples were all executed in the same batch apparatus and since similar methionine and dimer contents were always obtained, indirect confirmation is again obtained, particularly by examples 3, 5 and 6, that the combination of the methionine process and DKP process is, by comparison with the pure methionine process, possible without problems and can thus be advantageously employed to recycle DKP filtrates (DKP mother liquors) from the Met-Met process, thereby allowing losses and environmental pollution to be markedly reduced. Example 7: Preparation of Hyd-Met (= 4-(methylthio)-2-(4-(2-(methylthio)ethyl)-2,5- d ioxoimidazolid in-1 -y I (butanoic acid) from DKP containing mother liquor

10 L of a DKP mother liquor (0.70 mol/kg Met equiv., d = 1 .05 kg/L) was adjusted to pH 2 with 30% H2SO4 solution in a beaker, resulting in the separation of about 600 mL of a brown oil, which sank to the bottom. HPLC analysis: approx. 63 area% Hyd-Met. For the purpose of purification 100 mL of the oil was dissolved in about 300 mL of ethyl acetate and the mixture transferred to a 1000 mL separating funnel and 400 mL of cold water added, resulting in the formation of two separate phases. After shaking and phase separation, the aqueous phase was run off and the organic phase extracted again by shaking with 400 mL of lukewarm water. Another 300 mL of water was then added and the mixture treated with 30% KOH solution until the pH had risen to > 9. After shaking, the phases were separated, with the brownish colour now present in the aqueous phase. The organic phase was separated off and the aqueous phase extracted again by shaking with 50 mL of ethyl acetate. After adding a further 300 mL of ethyl acetate, the funnel contents were again adjusted to pH 2 with 20% HCI solution, shaken and the phases separated. The aqueous phase was finally extracted one more time by shaking with 50 mL of ethyl acetate and the organic phases were combined. HPLC analysis: approx. 5.7% of Met hydantoin. The combined organic phases were extracted again by shaking with three 400 mL volumes of lukewarm water. HPLC analysis: contains 2.4% of hydantoin. The organic phase was diluted with a further 50 mL of ethyl acetate and extracted by shaking with three 400 mL volumes of lukewarm water. The organic phase was then diluted with ethyl acetate to a total volume of about 300 mL and dried over MgSC . After filtering off the MgSC solid, the solution was filtered through a silica gel 60 column (200-500 pm, 15 cm, 4 cm diameter) over a period of about 20 min. This resulted in most of the brownish black colour remaining on the silica gel. The light brown, clear solution was evaporated over the weekend under a stream of nitrogen.

Yield: 68.2 g of a brownish oil that gradually underwent partial crystallization after a few days. Hyd-Met content: 62.3%.

Example 8: Hydrolysis of Hyd-Met (II) to methionine

The DKP process gives rise to significant amounts of the dimeric methionine derivative Hyd-Met. The behaviour of this novel compound when introduced into a hydrolysis column (HC) was therefore investigated. To this end, a number of hydrolysis experiments were carried out on a small scale. The hydrolysis conditions were relatively mild (100°C, 0 barg, 0-5 equiv. KOH), so as to be able to monitor the progress of the reaction and to detect in the HPLC any intermediate products that occurred. It was found that Hyd-Met selectively reacts to form the urea derivative BMU (2-(3-(1-carboxy-3- (methylthio)propyl)ureido)-4-(methylthio)butanoic acid). This compound is known and is also known in the methionine process. Example 9: Hydrolysis of Hyd-Met (II) and methionine hydantoin to methionine

In a further experiment, a mixture consisting of Hyd-Met and hydantoin in a molar ratio of 1 :1 was hydrolysed with HR = 2.15 at temp.= 100°C. This found that the reactants selectively give rise to the formation of only two primary products: BMU (from Hyd-Met) and Hyd-acid (from methionine hydantoin). The rates of hydrolysis of the two reactants Hyd-Met and methionine hydantoin differ markedly (cf. Table 3). Thus, the conversion of Hyd-Met is after 60 min already greater than 95%, whereas only about 5% of the methionine hydantoin had reacted by this time. After just 13 min, the degree of conversion of Hyd-Met was already 54%.

This result shows that the compound Hyd-Met that forms as a by-product during the DKP synthesis is hydrolysed within a very short time after introduction into the hydrolysis column of a methionine production facility. The primary hydrolysis product formed here is BMU, which reacts further to methioninate under the conditions prevailing therein.

Table 3: Conversion/time course of the hydrolysis

Example 10: Preparation of BMU (2-(3-(1-carboxy-3-(methylthio)propyl)ureido)-4- (methylthio)butanoic acid)

An initial charge of 10 g (20.3 mMol; w = 62.3%) of Hyd-Met in 425 g of water was treated with 65.7 mL of 1 M KOH solution. This was then heated to boiling temperature and boiled under reflux for 2 h. The solution was cooled to 20°C and slowly adjusted to pH 3 with cone. HCI. A clear solution was obtained by adding a little activated carbon and then filtering off the carbon. The filtrate was adjusted to pH 2 with cone. HCI and extracted with two 100 ml volumes of MtBE. The organic phase was dried over MgSC and then filtered and concentrated.

Yield: 2.1 g (6.5 mMol, 32% of theor.) of BMU (white solid).

It was found that 2 equiv. of KOH is sufficient to completely cleave Hyd-Met to BMU at 100°C. It should be noted here that 1 equiv. of OH- is needed at the outset in order to neutralize the carboxylic acid group of the Hyd-Met.

Example 11 : Hydrolysis of BMU to Hyd-Met and methionine

In example 8 it was described that BMU is obtained as the primary reaction product in the hydrolysis of Hyd-Met. This example examined which reaction products are formed when BMU is broken down hydrolytically. To this end, dilute aqueous BMU solutions having a concentration of 0.031 mol.L'¹ were hydrolysed at 100°C in aqueous solutions to which were added varying amounts of KOH and the progress of the reaction monitored by HPLC. The results for the course of the reactions with KOH are shown in Table 4. From this it can be seen that, with 2 mol. equiv. of KOH, a decrease in the BMU content occurs alongside a commensurate increase in the content of Hyd-Met and methionine.

Table 4: Conversion/time course of the hydrolysis

Claims

Claims:

1. Chemical compound of formula II (Hyd-Met)

2. Composition comprising Hyd-Met (II) and water.

3. Composition comprising methionine hydantoin, DKP (I), Hyd-Met (II), BMU (III)

optionally methionylmethionine and water.

4. Composition according to Claim 2, comprising 0.1 % to 40% by weight of methionine hydantoin, 0.1% to 20% by weight of Hyd-Met, 0.1% to (maximum) 2% by weight of BMU, optionally 0.1% to 5% by weight of DKP and water.

5. Use of compound II according to Claim 1 for producing methionylmethionine and/or DL- methionine.

6. Use of a composition according to any of Claims 2 to 4 for producing methionylmethionine and/or DL-methionine.

7. Process for producing compound II according to Claim 1 , characterized in that the compound II is isolated from an alkaline DKP containing mother liquor of a process for producing Met-Met via DKP by acidification to pH 1 to 3 by addition of mineral acid.

8. Process according to Claim 7, characterized in that the DKP containing mother liquor is obtained from a isolation step in which DKP is isolated from a DKP containing reaction liquid which has been previously obtained by the reaction of an alkaline base with methionine hydantoin at a higher temperature of 195 to 205 °C for a reaction time of 1 to 2 hours.

9. Process for producing a composition according to any of Claims 2 to 4, characterized in that 3-methylthiopropionaldehyde is reacted with HCN, NH3 and CO2 in the presence of at least 20% to 80% by weight of water, based on the total amount of 3- methylthiopropionaldehyde, HCN, NH3 and CO2 and water used, at a temperature of 90 to 220°C.

10. Process according to Claim 9, characterized in that the reaction is carried out at temperatures of 95 to 150°C.

11 . Process for producing DL-methionine by alkaline hydrolysis of compound II according to Claim 1 to the alkali metal salt of DL-methionine and subsequent neutralization with acid.

12. Process according to Claim 11 , characterized in that the hydrolysis is carried out at temperatures of 160-180°C and with 1 - 5 mol. equiv. of base.

13 Process according to Claim 12, characterized in that the hydrolysis is carried out, with 1 .2- 5 mol. equiv. of base.

14. Process for producing DL-methionine by alkaline hydrolysis of a composition according to Claim 2, 3 or 4 to form the alkali metal salt of methionine and subsequent neutralization with acid to DL-methionine.

15. Process for producing methionylmethionine and DL-methionine, characterized in that a. an aqueous solution comprising methionine hydantoin together with alkali metal base is reacted to form methionine diketopiperazine (DKP, I), b. the DKP from a. is brought to crystallization by concentrating or cooling the reaction solution from a., c. the crystallized DKP from b. is separated from the DKP mother liquor, d. the DKP separated off in c. is mixed into water and the mixture brought, by addition of appropriate amounts of alkali, to a pH of 10 to 14, measured using a pH electrode at 20°C, and is hydrolysed at a temperature of 90 to 150°C with a residence time of 30 to 180 min to give a corresponding aqueous solution or suspension of the alkali metal salt of methionylmethionine, 19 e. the pH of the solution or suspension from d., measured using a pH electrode at 20°C, is lowered, by mixing with appropriate amounts of mineral acid solution, to a pH of 4 to 6, f. evaporation of water and/or cooling is/are used to produce a suspension consisting of a solids fraction that mainly comprises methionylmethionine, and residual amounts of a methionylmethionine-containing mother liquor, g. the solids fraction from f. is separated from the mother liquor and h. this is washed and/or dried, affording methionylmethionine, and i. the methionylmethionine-containing mother liquor from g. undergoes a cyclization reaction giving rise to an aqueous solution or suspension comprising methionine diketopiperazine, which is then recycled to step b., and j. the DKP mother liquor comprising methionine diketopiperazine, Hyd-Met (II), BMU (III), optionally Met-Met and Met from c. is combined with a methionine hydantoin solution and k. the composition formed in j. is subjected to an alkaline hydrolysis to the alkali metal methioninate in the corresponding hydrolysis part of a methionine production facility, l. the alkali metal methioninate from k. is neutralized with acid, giving rise to a methionine suspension, m. the methionine from the suspension in I. is isolated, washed and dried.

16. Process according to Claim 15, characterized in that the pH in step d. is brought to 13.

17. Process according to Claim 15 or 16, characterized in that the pH in step e. is lowered to 4.5 to 5.5.

18. Process according to any of Claims 15 to 17, characterized in that the composition obtained in j. is formed by combining the DKP mother liquor from c. and the methionine hydantoin solution from the methionine process in a weight ratio of from 1 :1 to 1 :1000.

19. Process for producing compound III (BMU) according to Claim 3, characterized in that compound II according to Claim 1 undergoes alkaline hydrolysis to the alkali metal salt of compound I and that this is converted by reaction with appropriate amounts of mineral acid into the free acid of compound III.

20. Process according to Claim 19, characterized in that the mineral acid is hydrochloric acid, sulfuric acid or phosphoric acid.