Search

CN-121990953-A - Methionine and preparation method thereof

CN121990953ACN 121990953 ACN121990953 ACN 121990953ACN-121990953-A

Abstract

The invention relates to the technical field of organic chemical synthesis, in particular to methionine and a preparation method thereof. The preparation method of methionine comprises the steps of (1) dissolving isonitrile acetate in an aprotic solvent to form a first solution, adding non-nucleophilic strong base into the first solution to react, then adding 2-haloethyl methyl sulfide to react to obtain a reaction solution containing 2-isocyano-4- (methylthio) butyrate, (2) adding ammonium salt of acid and an alcohol solvent into the reaction solution of the 2-isocyano-4- (methylthio) butyrate obtained in the step (1) to react to obtain a 2-amino-4- (methylthio) butyrate solution, and (3) adding alkali into the 2-amino-4- (methylthio) butyrate solution obtained in the step (2) to perform saponification reaction, and then adjusting pH to 5-7 to obtain methionine. The preparation method provided by the invention avoids using high-toxicity reagents, and the reaction is safer.

Inventors

  • WANG JIAQI
  • LI WEI
  • HUANG MIN
  • WANG SIDA

Assignees

  • 万华化学集团股份有限公司

Dates

Publication Date
20260508
Application Date
20260106

Claims (10)

  1. 1. A method for producing methionine, comprising the steps of: (1) Dissolving isocyanato acetate in an aprotic solvent to form a first solution, adding non-nucleophilic strong base into the first solution to react to generate carbanion, and then adding 2-halogenated ethyl methyl sulfide to perform C-alkylation reaction to obtain a reaction solution containing 2-isocyano-4- (methylthio) butyrate; (2) Adding ammonium salt of acid and alcohol solvent into the reaction solution of the 2-isocyano-4- (methylthio) butyrate obtained in the step (1) for reaction, wherein isocyano undergoes ammonolysis reaction to obtain 2-amino-4- (methylthio) butyrate solution; (3) Adding alkali into the 2-amino-4- (methylthio) butyrate solution obtained in the step (2) to carry out saponification reaction, and then adjusting the pH value to 5-7 to obtain methionine.
  2. 2. The method of claim 1, wherein the non-nucleophilic strong base is added to the first solution as a non-nucleophilic strong base solution; preferably, the concentration of the non-nucleophilic strong base in the non-nucleophilic strong base solution is 1-3mol/L; preferably, the non-nucleophilic strong alkali solution is added into the first solution in a dropwise manner; Preferably, the system temperature is-10 ℃ in the process of adding the non-nucleophilic strong alkali solution into the first solution; preferably, the molar ratio of the non-nucleophilic strong base to the isonitrile acetate in the non-nucleophilic strong base solution is (1-1.5): 1; preferably, the molar ratio of the non-nucleophilic strong base to the isonitrile acetate in the non-nucleophilic strong base solution is (1-1.1): 1; preferably, the solvent in the non-nucleophilic strong base solution is selected from aprotic solvents; Preferably, the solvent in the non-nucleophilic strong base solution is selected from tetrahydrofuran; Preferably, adding non-nucleophilic strong base into the first solution for reaction for 20-40min; preferably, the temperature at which the non-nucleophilic strong base is added to the first solution for reaction is-20-10 ℃.
  3. 3. The preparation method according to claim 1 or 2, wherein the addition process of the 2-haloethyl methyl sulfide is dropwise addition; Preferably, the temperature during the addition of 2-haloethylmethyl sulfide is from-20 to 10 ℃, preferably from-10 to 0 ℃; Preferably, the temperature of the C-alkylation reaction is 0-50 ℃, and the reaction time is 2-12h; preferably, the temperature of the C-alkylation reaction is 15-25 ℃; preferably, the C-alkylation reaction time is from 4 to 8 hours; preferably, the molar ratio of the 2-haloethyl methyl sulfide to the isonitrile acetate is (1-1.5): 1; Preferably, the molar ratio of the 2-haloethyl methyl sulfide to the isonitrile acetate is (1-1.1): 1; Preferably, the concentration of the isocyanato acetate in the first solution is 0.3-2mol/L.
  4. 4. A process according to any one of claims 1 to 3, wherein the 2-haloethylmethyl sulfide is at least one selected from the group consisting of 2-bromoethylmethyl sulfide and 2-chloroethylmethyl sulfide; preferably, the isocyanato acetate is selected from at least one of methyl isocyanato acetate or ethyl isocyanato acetate; preferably, the non-nucleophilic strong base is selected from at least one of sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, and potassium t-butoxide; preferably, the aprotic polar solvent is at least one selected from the group consisting of N, N-dimethylformamide, dimethylsulfoxide, and N-methylpyrrolidone.
  5. 5. The process according to any one of claims 1 to 4, wherein the temperature of the reaction in step (2) is 40 to 120 ℃ and the reaction time is 3 to 8 hours; preferably, the temperature of the reaction in the step (2) is 60-100 ℃ and the reaction time is 3-5h.
  6. 6. The process according to any one of claims 1 to 5, wherein the molar ratio of the ammonium salt of the acid to the isonitrile acetate in step (1) is (2 to 10): 1; Preferably, the ratio of the alcohol solvent to the isonitrile acetate is (0.3-1) L:1mol.
  7. 7. The method according to any one of claims 1 to 6, wherein the ammonium salt of an acid is at least one selected from ammonium formate and ammonium acetate; Preferably, the alcohol solvent is at least one selected from methanol and ethanol.
  8. 8. The process according to any one of claims 1 to 7, wherein in step (3), the amount of the base added to the isocyanato acetate in step (1) is (2-4): 1; preferably, the addition amount of the base and the isonitrile acetate in the step (1) are (2-2.5): 1; preferably, the base is selected from at least one of alkali metal hydroxides, preferably sodium hydroxide, potassium hydroxide; preferably, the base is added in the form of an aqueous base; preferably, the concentration of the alkali in the aqueous alkali solution is 5-7mol/L; preferably, the pH is adjusted by at least one of carbon dioxide, hydrochloric acid, sulfuric acid, carbonic acid.
  9. 9. The process according to any one of claims 1 to 8, wherein the temperature of the reaction in step (3) is 20 to 100 ℃ and the reaction time is 1 to 8 hours; preferably, the reaction temperature in the step (3) is 20-80 ℃ and the reaction time is 2-4h.
  10. 10. Methionine, characterized in that it is produced by the process according to any one of claims 1 to 9.

Description

Methionine and preparation method thereof Technical Field The invention relates to the technical field of organic chemical synthesis, in particular to methionine and a preparation method thereof. Background Methionine is an essential sulfur-containing amino acid, which is of vital importance in the diet of humans and animals. Currently, the industrial production of DL-methionine mainly adopts a chemical synthesis method, wherein the hydantoin method is the most widely used process. For example, CN103764240B is prepared with acrolein, methyl mercaptan and toxic Hydrogen Cyanide (HCN) as initial material, and through synthesizing methyl thio-propanal-cyanohydrin (MMP-CN) with 3-methyl thio-propanal and hydrocyanic acid, the methyl thio-propanal-cyanohydrin reacts with ammonia and CO 2 to synthesize 5- (2-methyl thio-ethyl) -hydantoin, and the hydantoin is hydrolyzed, acidified and crystallized to obtain methionine. The traditional method also has a plurality of remarkable limitations, and the dependence on highly toxic chemicals such as hydrogen cyanide, acrolein and methyl mercaptan brings serious potential safety hazards and environmental risks. There is a need in the art for a green, safe, high yield process for the preparation of methionine. Disclosure of Invention The invention provides methionine and a preparation method thereof, which are used for solving the problems of the prior art that a green, safe and high-yield preparation method of methionine is needed. In a first aspect, the present invention provides a method for producing methionine, comprising the steps of: (1) Under the action of non-nucleophilic strong alkali, carrying out C-alkylation reaction on isocyanato acetate and 2-halogenated ethyl methyl sulfide in an aprotic solvent to obtain a reaction solution containing 2-isocyano-4- (methylthio) butyrate; (2) Adding ammonium salt of acid and alcohol solvent into the reaction solution of the 2-isocyano-4- (methylthio) butyrate obtained in the step (1) for reaction, wherein isocyano undergoes ammonolysis reaction to obtain 2-amino-4- (methylthio) butyrate solution; (3) Adding alkali into the 2-amino-4- (methylthio) butyrate solution obtained in the step (2) to carry out saponification reaction, and then adjusting the pH value to 5-7 to obtain methionine. In the method for producing methionine provided by the present invention, in steps (1) to (3), the main reaction paths are exemplified as follows: Step (1) Step (2) Step (3) In an alternative embodiment, the non-nucleophilic strong base is added to the first solution as a non-nucleophilic strong base solution; In an alternative embodiment, the concentration of the non-nucleophilic strong base in the non-nucleophilic strong base solution is 1-3mol/L; in an alternative embodiment, the non-nucleophilic strong base solution is added to the first solution by dropwise addition; in an alternative embodiment, the system temperature is-10 ℃ during the addition of the non-nucleophilic strong base solution to the first solution; In an alternative embodiment, the molar ratio of the non-nucleophilic strong base to the isonitrile acetate is (1-1.5): 1; In an alternative embodiment, the molar ratio of the non-nucleophilic strong base to the isonitrile acetate is (1-1.1): 1; In an alternative embodiment, the solvent in the non-nucleophilic strong base solution is selected from aprotic solvents; in an alternative embodiment, the solvent in the non-nucleophilic strong base solution is selected from tetrahydrofuran; in an alternative embodiment, the non-nucleophilic strong base is added to the first solution for a reaction period of 20 to 40 minutes; In an alternative embodiment, the temperature of the reaction carried out by adding non-nucleophilic strong base into the first solution is-20-10 ℃. In an alternative embodiment, the 2-haloethyl methyl sulfide is added dropwise; In an alternative embodiment, the temperature during the addition of 2-haloethyl methyl sulfide is from-20 to 5 ℃, preferably from-10 to 0 ℃; in an alternative embodiment, the C-alkylation reaction is carried out at a temperature of from 0 to 50℃and for a reaction time of from 2 to 12 hours; in an alternative embodiment, the temperature of the C-alkylation reaction is 15-25 ℃; In an alternative embodiment, the C-alkylation reaction time is from 4 to 8 hours; in an alternative embodiment, the molar ratio of 2-haloethyl methyl sulfide to isonitrile acetate is (1-1.5): 1; in an alternative embodiment, the molar ratio of 2-haloethyl methyl sulfide to isonitrile acetate is (1-1.1): 1; in an alternative embodiment, the concentration of the isonitrile acetate in the first solution is from 0.3 to 2mol/L. In an alternative embodiment, the 2-haloethyl methyl sulfide is selected from at least one of 2-bromoethyl methyl sulfide, 2-chloroethyl methyl sulfide; In an alternative embodiment, the isocyanato acetate is selected from at least one of methyl isocyanato acetate or ethyl isocyanato acetate; in an