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CA-3198877-C - METHOD FOR PREPARING GLUFOSINATE OR ANALOGUES THEREOF

CA3198877CCA 3198877 CCA3198877 CCA 3198877CCA-3198877-C

Abstract

The present invention relates to a method for preparing glufosinate of formula (I) or analogues thereof in a continuous manner. (see formula I) The method of the present application is in a continuous manner and can simplify the production without separating intermediates, improve the production efficiency, and reduce the production costs.

Inventors

  • Min Xu
  • Yongjiang LIU
  • Lei Zhou
  • Wei Zeng
  • Ke Cheng

Assignees

  • LIER CHEMICAL CO., LTD.

Dates

Publication Date
20260505
Application Date
20220719
Priority Date
20210720

Claims (20)

  1. WHAT IS CLAIMED IS: 1. A method for preparing glufosinate of formula (I) or analogues thereof in a continuous manner, (I) characterized in that the method comprises: a) feeding a compound of formula (II) and a compound of formula (V) into a :first reactor set and reacting said compound of formula (II) and said compound of formula (V) therein to obtain a product stream of the first reactor set, (II) Helli fi',, ~,X fiN"PG (V) b) feeding the product stream of the :first reactor set into a second reactor set, reacting at a temperature in the range of from 50°C to 200°C to obtain a product stream of the second reactor set; and c) subjecting the product stream of the second reactor set to an acidic hydrolysis or a basic hydrolysis to obtain the glufosinate of formula (I) or analogues thereof; wherein X represents -OR2 or -NR2R', R1, R2 and R1 are each independently selected from a substituted or unsubstituted hydrocarbyl group; R' is hydrogen or has the same definition as R2; Hal1 and Hal2 are each independently halogen; and PG is hydrogen or an amino protecting group, and when PG is the amino protecting group, the method further comprises a step of removing the amino protecting group.
  2. 2. The method of claim 1, characterized in that, in the step a), the molar ratio of the compound of formula (V) to the compound of formula (II) is 1:(0.8-10).
  3. 3. The method of claim 1 or claim 2, characterized in that, R1, R2 and R1 are each independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, 23 Date Re<;ue/Date Received 2024-04-29 hexyl, phenyl, phenylmethyl, phenylethyl, phenylpropyl, methylphenyl, ethylphenyl, and propy lpheny L
  4. 4. A method for preparing glufosinate of formula (I) or analogues thereof in a continuous manner, (I) characterized in that the method comprises: ao) feeding a compound of formula (III) and a compound of formula (IV) into aAo reactor set and reacting said compound of formula (III) and said compound of formula (IV) therein to obtain a product stream of the Ao reactor set, a) feeding the product stream of the Ao reactor set and a compound of formula (V) into a first reactor set and reacting said product stream of the Ao reactor set and said compound of formula (V) therein to obtain a product stream of the first reactor set, Hai"~x (V) HN~PG b) feeding the product stream of the first reactor set into a second reactor set, reacting in the second reactor set at a temperature in the range of from 50°C to 200°C to obtain a product stream of the second reactor set; and c) subjecting the product stream of the second reactor set to an acidic hydrolysis or a basic hydrolysis to obtain the glufosinate of formula (I) or analogues thereof; wherein R1 is Rs or&; and X represents -OR2 or -NR2R', R2, R3, &i, Rs and R6 are each independently selected from a substituted or unsubstituted hydrocarbyl group; R' is hydrogen or has the same definition as R2; Hal 1 and Hal2 are each independently halogen; and PG is hydrogen or an amino protecting group, and when PG is the amino protecting group, the method further comprises a step of removing the amino protecting group. 24 Date Re<;ue/Date Received 2024-04-29
  5. 5. The method of claim 4, characterized in that, R2, R3, R-4, Rs and R6 are each independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, phenyl, phenylmethyl, phenylethyl, phenylpropyl, methylphenyl, ethylphenyl, and propy lpheny 1.
  6. 6. The method of claim 4, characterized in that, in the step ao), the molar ratio of the compound of formula (III) to the compound of formula (IV) is 1.5:1 - 1:1.5.
  7. 7. The method of claim 4, characterized in that the step ao) has a reaction temperature in the range of from -50°C to 100°C.
  8. 8. The method of claim 1 or 4, characterized in that, R1 is selected from methyl and ethyl, and R2 is selected from methyl, ethyl, propyl, isopropyl, butyl and isobutyl.
  9. 9. The method of claim 1 or 4, characterized in that, Ha11 and Hal2 are chlorine.
  10. 10. The method of claim 1 or 4, characterized in that, during step b), the reacting takes place at a temperature in the range of from 80°C to 130°C.
  11. 11. The method of claim 1 or 4, characterized in that the step a) has a reaction temperature in the range of from -50°C to 200°c.
  12. 12. The method of claim 1 or 4, characterized in that the step b) has a reaction time in the range of from 1 hour to 30 hours.
  13. 13. The method of claim 4, characterized in that, the Ao reactor set consists of one or more microchannel reactors.
  14. 14. The method of claim 1 or 4, characterized in that, the first reactor set consists of one or more microchannel reactors, and/or the second reactor set consists of one or more microchannel reactors or one or more stirred-tank reactors.
  15. 15. The method of claim 4, characterized in that, in the step a), the molar ratio of Date Re<;ue/Date Received 2024-04-29 the compound of formula (V) to the total molar amount of P-containing compounds in terms of Pin the product stream of the Ao reactor set is 1:(0.8-10).
  16. 16. The method of claim 1 or 4, characterized in that a base is added at the beginning of, during or after the reaction of step a).
  17. 17. The method of claim 1 or 4, characterized in that the steps a), b) and c) are each independently carried out without solvent or in an inert solvent.
  18. 18. The method of claim 4, characterized in that the step ao) is carried out without solvent or in an inert solvent.
  19. 19. The method of claim 1 or 4, characterized in that the feeding in the step a) and/or step b) is a continuous feeding.
  20. 20. The method of claim 14, characterized in that, the reaction time in the first reactor set is in the range of 1-300 seconds.

Description

Method For Preparing Glufosinate or Analogues Thereof FIELD OF THE INVENTION The present invention relates to a method for preparing glufosinate or analogues thereof. BACKGROUND OF THE INVENTION Glufosinate is an important herbicide. It is a highly potent, broad-spectrum, low toxicity, non-selective (sterilant) organophosphorus herbicide with certain systemic action developed by Hoechst in the 1980s. It can control annual or perennial dicotyledon weeds and gramineae weeds. Existing methods for preparing glufosinate have complex processes and high costs. For example, the method most commonly used for preparing glyphosate in the industrial production is the Strecker method (see e.g., US6359162Bl). In this method, after the addition reaction between methyl phosphite and acrolein, a Strecker reaction is performed, and the final product is then obtained by hydrolysis and purification. However, this preparation method comprises multiple steps, and employs highly toxic reagents such as sodium cyanide. Further, WO2021/147894 discloses a method for preparing glufosinate, and specifically discloses several steps for the preparation, and the steps as a whole take place in a separate manner. In other words, WO2021/14 7894 does not relate to glufosinate preparation in a continuous manner. SUMMARY OF THE INVENTION The present invention provides a method for preparing glufosinate or analogues thereof, in particular, a method for preparing gluf osinate of formula (I) or analogues thereof in a continuous manner. The continuous preparation method of the present invention can simplify production without separating intermediates, improve the production efficiency, and reduce the production costs. The method of the present invention is carried out in a continuous manner, and is especially suitable for preparing L-glufosinate at low costs. In a first aspect, the present invention provides a method for preparing gluf osinate of formula (I) or analogues thereof, (I) characterized in that, the method comprises: a) feeding a compound of formula (II) and a compound of formula (V) into a first reactor 1 Date Re9ue/Date Received 2023-10-26 set, after reaction, a product stream of the first reactor set is obtained, (II) Hal 2~x HN"PG (V) b) feeding the product stream of the first reactor set into a second reactor set, reacting at a temperature in the range of from 50°C to 200°C, preferably from 80°C to 130°C, to obtain a product stream of the second reactor set; and c) subjecting the product stream of the second reactor set to an acidic hydrolysis or a basic hydrolysis to obtain the glufosinate of formula (I) or analogues thereof; wherein X represents -OR2 or-NR2R', R1, R2 and R1 are each independently selected from a substituted or unsubstituted hydrocarbyl group, such as a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkaryl group, and a substituted or unsubstituted aralkyl group; for example, R1, R2 and R1 are each independently selected from a substituted or unsubstituted C 1-C6 alky 1 group, a substituted or unsubstituted C6-C 12 ary 1 group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C1-C12 alkaryl group, and a substituted or unsubstituted C1-C12 aralkyl group; for example, R1, R2 and R1 are each independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, phenyl, phenylmethyl, phenylethyl, phenylpropyl, methylphenyl, ethylphenyl, and propylphenyl; for example, R1 is selected from methyl and ethyl, and R2 is selected from methyl, ethyl, propyl, isopropyl, butyl and isobutyl; R' is hydrogen or has the same definition as R2; Hal1 and Hal2 are each independently halogen, preferably chlorine; PG is hydrogen or an amino protecting group, and when PG is the amino protecting group, a step of removing the amino protecting group is further comprised. In a second aspect, the present invention provides a method for preparing glufosinate of formula (I) or analogues thereof, (I) characterized in that the method comprises: 2 Date Re9ue/Date Received 2023-10-26 ao) feeding a compound of formula (III) and a compound of formula (IV) into a Ao reactor set, after reaction, a product stream of the Ao reactor set is obtained, Hal1 OR3 II 11 p, p R5 / 'Hal 1 Rs/ 'oR4 (III) (IV) a) feeding the product stream of the Ao reactor set and a compound of formula (V) into a first reactor set, after reaction, a product stream of the first reactor set is obtained, Hal2, --,,,,,.,.__ .Jl 1 ·x (V) HN,PG b) feeding the product stream of the first reactor set into a second reactor set, reacting in the second reactor set at a temperature in the range of from 50°C to 200°C, preferably from 80°C to 130°C, to obtain a product stream of the second reactor set; and c) subjecting the product stream of the second reactor set to an acidic hydrolysis or a basic hydrolysis to obtain t