SALT-FREE PRODUCTION OF METHIONINE FROM METHIONINE NITRILE

Abstract

The invention refers to the use of a particulate catalyst containing 60.0 to 99.5 wt. % ZrO.sub.2 stabilised with an oxide of the element Hf and at least one oxide of the element M, wherein M=Ce, Si, Ti, or Y, for the hydrolysis reaction of methionine amide to methionine, wherein the median particle size x.sub.50 of the particulate catalyst is in the range of from 0.8 to 9.0 mm, preferably of from 1.0 to 7.0 mm. The invention also refers to a process for preparing methionine comprising a step of contacting a solution or suspension comprising methionine amide and water with said particulate catalyst to provide a reaction mixture comprising methionine and/or its ammonium salt from which methionine can be isolated.

Claims

1. A method of catalyzing the hydrolysis reaction of methionine amide to methionine, the method comprising contacting a solution or suspension comprising methionine amide and water with a particulate catalyst to produce a reaction mixture comprising methionine, wherein the particulate catalyst comprises: 60.0 to 99.5 wt. % ZrO.sub.2; an oxide of the element Hf; and at least one oxide of the element M, wherein M=Ce, Si, Ti, or Y, wherein the ZrO.sub.2 is stabilized by the oxide of the element Hf and the at least one oxide of the element M, and wherein the median particle size x.sub.50 of the particulate catalyst is in the range of from 0.8 to 9.0 mm.

2. The method of claim 1, wherein the element M=Si, Ti, or Y.

3. The method of claim 1, wherein the particle size x.sub.10 of the particulate catalyst is in the range of from 0.5 to 8.0 mm.

4. The method of claim 1, wherein the particulate catalyst comprises 0.1 to 40 wt. % of oxides of the elements Hf, Ce, Si, Ti, and Y.

5. The method of claim 1, wherein the particulate catalyst comprises: 0.5 to 3.0 wt. % HfO.sub.2 and at least one selected from the group consisting of 0.1 to 40 wt. % TiO.sub.2, 0.2 to 6 wt. % SiO.sub.2, 3 to 10 wt. % Y.sub.2O.sub.3, and 5 to 25 wt. % CeO.sub.2, each weight percentage relative to the weight of the particulate catalyst.

6. The method of claim 1, wherein the particulate catalyst has a BET surface area of from 30 to 250 m.sup.2/g.

7. The method of claim 1, wherein the particulate catalyst has an average pore volume of from 0.20 to 0.50 mL/g.

8. The method of claim 1, wherein the particulate catalyst has a median pore diameter of from 20 to 200 nm.

9. The method of claim 1, wherein the ZrO.sub.2 is triclinic or monoclinic.

10. The method of claim 1, wherein the particulate catalyst further comprises an inactive component as a carrier and/or a binder material.

11. The method of claim 1, wherein the particulate catalyst has a shaped form.

12. (canceled)

13. The method of claim 1, wherein the solution or suspension is contacted with the particulate catalyst at a temperature of from 70 to 200° C.

14. The method of claim 1, wherein the solution or suspension comprises 1 to 30 wt. % methionine amide.

15. The method of claim 1, wherein the solution or suspension further comprises one or more ketone compounds at a concentration of 0.1 to 2 moleq, relative to the methionine amide concentration in the solution or suspension.

16. The method of claim 1, wherein the solution or suspension further comprises an alkali metal or alkaline earth metal hydroxide at a concentration of 0.01 to 0.5 moleq, relative to the methionine amide concentration in the solution or suspension.

17. The method of claim 1, wherein the solution or suspension further comprises NH.sub.3 at a concentration of 0 to 10 moleq, relative to the methionine amide concentration in the solution or suspension.

18. The method of claim 1, wherein the reaction is carried out in a continuous mode employing the particulate catalyst in a fixed-bed type reactor or a trickle-bed type reactor.

19. The method of claim 1, wherein the reaction is carried out in a continuous mode with a weight-hourly-space-velocity (WHSV) rate of 0.0001 to 10 g(methionine amide)/h/g(catalyst).

20. The method of claim 1, wherein the reaction is carried out in a batch mode, and the particulate catalyst is used in an amount of from 0.01 to 5 moleq ZrO.sub.2 per mol methionine amide.

21. A process for preparing methionine, comprising: a. reacting methylmercaptopropionaldehyde with hydrocyanic acid and ammonia or reacting 2-hydroxy-4-(methylthio)butyronitrile with ammonia to provide a reaction mixture comprising methionine nitrile, b. optionally separating of all or a part of residual ammonia from the reaction mixture of step a., c. hydrolysing the reaction mixture obtained in step a. or b. in the presence of a carbonyl catalyst, a base catalyst, and water or in the presence of a CeO.sub.2 containing catalyst and water to provide a solution or suspension comprising methionine amide or a mixture of methionine amide and methionine, d. optionally separating all or a part of the residual ammonia or residual ammonia and carbonyl catalyst from the solution or suspension of step c., e. preparing methionine by contacting the solution or suspension obtained from step c. or d. and water with the catalyst of claim 1, f. optionally separating all or a part of the residual ammonia or residual ammonia and carbonyl catalyst from the solution or suspension of step e. to obtain a reaction liquid comprising methionine, g. isolating methionine by crystallisation and optionally subsequent re-crystallisation from the reaction liquid comprising methionine obtained from step f., obtaining a mother liquor, and h. optionally recycling the mother liquor from step g. into step e. to react unreacted methionine amide.

Description

EXAMPLES

[0064] Analytical Methods

[0065] HPLC-Chromatography:

[0066] Chromatographic analyses of 2-hydroxy-4-(methylthio)butanenitrile (MMP-CN), 2-amino-4-(methylthio)butanenitrile (MMP-AN), 2-amino-4-(methylthio)butaneamide (methionine amide), 3-(methylthio)-1-propanone (MMP), and methionine (Met) were performed using HPLC systems from JASCO or Agilent with an RP-18 column (250×4.6 mm; 5 μm) and a subsequent UV detection at 210 nm. As eluent, a mixture consisting of 3.3 g H.sub.3PO.sub.4, 6.8 g CH.sub.3CN, and 89.9 g H.sub.2O was used with a flow of 1 mL/min. 10 μL of the respective sample solution (50 mg sample in 25 mL H.sub.2O) were injected into the eluent for analysis. Calibration was done in advance by injection of suitable standard stock solutions of the analyst and a subsequent comparison of peak areas with external standards as commonly done in organic chemical syntheses.

[0067] BET Surface Area

[0068] The BET surface areas were determined by physical adsorption of nitrogen on the surface of the solid and by calculating the amount of adsorbate gas corresponding to a monomolecular layer on the surface according to the Brunauer, Emmett, and Teller (BET) method. The samples used (0.2-0.9 g) were degassed at 150° C. for 20 min under vacuum prior to the measurement. The determination was then carried out at the temperature of liquid nitrogen (77 K). The amount of gas adsorbed was measured by a static-volumetric, 3-point measurement using a TriStar 3000 Miromeritics instrument. The method is described in general in DIN ISO 9277-5 (2003) and was being applied accordingly.

[0069] Particle Size Distribution of Powders

[0070] The particle size distribution of powders was measured by laser diffraction according to ISO 13320:2009 and analysed also according to ISO 9276 regarding their x.sub.10, x.sub.50, and x.sub.50 particle sizes, representing the particle sizes corresponding to 10%, 50%, or 90% of the cumulative undersize distribution by volume, respectively. A spatula of sample material was added to 10 mL water+0.5 g/L tetrasodium pyrophosphate, ultrasonicated for 1 min and analysed with a LS 13320 laser diffraction spectrometer (Beckman-Coulter) with Universal Liquid Module (ULM).

[0071] Particle Size Distribution of Particulate Catalysts

[0072] The particle size distributions of particulate catalysts was measured by optical analysis of a series of catalyst particles (200 mL sample volume) using a CCD camera in a Camsizer (Retsch Technology GmbH) according to ISO 13322-1:2014 and analysed also according to ISO 9276 regarding their x.sub.10, x.sub.50, and x.sub.50 particle sizes, representing the particle sizes corresponding to 10%, 50%, or 90% of the cumulative undersize distribution by volume, respectively.

[0073] X-Ray Powder Diffraction

[0074] X-ray powder diffraction (XRPD) is a non-destructive analytical technique for determination of crystalline phases in solid samples. XRPD measurements including the determination of the degree of crystallinity were conducted as follows. 0.5-2.0 g of the material were analysed in the Cubix.sup.3 Pharma X-ray powder diffractometer from PANalytical using the following parameters:

[0075] X-ray tube: LFF-Cu X-ray tube, Cu Kα, λ=0.1542 nm

[0076] Generator settings: 40 mA, 40 KV

[0077] Detector: X'Celerator

[0078] Rotation: Yes/1 Rev./s

[0079] 2-Theta range: 5°-100°

[0080] Step (° 2Θ) 0.0170

[0081] Time per step: 40 s

[0082] The results were evaluated by using the current version of the PANalytical HighScore Plus software and up-to-date version of the ICDD database with crystalline reference phases.

[0083] X-Ray Fluorescence Analysis

[0084] X-ray fluorescence analysis (XRF) is a non-destructive analytical technique for determination of elemental composition in solid and liquid samples. In XRF, elements from F to U can be detected and quantified. For sample preparation, a small amount of the material was uniformly distributed on top of a thick layer of boreox (binding additive) in an aluminium cup and pressed into a flat powder pellet. The samples were analysed using a wavelength dispersive XRF spectrometer Axios from PANalytical using a UniQuant semi-quantitative application. The semi-quantitative evaluation was carried out using the Software UniQuant V 5. This software tool is based on the fundamental parameter algorithm; in this approach, a set of suitable calibration samples is measured and the measured intensities of the fluorescence lines are compared with the calculated intensities (the calculation is carried out using an established physical model).

[0085] Pore Analyses

[0086] The pore volume and median pore diameter was determined in accordance with DIN 66134 (N.sub.2-sorption according to Barret, Joyner, Halenda).

[0087] Exemplary Preparation of Catalysts Used (not Part of the Invention)

[0088] The catalysts used according to the present invention are not subject to any limitation regarding their preparation, provided that the procedure used for their preparation gives catalysts with the features as those used according to the present invention. For example, the catalysts used in examples 13-19, table 3, according to the present invention were prepared in accordance to the published patent application EP 3026038 A1 and analysed regarding the following analytical parameters (results in table 3): x.sub.10, x.sub.50, and x.sub.50 particle sizes, Brunauer, Emmett, and Teller (BET) surface area, X-ray powder diffraction (XRPD), X-ray fluorescence analysis (XRF, elemental composition), pore volume and median pore diameter.

[0089] For example, the ZrO.sub.2-catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2 which was used for examples 4-8, 12, 16, 28-37 was prepared according to example 1 of the published patent application EP 3026038 A1:

[0090] Thus, the pore volume of 1215 g zirconium hydroxide particles (containing 1.6 wt. % HfO.sub.2) XZO 1501/09 from MEL Chemicals was determined to 850 mL. 136 g Y(NO.sub.3).sub.3×6 H.sub.2O were dissolved in 263 g H.sub.2O, resulting in a solution of 340 mL, which corresponds to 40% of the total pore volume. 380 g H.sub.2O were added to obtain a solution with a total volume of 680 mL, which corresponds to 80% of the total pore volume. The zirconium hydroxide material was impregnated in an Eirich intensive mixer type R by spraying the yttrium nitrate solution under moderate stirring conditions (215 rpm) onto the zirconium hydroxide for a period of 10 minutes. Subsequently, the wet powder was transformed into granules under stirring conditions (3000 rpm) for 1 hour. The material was sieved through a mesh sieving machine with mesh 2 to obtain granules with a particle size in the range of from 0.8 to 5 mm. Afterwards, the granules were dried at 120° C. for 2 hours and then calcined at 450° C. for 2 hours. The granules were sieved again through a mesh sieving machine with mesh 3 to obtain granules with a particle size in the range of from 0.8 to 2.5 mm. The mixed oxide contained 4 wt. % Y.sub.2O.sub.3. The obtained particles were analysed regarding the following analytical parameters (results in brackets): their x.sub.10 (1.27 mm), x.sub.50 (1.82 mm), and x.sub.50 (2.43 mm) particle sizes, Brunauer, Emmett, and Teller (BET) surface area (125 m.sup.2/g), X-ray powder diffraction (XRPD, triclinic crystalline phase), X-ray fluorescence analysis (XRF, elemental composition 94 wt. % ZrO.sub.2, 2 wt. % HfO.sub.2, 4 wt. % Y.sub.2O.sub.3), pore volume (0.4 mL/g) and median pore diameter (30 nm), as also depicted in example 16, table 3.

Example 1 (not Part of the Invention): Synthesis of 2-Amino-4-(Methylthio)Butanenitrile Starting from 2-hydroxy-4-(methylthio)butanenitrile

[0091] 10.1 g 2-hydroxy-4-(methylthio)butanenitrile (MMP-CN; 90 wt. % in water, 69.3 mmol, 1 moleq) were mixed with 26.0 g NH.sub.3 (32 wt. % in water, 7 moleq, 48.8 mmol) in a glass reactor and sealed subsequently. The light beige coloured and turbid emulsion containing 25 wt. % MMP-CN was stirred and heated to 50° C. for 30 minutes by means of a water bath. The obtained light yellow solution was analysed by HPLC chromatography confirming a 100% conversion of MMP-CN with a selectivity of 98.8% towards 2-amino-4-(methylthio)butanenitrile (MMP-AN; 67.2 mmol) and 2-amino-4-(methylthio)butaneamide (methionine amide; 1.2 mmol). Only traces of the iminodinitrile side-product 2,2′-bis-(2-methylmercaptoethyl)iminodiacetonitril (DN1, <0.1%), formed by reaction of MMP-CN with MMP-AN, as well as small amounts of 3-(methylthio)-1-propanone (MMP; <1%), formed by back reaction of MMP-CN to MMP and HCN, were observed.

##STR00002##

Example 2 (not Part of the Invention): Direct Conversion of the Obtained 2-Amino-4-(methylthio)butanenitrile Towards a Mixture Comprising 2-amino-4-(methylthio)butaneamide and methionine using a CeO.SUB.2 .Catalyst

[0092] To the reaction solution obtained according to example 1 comprising 8.75 g MMP-AN (67.2 mol), 0.18 g methionine amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 moleq), and 19.9 g water, another 36.2 g water (MMP-AN concentration 12 wt. %) and 1.0 g (5.8 mmol, 0.09 moleq) CeO.sub.2 catalyst, manufactured according to EP 1506940 B1, example 1, were added. The glass reactor was again sealed and heated to 60° C. for 30 minutes by means of a pre-heated water bath while the reaction was stirred. Subsequently, the reaction solution was rapidly cooled to room temperature and analysed by HPLC chromatography confirming a 100% conversion of MMP-AN with a selectivity of 70% to 2-amino-4-(methylthio)butaneamide (methionine amide; 47.0 mmol) and 30% to methionine (Met; 20.2 mmol).

Example 3 (not Part of the Invention): Direct Conversion of the Obtained 2-Amino-4-(methylthio)butanenitrile Towards a Mixture of 2-amino-4-(methylthio)butaneamide and Methionine Using a Carbonyl Compound and Alkali Metal Hydroxide as Catalysts

[0093] The reaction solution obtained according to example 1 comprising 8.75 g MMP-AN (67.2 mol), 0.18 g methionine amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 moleq), and 19.9 g water was cooled to 35° C. 7 g water, 4.0 g acetone (68.8 mmol, 1 moleq), and 2.0 g of an aqueous 10 wt. % KOH (3.4 mmol, 0.05 moleq) were added (MMP-AN concentration 18 wt. %). The glass reactor was again sealed and kept at 35° C. for 90 minutes by means of a water bath while the reaction was stirred. Subsequently, the reaction solution was rapidly cooled to room temperature, ammonia and acetone were removed at 30° C. under vacuum. The obtained product was analysed by HPLC chromatography confirming a 100% conversion of MMP-AN with a selectivity of 98.6% to methionine amide (65.4 mmol) and Met (2.0 mmol).

Example 4-8: Conversion of Methionine Amide to Methionine in an Autoclave with a ZrO.SUB.2 .Catalyst Under Varying Conditions

[0094] The volatile components of the methionine amide containing solution obtained from examples 2 or 3, in particular acetone and ammonia, were removed and the mixture obtained was adjusted to the following composition by addition of water and/or 32 wt. % aqueous ammonia as described in table 1: methionine amide (11.2%), KOH (0-0.1 moleq), NH.sub.3 (0.5-3.5 moleq). The reaction solution was transferred to a steel autoclave. The metal oxide catalyst (0.18 moleq ZrO.sub.2-catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2, manufactured according to the exemplary catalyst preparation procedure above) was then introduced in the form of a particulate catalyst (e.g. pellets) in a catalyst basket to prevent the particles from being destroyed by stirring the reaction solution. The autoclave was closed and heated to the desired temperature (110-170° C.) according to table 1 or 2 within one hour under stirring. The progress of the reaction was monitored after 15 minutes by HPLC analysis and finally terminated after 90 min by rapid cooling to room temperature and subsequent HPLC analysis of the reaction mixture.

TABLE-US-00001 TABLE 1 Results with a ZrO.sub.2 catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 Temp. NH.sub.3 Yield Conversion Selectivity Conversion after Expl. [° C.] [eq] [%] [%] [%] 15 min [%] 4 110 2 86.7 88 98.5 51.8 5 170 2 84.2 100 84.2 85.6 6 140 0.5 93.6 100 93.6 83.4 7 140 3.5 93.8 98.2 95.5 72.5 8 140 2 98.3 100 98.3 90.1

Example 9-11 (not Part of the Invention, for Comparison): Conversion of Methionine Amide to Methionine in an Autoclave with a TiO.SUB.2 .Catalyst Under Varying Conditions

[0095] The reaction was performed as described for examples 4-8 but instead of 0.18 moleq of the ZrO.sub.2 catalyst, 0.27 moleq TiO.sub.2 “Aerolyst 7711” from Evonik, Germany was employed.

TABLE-US-00002 TABLE 2 Results with a TiO.sub.2 catalyst (not part of the invention, for comparison) Temp. NH.sub.3 Yield Conversion Selectivity Conversion after Expl. [° C.] [eq] [%] [%] [%] 15 min [%] 9 110 2 62.2 63.7 97.8 29.2 10 170 2 86.9 100 86.9 84.1 11 140 2 86.5 97.8 88.5 90.1

[0096] The comparison of the results in table 1 with those in table 2 reveals that the ZrO.sub.2 catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2 performs significantly better than the TiO.sub.2 catalyst with regard to conversion of starting material as well as selectivity to and yield of Methionine.

Example 12: Conversion of Methionine Amide to Methionine Using a ZrO.SUB.2 .Catalyst Stabilised with 4 wt. %

[0097] Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2 The volatile components of the methionine amide containing solution obtained from examples 2 or 3, in particular acetone and/or ammonia, were removed and the mixture obtained was adjusted to the following composition by addition of water: Water (140 g), methionine amide (18.5 g, 0.125 mol), KOH (0.33 g, 0.0059 mol, 0.05 moleq), methionine (0.7 g, 0.005 mol, 0.4 moleq). 32 wt. % aqueous ammonia solution (15.0 g, 0.282 mol, 2 moleq) was added. The reaction solution was transferred to a steel autoclave. A particulate ZrO.sub.2-catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 (3.0 g, 0.024 mmol, 0.20 moleq) and containing 2 wt. % HfO.sub.2, manufactured according to the exemplary catalyst preparation procedure above, was introduced into the autoclave in the form of catalyst pellets in a catalyst basket. The autoclave was closed, stirred continuously with the aid of a gas agitator and heated to 140° C. The progress of the reaction was monitored every 15 minutes by HPLC analysis and finally terminated after 90 minutes. The reaction solution was rapidly cooled by the addition of water and diluted to a total quantity of 660 g. HPLC analysis of this solution revealed a 100% conversion of methionine amide and a methionine content of 2.86%, corresponding to a total content of 18.9 g methionine (0.127 mol, 98.1% yield, 98.1% selectivity). For control purposes, the volatile components of the solution were removed at the rotary evaporator. The obtained off-white powder was weighed and analysed by HPLC, confirming the above measured values for conversion, yield, and selectivity of 100%, 98.1%, and 98.1%, respectively.

Example 13-19: Conversion of Methionine Amide to Methionine by Using Different Particulate ZrO.SUB.2 .Catalysts

[0098] The volatile components of the methionine amide containing solution obtained from examples 2 or 3, in particular acetone and/or ammonia, were removed and the mixture obtained was adjusted to a methionine amide concentration of 12.4%. 50 g of the reaction solution (6.2 g, 41.9 mmol methionine amide) was transferred to a steel autoclave and a particulate ZrO.sub.2-catalyst according to table 3 (3.0 g, 0.024 mmol, 0.57 moleq) was introduced into the autoclave in a catalyst basket. The autoclave was closed, stirred continuously, and heated to 120° C. within 60 min. After 30 min, a sample was taken and analysed by HPLC analysis regarding the methionine amide conversion as well as yield and selectivity towards methionine.

Examples 20-27 and A-E (not Part of the Invention, for Comparison): Conversion of Methionine Amide to Methionine by Using Different ZrO.SUB.2 .Catalysts

[0099] The reaction was performed as described for examples 13-19 but the catalysts listed in table 4a and 4b were employed instead. The powder catalysts were not sieved in advance but used as received from commercial sources (e.g., Sigma Aldrich).

[0100] The comparison of the results in table 3 with those in table 4a reveals that the particulate ZrO.sub.2 catalysts stabilised with CeO.sub.2, Y.sub.2O.sub.3, SiO.sub.2, or TiO.sub.2, or TiO.sub.2 and SiO.sub.2, each also containing HfO.sub.2, perform significantly better under the given conditions (86 to 100% yield of methionine, examples 13 to 19) than the particulate ZrO.sub.2 catalysts HfO.sub.2 and stabilised with La.sub.2O.sub.3 or WO.sub.3 (65 to 82%, yield of methionine, examples 20, 21) with regard to conversion of starting material and yield of methionine.

[0101] The comparison of the results of table 3 with those in table 4a further reveals that the particulate catalysts containing ZrO.sub.2 stabilised with Y.sub.2O.sub.3, SiO.sub.2, or TiO.sub.2, or TiO.sub.2 and SiO.sub.2, each also stabilised with HfO.sub.2, perform significantly better under the given conditions (86 to 100% yield of methionine, examples 13 to 19) than the powder catalysts also stabilised with Y.sub.2O.sub.3, SiO.sub.2 or TiO.sub.2, each also containing HfO.sub.2, (18 to 23% yield of methionine, examples 22 to 24) or powder catalysts containing HfO.sub.2 and stabilised with CaO or Sc.sub.2O.sub.3 (18 to 25% yield of methionine, examples 25 to 27) which could not be expected.

[0102] In addition, the particulate catalysts used according to the invention in table 3 with a triclinic or monoclinic crystal phase turned out to be superior over the powder catalysts in table 4a and 4b (examples 22 to 26, A and E) with either, cubic, orthorhombic, or rhomboedric crystal phases.

[0103] The particulate catalysts used according to the invention in table 3 with BET surface areas of from 55 to 145 m.sup.2/g turned out to be superior over the powder catalysts in table 4a and 4b (examples 22 to 27, A and E) with BET surface areas of from <1 to 11 m.sup.2/g.

[0104] The particulate catalysts used according to the invention in table 3 with pore volumes of from 0.24 to 0.49 mL/g and median pore diameters of from 23 to 160 nm turned out to be superior over the powder catalysts in table 4a and 4b (examples 22 to 27, A and E) with pore volumes of from 0 to 0.38 mL/g and median pore diameters of from 0 to 128 nm.

TABLE-US-00003 TABLE 3 Examples of conversion of methionine amide (Met-Amide) to methionine by using different particulate ZrO.sub.2 catalysts after 30 min at 120° C. Median BET Total Median Con- Particle particle Particle surface pore pore version Selec- Ex- size x.sub.10 size x.sub.50 size x.sub.90 area volume diameter Crystal ZrO.sub.2 HfO.sub.2 TiO.sub.2 SiO.sub.2 Y.sub.2O.sub.3 CeO.sub.2 Met- Yield tivity ample (mm) (mm) (mm) (m.sup.2/g) (mL/g) (nm) phase wt. % wt. % wt. % wt. % wt. % wt. % amide Met Met 13 2.84 3.06 3.13 105 0.24 156 Triclinic 81 1.7 — — — 17.3 100% 100% 100% 14 3.30 3.43 3.54 55 0.3 40 Monoclinic 98 1.6 0.15 0.25 — — 100%  98%  98% 15 5.82 6.18 6.48 83.7 0.44 29 Triclinic 60 1.8 38.2 — — — 100%  96%  96% 16 1.27 1.82 2.43 125 0.4 30 Triclinic 94 2 — — 4 —  99%  86%  87% 17 1.08 1.31 1.55 145 0.49 23 Triclinic 93 2 — 5 — —  97%  97% 100% 18 3.12 3.20 3.30 134 0.25 98 Triclinic 90 2.7 — — 7.3 —  93%  93% 100% 19 2.92 2.98 3.03 133 0.3 75 Triclinic 94 1.6 1.2 3.2 — —  92%  92% 100%

TABLE-US-00004 TABLE 4a (not part of the invention, for comparison): Examples of conversion of methionine amide to methionine by using different ZrO.sub.2 catalysts after 30 min at 120° C. Median Particle particle Particle size x.sub.10 size x.sub.50 size x.sub.90 Me- (mm; (mm; (mm; BET dian if not if not if not sur- Total pore noted noted noted face pore diam- Ex- other- other- other- area volume eter Crystal ZrO.sub.2 HfO.sub.2 TiO.sub.2 ample wise) wise) wise) (m.sup.2/g) (mL/g) (nm) phase wt. % wt. % wt. % 20 2.92 2.98 3.04 114 0.26 25 Triclinic, 83 1.5 — trace mono- clinic 21 2.98 3.06 3.17 114 0.25 39 Triclinic 90 1.6 — 22 0.1 0.4 1.1 3.2 0.015 12 Cubic 78 2 — 23 0.1 μm  0.6 μm  3.1 μm 4.6 0 0 Triclinic 65.5 1.5 — 24   4 μm   21 μm   56 μm <1 0 0 Ortho- 59.5 1.5 39 rhombic 25 0.3 μm  0.5 μm  0.7 μm 9.5 0 0 Rhom- 92 1.7 — boedric 26 0.2 μm  1.2 μm  4.6 μm 1.8 0 0 Ortho- 61 2 — rohombic 27  67 μm  117 μm  173 μm <1 0 0 Triclinic 61 2 — Con- ver- sion Selec- Ex- SiO.sub.2 Y.sub.2O.sub.3 WO.sub.3 La.sub.2O.sub.3 CaO Sc.sub.2O.sub.3 Met- Yield tivity ample wt. % wt. % wt. % wt. % wt. % wt. % amide Met Met 20 — — 15.5 — — — 82% 80%  98% 21 — — — 8.4 — — 65% 65% 100% 22 — 20 — — — — 20% 18%  90% 23 33 — — — — — 25% 23%  92% 24 — — — — — — 19% 18%  95% 25 — — — — — 6.3 41% 25%  61% 26 — — — — 37 — 22% 18%  82% 27 — — — — 37 — 21% 20%  95%

TABLE-US-00005 TABLE 4b (not part of the invention, for comparison): Examples of conversion of methionine amide to methionine by using different ZrO.sub.2 catalysts after 30 min at 120° C. Median Particle particle Particle size x.sub.10 size x.sub.50 size x.sub.90 (mm; (mm; (mm; BET Total Median Con- if not if not if not surface pore pore version Selec- Ex- noted noted noted area volume diameter Crystal ZrO.sub.2 HfO.sub.2 CeO.sub.2 Met- Yield tivity ample otherwise) otherwise) otherwise) (m.sup.2/g) (mL/g) (nm) phase wt. % wt. % wt. % amide Met Met A 0.3 μm  0.6 μm  0.8 μm 11 0.38 116 Monoclinic, 81.3 1.7 17 90 83 92 tetragonal B 2.06 3.03 4.73 <1 <0.01 n.a. Monoclinic 99.7 — 15 1 7 C 3.83 4.95 6.06 <1 <0.01 n.a. Monoclinic, 98 2 23 16 70 trace Tetragonal D 5.14 9.19 10.06 <1 <0.01 n.a. Monoclinic, 98 2 19 16 83 trace Tetragonal E 8.4 μm 18.9 μm 32.6 μm 5.9 0.27 128 Monoclinic 98 2 22 20 87 n.a. = not applicable

Example 28-34: Conversion of Methionine Amide to Methionine Using a Continuous Reaction Mode with a ZrO.SUB.2 .Catalyst Under Varying Conditions

[0105] A fixed-bed reactor with an inner diameter of 25 mm was filled according to table 5 with the amount of a ZrO.sub.2-catalyst stabilised with 2 wt. % HfO.sub.2 and 4 wt. % Y.sub.2O.sub.3, manufactured according to the exemplary catalyst preparation procedure above. The catalyst bed was fixed with inert glass wool and a filling of 50 g inert glass granules (diameter 2 mm) below and above the catalyst bed each in order to assure a pre-heated reaction solution to the desired temperature upon catalyst contact. The fixed bed-reactor was double walled and heated by means of an oil bath pumped through the outer mantle of the reactor. The temperature inside the reactor was monitored by a thermocouple inside the catalyst bed to assure the desired temperature according to table 5. The pressure in the reactor was fixed to 4 bara (8 bara for T=160° C.).

[0106] The volatile components of the methionine amide containing solution obtained from examples 2 or 3, in particular acetone and/or ammonia, were removed and the mixture obtained was adjusted to the following composition by addition of water and/or 32 wt. % aqueous ammonia as described in table 5. The solution was directly fed from the bottom to the fixed bed reactor with a WHSV rate according to table 5.

[0107] The reaction solution was cooled to room temperature after passing the fixed-bed reactor and analysed by HPLC chromatography regularly. After having achieved a steady-state (after about 24-48 h, three more HPLC analyses after additional 24 h, 48 h and 72 h were conducted regarding the conversion of methionine amide as well as yield of and selectivity towards Met. All three analyses were in each of the cases identical within the HPLC analysis error margin and thus only one of them is listed in table 5.

TABLE-US-00006 TABLE 5 Conversion of methionine amide (Met-Amide) to methionine by using different particulate ZrO.sub.2 catalysts in a continuous reaction mode under varying conditions cata- WHSV X lyst resi- [g(Met- Met- inven- c(Met- dent amide)/ A- Y S tory amide) time h/g(cata- T NH.sub.3 mide Met Met Ex. [g] [wt. %] [min] lyst)] [° C.] [eq] [%] [%] [%] 28 90  3 35 0.03  140 0 93 93 100 29 30  3 70 0.015 160 0 88 88 100 30 30  3 70 0.015 160 3 87 87 100 31 30  6 70 0.03  160 3 87 87 100 32 30  9 70 0.045 140 3 81 81 100 33 30 13 70 0.065 140 3 72 72 100 34 30 17 70 0.085 140 3 77 65  84 X = conversion; Y = yield; S = selectivity

Example 35: Evaluation of Catalyst Lifetime and Deactivation Behaviour Using a Continuous Reaction Mode for 24 Days

[0108] A fixed-bed reactor with an inner diameter of 25 mm was filled with 90 g of a ZrO.sub.2-catalyst stabilised with and 4 wt. % Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2, manufactured according to the exemplary catalyst preparation procedure above. The catalyst bed was fixed with inert glass wool and a filling of 50 g inert glass granules (diameter 2 mm) below and above the catalyst bed each in order to assure a pre-heated reaction solution to the desired temperature upon catalyst contact. The fixed bed-reactor was double walled and heated by means of an oil bath pumped through the outer mantle of the reactor. The temperature inside the reactor was being monitored by a thermocouple inside the catalyst bed to assure the desired temperature of 140° C. The pressure in the reactor was being fixed to 4 bara. The volatile components of the methionine amide containing solution obtained from examples 2 or 3, in particular acetone and/or ammonia, were removed and the mixture obtained was adjusted to a methionine amide concentration of 3.0 wt. % by addition of water. The solution was directly fed from the bottom to the fixed bed reactor with a flow rate of 90 mL/h, resulting in a resident time of 35 min and a weight hour space velocity (WHSV) rate of 0.03 g(methionine amide)/h/g(catalyst). This solution was fed to the fixed-bed reactor for 24 days without any changes in the catalyst performance as reported in example 28, table 5 (yield Met 93%, conversion methionine amide 93%, selectivity towards Met 100%).

[0109] This example shows that the catalyst being used in a continuous reaction mode is not deactivated within a period of at least 24 days. The methionine yield of 93% is quite high and the selectivity of 100% indicates that practically no by-products are formed.

Example 36 Direct Conversion of the Reaction Solution Obtained from Example 2 in a Continuous Reaction Mode

[0110] The fixed bed reactor was prepared with the ZrO.sub.2-catalyst as described in example 35 but instead of 90 g only 30 g of a ZrO.sub.2-catalyst stabilised with 4 wt. % Y.sub.2O.sub.3 and containing 2 wt. % HfO.sub.2, manufactured according to the exemplary catalyst preparation procedure above, was employed. The solution obtained from example 2 comprising 7.0 g methionine amide (47 mmol), 3.0 g Met (20 mmol), 7.47 g NH.sub.3 (439 mmol, 6 moleq), and 56.0 g water (methionine amide concentration 10 wt. %; Met concentration 4 wt. %) was diluted with water to a methionine amide concentration of 5 wt. % and a Met concentration of 2 wt. % and directly fed from the bottom to the fixed bed reactor with a flow rate of 15 mL/h at 140° C., resulting in a resident time of 70 min and in a weight hour space velocity (WHSV) rate of 0.025 g(methionine amide)/h/g(catalyst).

[0111] After 72 h continuous running, the product stream was analysed by HPLC analysis and revealed a 79% conversion of methionine amide, due to the initially higher Met concentration, with a yield of 74% of Met and a selectivity of 94% towards Met.

Example 37: Direct Conversion of the Reaction Solution Obtained from a Reaction Similar to Example 2 in a Continuous Reaction Mode

[0112] The fixed bed reactor was prepared with the ZrO.sub.2-catalyst as described in example 36. In another reaction according to example 2, a reaction solution comprising 3.0 g methionine amide (20 mmol), 7.0 g Met (47 mmol), 7.47 g NH.sub.3 (439 mmol, 6 moleq), and 56.0 g water (methionine amide concentration 4 wt. %; Met concentration 10 wt. %) was diluted with water to a methionine amide concentration of 2 wt. % and a Met concentration of 5 wt. % and directly fed from the bottom to the fixed bed reactor with a flow rate of 15 mL/h at 140° C., resulting in a resident time of 70 min and in a weight hour space velocity (WHSV) rate of 0.01 g(methionine amide)/h/g(catalyst).

[0113] After 72 h continuous running, the product stream was analysed by HPLC analysis and revealed a 65% conversion of methionine amide, due to the initially higher Met concentration, with a yield of 62% of Met and a selectivity of 96% towards Met.