Process for the preparation of methionine

Abstract

The present invention relates to a process for the preparation of methionine comprising the step of contacting a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile and/or 2-amino-4-(methylthio)butaneamide with water in the presence of a catalyst to give a methionine comprising mixture, wherein the catalyst comprises CeO.sub.2 comprising particles, wherein the CeO.sub.2 comprising particles comprise from 50 to 100 wt.-% of CeO.sub.2, have a BET surface area of from 35 to 65 m.sup.2/g measured according to DIN ISO 9277-5 (2003), a mean maximum Feret diameter x.sub.Fmax, mean of from 10 to 40 nm and a mean minimum Feret diameter x.sub.Fmin, mean of from 5 to 30 nm, both measured according to DIN ISO 9276-6 (2012).

Claims

1. A process for the preparation of methionine, comprising contacting a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile and/or 2-amino-4-(methylthio)butaneamide with water in the presence of a catalyst to produce a mixture comprising methionine, wherein the catalyst comprises particles comprising CeO.sub.2, wherein the particles comprise from 50 to 100 wt.-% of CeO.sub.2, wherein the particles have a BET surface area of from 35 to 65 m.sup.2/g measured according to DIN ISO 9277-5 (2003), and wherein the particles have a mean maximum Feret diameter x.sub.Fmax, mean of from 10 to 40 nm and a mean minimum Feret diameter x.sub.Fmin, mean of from 5 to 30 nm, both measured according to DIN ISO 9276-6 (2012).

2. The process of claim 1, wherein the catalyst comprises from 25 to 100 wt.-% of the CeO.sub.2, based on the total weight of the catalyst.

3. The process of claim 1, wherein the particles have a mean minimum Feret diameter x.sub.Fmin, mean of from 9 to 25 nm.

4. The process of claim 1, wherein the particles have a mean maximum Feret diameter x.sub.Fmax, mean of from 13 to 36 nm.

5. The process of claim 1, wherein the mean minimum Feret diameter x.sub.Fmin, mean of the particles is always smaller than the mean maximum Feret diameter x.sub.Fmax, mean of the particles.

6. The process of claim 1, wherein the particles have a mean aspect ratio x.sub.Fmin, mean/x.sub.Fmax, min of from 0.55 to 0.85, measured according to DIN ISO 9276-6 (2012).

7. The process of claim 1, wherein the particles have a lattice plane distance of from 0.24 to 0.32 nm.

8. The process of claim 1, wherein the particles comprise octahedral particles.

9. The process of claim 1, wherein the particles have a mean equivalent circular diameter x.sub.A, mean of from 5 to 45 nm, measured according to DIN ISO 9276-6 (2012).

10. The process of claim 1, wherein the particles have a crystallinity of at least 50%.

11. The process of claim 1, wherein the contacting is performed at a temperature of at most 90° C. with a solution or suspension comprising 2-amino-4-(methylthio)butanenitrile.

12. The process of claim 1, further comprising at least one contacting the mixture comprising methionine with the catalyst and/or with a second catalyst comprising particles comprising CeO.sub.2.

13. The process of claim 12, wherein the at least one further contacting is performed at a temperature ranging from 70 to 140° C.

14. The process of claim 1, further comprising separating the catalyst from the mixture comprising methionine by a continuous cross-flow filtration.

15. The process of claim 1, wherein the contacting is accompanied by a vacuum distillation or by stripping of the reaction solution or suspension with water vapor.

Description

EXAMPLES

1. Analytical Methods

1.1 HPLC-Chromatography

(1) Chromatographic analyses of 2-hydroxy-4-(methylthio)butanenitrile (MMP-CN), 2-amino-4-(methylthio)butanenitrile (MMP-AN), 2-amino-4-(methylthio)butaneamide (Met-amide), 3-(methylthio)propionaldehyde (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.

1.2 BET Surface Area

(2) The BET surface areas A.sub.BET 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 Miromertrics instrument. The method is described in general in DIN ISO 9277-5 (2003) and was being applied accordingly.

1.3 X-Ray Powder Diffraction and Degree of Crystallinity

(3) 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 performed as follows. 0.5-2.0 g of the material were analyzed in the Cubix3 Pharma X-ray powder diffractometer from PANalytical using the following parameters:

(4) X-ray tube: LFF-Cu X-ray tube, Cu Kα, λ=0.1542 nm

(5) Generator settings: 40 mA, 40 KV

(6) Detector: X'Celerator

(7) Rotation: Yes/1 Rev./s

(8) 2-Theta range: 5°-100°

(9) Step (° 2Θ): 0.017°

(10) Time per step: 40 s

(11) 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. The crystallinity of the material was determined using the constant background method implemented in the HighScore Plus PANalytical software. This method is based on the following equation:

(12) $\mathrm{Crystallinity}\left[\%\right]=\frac{100\times A}{A+B-C}$
wherein A is the integral area underneath the crystalline reflections, B represents the area of the amorphous background and is the integral area between the crystalline reflections and the instrument background line, and C is the integral area below the instrument background line caused by air scattering of X-rays, fluorescence radiation and other instrument factors.

(13) The integral area A was determined in the X-ray diffractograms by laying down the background line, which separates the crystalline reflections from the apparent amorphous background. The instrument background line (constant background) and thus the integral area C was determined by measuring a CeO.sub.2 NIST certified reference material with 100% crystallinity. The integral area B is determined in the measured samples by laying down the amorphous background and by applying the constant instrument background determined in the CeO.sub.2 NIST certified reference material.

(14) 1.4 High-Resolution Transmission Electron Microscopy (HR-TEM):

(15) A Jeol 2010F field emission transmission electron microscope was operated at 200 keV acceleration voltage. The calibration, quality and stability of the system was carried out with the Magical no. 641 standard (Norrox Scientific Ltd., Beaver Pond, Ontario, Canada). High resolution transmission electron microscopy (HR-TEM) was used for determination of the distance between lattice planes. Samples were prepared by manually dispersing 10 mg of a powder in 2 mL of chloroform or 2 mL of a 2:1 mixture of isopropanol/water in a clean test tube. The dispersion was agitated for 3 minutes using a UP100H ultrasonic probe (Hielscher) which was introduced deep into the test tube to 1 cm distance to the bottom. During this time, the test tube was located additionally in a Sonorex Super RK102H ultrasonic bath (Bandelin, 240 W peak energy input). HR-TEM supports coated with holey carbon foil were used as a support (CF200-Cu Carbon film on 200 mesh copper grids; producer: Electron Microscopy Sciences, Hatfield, Pa.). 10 μL of the dispersion were transferred onto the carbon foil using a Transferpette (Brand).

(16) For spot analyses of the nanoparticles, energy dispersive X-ray nano-spot-analyses (EDX) were performed using a Noran SiLi detector with a 30 mm.sup.2 crystal and a Noran System Six device.

(17) For statistical evaluation of the maximum Feret diameter x.sub.Fmax, minimum Feret diameter x.sub.Fmin, aspect ratio x.sub.Fmin/x.sub.Fmax, projection area A, and equivalent circular diameter x.sub.A of the nanoparticles, 500 particles of a sample were selected manually from a HR-TEM analysis and evaluated according to DIN ISO 9276-6 (2012) using the I-TEM software of Soft Imaging Systems (SIS), Munster, Germany. The obtained values were used for the calculation of the corresponding mean values x.sub.Fmax, mean, x.sub.Fmin, mean, x.sub.Fmin, mean/x.sub.Fmax, mean, A.sub.mean, and x.sub.A, mean.

2. Preparation of Catalysts According to the Invention

(18) The catalysts 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 according to the present invention. For example, the catalysts #1 to #6 according to the present invention were prepared in accordance to example 1 of the published patent application EP 1 506 940.

(19) 1200 g/h of a 2-ethylhexanoic acid (51 wt.-%) solution of cerium(III) 2-ethylhexanoate (49 wt.-%) or a mixture of cerium(III) 2-ethylhexanoate and zirconium(IV) 2-ethylhexanoate (total 49 wt.-%) in corresponding ratios according to the catalysts used in table 1 were atomized through a nozzle with a diameter of 1 mm into a reaction chamber using air (3 m.sup.3/h). Here, an oxyhydrogen gas flame consisting of hydrogen (3.5 m.sup.3/h) and primary air (15 m.sup.3/h) was burning, in which the aerosol was reacted. In addition, 10 m.sup.3/h of secondary air were introduced into the reaction chamber. A restrictor with a length of 150 mm and a diameter of 15 mm, through which the reaction mixture was passed, was installed in the reaction chamber below the flame. After cooling, the CeO.sub.2 or (CeO.sub.2).sub.x—(ZrO.sub.2).sub.(1-x) (x=0.8, 0.7, 0.5) powder was separated from gaseous substances using a filter. Catalysts comprising particles comprising CeO.sub.2, (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5, (CeO.sub.2).sub.0.7—(ZrO.sub.2).sub.0.3, and (CeO.sub.2).sub.0.8—(ZrO.sub.2).sub.0.2 were prepared.

(20) The powder of the different catalysts was analyzed for their Brunauer, Emmett, and Teller (BET) surface area A.sub.BET, degree of crystallinity, and their mean maximum Feret diameter x.sub.Fmax, mean, minimum Feret diameter x.sub.Fmin, mean, mean aspect ratio x.sub.Fmin, means/x.sub.Fmax, mean, lattice plane distance, and mean equivalent circular diameter x.sub.A, mean using high resolution transmission electron microscope (HR-TEM) and a subsequent graphical analysis of 500 particles. The catalysts #7 and #8 were purchased from Wako Pure Chemicals Ltd., the catalyst #9 was purchased from Kanto Chemical Co., Inc., and the catalyst #10 was purchased from Daiichi Kigenso Kagaku Kogyo Co., Ltd., respectively, and analyzed for the same parameters as the catalysts according to the present invention.

(21) TABLE-US-00001 TABLE 1 Summary of the tested catalysts Lattice plane Crystallinity distance A.sub.BET x.sub.A, mean x.sub.Fmax, mean x.sub.Fmin, mean x.sub.Fmin, mean/ Catalyst # Catalyst composition [%] [nm] [m.sup.2/G] [nm] [nm] [nm] x.sub.Fmax, mean #1 CeO.sub.2 82 0.30-0.31 64 12.5 15.7 10.6 0.69 #2 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 63 0.28-0.32 42 20.1 25.2 18.0 0.72 #3 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 58 0.28-0.31 43 20.0 24.6 18.0 0.74 #4 (CeO.sub.2).sub.0.8—(ZrO.sub.2).sub.0.2 89 0.30-0.31 36 26.4 32.7 23.5 0.73 #5 (CeO.sub.2).sub.0.7—(ZrO.sub.2).sub.0.3 85 0.30-0.31 36 28.0 35.2 24.9 0.71 #6 CeO.sub.2 72 0.30-0.31 64 10.8 13.7 9.4 0.70 #7.sup.1 CeO.sub.2 80 0.32-0.40 23 21.9 26.7 18.6 0.89 #8.sup.1 CeO.sub.2 96 0.30-0.31 3.9 48.1 59.9 41.9 0.71 #9.sup.1 CeO.sub.2 80 0.31 57 5.7 24.6 4.7 0.23 #10.sup.1  CeO.sub.2 59 0.28-0.32 159.6 4.1 5.1 3.6 0.73 (.sup.1comparative examples).

3. Synthesis Examples

3.1 Synthesis of 2-amino-4-(methylthio)butanenitrile Starting from 2-hydroxy-4-(methyl-thio)butanenitrile

(22) 10.1 g 2-hydroxy-4-(methylthio)butanenitrile (MMP-CN; 90 wt.-% in water, 69.3 mmol, 1 mol.eq.) were mixed with 26.0 g NH.sub.3 (32 wt.-% in water, 7 mol.eq., 48.8 mmol) in a glass reactor and sealed subsequently. The slightly beige colored and turbid emulsion containing 25 wt.-% MMP-CN was stirred and heated to 50° C. for 30 minutes by means of a pre-heated water bath. The obtained light yellow solution was analyzed 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 (Met-amide; 1.2 mmol).

3.2 Direct Conversion of the Obtained 2-amino-4-(methylthio)butanenitrile Towards a Mixture Comprising 2-amino-4-(methylthio)butaneamide and methionine

(23) To the reaction solution obtained according to example 3.1 comprising 8.75 g MMP-AN (67.2 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 mol.eq.), and 19.9 g water, another 36.2 g water (MMP-AN concentration 12 wt.-%) and 1.0 g (5.8 mmol, 0.09 mol.eq.) of the CeO.sub.2-containing catalyst according to table 2 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 analyzed by HPLC chromatography. In addition, the reaction was also carried in the presence of ZrO.sub.2 (catalyst #11) and without the presence of any catalyst (none). Results of the conversion of MMP-AN, the selectivity towards methionine (Met), the combined selectivity towards Met-amide and Met, the ratio of Met:Met-amide, the yield of Met, and the combined yield of Met-amide and Met are listed in table 2.

(24) TABLE-US-00002 TABLE 2 Summary of the results of example 3.2 Y [%] S [%] X [%] Met + Y [%] Ratio Y Met + S [%] Cat. # Catalyst composition MMP-AN Met-amide Met Met:Met-amide Met-amide Met #1 CeO.sub.2 89 79 28 0.5 89 31 #2 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 93 89 64 1.8 96 69 #3 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 85 75 47 1.7 88 55 #4 (CeO.sub.2).sub.0.8—(ZrO.sub.2).sub.0.2 92 83 22 0.4 90 24 #5 (CeO.sub.2).sub.0.7—(ZrO.sub.2).sub.0.3 91 82 28 0.5 90 31 #6 CeO.sub.2 95 87 37 0.7 92 39 #7.sup.1 CeO.sub.2 46 28 2 0.08 61 4 #8.sup.1 CeO.sub.2 33 24 1 0.04 73 3 #9.sup.1 CeO.sub.2 85 97 17 0.3 79 20 #10.sup.1  CeO.sub.2 91 82 31 0.6 91 34 #11.sup.1  ZrO.sub.2 35 24 2 0.07 70 6 none.sup.1 — 18 11 0 0 63 0 (.sup.1comparative examples, X = conversion, Y = yield, S = selectivity)

3.3 Direct Full Conversion of the Obtained 2-amino-4-(methylthio)butanenitrile Towards Methionine

(25) The reaction solution obtained according to example 3.1 comprising 8.76 g MMP-AN (67.3 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 mol.eq.), and 19.9 g water was transferred to a stainless steel autoclave reactor and another 36.2 g water (MMP-AN concentration 12 wt.-%) and 4.0 g (23 mmol, 0.35 mol.eq.) of the CeO.sub.2-containing catalyst according to table 3 were added. The reactor was sealed and heated to 75° C. for 120 minutes by means of an electric block heater while the reaction was stirred. Subsequently, the reaction solution was rapidly cooled to room temperature and analyzed by HPLC chromatography. Results of the conversion of MMP-AN, the selectivity towards methionine (Met), the combined selectivity towards Met-amide and Met, the ratio of Met:Met-amide, the yield of Met, and the combined yield of Met-amide and Met are listed in table 3.

(26) TABLE-US-00003 TABLE 3 Summary of the results of example 3.3 Y [%] S [%] X [%] Met + Y [%] Ratio Y Met + S [%] Cat. # Catalyst composition MMP-AN Met-amide Met Met:Met-amide Met-amide Met #1 CeO2 100 100 100 16 100 100 #2 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 100 99.5 99.5 —.sup.2 99.5 99.5 #3 (CeO.sub.2).sub.0.5—(ZrO.sub.2).sub.0.5 100 100 100 99 100 100 #4 (CeO.sub.2).sub.0.8—(ZrO.sub.2).sub.0.2 100 100 99 19 100 99 #5 (CeO.sub.2).sub.0.7—(ZrO.sub.2).sub.0.3 100 99 99 —.sup.2 99 99 #6 CeO.sub.2 100 100 100 99 100 100 #2 + 3 13 wt.-% CeO2 75 56 22  1 74 29 eq. #9.sup.1 87 wt.-% ZrO2 #7.sup.1 CeO.sub.2 100 87 35   0.7 87 35 #8.sup.1 CeO.sub.2 95 94 31   0.5 99 33 #9.sup.1 CeO.sub.2 100 86 81 16 86 81 #10.sup.1  CeO.sub.2 100 98 98 —.sup.2 98 98 (.sup.1comparative examples; .sup.2no Met-amide was detected, X = conversion, Y = yield, S = selectivity)

3.4 Direct Conversion of the Obtained 2-amino-4-(methylthio)butanenitrile Towards a Mixture Comprising 2-amino-4-(methylthio)butaneamide and methionine at Different Start Concentrations of the Obtained 2-amino-4-(methylthio)butanenitrile

(27) To the reaction solution obtained according to example 3.1 comprising 8.75 g MMP-AN (67.2 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 mol.eq.), and 19.9 g water, another 0 g, 36.2 g, or 110 g water (MMP-AN concentration 24 wt.-%, 12 wt.-%, or 6 wt.-%) and 0.5 g catalyst #2 according to table 1 (2.9 mmol, 0.04 mol.eq.) 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 analyzed by HPLC chromatography. Results of the conversion of MMP-AN, the selectivity towards methionine (Met), the combined selectivity towards Met-amide and Met, the ratio of Met:Met-amide, the yield of Met, and the combined yield of Met-amide and Met are listed in table 4.

(28) TABLE-US-00004 TABLE 4 Summary of the results of example 3.4 Y [%] S [%] C [%] X [%] Met + Y [%] Ratio Y Met + S [%] MMP-AN MMP-AN Met-amide Met Met:Met-amide Met-amide Met 6 92 80 54 2.1 87 59 12 72 58 19 0.6 81 26 24 47 36 8 0.3 76 17 C = concentration, X = conversion, Y = yield, S = selectivity.

3.5 Direct Conversion of the Obtained 2-amino-4-(methylthio)butanenitrile Towards a Mixture Comprising 2-amino-4-(methylthio)butaneamide and methionine at Different Temperatures

(29) The reaction solution obtained according to example 3.1 comprising 8.75 g MMP-AN (67.2 mol), 0.18 g Met-amide (1.2 mmol), 7.14 g NH.sub.3 (419 mmol, 6 mol.eq.), and 19.9 g water was transferred to a stainless steel autoclave reactor and another 36.2 g water (MMP-AN concentration 12 wt.-%) and 1.0 g catalyst #2 according to table 1 (5.8 mmol, 0.09 mol.eq.) were added. The reactor was sealed and heated to 90 or 105° C. for 60 minutes by means of an electric block heater while the reaction was stirred. Subsequently, the reaction solution was rapidly cooled to room temperature and analyzed by HPLC chromatography. Results of the conversion of MMP-AN, the selectivity towards methionine (Met), the combined selectivity towards Met-amide and Met, the ratio of Met:Met-amide, the yield of Met, and the combined yield of Met-amide and Met are listed in table 5. Compared to the reaction 90° C., 4% oxidized Met, methionine sulfoxide, was observed when the conversion of MMP-AN was performed at the higher temperature of 105° C.

(30) TABLE-US-00005 TABLE 5 Summary of the results of example 3.5 Y [%] S [%] Temperature X [%] Met + Y [%] Ratio Y Met + S [%] [° C.] MMP-AN Met-amide Met Met:Met-amide Met-amide Met 90 100% 97% 95% 48 97% 95% 105 100% 93% 91% 50 93% 91% X = conversion, Y = yield, S = selectivity.

3.6 Reacting the Obtained Solution Comprising 2-amino-4-(methylthio)butaneamide and methionine at Elevated Temperatures for Full Conversion to methionine

(31) The reaction solution obtained according to example 3.2 with catalyst #2 according to table 2 comprising 3.64 g Met-amide (24.6 mmol), 6.52 g Met (43.8 mmol), 7.88 g NH.sub.3 (463 mmol, 6.5 mol.eq.), 55.4 g water, and 1.0 g catalyst #2 according to table 1 (5.8 mmol, 0.09 mol.eq.) was transferred to a stainless steel autoclave reactor and heated to 120° C. for 120 minutes by means of an electric block heater while the reaction was stirred. Subsequently, the reaction solution was rapidly cooled to room temperature. The solution was analyzed by HPLC chromatography revealing 100% conversion of Met-amide with a selectivity to Met of 98%, which equals to a yield of Met of 98%.

3.7 Separating the Catalyst from a Methionine Comprising Mixture by a Continuous Cross-Flow Filtration

(32) A methionine comprising mixture comprising 3 wt.-% Met and 1 wt.-% of catalyst #1 according to table 1 was pumped through an Al.sub.2O.sub.3 channel (support) covered by a membrane made of Al.sub.2O.sub.3 with a membrane pore diameter of 50 nm or covered by a membrane made of ZrO.sub.2 with a nominal molecular weight cutoff (NMWC) of 150 or 25 kD. In each of the cases, the permeate was analyzed by HPLC chromatography and revealed a successful and unhindered passing of Met through the membrane with an identical Met concentration of 3% as compared to the starting methionine comprising mixture. In each of the cases, a particle size distribution analysis by laser diffraction as well as dynamic light scattering of the permeate solution revealed that the catalyst was fully retained in the retentate and did not pass the membrane.