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CN-116478207-B - Preparation method of glufosinate-ammonium

CN116478207BCN 116478207 BCN116478207 BCN 116478207BCN-116478207-B

Abstract

The application relates to a preparation method of glufosinate. Specifically, it relates to a process for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, which comprises reacting a compound of formula (II) with a compound of formula (III) and hydrolyzing the reaction product to obtain a compound of formula (I). The method of the application has the advantages that the construction condition of the P-C bond is milder due to higher substrate reactivity, the reaction temperature is lower, and racemization of the L-configuration at high temperature can be reduced, thereby improving the maintenance of the L-configuration during the preparation of the L-glufosinate.

Inventors

  • TANG WENJIE
  • WU CHENGJUN
  • LI NAN
  • TANG XIANZHONG
  • XU KAIKAI
  • XU JIANJIE
  • MAO CHUNHUI

Assignees

  • 宁夏永农生物科学有限公司
  • 永农生物科学有限公司

Dates

Publication Date
20260508
Application Date
20230412

Claims (15)

  1. 1. A process for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, comprising the steps of: 1) Reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion with a compound of formula (III) in the presence of an organic solvent at a temperature of 30-130 ℃, And 2) Hydrolyzing the reaction product of step 1) in the presence of an acid or a base to obtain a compound of formula (I), Wherein, the X is halogen; y is-OR 3 ; Z is hydrogen or an amino protecting group selected from-C (O) R 7 , wherein R 7 is selected from C 1 -C 6 alkyl; R 1 and R 2 are each independently selected from hydrogen, C 1 -C 6 alkyl or C 6 -C 10 aryl; R 3 and R 6 are each independently selected from C 1 -C 6 alkyl; And * For identifying chiral carbon atoms.
  2. 2. The method of claim 1, wherein the amino protecting group is selected from ethoxycarbonyl groups.
  3. 3. The process of claim 1, wherein the enantiomer of glufosinate is L-glufosinate or D-glufosinate, and/or the mixture of any ratio of enantiomers of glufosinate comprises L-glufosinate and D-glufosinate of 0.1:99.9 to 99.9:0.1.
  4. 4. A process according to claim 3, wherein the mixture of enantiomers of glufosinate in any ratio comprises 50:50 to 99.9:0.1L-glufosinate and D-glufosinate.
  5. 5. The method of claim 1, wherein, Halogen is selected from fluorine, chlorine or bromine; C 1 -C 6 alkyl is selected from methyl, ethyl, propyl or isopropyl; the C 6 -C 10 aryl is selected from phenyl or naphthyl.
  6. 6. The method of claim 1, wherein each R 1 、R 2 is independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, or phenyl, and each R 3 、R 6 、R 7 is independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, or hexyl.
  7. 7. The process of claim 1, wherein the compound of formula (III) is prepared from a composition comprising a compound of formula (IV) and HOR 6 , a compound of formula (V) and a compound of formula (VII), a compound of formula (VI), a compound of formula (VII) and HOR 6 , or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII), Wherein R 1 、R 2 、R 6 and X are as defined in claim 1, in the presence of an acid-binding agent.
  8. 8. The method of claim 7, wherein the acid-binding agent is selected from NR 11 R 12 R 13 , wherein R 11 、R 12 and R 13 are each independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, ternary to six membered heterocycloalkyl, and, C 6 -C 10 aryl or five to ten membered heteroaryl, or any two of R 11 、R 12 and R 13 together with the N atom to which they are attached form a three to six membered heterocycloalkyl, wherein said C 1 -C 6 alkyl, c 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, ternary to hexacyclic heterocycloalkyl, C 6 -C 10 aryl or five to ten membered heteroaryl optionally substituted with halogen, Carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 3 -C 6 cycloalkyl or C 6 -C 10 aryl substitution.
  9. 9. The method of claim 7 or 8, wherein the molar ratio of the composition to the acid-binding agent is 1:0.01-5.
  10. 10. The method of claim 9, wherein the molar ratio of the composition to the acid-binding agent is 1:0.1-1.5.
  11. 11. The process according to claim 1, wherein in step 1), the organic solvent is selected from at least one of an aromatic hydrocarbon solvent, an alkane solvent, a halogenated hydrocarbon solvent, an ether solvent, an ester solvent, an amide solvent and a sulfur-containing solvent, and/or, In step 2), the acid is selected from at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid and acetic acid, and/or the base is selected from an alkali metal or alkaline earth metal hydroxide, carbonate, bicarbonate or basic carbonate, ammonia, an organic base or an organic amine.
  12. 12. The process according to claim 11, wherein in step 1), the organic solvent is selected from at least one of toluene and chlorobenzene, and/or, In step 2), the acid is selected from hydrochloric acid or sulfuric acid, and/or the base is selected from sodium hydroxide or triethylamine.
  13. 13. A process according to claim 12, wherein in step 1) the reaction is carried out for 1 to 25 hours and/or, In step 2), the hydrolysis is carried out at a temperature of 30-140 ℃ for 0.5-36 hours.
  14. 14. A process according to claim 13, wherein in step 1) the reaction is carried out at a temperature of from 30 to 95℃and/or, In step 2), the hydrolysis is carried out at a temperature of 60-110 ℃.
  15. 15. Use of a composition for the preparation of glufosinate-ammonium of formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion, The composition comprises a compound of formula (IV) and HOR 6 , a compound of formula (V) and a compound of formula (VII), a compound of formula (VI), a compound of formula (VII) and HOR 6 , or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII); wherein R 1 、R 2 、R 6 , X and X are as defined in claim 1.

Description

Preparation method of glufosinate-ammonium Technical Field The application relates to the field of pesticide herbicides, in particular to a preparation method of glufosinate-ammonium. Background Glufosinate has the chemical name 4- [ hydroxy (methyl) phosphono ] -DL-homoalanine, which was developed and produced by helson corporation, germany. The herbicide is a glutamine synthesis inhibitor and a nonselective contact herbicide, and has the action mechanism of inhibiting glutamine synthetase activity in plants, so that glutamine synthesis is blocked, nitrogen metabolism is disturbed, ammonium ions are accumulated, thereby interfering with metabolism of the plants and leading the plants to die. The glufosinate-ammonium molecule contains a chiral carbon and has two different configurations, namely L-glufosinate-ammonium and D-glufosinate-ammonium, wherein only L-isomer has herbicidal activity and is easy to decompose in soil, the glufosinate-ammonium molecule has low toxicity to human beings and animals, the environmental pressure can be greatly reduced, and the activity and the control effect on resistant weeds are better than those of common glufosinate-ammonium. With the remarkable problems of paraquat inhibition and glyphosate resistance, the global glufosinate resistance gene is further widely introduced into tens of crops such as rice, wheat, corn, beet, tobacco, soybean, cotton, potato, tomato, rape and sugarcane, and the like, so that the substitution process of glufosinate for the other two is accelerated by the factors. Although most of the glufosinate commercial products sold on the market at present are racemates thereof, with technical innovation and progress, the L-glufosinate enters the mainstream market to be impossible. The existing method for preparing chiral pure L-glufosinate mainly comprises a chemical method and a biological method. Wherein the chemical method comprises a chemical resolution method and a chemical synthesis method. The chemical resolution method is to resolve racemic D, L-glufosinate or derivatives thereof synthesized by an external chemical method through chiral resolution reagents, thereby preparing optically pure L-glufosinate. Patent specification publication No. WO1995023805A1 discloses a process for obtaining single [ L ] -or [ D ] -homoalanin-4-yl- (meth) phosphonic acid and salts thereof by resolution of one of the diastereoisomeric salts by salifying with a chiral base such as quinine and cinchonine and the like. The method needs to use expensive chiral resolution reagent, has lower yield and has no obvious industrialization advantage. The preparation of L-glufosinate by chemical synthesis can be further subdivided into asymmetric synthesis and total synthesis using natural or fermentatively derived L-amino acids as starting materials. The latter has more direct and simple synthetic route and good ee value maintenance than other methods because it does not need to construct chiral centers of amino acid structures, and is getting more and more attention from related enterprises and research institutions at home and abroad. The patent specification with publication number US5442088A discloses a method for obtaining L-glufosinate-ammonium hydrochloride by using L-homoserine lactone or derivatives thereof as raw materials, performing ring-opening chlorination, esterification, condensation with methyl phosphite diester, and finally hydrolyzing and refining. The multistep reaction process unit is convenient to operate, but the activity of the chlorinated substrate of the Arbuzov reaction raw material is lower, the Arbuzov reaction can be performed at a higher temperature, meanwhile, the chlorinated alkane byproduct further reacts with methyl phosphite diester at a high temperature to increase the unit consumption, and in addition, the L-type ee value is reduced to a certain extent due to racemization of part of raw materials or products. The patent specification with the publication number of CN113490671B discloses that halogenated homoserine ester with or without protection of amino is taken as a raw material, condensed with methyl phosphonite monochloro ester to obtain an intermediate, and then hydrolyzed to obtain L-glufosinate. The method takes homoserine as a raw material, and synthesizes the homoserine through multi-step reactions such as cyclization, chlorination, esterification, protecting group protection and the like, and the reaction steps are long. In recent years, along with the problems of paraquat inhibition and glyphosate resistance, the demand of glufosinate is continuously increased, so that the development of the glufosinate synthesis method which has the advantages of mild reaction conditions, higher yield, lower cost and simple operation has extremely important significance for herbicide use reduction and synergy. Disclosure of Invention For the sake of brevity, the "compound of formula (N) (e.g., compound of formula (II)" described hereinafter may