EP4232429A1 - Method for catalytic production of a methionine analogue - Google Patents
Method for catalytic production of a methionine analogueInfo
- Publication number
- EP4232429A1 EP4232429A1 EP21806311.3A EP21806311A EP4232429A1 EP 4232429 A1 EP4232429 A1 EP 4232429A1 EP 21806311 A EP21806311 A EP 21806311A EP 4232429 A1 EP4232429 A1 EP 4232429A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- acid
- hydroxy
- catalyst
- hmtba
- hmtbn
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 41
- 230000003197 catalytic effect Effects 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title description 8
- 125000001360 methionine group Chemical class N[C@@H](CCSC)C(=O)* 0.000 title 1
- PICCHNWCTUUCAQ-UHFFFAOYSA-N 2-hydroxypentanethioic s-acid Chemical compound CCCC(O)C(O)=S PICCHNWCTUUCAQ-UHFFFAOYSA-N 0.000 claims abstract description 62
- VWWOJJANXYSACS-UHFFFAOYSA-N 2-hydroxy-4-methylsulfanylbutanenitrile Chemical compound CSCCC(O)C#N VWWOJJANXYSACS-UHFFFAOYSA-N 0.000 claims abstract description 47
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 43
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 34
- 239000002253 acid Substances 0.000 claims abstract description 33
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 claims abstract description 21
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- ADHNRHXQGKLXBY-UHFFFAOYSA-N 2-hydroxy-4-methylselanylbutanenitrile Chemical compound C[Se]CCC(O)C#N ADHNRHXQGKLXBY-UHFFFAOYSA-N 0.000 claims abstract description 7
- HYAVVFBCHISBDZ-UHFFFAOYSA-N CCCC(O)C(O)=[Se] Chemical compound CCCC(O)C(O)=[Se] HYAVVFBCHISBDZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 57
- 230000008569 process Effects 0.000 claims description 20
- 235000011054 acetic acid Nutrition 0.000 claims description 19
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- 235000019253 formic acid Nutrition 0.000 claims description 9
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims description 6
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 235000021317 phosphate Nutrition 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 3
- 239000004310 lactic acid Substances 0.000 claims description 3
- 235000014655 lactic acid Nutrition 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 3
- 229940107700 pyruvic acid Drugs 0.000 claims description 3
- 229910052785 arsenic Inorganic materials 0.000 claims description 2
- 229910052732 germanium Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 229910052750 molybdenum Inorganic materials 0.000 claims description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
- 229910052721 tungsten Inorganic materials 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 29
- 229930182817 methionine Natural products 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 14
- 150000001261 hydroxy acids Chemical class 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 150000003863 ammonium salts Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 229910021653 sulphate ion Inorganic materials 0.000 description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 229910052711 selenium Inorganic materials 0.000 description 5
- 239000011669 selenium Substances 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 229910052593 corundum Inorganic materials 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 229910001845 yogo sapphire Inorganic materials 0.000 description 4
- DOLNLDKZJKDWLS-UHFFFAOYSA-N 2-hydroxypentanethioamide Chemical compound CCCC(O)C(N)=S DOLNLDKZJKDWLS-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
- 229910010413 TiO 2 Inorganic materials 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 150000002741 methionine derivatives Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 239000001166 ammonium sulphate Substances 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 235000019728 animal nutrition Nutrition 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- -1 extrudates Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011949 solid catalyst Substances 0.000 description 2
- 238000004438 BET method Methods 0.000 description 1
- WTORCVUCZFXXCR-UHFFFAOYSA-N CCCC(O)C(N)=[Se] Chemical compound CCCC(O)C(N)=[Se] WTORCVUCZFXXCR-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000012072 active phase Substances 0.000 description 1
- BIGPRXCJEDHCLP-UHFFFAOYSA-N ammonium bisulfate Chemical compound [NH4+].OS([O-])(=O)=O BIGPRXCJEDHCLP-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000909 electrodialysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000006262 metallic foam Substances 0.000 description 1
- QPJSUIGXIBEQAC-UHFFFAOYSA-N n-(2,4-dichloro-5-propan-2-yloxyphenyl)acetamide Chemical compound CC(C)OC1=CC(NC(C)=O)=C(Cl)C=C1Cl QPJSUIGXIBEQAC-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 238000004375 physisorption Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003342 selenium Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/02—Boron or aluminium; Oxides or hydroxides thereof
- B01J21/04—Alumina
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
- B01J21/063—Titanium; Oxides or hydroxides thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
- B01J21/066—Zirconium or hafnium; Oxides or hydroxides thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/02—Sulfur, selenium or tellurium; Compounds thereof
- B01J27/053—Sulfates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/60—Catalysts, in general, characterised by their form or physical properties characterised by their surface properties or porosity
- B01J35/61—Surface area
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
- B01J37/20—Sulfiding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
Definitions
- TITLE Process for the catalytic production of a methionine analogue
- the invention relates to an improvement in a process for the manufacture of 2-hydroxy-4-methylthiobutyric acid, an analogue of methionine, or its selenium counterpart, 2-hydroxy-4-methylselenobutyric acid, from 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile, respectively.
- HMTBA 2-Hydroxy-4-methylthiobutyric acid
- HMTBA 2-Hydroxy-4-methylthiobutyric acid
- its salts 2-Hydroxy-4-methylthiobutyric acid
- its chelates in particular metal chelates (of Zn, Ca, Mn, Mg, Cu, Na... )
- its esters such as the isopropyl and tert-butyl esters of HMTBA
- the selenium derivatives of this acid, these salts, these chelates and these esters are also constituents of major interest in animal nutrition.
- 2-hydroxy-4-methylthiobutyric acid can be carried out by different processes involving various synthetic intermediates, and in particular 2-hydroxy-4-methylthiobutyronitrile (HMTBN) and 2-hydroxy-4-methylthiobutyramide (HMTBM).
- HMTBN 2-hydroxy-4-methylthiobutyronitrile
- HMTBM 2-hydroxy-4-methylthiobutyramide
- HMTBA 2-hydroxy-4-methylthiobutyric acid
- HMTBN 2-hydroxy-4-methylthiobutyronitrile
- HMTBM 2-hydroxy-4-methylthiobutyramide
- This process has the disadvantage of using large quantities of sulfuric acid, the latter being generally used in excess relative to the HMTBN, resulting in the formation of large quantities of co-products such as ammonium bisulfate, which must be separated and which, moreover, are difficult to recycle.
- This process also requires long residence times of the order of a few hours.
- a method for manufacturing the ammonium salt of HMTBA from the nitrile precursor of HMTBA, HMTBN is known, according to which the HMTBN in aqueous solution, brought into contact with a titanium-based catalyst, is converted in a single step to the ammonium salt of HMTBA.
- This synthesis also leads to the formation of methionine and HMTBM, and the announced yields of ammonium salt of HMTBA are of the order of 1%. They are too insufficient to consider an application of this process on an industrial scale.
- the present invention provides an alternative to the existing processes making it possible both to dispense with the use of sulfuric acid and to combine the hydration and hydrolysis stages in a single catalyzed stage and to lead to yields of HMTBA or in its seleniated counterpart, exceptionally and unexpectedly elevated.
- HMTBN hydroxy-nitrile intermediate
- the hydroxy-nitrile intermediate could be converted into 2-hydroxy-4-methylthiobutyric acid (or into seleno-hydroxy-methionine) in a single step, in the presence at least one catalyst and a weak acid.
- the accessibility and performance of this conversion are such that its transposition to industrial production of the hydroxy-analogue of methionine is feasible.
- the present invention represents a real advance. Significant yields are obtained in very short times and this process makes it possible to avoid the consumption of sulfuric acid and the formation of co-products or synthesis intermediates.
- the invention provides a process for preparing the hydroxy-analog of methionine or the hydroxy-analog of selenated methionine by catalytic conversion of 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile, respectively, said conversion being carried out in the presence of water and at least one weak acid and a catalyst comprising at least one of alumina, titanium dioxide and zirconia.
- the hydroxy-nitrile compound is directly transformed into hydroxy-acid, after conversion of the ammonium salt of the hydroxy-acid according to conventional techniques, without having to resort to a cumbersome separation step resulting in an economic gain. considerable.
- hydroxy-acid is used to designate either 2-hydroxy-4-methylthiobutyric acid or 2-hydroxy-4-methylselenobutyric acid, taken together or separately.
- hydroxy-nitrile refers to both 2-hydroxy-4-methylthiobutyronitrile and 2-hydroxy-4-methylselenobutyronitrile, taken together or separately
- hydroxy-amide refers to 2-hydroxy-4- methylthiobutyramide or 2-hydroxy-4-methylselenobutyramide, taken together or alone.
- weak acid any organic or mineral acid whose constant pK a is at least 1 and at most 10 at 25° C. or any compound or any mixture which behaves in this way.
- HF hydrofluoric acid
- HOCI hypochlorous acid
- H3BO3 boric acid
- sulfurous acid H2SO3
- hydrocyanic acid HN
- titanium dioxide and zirconia are meant all the polymorphs, if any, of aluminum oxide Al2O3, titanium dioxide TiC>2 and zirconium dioxide ZrO2, respectively, these forms being well known to the skilled person.
- the catalyst can also be a combination of two or even three of alumina, titanium dioxide and zirconia. It can also comprise any other entity promoting its catalytic function.
- the weak acid is preferably an organic acid having one or more carboxylic groups or a mineral acid, having a pKa of at least 1 at 25° C., and preferably of at most 10, even more preferably of at most 7. at 25°C. In a practical interest, it has a boiling point less than or equal to 170°C and preferably less than or equal to 150°C, or even less than or equal to 120°C, in order to be more easily separated from the reaction medium, usually by distillation.
- Such acids which can be used according to the invention are chosen in particular from formic acid, acetic acid, propionic acid, linear or branched butanoic acid, pentanoic acid, carbonic acid, glycolic acid, thioacetic acid, cyanoacetic acid, lactic acid, pyruvic acid, oxalic acid, methionine or its selenium equivalent, or the hydroxy analogue of methionine or its selenium equivalent. These acids can be used alone or in any mixture with each other.
- the acids used are formic acid, acetic acid and/or propionic acid.
- the weak acid is a mineral acid such as phosphoric acid, dihydrogen phosphate acid, used alone or in a mixture.
- Said weak acid is added in a molar ratio of weak acid to hydroxynitrile of 0.001 to 50, or even 0.001 to 30 and even 0.001 to 10 or even 0.001 to 1.
- the molar concentration of the weak acid in the reaction medium varies from 0.05 M to 10 M, preferentially from 0.1 M to 2 M and even more preferentially from 0.2 M to 1 M.
- the catalyst is chosen from alumina, titanium dioxide and zirconia; this compound constitutes at least the active phase of the catalyst, optionally the support.
- the catalyst can comprise any other compound that does not affect the performance of the catalyst, or even reinforces it.
- the catalyst consists of one of said oxides.
- the catalyst can be doped and/or supported. It can be doped with any element or compound conventionally used and well known to those skilled in the art.
- the catalyst can be doped with one or more compounds chosen from sulphates (SO4), phosphates (PO4), tungstates (WO3), borates (B2O3), heteropolyacids corresponding to one of the formulas H n XM 12 0 4 o and H ⁇ MisOsz in which n is an integer preferably not exceeding 10, X represents Si, Ge, P or As and M represents Mo or W, such as the phosphomolybdic acid of formula H 5 P 2 MOI S O 62 , as well as any other doping compound bringing acidity to the catalyst.
- the following compounds PO4, SO4 and H 8 P 2 MOI 8 O S 2 are to be preferred.
- the catalyst does not consist of alumina, titanium dioxide and/or zirconia, it can also be supported by any other compound conventionally used and well known to those skilled in the art, and in particular silica and silicoaluminates.
- all of the solid catalysts mentioned above can be in powder form or preferably in the form of beads, extrudates, tablets, trilobes or any other form allowing it to be used in a continuous reactor, of the fixed bed or others or in batch mode in an open reactor or under pressure.
- Said catalyst advantageously has a specific surface of at least 10 m 2 /g. Below this limit, the performance of the catalyst drops rapidly with in particular a decline in the selectivity for hydroxy-acid in favor of that for hydroxy-amide and a reduction in the conversion of hydroxy-nitrile. This observation applies to the selenium equivalent.
- the specific surface is at least 50 m 2 /g.
- the upper limit of the specific surface is not decisive in the context of the invention, the latter being imposed by the active phases commercially available.
- the specific surface values indicated in this text are determined by the most common method, namely nitrogen physisorption and calculated by the BET method.
- the catalyst is present in a concentration by mass of 0.1% to 200% relative to the mass of HMTBN, preferably from 0.5% to 100% and better still. another 1% to 50%.
- the solid catalyst, doped or not can be immobilized in a reactor in the form of grains or extrudates or any other form or supported on a metal foam.
- the reactor associated with this type of catalyst is preferably a tubular or multitubular fixed bed, operating in trickling or isothermal or adiabatic flooded mode, or an exchanger reactor coated with catalyst.
- the conversion of HMTBN within the scope of the invention is advantageously carried out at a temperature ranging from 20° C. to 200° C., preferably from 50° C. to 180° C., and even better still from 80° C. to 170° C. vs. It has been observed, over a reaction period ranging from the order of 10 minutes to 3 hours, that at a temperature below 20°C, the reaction is greatly slowed down, and that from 180°C, the higher the temperature, the more the selectivity for methionine and dinitrile and polypeptide of methionine increases at detriment of that of 2-hydroxy-4-methylthiobutyric acid. It is in the range of 100° C. to 180° C. that it is observed that the selectivity for the hydroxy acid is the highest.
- the contact times between the reaction mixture containing the water, the hydroxy-nitrile and the acid with the catalyst range from 30 seconds to 1 hour, preferably from 1 minute to 30 minutes. and even more preferably from 2 minutes to 20 minutes.
- Hydroxy-nitrile is usually in aqueous solution. This may have been prepared for the implementation of the method.
- the weak acid used in the reaction can be added to the aqueous hydroxy-nitrile solution or added via a mixer before entering the catalytic reactor.
- the concentration of hydroxy-nitrile can have an influence on the performance of the process, especially when it is too high.
- the hydroxy-nitrile is in aqueous solution in a concentration ranging from 0.01 M to 10 M, preferably from 0.05 M to 1 M. beyond 1 M, if the conversion to hydroxy-nitrile remains high, the selectivity for hydroxy-acid decreases whereas those for hydroxy-amide, for dinitrile and even for polypeptide, respectively, rise.
- the invention also relates to the implementation of the method of the invention continuously.
- the process is carried out under a pressure which can range from 1 to 20 bar, preferably from 2 to 10 bar.
- the invention provides a device comprising a tank for the hydroxy-nitrile solution and in which a weak acid is added.
- the resulting hydroxy acid solution is pumped to a reactor which includes the catalyst and which is heated by means of a mantle or an oven to a temperature of 80 to 180°C.
- the reaction medium is withdrawn to a gas/liquid separator from which the gases will be removed and from which the liquid is treated to recover the hydroxy acid.
- the solution is then evaporated to separate the excess water used and the weak acid which may or may not form an azeotrope, these compounds then being advantageously recycled in the process.
- the phase containing the hydroxy-acid can undergo stripping to remove all or part of the ammonia which makes up the ammonium salt of the hydroxy-acid.
- Complementary steps of electrodialysis or other technologies known to those skilled in the art can be considered to fully recover the hydroxy acid in its acid form (2-hydroxy-4-methylthiobutyric acid or the corresponding selenium acid) and recycle all of the ammonia formed during the hydrolysis of the HMBTM intermediate in the catalytic stage.
- the recovered ammonia will be recycled upstream of the process for manufacturing the hydroxy acid, as in the synthesis of HCN.
- FIG. 1 shows the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time, of a reaction according to a process of the invention under the conditions described in example 1 .
- FIG. 2 shows the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time, of a reaction according to a process of the invention under the conditions described in Example 2 .
- examples 1-6 illustrate various variants of a method of the invention
- examples 7 and 8 illustrate a technique for doping a catalyst to obtain a doped catalyst which can be used in a process of the invention, according to a variant such as that which is the subject of example 6
- Example 9 illustrates a step for separating the hydroxy-acid salt into the hydroxy-acid
- Examples 10 to 15 illustrate methods outside the invention, by way of comparison.
- Example 1 Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
- Example 2 Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
- HMTBN In a 1 liter screw-top flask, 13.1 g of HMTBN are introduced with 990 ml of H2O and 10 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes) and containing 4 grams of TiC >2 (anatase, 150 m 2 /g, Norpro, ST 61120). The HMTBA salt obtained is converted into HMTBA by stripping of ammonia according to a technique illustrated in Example 9.
- the yield of HMTBA is 95% and 5% of methionine.
- Example 3 Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
- HMTBN Into a 1 liter screw-top flask were added 13.1 g of HMTBN along with 800 ml of HLO and 200 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes). The reactor contains 4 grams of TiC>2 (anatase, 150 m 2 /g, Norpro, ST 61120). The HMTBA salt obtained is converted into HMTBA by stripping of ammonia according to a technique illustrated in Example 9.
- a 1 liter screw top flask was charged with 13.1 g of HMTBN along with 990 ml of F and 10 ml of formic acid.
- the solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes).
- the reactor contains 4 grams of TiC>2 (anatase, 150 m 2 /g, Norpro, ST 61120).
- the HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
- the yield of HMTBA is 90% and 10% of methionine.
- Example 5 Preparation of HMTBA in the presence of an alumina doped with sulphate and acetic acid, according to the invention
- the HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
- the HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
- the yield of HMTBA is 74% and 16% of methionine.
- Example 7 Preparation of TiO2 doped with 10% by weight of sulphate (SO 4 ) with sulfuric acid.
- Example 8 Preparation of TiO2 doped with 10% weight of sulphate (SO 4 ) with ammonium sulphate
- the ammonium salt solution of HMTBA obtained according to the invention is concentrated in organics up to an organic content of 87% by weight.
- the temperature of the medium changes from 100 to 130°C (atmospheric pressure). After this concentration step, the conversion to HMTBA is 21% (mol).
- a steam stripping phase is performed.
- the stripping water is introduced in liquid form.
- the organic content is kept constant at 87% by weight.
- the temperature is stationary between 115 and 121°C.
- the stripping flow rate is between 3.8 and 4.3 ml/min. After 200 minutes under these conditions, a conversion to HMTBA of 47% is obtained.
- a new stripping step is carried out to lead to HMTBA in yields close to 100%.
- the solution is analyzed by HPLC, no reaction is observed.
- Example 13 Preparation of HMTBA in the presence of a gamma phase alumina, according to the prior art
- Example 14 Preparation of HMTBA in the presence of a gamma phase alumina, according to the prior art
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Abstract
The invention relates to a method for preparing 2-hydroxy-4-methylthiobutyric acid (HMTBA) or 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) by catalytic conversion of 2-hydroxy-4-methylthiobutyronitrile or of 2-hydroxy-4-methylselenobutyronitrile, respectively, characterized in that said conversion is carried out in the presence of water and of at least one weak acid and a catalyst comprising at least one of alumina, titanium dioxide and zirconia.
Description
DESCRIPTION DESCRIPTION
TITRE : Procédé de fabrication catalytique d’un analogue de la méthionineTITLE: Process for the catalytic production of a methionine analogue
L’invention porte sur une amélioration d’un procédé de fabrication de l’acide 2-hydroxy- 4-méthylthiobutyrique, un analogue de la méthionine, ou de son correspondant sélénié, l’acide 2-hydroxy-4-méthylsélénobutyrique, à partir du 2-hydroxy-4-méthylthiobutyronitrile ou du 2- hydroxy-4-méthylsélénobutyronitrile, respectivement. The invention relates to an improvement in a process for the manufacture of 2-hydroxy-4-methylthiobutyric acid, an analogue of methionine, or its selenium counterpart, 2-hydroxy-4-methylselenobutyric acid, from 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile, respectively.
L’acide 2-hydroxy-4-méthylthiobutyrique (HMTBA), qui est l’analogue hydroxy de la méthionine, ses sels, ses chélates, notamment les chélates métalliques (de Zn, Ca, Mn, Mg, Cu, Na...) et ses esters, comme les esters isopropylique et tertiobutylique de l’HMTBA, sont largement utilisés en nutrition animale. Les dérivés séléniés de cet acide, de ces sels, de ces chélates et de ces esters sont eux aussi des constituants d’intérêts majeurs en nutrition animale. 2-Hydroxy-4-methylthiobutyric acid (HMTBA), which is the hydroxy analogue of methionine, its salts, its chelates, in particular metal chelates (of Zn, Ca, Mn, Mg, Cu, Na... ) and its esters, such as the isopropyl and tert-butyl esters of HMTBA, are widely used in animal nutrition. The selenium derivatives of this acid, these salts, these chelates and these esters are also constituents of major interest in animal nutrition.
La préparation de l’acide 2-hydroxy-4-méthylthiobutyrique peut être opérée par différents procédés mettant en jeu divers intermédiaires de synthèse, et en particulier le 2-hydroxy-4- méthylthiobutyronitrile (HMTBN) et le 2-hydroxy-4-méthylthiobutyramide (HMTBM). The preparation of 2-hydroxy-4-methylthiobutyric acid can be carried out by different processes involving various synthetic intermediates, and in particular 2-hydroxy-4-methylthiobutyronitrile (HMTBN) and 2-hydroxy-4-methylthiobutyramide (HMTBM).
Le document US2001/0001 105A1 décrit un procédé en continu d’une synthèse de l’acide 2-hydroxy-4-méthylthiobutyrique (HMTBA) à partir du 2-hydroxy-4-méthylthiobutyronitrile (HMTBN) selon laquelle, dans une première étape, l’HMTBN est hydrolysé en 2-hydroxy-4- méthylthiobutyramide (HMTBM) en présence d’une solution aqueuse d’un acide minéral tel que l’acide sulfurique, puis, dans une seconde étape, l’HMTBM est hydrolysé en HMTBA. Ce procédé présente l’inconvénient de recourir à des grandes quantités d’acide sulfurique, celui-ci étant généralement employé en excès par rapport à l’HMTBN, entraînant la formation de grandes quantités de co-produits comme le bisulfate d’ammonium, qui doivent être séparées et qui en outre sont difficilement recyclables. Ce procédé nécessite de plus des temps de séjours longs de l’ordre de quelques heures. Document US2001/0001 105A1 describes a continuous process for the synthesis of 2-hydroxy-4-methylthiobutyric acid (HMTBA) from 2-hydroxy-4-methylthiobutyronitrile (HMTBN) according to which, in a first step, the HMTBN is hydrolyzed to 2-hydroxy-4-methylthiobutyramide (HMTBM) in the presence of an aqueous solution of a mineral acid such as sulfuric acid, then, in a second step, the HMTBM is hydrolyzed to HMTBA. This process has the disadvantage of using large quantities of sulfuric acid, the latter being generally used in excess relative to the HMTBN, resulting in the formation of large quantities of co-products such as ammonium bisulfate, which must be separated and which, moreover, are difficult to recycle. This process also requires long residence times of the order of a few hours.
On connait selon le document W02004/089863A1 , un procédé de fabrication du sel d’ammonium de l’HMTBA à partir du précurseur nitrile de l’HMTBA, l’HMTBN, selon lequel l’HMTBN en solution aqueuse, mis en présence d’un catalyseur à base de titane, est converti en une seule étape en sel d’ammonium de l’HMTBA. Cette synthèse conduit aussi à la formation de la méthionine et de l’HMTBM, et les rendements annoncés en sel d’ammonium de l’HMTBA sont de l’ordre de 1 %. Ils sont trop insuffisants pour envisager une application de ce procédé à l’échelle industrielle. According to document W02004/089863A1, a method for manufacturing the ammonium salt of HMTBA from the nitrile precursor of HMTBA, HMTBN, is known, according to which the HMTBN in aqueous solution, brought into contact with a titanium-based catalyst, is converted in a single step to the ammonium salt of HMTBA. This synthesis also leads to the formation of methionine and HMTBM, and the announced yields of ammonium salt of HMTBA are of the order of 1%. They are too insufficient to consider an application of this process on an industrial scale.
La présente invention fournit une alternative aux procédés existants permettant à la fois de s’affranchir de l’utilisation d’acide sulfurique et de combiner les étapes d’hydratation et d’hydrolyse en une seule étape catalysée et de conduire à des rendements en HMTBA ou en son correspondant sélénié, exceptionnellement et inattendument élevés.
Il a été découvert selon l’invention que l’intermédiaire hydroxy-nitrile (HMTBN ou son équivalent sélénié) pouvait être transformé en acide 2-hydroxy-4-methylthiobutyrique (ou en séléno-hydroxy-méthionine) en une seule étape, en présence d’au moins un catalyseur et d’un acide faible. L’accessibilité et les performances de cette conversion sont telles que sa transposition à une production industrielle de l’hydroxy-analogue de la méthionine est réalisable. Par rapport aux procédés de synthèse connus et les améliorations mises au point qui pourraient y être apportées mais qui sont insuffisamment bénéfiques pour que les procédés industriels classiques soient modifiés, la présente invention représente une réelle avancée. Des rendements significatifs sont obtenus en des temps très courts et ce procédé permet d’éviter la consommation d’acide sulfurique et la formation de co-produits ou d’intermédiaires de synthèse. The present invention provides an alternative to the existing processes making it possible both to dispense with the use of sulfuric acid and to combine the hydration and hydrolysis stages in a single catalyzed stage and to lead to yields of HMTBA or in its seleniated counterpart, exceptionally and unexpectedly elevated. It has been discovered according to the invention that the hydroxy-nitrile intermediate (HMTBN or its selenated equivalent) could be converted into 2-hydroxy-4-methylthiobutyric acid (or into seleno-hydroxy-methionine) in a single step, in the presence at least one catalyst and a weak acid. The accessibility and performance of this conversion are such that its transposition to industrial production of the hydroxy-analogue of methionine is feasible. Compared to the known synthetic methods and the improvements developed which could be made thereto but which are insufficiently beneficial for the conventional industrial methods to be modified, the present invention represents a real advance. Significant yields are obtained in very short times and this process makes it possible to avoid the consumption of sulfuric acid and the formation of co-products or synthesis intermediates.
L’invention apporte un procédé de préparation de l’hydroxy-analogue de la méthionine ou l’hydroxy-analogue de la méthionine séléniée par conversion catalytique du 2-hydroxy-4- méthylthiobutyronitrile ou du 2-hydroxy-4-méthylsélénobutyronitrile, respectivement, ladite conversion étant effectuée en présence d’eau et d’au moins un acide faible et un catalyseur comprenant au moins l’un de l’alumine, du dioxyde de titane et de la zircone. The invention provides a process for preparing the hydroxy-analog of methionine or the hydroxy-analog of selenated methionine by catalytic conversion of 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile, respectively, said conversion being carried out in the presence of water and at least one weak acid and a catalyst comprising at least one of alumina, titanium dioxide and zirconia.
Selon l’invention, le composé hydroxy-nitrile est directement transformé en hydroxy- acide, après conversion du sel d’ammonium de l’hydroxy-acide selon des techniques classiques, sans avoir à recourir à une étape lourde de séparation entraînant un gain économique considérable. According to the invention, the hydroxy-nitrile compound is directly transformed into hydroxy-acid, after conversion of the ammonium salt of the hydroxy-acid according to conventional techniques, without having to resort to a cumbersome separation step resulting in an economic gain. considerable.
Avant d’exposer l’invention plus en détails, certains termes employés dans le présent texte sont définis. Before exposing the invention in more detail, certain terms used in this text are defined.
Le terme hydroxy-acide est utilisé pour désigner indifféremment l’acide 2-hydroxy-4- méthylthiobutyrique ou l’acide 2-hydroxy-4-méthylsélénobutyrique, pris ensemble ou isolément. De même, le terme hydroxy — nitrile se rapporte aussi bien au 2-hydroxy-4-méthylthiobutyronitrile qu’au 2-hydroxy-4-méthylsélénobutyronitrile, pris ensemble ou isolément, et le terme hydroxy- amide concerne le 2-hydroxy-4-méthylthiobutyramide ou le 2-hydroxy-4- méthylsélénobutyramide, pris ensemble ou isolément. The term hydroxy-acid is used to designate either 2-hydroxy-4-methylthiobutyric acid or 2-hydroxy-4-methylselenobutyric acid, taken together or separately. Similarly, the term hydroxy-nitrile refers to both 2-hydroxy-4-methylthiobutyronitrile and 2-hydroxy-4-methylselenobutyronitrile, taken together or separately, and the term hydroxy-amide refers to 2-hydroxy-4- methylthiobutyramide or 2-hydroxy-4-methylselenobutyramide, taken together or alone.
Par acide faible selon l’invention, on entend tout acide organique ou minéral dont la constante pKa est d’au moins à 1 et d’au plus 10 à 25°C ou tout composé ou tout mélange se comportant ainsi. A titre d’illustration d’un acide organique faible, on peut citer les acides et polyacides carboxyl iques, porteurs ou non d’une ou plusieurs fonctions par exemple choisies parmi OH, C=O, tels que l’acide acétique, l’acide formique, et à titre d’illustration d’un acide minéral faible, on peut citer l’acide phosphorique, l’acide dihydrogénophosphate, l’acide fluorhydrique (HF), l’acide hypochloreux (HOCI), l’acide borique (H3BO3), l’acide sulfureux (H2SO3), l’acide cyanhydrique (HCN).
Le terme catalyseur tel qu’employé renvoie généralement à la phase active du catalyseur, sans exclure le fait que le catalyseur peut être dopé et/ou supporté. By weak acid according to the invention is meant any organic or mineral acid whose constant pK a is at least 1 and at most 10 at 25° C. or any compound or any mixture which behaves in this way. By way of illustration of a weak organic acid, mention may be made of carboxylic acids and polyacids, whether or not bearing one or more functions, for example chosen from OH, C=O, such as acetic acid, formic acid, and as an illustration of a weak mineral acid, mention may be made of phosphoric acid, dihydrogen phosphate acid, hydrofluoric acid (HF), hypochlorous acid (HOCI), boric acid ( H3BO3), sulfurous acid (H2SO3), hydrocyanic acid (HCN). The term catalyst as used generally refers to the active phase of the catalyst, without excluding the fact that the catalyst may be doped and/or supported.
Par alumine, dioxyde de titane et zircone, on entend tous les polymorphes, le cas échéant, de l’oxyde d’aluminium AI2O3, du dioxyde de titane TiC>2 et du dioxyde de zirconium ZrÛ2, respectivement, ces formes étant bien connues de l’homme du métier. Le catalyseur peut aussi être une combinaison par deux, voire par trois, de l’alumine, du dioxyde de titane et de la zircone. Il peut aussi comprendre toute autre entité favorisant sa fonction catalytique. By alumina, titanium dioxide and zirconia are meant all the polymorphs, if any, of aluminum oxide Al2O3, titanium dioxide TiC>2 and zirconium dioxide ZrO2, respectively, these forms being well known to the skilled person. The catalyst can also be a combination of two or even three of alumina, titanium dioxide and zirconia. It can also comprise any other entity promoting its catalytic function.
Les caractéristiques, applications et avantages de l’invention sont ci-après exposés plus en détails, étant entendu que ces caractéristiques peuvent être considérées indépendamment les unes des autres, ou en combinaison, quelle que soit la combinaison. The characteristics, applications and advantages of the invention are set out below in more detail, it being understood that these characteristics can be considered independently of each other, or in combination, whatever the combination.
L’acide faible est de préférence un acide organique possédant un ou plusieurs groupes carboxyliques ou un acide minéral, présentant un pKa d’au moins 1 à 25°C, et de préférence d’au plus 10, mieux encore d’au plus 7 à 25°C. Dans un intérêt pratique, il possède un point d’ébullition inférieur ou égal à 170°C et de préférence inférieur ou égal à 150°C, voire inférieur ou égal à 120°C, afin d’être plus facilement séparé du milieu réactionnel, généralement par distillation. De tels acides utilisables selon l’invention sont notamment choisis parmi l’acide formique, l’acide acétique, l’acide propionique, l’acide butanoique linéaire ou ramifié, l’acide pentanoïque, l’acide carbonique, l’acide glycolique, l’acide thioacétique, l’acide cyanoacétique, l’acide lactique, l’acide pyruvique, l’acide oxalique, la méthionine ou son équivalent sélénié, ou l’hydroxy-analogue de la méthionine ou son équivalent sélénié. Ces acides peuvent être utilisés seuls ou en un quelconque mélange entre eux. Selon une variante, ils sont choisis parmi l’acide formique, l’acide acétique, l’acide propionique, l’acide butanoique linéaire ou ramifié, l’acide pentanoïque, l’acide carbonique, l’acide glycolique, l’acide thioacétique, l’acide cyanoacétique, l’acide lactique, l’acide pyruvique et l’acide oxalique. De préférence, les acides utilisés sont l’acide formique, l’acide acétique et/ou l’acide propionique. Selon une autre variante de l’invention, l’acide faible est un acide minéral tel que l’acide phosphorique, l’acide dihydrogénophosphate, utilisés seuls ou en mélange. The weak acid is preferably an organic acid having one or more carboxylic groups or a mineral acid, having a pKa of at least 1 at 25° C., and preferably of at most 10, even more preferably of at most 7. at 25°C. In a practical interest, it has a boiling point less than or equal to 170°C and preferably less than or equal to 150°C, or even less than or equal to 120°C, in order to be more easily separated from the reaction medium, usually by distillation. Such acids which can be used according to the invention are chosen in particular from formic acid, acetic acid, propionic acid, linear or branched butanoic acid, pentanoic acid, carbonic acid, glycolic acid, thioacetic acid, cyanoacetic acid, lactic acid, pyruvic acid, oxalic acid, methionine or its selenium equivalent, or the hydroxy analogue of methionine or its selenium equivalent. These acids can be used alone or in any mixture with each other. According to a variant, they are chosen from formic acid, acetic acid, propionic acid, linear or branched butanoic acid, pentanoic acid, carbonic acid, glycolic acid, thioacetic acid , cyanoacetic acid, lactic acid, pyruvic acid and oxalic acid. Preferably, the acids used are formic acid, acetic acid and/or propionic acid. According to another variant of the invention, the weak acid is a mineral acid such as phosphoric acid, dihydrogen phosphate acid, used alone or in a mixture.
Ledit acide faible est ajouté dans un rapport molaire de l’acide faible à l’hydroxy-nitrile de 0,001 à 50, voire de 0,001 à 30 et même de 0,001 à 10 ou encore de 0,001 à 1. En pratique, la concentration molaire de l’acide faible dans le milieu réactionnel varie de 0,05 M à 10 M, préférentiellement de 0,1 M à 2 M et encore plus préférentiellement de 0,2 M à 1 M. Said weak acid is added in a molar ratio of weak acid to hydroxynitrile of 0.001 to 50, or even 0.001 to 30 and even 0.001 to 10 or even 0.001 to 1. In practice, the molar concentration of the weak acid in the reaction medium varies from 0.05 M to 10 M, preferentially from 0.1 M to 2 M and even more preferentially from 0.2 M to 1 M.
Selon l’invention, le catalyseur est choisi parmi l’alumine, le dioxyde de titane et la zircone ; ce composé constitue au moins la phase active du catalyseur, optionnellement le support. Ainsi, si le catalyseur n’est pas en totalité constitué de l’un ou plusieurs desdits oxydes, il peut comprendre tout autre composé n’affectant pas les performances du catalyseur, voire les renforçant. Dans une variante de l’invention, le catalyseur consiste en l’un desdits oxydes.
Le catalyseur peut être dopé et/ou supporté. Il peut être dopé par tout élément ou composé classiquement utilisé et bien connu de l’homme du métier. A titre d’illustration, le dopage du catalyseur peut être réalisé par un ou plusieurs composés choisis parmi les sulfates (SO4), les phosphates (PO4), les tungstates (WO3), les borates (B2O3), les hétéropolyacides répondant à l’une des formules HnXM1204oet H^MisOsz dans lesquelles n est un nombre entier ne dépassant de préférence pas 10, X représente Si, Ge, P ou As et M représente Mo ou W, comme l’acide phosphomolybdique de formule H5P2MOISO62, ainsi que tout autre composé dopant apportant de l’acidité au catalyseur. Les composés suivants PO4, SO4 et H8P2MOI8OS2 sont à privilégier. Si le catalyseur ne consiste pas en alumine, dioxyde de titane et/ou zircone, il peut aussi être supporté par tout autre composé classiquement utilisé et bien connu de l’homme du métier, et en particulier la silice et les silicoaluminates. According to the invention, the catalyst is chosen from alumina, titanium dioxide and zirconia; this compound constitutes at least the active phase of the catalyst, optionally the support. Thus, if the catalyst is not entirely made up of one or more of said oxides, it can comprise any other compound that does not affect the performance of the catalyst, or even reinforces it. In a variant of the invention, the catalyst consists of one of said oxides. The catalyst can be doped and/or supported. It can be doped with any element or compound conventionally used and well known to those skilled in the art. By way of illustration, the catalyst can be doped with one or more compounds chosen from sulphates (SO4), phosphates (PO4), tungstates (WO3), borates (B2O3), heteropolyacids corresponding to one of the formulas H n XM 12 0 4 o and H ^ MisOsz in which n is an integer preferably not exceeding 10, X represents Si, Ge, P or As and M represents Mo or W, such as the phosphomolybdic acid of formula H 5 P 2 MOI S O 62 , as well as any other doping compound bringing acidity to the catalyst. The following compounds PO4, SO4 and H 8 P 2 MOI 8 O S 2 are to be preferred. If the catalyst does not consist of alumina, titanium dioxide and/or zirconia, it can also be supported by any other compound conventionally used and well known to those skilled in the art, and in particular silica and silicoaluminates.
Selon l’invention, l’ensemble des catalyseurs solides mentionnés ci-dessus peuvent être sous forme de poudre ou préférentiellement sous forme de billes, extrudés, tablettes, trilobés ou toute autre forme lui permettant d’être utilisé dans un réacteur continu, de type lit fixe ou autres ou en mode batch dans un réacteur ouvert ou sous pression. According to the invention, all of the solid catalysts mentioned above can be in powder form or preferably in the form of beads, extrudates, tablets, trilobes or any other form allowing it to be used in a continuous reactor, of the fixed bed or others or in batch mode in an open reactor or under pressure.
Ledit catalyseur a avantageusement une surface spécifique d’au moins 10 m2/g. En- dessous de cette limite, les performances du catalyseur chutent rapidement avec notamment un déclin de la sélectivité en hydroxy-acide au profit de celle en hydroxy-amide et une diminution de la conversion de l’hydroxy-nitrile. Cette observation s’applique à l’équivalent sélénié. Avantageusement, la surface spécifique est d’au moins 50 m2/g. La limite supérieure de la surface spécifique n’est pas déterminante dans le cadre de l’invention, celle-ci étant imposée par les phases actives disponibles dans le commerce. Les valeurs de surface spécifique indiquées dans le présent texte sont déterminées par la méthode la plus courante soit la physisorption d’azote et calculées par la méthode BET. Said catalyst advantageously has a specific surface of at least 10 m 2 /g. Below this limit, the performance of the catalyst drops rapidly with in particular a decline in the selectivity for hydroxy-acid in favor of that for hydroxy-amide and a reduction in the conversion of hydroxy-nitrile. This observation applies to the selenium equivalent. Advantageously, the specific surface is at least 50 m 2 /g. The upper limit of the specific surface is not decisive in the context of the invention, the latter being imposed by the active phases commercially available. The specific surface values indicated in this text are determined by the most common method, namely nitrogen physisorption and calculated by the BET method.
Dans une mise en œuvre préférée du procédé de l’invention, le catalyseur est présent en une concentration massique de 0,1 % à 200% par rapport é la masse d’HMTBN, de préférence de 0,5% à 100% et mieux encore de 1 % à 50%. In a preferred implementation of the process of the invention, the catalyst is present in a concentration by mass of 0.1% to 200% relative to the mass of HMTBN, preferably from 0.5% to 100% and better still. another 1% to 50%.
Selon l’invention, des équipements différents peuvent être envisagés pour réaliser la réaction en batch ou continu : le catalyseur solide dopé ou non peut être immobilisé dans un réacteur sous forme de grains ou d’extrudés ou tout autre forme ou supporté sur une mousse métallique. Le réacteur associé à ce type de catalyseur est préférentiellement un lit fixe tubulaire ou multitubulaire, fonctionnant en mode ruisselant ou noyé isotherme ou adiabatique, ou un réacteur échangeur enduit de catalyseur. According to the invention, different equipment can be envisaged to carry out the reaction in batch or continuous: the solid catalyst, doped or not, can be immobilized in a reactor in the form of grains or extrudates or any other form or supported on a metal foam. . The reactor associated with this type of catalyst is preferably a tubular or multitubular fixed bed, operating in trickling or isothermal or adiabatic flooded mode, or an exchanger reactor coated with catalyst.
La conversion de l’HMTBN dans le cadre de l’invention est avantageusement effectuée à une température allant de 20°C à 200°C, de préférence de 50°C à 180°C, et mieux encore de 80°C à 170°C. Il a été constaté, sur une période de réaction allant de l’ordre de 10 minutes à 3
heures, qu’à une température inférieure à 20°C, la réaction est fortement ralentie, et qu’à compter de 180°C, plus la température augmente, plus la sélectivité en méthionine et dinitrile et polypeptide de la méthionine s’accroît au détriment de celle en l’acide 2-hydroxy-4- méthylthiobutyrique. C’est sur la plage de 100°C à 180°C, qu’on observe que la sélectivité en hydroxy-acide est la plus élevée. The conversion of HMTBN within the scope of the invention is advantageously carried out at a temperature ranging from 20° C. to 200° C., preferably from 50° C. to 180° C., and even better still from 80° C. to 170° C. vs. It has been observed, over a reaction period ranging from the order of 10 minutes to 3 hours, that at a temperature below 20°C, the reaction is greatly slowed down, and that from 180°C, the higher the temperature, the more the selectivity for methionine and dinitrile and polypeptide of methionine increases at detriment of that of 2-hydroxy-4-methylthiobutyric acid. It is in the range of 100° C. to 180° C. that it is observed that the selectivity for the hydroxy acid is the highest.
Dans le cadre de l’invention, les temps de contact entre le mélange réactionnel contenant, l’eau, l’hydroxy-nitrile et l’acide avec le catalyseur vont de 30 secondes à 1 h, de préférence de 1 minutes à 30 minutes et encore plus préférentiellement de 2 minutes à 20 minutes. In the context of the invention, the contact times between the reaction mixture containing the water, the hydroxy-nitrile and the acid with the catalyst range from 30 seconds to 1 hour, preferably from 1 minute to 30 minutes. and even more preferably from 2 minutes to 20 minutes.
L’hydroxy-nitrile est généralement en solution aqueuse. Celle-ci peut avoir été préparée en vue de la mise en œuvre du procédé. L’acide faible utilisé dans la réaction peut être ajouté à la solution aqueuse d’hydroxy-nitrile ou ajouté via un mélangeur avant l’entrée dans le réacteur catalytique. Hydroxy-nitrile is usually in aqueous solution. This may have been prepared for the implementation of the method. The weak acid used in the reaction can be added to the aqueous hydroxy-nitrile solution or added via a mixer before entering the catalytic reactor.
La concentration de l’hydroxy-nitrile peut avoir une influence sur les performances du procédé et notamment lorsqu’elle est trop élevée. Ainsi, selon une variante de l’invention, l’hydroxy-nitrile est en solution aqueuse en une concentration allant de 0,01 M à 10 M, de préférence de 0,05 M à 1 M. On a relevé qu’au-delà de 1 M, si la conversion en hydroxy-nitrile reste forte, la sélectivité en hydrox-acide diminue alors que celles en hydroxy-amide, en dinitrile et même en polypeptide, respectivement, s’élèvent. The concentration of hydroxy-nitrile can have an influence on the performance of the process, especially when it is too high. Thus, according to a variant of the invention, the hydroxy-nitrile is in aqueous solution in a concentration ranging from 0.01 M to 10 M, preferably from 0.05 M to 1 M. beyond 1 M, if the conversion to hydroxy-nitrile remains high, the selectivity for hydroxy-acid decreases whereas those for hydroxy-amide, for dinitrile and even for polypeptide, respectively, rise.
L’invention concerne aussi la mise en œuvre du procédé de l’invention en continu. Selon cette variante, le procédé est conduit sous une pression pouvant aller de 1 à 20 bar, de préférence de 2 et 10 bar. Ainsi, l’invention fournit un dispositif comprenant une cuve pour la solution d’hydroxy-nitrile et dans laquelle un acide faible est ajouté. La solution d’hydroxy-acide résultante est pompée vers un réacteur qui comprend le catalyseur et qui est chauffé au moyen d’un manchon ou d’un four à une température de 80 à 180°C. Le milieu réactionnel est soutiré vers un séparateur gaz/liquide duquel les gaz seront retirés et depuis lequel le liquide est traité pour récupérer l’hydroxy-acide. La solution est alors évaporée pour séparer l’excès d’eau utilisé et l’acide faible qui peuvent former un azéotrope ou non, ces composés étant ensuite avantageusement recyclés dans le procédé. Ensuite, la phase contenant l’hydroxy-acide peut subir un stripping pour retirer tout ou partie de l’ammoniaque qui compose le sel d’ammonium de l’hydroxy-acide. Des étapes complémentaires d’électrodialyse ou d’autres technologies connues de l’homme du métier peuvent être envisagées pour récupérer entièrement l’hydroxy- acide sous sa forme acide (acide 2-hydroxy-4-methylthiobutyrique ou l’acide sélénié correspondant) et recycler en totalité l’ammoniaque formé lors de l’hydrolyse de l’intermédiaire HMBTM dans l’étape catalytique. Avantageusement, l’ammoniaque récupéré sera recyclé en amont du procédé de fabrication de l’hydroxy-acide, comme dans la synthèse de l’HCN.
L’invention et ses avantages par rapport à l’art antérieur sont illustrés dans les exemples ci-après, à l’appui des figures suivantes : The invention also relates to the implementation of the method of the invention continuously. According to this variant, the process is carried out under a pressure which can range from 1 to 20 bar, preferably from 2 to 10 bar. Thus, the invention provides a device comprising a tank for the hydroxy-nitrile solution and in which a weak acid is added. The resulting hydroxy acid solution is pumped to a reactor which includes the catalyst and which is heated by means of a mantle or an oven to a temperature of 80 to 180°C. The reaction medium is withdrawn to a gas/liquid separator from which the gases will be removed and from which the liquid is treated to recover the hydroxy acid. The solution is then evaporated to separate the excess water used and the weak acid which may or may not form an azeotrope, these compounds then being advantageously recycled in the process. Then, the phase containing the hydroxy-acid can undergo stripping to remove all or part of the ammonia which makes up the ammonium salt of the hydroxy-acid. Complementary steps of electrodialysis or other technologies known to those skilled in the art can be considered to fully recover the hydroxy acid in its acid form (2-hydroxy-4-methylthiobutyric acid or the corresponding selenium acid) and recycle all of the ammonia formed during the hydrolysis of the HMBTM intermediate in the catalytic stage. Advantageously, the recovered ammonia will be recycled upstream of the process for manufacturing the hydroxy acid, as in the synthesis of HCN. The invention and its advantages over the prior art are illustrated in the examples below, with the support of the following figures:
[FIG. 1] montre la conversion de l’HMTBN, la sélectivité en HMTBA, la sélectivité en méthionine et la sélectivité en HMTBM, en fonction du temps, d’une réaction selon un procédé de l’invention dans les conditions décrites à l’exemple 1 . [FIG. 1] shows the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time, of a reaction according to a process of the invention under the conditions described in example 1 .
[FIG. 2] montre la conversion de l’HMTBN, la sélectivité en HMTBA, la sélectivité en méthionine et la sélectivité en HMTBM, en fonction du temps, d’une réaction selon un procédé de l’invention dans les conditions décrites à l’exemple 2. [FIG. 2] shows the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time, of a reaction according to a process of the invention under the conditions described in Example 2 .
Dans la partie expérimentale qui suit : les exemples 1-6 illustrent diverses variantes d’un procédé de l’invention ; les exemples 7 et 8 illustrent une technique de dopage d’un catalyseur pour obtenir un catalyseur dopé qui peut être utilisé dans un procédé de l’invention, selon une variante telle que celle objet de l’exemple 6 ; l’exemple 9 illustre une étape de séparation du sel d’hydroxy-acide en hydroxy-acide ; et les exemples 10 à 15 illustrent des procédés hors invention, à titre comparatif. In the experimental part which follows: examples 1-6 illustrate various variants of a method of the invention; examples 7 and 8 illustrate a technique for doping a catalyst to obtain a doped catalyst which can be used in a process of the invention, according to a variant such as that which is the subject of example 6; Example 9 illustrates a step for separating the hydroxy-acid salt into the hydroxy-acid; and Examples 10 to 15 illustrate methods outside the invention, by way of comparison.
Exemple 1 : Préparation de l’HMTBA en présence d’un dioxyde de titane et d’acide acétique, selon l’invention Example 1: Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
Dans un flacon à vis de 1 litre, on introduit 14,0 g d’HMTBN avec 2000 ml d’F et 60 mg d’acide acétique. La solution est agitée à température ambiante avec un flux d’azote et injectée dans un réacteur tubulaire chauffé à 120°C avec un débit de 0,05 ml/min (temps de contact 24 minutes) et contenant 60 grammes de TiC>2 (anatase, 150 m2/g, Norpro, ST 61 120). In a 1 liter screw top flask, 14.0 g of HMTBN are added with 2000 ml of F and 60 mg of acetic acid. The solution is stirred at room temperature with a stream of nitrogen and injected into a tubular reactor heated to 120° C. with a flow rate of 0.05 ml/min (contact time 24 minutes) and containing 60 grams of TiC>2 ( anatase, 150 m 2 /g, Norpro, ST 61 120).
La réaction est suivie par HPLC. Le rendement en HMTBA est de 88%. The reaction is followed by HPLC. The yield of HMTBA is 88%.
Exemple 2 : Préparation de l’HMTBA en présence d’un dioxyde de titane et d’acide acétique, selon l’invention Example 2: Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below.
OH 2 eq 160°C OH OH 2 eq 160°C OH
0,1 mol/L 0,1 ml/min Rendement : 95%0.1 mol/L 0.1 ml/min Yield: 95%
Dans un flacon à vis de 1 litre, on introduit 13,1 g d’HMTBN avec 990 ml d’H2O et 10 ml d’acide acétique. La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes) et contenant 4 grammes de TiC>2 (anatase, 150 m2/g, Norpro, ST 61120). Le sel d’HMTBA obtenu est converti en HMTBA par strippage de l’ammoniac selon une technique illustrée à l’exemple 9. In a 1 liter screw-top flask, 13.1 g of HMTBN are introduced with 990 ml of H2O and 10 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes) and containing 4 grams of TiC >2 (anatase, 150 m 2 /g, Norpro, ST 61120). The HMTBA salt obtained is converted into HMTBA by stripping of ammonia according to a technique illustrated in Example 9.
La réaction est suivie par HPLC : la conversion de l’HMTBN, la sélectivité en HMTBA, la sélectivité en méthionine et la sélectivité en HMTBM, en fonction du temps sont représentées sur la [FIG. 1], The reaction is monitored by HPLC: the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time are represented in [FIG. 1],
Le rendement en HMTBA est de 95% et de 5% en méthionine. The yield of HMTBA is 95% and 5% of methionine.
Exemple 3 : Préparation de l’HMTBA en présence d’un dioxyde de titane et d’acide acétique, selon l’invention Example 3: Preparation of HMTBA in the presence of titanium dioxide and acetic acid, according to the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below.
OH 30 eq 160°C OH OH 30 eq 160°C OH
0,1 mol/L 0,1 ml/min Rendement : 89%0.1 mol/L 0.1 ml/min Yield: 89%
Dans un flacon à vis de 1 litre on a introduit 13,1 g d’HMTBN avec 800 ml d’HLO et 200 ml d’acide acétique. La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes). Le réacteur contient 4 grammes de TiC>2 (anatase, 150 m2/g, Norpro, ST 61120). Le sel d’HMTBA obtenu est converti en HMTBA par strippage de l’ammoniac selon une technique illustrée à l’exemple 9. Into a 1 liter screw-top flask were added 13.1 g of HMTBN along with 800 ml of HLO and 200 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes). The reactor contains 4 grams of TiC>2 (anatase, 150 m 2 /g, Norpro, ST 61120). The HMTBA salt obtained is converted into HMTBA by stripping of ammonia according to a technique illustrated in Example 9.
La réaction est suivie par HPLC : la conversion de l’HMTBN, la sélectivité en HMTBA, la sélectivité en méthionine et la sélectivité en HMTBM, en fonction du temps sont représentées sur la [FIG. 2], The reaction is monitored by HPLC: the conversion of HMTBN, the selectivity for HMTBA, the selectivity for methionine and the selectivity for HMTBM, as a function of time are represented in [FIG. 2],
Le rendement en HMTBA est de 89% et de 11 % en méthionine.
Exemple 4 : Préparation de l’HMTBA en présence d’un dioxyde de titane et d’acide formique, selon l’invention The yield of HMTBA is 89% and 11% of methionine. Example 4 Preparation of HMTBA in the Presence of a Titanium Dioxide and Formic Acid, According to the Invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
0,1 mol/L °>1 ml/mm Rendement : 90%0.1 mol/L °> 1 ml/mm Yield: 90%
Dans un flacon à vis de 1 litre on a introduit 13,1 g d’HMTBN avec 990 ml d’F et 10 ml d’acide formique. La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes). Le réacteur contient 4 grammes de TiC>2 (anatase, 150 m2/g, Norpro, ST 61120). A 1 liter screw top flask was charged with 13.1 g of HMTBN along with 990 ml of F and 10 ml of formic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes). The reactor contains 4 grams of TiC>2 (anatase, 150 m 2 /g, Norpro, ST 61120).
La réaction est suivie après 2 heures par HPLC. The reaction is followed after 2 hours by HPLC.
Le sel d’HMTBA obtenu est converti en HMTBA par strippage de l’ammoniac selon une technique illustrée à l’exemple 9. The HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
Le rendement en HMTBA est de 90% et 10% en méthionine. The yield of HMTBA is 90% and 10% of methionine.
Exemple 5 : Préparation de l’HMTBA en présence d’une alumine dopée au sulfate et d’acide acétique, selon l’invention Example 5: Preparation of HMTBA in the presence of an alumina doped with sulphate and acetic acid, according to the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
0,1 mol/L °’1 ml/min Rendement : 96%0.1 mol/L °' 1 ml/min Yield: 96%
Dans un flacon à vis de 1 litre on a introduit 13,1 g d’HMTBN avec 800 ml d’H2O et 200 ml d’acide acétique. La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes). Le réacteur contient 4 grammes de AI2O3 (gamma, 300 m2/g, IFPEN, 33006 GFSA 401 , alumine dopée avec 10% en poids de fonction sulfate). In a 1 liter screw-top flask 13.1 g of HMTBN were added with 800 ml of H2O and 200 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes). The reactor contains 4 grams of Al2O3 (gamma, 300 m 2 /g, IFPEN, 33006 GFSA 401, alumina doped with 10% by weight of sulphate function).
La réaction est suivie après 2 heures par HPLC. The reaction is followed after 2 hours by HPLC.
Le sel d’HMTBA obtenu est converti en HMTBA par strippage de l’ammoniac selon une technique illustrée à l’exemple 9. The HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
Le rendement en HMTBA est de 96% et 4% en méthionine.
Exemple 6 : Préparation de l’HMTBA en présence d’une zircone et d’acide acétique, selon l’invention The yield of HMTBA is 96% and 4% of methionine. Example 6: Preparation of HMTBA in the presence of a zirconia and acetic acid, according to the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
OH 30 eq 160°C OHOH 30 eq 160°C OH
0,1 mol/L °’1 ml/mm Rendement : 74%0.1 mol/L °' 1 ml/mm Yield: 74%
Dans un flacon à vis de 1 litre on a introduit 13,1 g d’HMTBN avec 800 ml d’HLO et 200 ml d’acide acétique. La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes). Le réacteur contient 6 grammes de ZrÛ2 (monoclinique, 100 m2/g, Norpro, XZ 16075). Into a 1 liter screw-top flask were added 13.1 g of HMTBN along with 800 ml of HLO and 200 ml of acetic acid. The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes). The reactor contains 6 grams of ZrO2 (monoclinic, 100 m 2 /g, Norpro, XZ 16075).
La réaction est suivie après 2 heures par HPLC. The reaction is followed after 2 hours by HPLC.
Le sel d’HMTBA obtenu est converti en HMTBA par strippage de l’ammoniac selon une technique illustrée à l’exemple 9. The HMTBA salt obtained is converted into HMTBA by stripping the ammonia according to a technique illustrated in Example 9.
Le rendement en HMTBA est de 74% et 16% en méthionine. The yield of HMTBA is 74% and 16% of methionine.
Exemple 7 : Préparation de TiO2 dopé par 10% poids de sulfate (SO4) par de l’acide sulfurique. Example 7: Preparation of TiO2 doped with 10% by weight of sulphate (SO 4 ) with sulfuric acid.
Dans un ballon d’un litre, on introduit 20 g de TiÛ2 (anatase, 150 m2/g, Norpro, ST 61120) en poudre avec 500 mL d’eau et 2,04 g d’acide sulfurique. La solution est agitée pendant 2 heures à température ambiante, puis l’eau est évaporée. La poudre obtenue est alors séchée à 200°C pendant 3 heures puis elle est calcinée à 700°C sous air pendant 2 heures. Une analyse élémentaire a été réalisée pour doser le soufre, on observe une quantité de soufre de 3,4% en masse de catalyseur, ce qui correspond à une quantité de sulfate de 10% en masse. 20 g of TiO 2 (anatase, 150 m 2 /g, Norpro, ST 61120) in powder form are introduced into a one-liter flask with 500 mL of water and 2.04 g of sulfuric acid. The solution is stirred for 2 hours at room temperature, then the water is evaporated. The powder obtained is then dried at 200° C. for 3 hours and then it is calcined at 700° C. in air for 2 hours. An elemental analysis was carried out to measure the sulfur, a quantity of sulfur of 3.4% by mass of catalyst is observed, which corresponds to a quantity of sulphate of 10% by mass.
Exemple 8 : Préparation de TiÛ2 dopé par 10% poids de sulfate (SO4) par du sulfate d’ammonium Example 8: Preparation of TiO2 doped with 10% weight of sulphate (SO 4 ) with ammonium sulphate
Dans un ballon d’un litre, on introduit 20 g de TiÛ2 (anatase, 150 m2/g, Norpro, ST 61120) en poudre avec 500 mL d’eau et 2,78 g de sulfate d’ammonium. La solution est agitée pendant 2 heures à température ambiante, puis l’eau est évaporée. La poudre obtenue est alors séchée à 200°C pendant 3 heures puis elle est calcinée à 700°C sous air pendant 2 heures. Une analyse élémentaire a été réalisée pour doser le soufre, on observe une quantité de soufre de 3,2% en masse de catalyseur, ce qui correspond à une quantité de sulfate de 9,8% en masse.
Exemple 9 : Conversion du sel d’ammonium d’HMTBA en HMTBA 20 g of TiO 2 (anatase, 150 m 2 /g, Norpro, ST 61120) in powder form are introduced into a one-liter flask with 500 mL of water and 2.78 g of ammonium sulphate. The solution is stirred for 2 hours at room temperature, then the water is evaporated. The powder obtained is then dried at 200° C. for 3 hours and then it is calcined at 700° C. in air for 2 hours. An elemental analysis was carried out to measure the sulfur, a quantity of sulfur of 3.2% by mass of catalyst is observed, which corresponds to a quantity of sulphate of 9.8% by mass. Example 9: Conversion of the ammonium salt of HMTBA to HMTBA
La solution de sel d’ammonium d’HMTBA obtenu selon l’invention est concentrée en organiques jusqu’à une teneur en organiques de 87% en poids. La température du milieu évolue de 100 à 130°C (pression atmosphérique). Après cette étape de concentration, la conversion en HMTBA s’élève à 21 % (mol). Ensuite, une phase de strippage à la vapeur d’eau est effectuée. L’eau de strippage est introduite sous forme liquide. La teneur en organique est maintenue constante à 87% poids. La température est stationnaire entre 115 et 121 °C. Le débit ée strippage est compris entre 3,8 et 4,3 ml/min. Après 200 minutes dans ces conditions, on obtient une conversion en HMTBA de 47%. Une nouvelle étape de strippage est effectuée pour conduire à l’HMTBA dans des rendements avoisinants 100%. The ammonium salt solution of HMTBA obtained according to the invention is concentrated in organics up to an organic content of 87% by weight. The temperature of the medium changes from 100 to 130°C (atmospheric pressure). After this concentration step, the conversion to HMTBA is 21% (mol). Then, a steam stripping phase is performed. The stripping water is introduced in liquid form. The organic content is kept constant at 87% by weight. The temperature is stationary between 115 and 121°C. The stripping flow rate is between 3.8 and 4.3 ml/min. After 200 minutes under these conditions, a conversion to HMTBA of 47% is obtained. A new stripping step is carried out to lead to HMTBA in yields close to 100%.
Exemple 10 : Préparation de l’HMTBA en présence d’acide acétique, hors invention Example 10: Preparation of HMTBA in the presence of acetic acid, outside the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
0,1 mol/L Rendement : 0%0.1 mol/L Yield: 0%
Dans un flacon à vis de 20 ml on a introduit 0,131 g d’HMTBN avec 8 ml d’H2O et 2 ml d’acide acétique. La solution est agitée à 160°C pendant dix minutes. In a 20 ml screw-top flask, 0.131 g of HMTBN was added with 8 ml of H2O and 2 ml of acetic acid. The solution is stirred at 160° C. for ten minutes.
La solution est analysée par HPLC, aucune réaction n’est observée. The solution is analyzed by HPLC, no reaction is observed.
Exemple 11 : Préparation de l’HMTBA en présence d’acide formique, hors invention Example 11: Preparation of HMTBA in the presence of formic acid, outside the invention
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
0,1 mol/L Rendement : 0%0.1 mol/L Yield: 0%
Dans un flacon à vis de 20 ml on a introduit 0,131 g d’HMTBN avec 9 ml d’H2O et 1 ml d’acide acétique. La solution est agitée à 160°C pendant dix minutes. In a 20 ml screw-top flask, 0.131 g of HMTBN was added with 9 ml of H2O and 1 ml of acetic acid. The solution is stirred at 160° C. for ten minutes.
La solution est analysée par HPLC, aucune réaction n’est observée.
Exemple 12 : Préparation de l’HMTBA en présence de dioxyde de titane, selon l’art antérieur The solution is analyzed by HPLC, no reaction is observed. Example 12: Preparation of HMTBA in the presence of titanium dioxide, according to the prior art
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
OH , n 0,J1 6 m0il°//Cm-in 0H NH2OH , n 0.J1 6 m 0 il°// C m-in 0H NH 2
0,1 mol/L Rendement : 1% Rendement : 15%0.1 mol/L Yield: 1% Yield: 15%
Dans un flacon à vis de 1 litre on a introduit 13,1 g d’HMTBN avec 1000 ml d’F . La solution est agitée à température ambiante avec un flux d’azote, la solution est injectée dans un réacteur tubulaire chauffé à 160°C avec un débit de 0,1 ml/min (temps de contact 10 minutes) et contenant 4 grammes de TiÛ2 (anatase, 150 m2/g, Norpro, ST 61120). In a 1 liter screw-top flask, 13.1 g of HMTBN were introduced with 1000 ml of F 2 . The solution is stirred at room temperature with a stream of nitrogen, the solution is injected into a tubular reactor heated to 160° C. with a flow rate of 0.1 ml/min (contact time 10 minutes) and containing 4 grams of TiO2 (anatase, 150 m 2 /g, Norpro, ST 61120).
La réaction est suivie par HPLC, le rendement en HMTBA est de 1 % et de 15% en méthionine. The reaction is monitored by HPLC, the yield of HMTBA is 1% and 15% of methionine.
Exemple 13 : Préparation de l’HMTBA en présence d’une alumine de phase gamma, selon l’art antérieur Example 13: Preparation of HMTBA in the presence of a gamma phase alumina, according to the prior art
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
Dans un flacon à vis de 10 ml, 0,4 g de y-Al203 (300 m2/g), puis 0,1 g d’HMTBN (97%) avec 1 mL d’eau ont été introduits. La solution a été chauffée à 90°C pendant 60 minutes au bout desquelles la solution a été filtrée et analysée par RMN du proton. In a 10 ml screw-top bottle, 0.4 g of y-Al203 (300 m 2 /g), then 0.1 g of HMTBN (97%) with 1 ml of water were introduced. The solution was heated at 90°C for 60 minutes after which the solution was filtered and analyzed by proton NMR.
Aucune conversion de l’HMTBN n’est observée No conversion of HMTBN is observed
Exemple 14: Préparation de l’HMTBAen présence d’une alumine de phase gamma, selon l’art antérieur Example 14: Preparation of HMTBA in the presence of a gamma phase alumina, according to the prior art
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the scheme below.
Dans un flacon à vis de 20 ml, 0,4 g de y-Al203 (300 m2/g), puis 1 ,1 g d’HMTBN (97%) avec 10 mL d’eau ont été introduits. La solution a été chauffée à 90°C pendant 18 heures au bout desquelles la solution a été filtrée et analysée par RMN du proton. In a 20 ml screw-top bottle, 0.4 g of y-Al203 (300 m 2 /g), then 1.1 g of HMTBN (97%) with 10 ml of water were introduced. The solution was heated at 90°C for 18 hours after which the solution was filtered and analyzed by proton NMR.
On observe un rendement en HMTBM de 30% et en HMTBA de 6%. A yield of HMTBM of 30% and of HMTBA of 6% is observed.
Exemple 15 : Préparation de l’HMTBA en présence de TiO2 anatase, selon l’art antérieur Example 15: Preparation of HMTBA in the presence of TiO 2 anatase, according to the prior art
La réaction d’hydrolyse de l’HMTBN et les conditions dans lesquelles elle est conduite sont décrites dans le schéma ci-dessous.
The hydrolysis reaction of HMTBN and the conditions under which it is carried out are described in the diagram below.
Dans un flacon à vis de 10 ml, 1 g de TiO2 (sous forme d’anatase) (90 m2/g), puis 1 ,1 g d’HMTBN (97%) avec 1 mL d’eau ont été introduits. La solution a été chauffée à 90°C pendant 96 heures au bout desquelles la solution a été filtrée et analysée par RMN du proton. In a 10 ml screw-top bottle, 1 g of TiO2 (in the form of anatase) (90 m 2 /g), then 1.1 g of HMTBN (97%) with 1 ml of water were introduced. The solution was heated at 90°C for 96 hours after which the solution was filtered and analyzed by proton NMR.
On n’observe aucune des traces d’HMTBM ni d’HMTBA. No traces of HMTBM or HMTBA were observed.
La comparaison des résultats des exemples 1 à 6 selon l’invention, avec ceux obtenus dans un procédé conduit sans catalyseur (exemples 10 et 11 ) ou sans acide faible (exemples 12 à 15) démontre un gain considérable des performances de la fabrication d’un hydroxy-acide dans un procédé de l’invention, qui est de plus inattendu.
The comparison of the results of examples 1 to 6 according to the invention, with those obtained in a process carried out without catalyst (examples 10 and 11) or without weak acid (examples 12 to 15) demonstrates a considerable gain in the performance of the manufacture of a hydroxy acid in a process of the invention, which is moreover unexpected.
Claims
1. Procédé de préparation de l’acide 2-hydroxy-4-méthylthiobutyrique (HMTBA) ou de l’acide 2-hydroxy-4-méthylsélénobutyrique (HMSeBA) par conversion catalytique du 2-hydroxy- 4-méthylthiobutyronitrile ou du 2-hydroxy-4-méthylsélénobutyronitrile, respectivement, caractérisé en ce que ladite conversion est effectuée en présence d’eau et d’au moins un acide faible et un catalyseur comprenant au moins l’un de l’alumine, du dioxyde de titane et de la zircone. 1. Process for the preparation of 2-hydroxy-4-methylthiobutyric acid (HMTBA) or 2-hydroxy-4-methylselenobutyric acid (HMSeBA) by catalytic conversion of 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy -4-methylselenobutyronitrile, respectively, characterized in that said conversion is carried out in the presence of water and at least one weak acid and a catalyst comprising at least one of alumina, titanium dioxide and zirconia .
2. Procédé selon la revendication 1 , caractérisé en ce que ledit acide faible est choisi parmi l’acide formique, l’acide acétique, l’acide propionique, l’acide butanoique linéaire ou ramifié, l’acide pentanoïque, l’acide carbonique, l’acide phosphorique, l’acide dihydrogenophosphate, l’acide glycolique, l’acide thioacétique, l’acide cyanoacétique, l’acide lactique, l’acide pyruvique et l’acide oxalique, de préférence il est choisi parmi l’acide acétique, l’acide formique et l’acide propionique. 2. Method according to claim 1, characterized in that said weak acid is chosen from formic acid, acetic acid, propionic acid, linear or branched butanoic acid, pentanoic acid, carbonic acid , phosphoric acid, dihydrogen phosphate acid, glycolic acid, thioacetic acid, cyanoacetic acid, lactic acid, pyruvic acid and oxalic acid, preferably it is chosen from the acid acetic acid, formic acid and propionic acid.
3. Procédé selon la revendication 1 ou 2, caractérisé en ce que l’acide faible est en au moins un équivalent molaire par rapport à l’hydroxy-nitrile, voire en excès, de préférence le rapport molaire de l’acide faible au 2-hydroxy-4-méthylthiobutyronitrile ou au 2-hydroxy-4- méthylsélénobutyronitrile, va de 0,001 à 50. 3. Method according to claim 1 or 2, characterized in that the weak acid is in at least one molar equivalent relative to the hydroxy-nitrile, or even in excess, preferably the molar ratio of the weak acid to 2 -hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile, ranges from 0.001 to 50.
4. Procédé selon l’une quelconque des revendications précédentes, caractérisé en ce que le catalyseur est en une concentration massique de 0,1 % à 200% par rapport à la masse d’HMTBN, de préférence de 0,5% à 100% et mieux encore de 1 % à 50%. 4. Method according to any one of the preceding claims, characterized in that the catalyst is in a concentration by mass of 0.1% to 200% relative to the mass of HMTBN, preferably from 0.5% to 100% and better still from 1% to 50%.
5. Procédé selon l’une quelconque des revendications 1 à 4, caractérisé en ce que le 2- hydroxy-4-méthylthiobutyronitrile ou le 2-hydroxy-4-méthylsélénobutyronitrile est en solution aqueuse en une concentration allant de 0,01 M à 10 M, de préférence de 0,05 M à1 M. 5. Method according to any one of claims 1 to 4, characterized in that 2-hydroxy-4-methylthiobutyronitrile or 2-hydroxy-4-methylselenobutyronitrile is in aqueous solution in a concentration ranging from 0.01 M to 10 M, preferably 0.05 M to 1 M.
6. Procédé selon l’une quelconque des revendications 1 à 5, caractérisé en ce que ledit catalyseur a une surface spécifique BET d’au moins 10 m2/g, de préférence d’au moins 50 m2/g. 6. Method according to any one of claims 1 to 5, characterized in that said catalyst has a BET specific surface of at least 10 m 2 /g, preferably at least 50 m 2 /g.
7. Procédé selon l’une quelconque des revendications 1 à 6, caractérisé en ce que ledit catalyseur est dopé, de préférence il est dopé avec un ou plusieurs composés choisis parmi les sulfates, les phosphates, les borates, les tungstates, les hétéropolyacides répondant à l’une des formules H,;XMi204oet Hr,X2Mi8O62 dans lesquelles n est un nombre entier ne dépassant de préférence pas 10, X représente Si, Ge, P ou As et M représente Mo ou W, comme l’acide phosphomolybdique de formule H6P2Mo18O62, ainsi que tout autre composé dopant apportant de l’acidité au catalyseur. 7. Method according to any one of claims 1 to 6, characterized in that said catalyst is doped, preferably it is doped with one or more compounds chosen from sulphates, phosphates, borates, tungstates, heteropolyacids corresponding to one of the formulas H, ; XMi 2 0 4 o and H r ,X 2 Mi 8 O 62 in which n is an integer preferably not exceeding 10, X represents Si, Ge, P or As and M represents Mo or W, such as phosphomolybdic acid of formula H 6 P 2 Mo 18 O62, as well as any other doping compound bringing acidity to the catalyst.
8. Procédé selon l’une quelconque des revendications 1 à 7, caractérisé en ce que la conversion est effectuée à une température allant de 20°C à 200°C, de préférence de 50°C à 180°C, et mieux encore de 80°C à 170°C.
8. Process according to any one of claims 1 to 7, characterized in that the conversion is carried out at a temperature ranging from 20°C to 200°C, preferably from 50°C to 180°C, and better still from 80°C to 170°C.
9. Procédé selon l’une quelconque des revendications 1 à 8, caractérisé en ce qu’il est conduit en continu.
9. Method according to any one of claims 1 to 8, characterized in that it is carried out continuously.
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FR2010876A FR3115537B1 (en) | 2020-10-23 | 2020-10-23 | Process for the catalytic production of an analogue of methionine |
PCT/FR2021/051837 WO2022084632A1 (en) | 2020-10-23 | 2021-10-20 | Method for catalytic production of a methionine analogue |
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EP (1) | EP4232429A1 (en) |
JP (1) | JP2023552239A (en) |
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CN (1) | CN116547268A (en) |
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JPH0393754A (en) * | 1989-09-04 | 1991-04-18 | Sumitomo Chem Co Ltd | Production of alpha-amino acid |
ES2164244T3 (en) | 1995-06-07 | 2002-02-16 | Novus Int Inc | CONTINUOUS HYDROLYSIS PROCEDURE FOR THE PREPARATION OF 2-HYDROXY-4-METHYLTIUTUTANIC ACID AND SALTS OF THE SAME. |
DE10316110A1 (en) | 2003-04-09 | 2004-10-28 | Degussa Ag | Process for the preparation of 2-hydroxy-4-methylthio-butyric acid ammonium salt |
FR2907785B1 (en) * | 2006-10-27 | 2009-01-16 | Tetrahedron Sas | PROCESS FOR THE PREPARATION OF 2-HYDROXY-4-METHYLSELENOBUTYRIC ACID, ALONE OR IN MIXTURE WITH ITS SULFUR ANALOGUE, AND THEIR USES IN NUTRITION, ESPECIALLY ANIMAL NUTRITION |
FR2919607B1 (en) * | 2007-07-31 | 2012-10-12 | Adisseo Ireland Ltd | PROCESS FOR THE CATALYTIC CONVERSION OF 2-HYDROXY-4-METHYLTHIOBUTANENITRILE (HMTBN) TO 2-HYDROXY-4-METHYLTHIOBUTANAMIDE (HMTBM) |
CN109912471B (en) * | 2019-04-02 | 2021-07-23 | 天宝动物营养科技股份有限公司 | Method for synthesizing methionine hydroxy analogue by continuously and rapidly hydrolyzing 2-hydroxy-4-methylthiobutyronitrile |
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