CN112574117B - Preparation method of glufosinate intermediate and analogue - Google Patents

Preparation method of glufosinate intermediate and analogue Download PDF

Info

Publication number
CN112574117B
CN112574117B CN202010996969.4A CN202010996969A CN112574117B CN 112574117 B CN112574117 B CN 112574117B CN 202010996969 A CN202010996969 A CN 202010996969A CN 112574117 B CN112574117 B CN 112574117B
Authority
CN
China
Prior art keywords
formula
compound
reaction
salt
hydrogen
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.)
Active
Application number
CN202010996969.4A
Other languages
Chinese (zh)
Other versions
CN112574117A (en
Inventor
刘永江
曾伟
周磊
左翔
程柯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lier Chemical Co Ltd
Guangan Lier Chemical Co Ltd
Original Assignee
Lier Chemical Co Ltd
Guangan Lier Chemical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lier Chemical Co Ltd, Guangan Lier Chemical Co Ltd filed Critical Lier Chemical Co Ltd
Publication of CN112574117A publication Critical patent/CN112574117A/en
Application granted granted Critical
Publication of CN112574117B publication Critical patent/CN112574117B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to a preparation method of glufosinate-ammonium hydantoin intermediate and analogues thereof, which comprises the steps of reacting a compound of a formula (II) or salts, enantiomers or a mixture of enantiomers in all proportions with a compound of a formula (III) to obtain a compound of a formula (IV), converting the compound of the formula (IV) into a compound of a formula (V), and reacting the compound of the formula (V) with a halogenating agent to obtain the compound of the formula (I). The hydantoin intermediate and the analogues thereof are used for preparing glufosinate-ammonium, so that the problems of high cost, low efficiency and the like in the prior art can be solved, and the preparation method has the advantage of cost.

Description

Preparation method of glufosinate intermediate and analogue
Technical Field
The invention relates to a preparation method of a glufosinate-ammonium hydantoin intermediate and an analogue thereof.
Background
Glufosinate, which is a broad-spectrum organophosphorus contact-type herbicide successfully developed by husker corporation in the 80 s, is a glutamine synthesis inhibitor, has weak internal absorption effect, is different from the early glyphosate root killing, is used for killing leaves firstly and then can be conducted in the xylem of plants through plant transpiration, has quick-acting property between paraquat and glyphosate, and is a non-selective contact-type herbicide. In the prior art, the preparation method of glufosinate-ammonium generally has the problems of complex reaction, low efficiency and high production cost.
Disclosure of Invention
The invention provides a preparation method of a glufosinate-ammonium hydantoin intermediate and analogues thereof shown in formula (I):
Figure GDA0002764510590000011
or a salt, enantiomer or a mixture of enantiomers thereof, in particular a racemic mixture thereof, in all proportions, comprising the steps of:
(a) reacting a compound of formula (II)
Figure GDA0002764510590000012
Or salts, enantiomers or mixtures of enantiomers in all ratios thereof, in particular enantiomers in the L-configuration thereof,
with compounds of the formula (III)
Figure GDA0002764510590000013
Reaction to give the compound of formula (IV)
Figure GDA0002764510590000021
Or salts, enantiomers or mixtures of enantiomers in all proportions, in particular mixtures of enantiomers thereof, especially in particular racemic mixtures thereof;
(b) converting the resulting compound of formula (IV) to a compound of formula (V)
Figure GDA0002764510590000022
Or salts, enantiomers or mixtures of enantiomers thereof in all proportions, in particular mixtures of enantiomers thereof, especially in particular racemic mixtures thereof;
(c) reacting the resulting compound of formula (V) with a halogenating agent to give a compound of formula (I), or a salt, enantiomer or mixture of enantiomers in all proportions thereof;
wherein:
hal is a halogen atom;
y is O or S;
R 1 is hydrogen or an amino protecting group;
R 2 is hydrogen, C 1 -C 4 Alkyl or benzyl.
The present invention further provides a process for the preparation of glufosinate intermediates of formula (VI) and analogues thereof:
Figure GDA0002764510590000023
or a salt, an enantiomer or a mixture of enantiomers thereof in all proportions, in particular a mixture of enantiomers thereof, in particular a racemic mixture thereof, comprising the steps of:
obtaining the compound of formula (I) according to the method
Figure GDA0002764510590000024
Or salts, enantiomers or mixtures of enantiomers in all ratios thereof, in particular mixtures of enantiomers thereof, in particular racemic mixtures thereof
(d) Reacting the resulting compound of formula (I), with a compound of formula (VII) without removing the amino protecting group or without removing the amino protection
Figure GDA0002764510590000031
(ii) by a rearrangement reaction to a compound of formula (VI), or a salt, enantiomer or mixture of enantiomers in all proportions thereof;
wherein:
hal is a halogen atom;
y is O or S;
R 1 is hydrogen or an amino protecting group;
R 2 is hydrogen, C 1 -C 4 Alkyl or benzyl;
R 3 is R 6 Or R 7 ；
R 4 Is an alkyl or aryl group;
R 5 is hydrogen or R 1 ；
R 6 And R 7 Each independently hydrogen, alkyl, alkenyl or aryl.
Further, the aforementioned R 1 Is hydrogen.
Further, Y is O, R 2 Is hydrogen.
Further, the aforementioned R 4 Is C 1 -C 6 An alkyl group.
Further, the aforementioned R 4 Is methyl.
Further, the aforementioned R 6 And R 7 Each independently is C 1 -C 6 An alkyl group.
Further, the aforementioned R 4 Is ethyl, R 6 Is ethyl, R 7 Is an ethyl group.
Further, in the step (c), the halogenating agent is a hydrohalic acid.
Further, the step (c) is carried out at 50 to 150 ℃.
The process of step (c) of the present invention is carried out by reacting a compound of formula (V) with a halogenating agent such as hydrogen halide or with a compound capable of generating hydrogen halide with a protic solvent, in particular with an alcohol or a carboxylic acid.
Especially when Hal is chlorine or bromine, the aforementioned halogenating agents include, for example, acid halides, especially compounds of formula (VIII) (group a):
Figure GDA0002764510590000032
wherein R is 8 Is alkyl, cycloalkyl, aryl, arylalkyl or heterocyclylalkyl, in each case optionally substituted. R 7 Preferably C 1 -C 10 Alkyl radical, C 3 -C 10 -cycloalkyl, aryl-C 1 -C 4 Alkyl, especially phenyl-C 1 -C 4 Alkyl, in each case the radicals mentioned may optionally be mono-or polysubstituted, where suitable substituents are OH, SH, halogen, C 1 -C 6 -alkoxy, C 1 -C 6 Alkylthio radical, C 1 -C 6 -alkyl and aryl, in particular phenyl, or heterocyclylmethyl, wherein the heterocyclyl is an unsaturated or saturated 5-or 6-membered heterocycle having 1 or 2 (preferably 1) heteroatoms selected from nitrogen, oxygen, sulfur, in particular furyl, tetrahydrofuryl, thienyl or pyridyl.
The aforementioned halogen (atom) is preferably F, Cl, Br, I, especially F, Cl, Br, especially F, Cl. R 3 Particularly preferably C 1 -C 4 Alkyl radical, C 3 -C 6 Cycloalkyl, benzyl or phenylethyl, in each case optionally 1 to 5 (preferably 1 to 3, particularly preferably mono-or disubstituted), where suitable substituents are OH, Cl, Br, F, C 1 -C 4 -alkoxy, C 1 -C 4 Alkylthio radical, C 1 -C 4 -alkyl and aryl, in particular phenyl; or a heterocyclylmethyl group, wherein the heterocyclyl group is in particular furyl, tetrahydrofuryl, thienyl or pyridyl.
The compounds of formula (VIII) are known and commercially available or can be readily prepared by known methods.
The foregoing halogenating agents also include (group B): reactive non-metal halides and reactive non-metal oxyhalides. For example, when Hal is chlorine, preference is given to oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfur dichloride, thionyl chloride and sulfuryl chloride, particular preference to phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, sulfuryl chloride and oxalyl chloride, very particular preference to thionyl chloride, sulfuryl chloride, phosphorus oxychloride and oxalyl chloride.
The compounds of group B are known compounds which are commercially available per se or are prepared by known methods.
Step (c) may optionally be carried out in the presence of a diluent.
When hydrogen halides, in particular hydrogen chloride, are used, suitable diluents are organic solvents, polar protic solvents, such as methanol, ethanol, n-propanol, isopropanol, n-butanol or isobutanol, and polar aprotic solvents, such as acetone, acetonitrile and acetates (e.g. ethyl acetate), ethers and cyclic ethers, such as diethyl ether, diisobutyl ether, THF, dioxane, or non-polar aprotic solvents, such as hydrocarbons, such as benzene, toluene or xylene, halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene or o-dichlorobenzene.
When a compound of group (a) or (B) is used, suitable diluents are polar protic solvents, such as alcohols or carboxylic acids.
Particularly suitable are alcohols, in particular methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol.
It may be advantageous to add a further diluent to the reaction mixture. Suitable diluents are ethers, such as dibutyl ether, THF, dioxane, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether, and hydrocarbons, such as benzene, toluene or xylene, halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene or o-dichlorobenzene, nitriles, such as acetonitrile, carboxylic esters, such as ethyl acetate or ketones, such as acetone or methyl isopropyl ketone.
Mixtures of the diluents may also be used.
Step (c) is generally carried out at a temperature of from 0 ℃ to 200 ℃, preferably from 50 ℃ to 150 ℃
Step (c) is preferably carried out at atmospheric pressure, in particular for low-boiling diluents, optionally also at elevated pressure.
For example, when used, the molar ratio of hydrogen halide or compound of formula (VIII) or group B compound to the starting compound of formula (V) is generally from 0.5:1 to 10:1, preferably from 1:1 to 5: 1.
The reaction is generally carried out by heating the starting material of the formula (V) with hydrogen halide or a compound of the formula (VIII) or a compound of group B, optionally in a diluent and optionally in a solvent, to the desired temperature. It is also possible to meter in the hydrogen halide or the compound of the formula (VIII) or the compound of group B continuously during the reaction.
For working up, after cooling, water or a base is optionally added to adjust the pH, the mixture is optionally concentrated by evaporation, and the end product is isolated, for example by filtration or extraction.
This step is preferably carried out in a diluent, and when the reaction mixture is cooled, the end product can be crystallized directly and isolated in a simple manner, for example by filtration. Suitable diluents for this purpose are alcohols, in particular methanol, ethanol, propanol, isopropanol, isobutanol, n-butanol, sec-butanol.
The reaction mixture can also be worked up anhydrous by the following method: when the reaction is complete, the diluent and, if appropriate, the solvent are distilled off and the remaining residue is extracted with a suitable extractant. Suitable extractants are in principle all solvents which are inert with respect to the end product and sufficiently soluble in the end product.
Examples thereof include aliphatic hydrocarbons such as n-pentane, n-hexane, cyclohexane, halogenated aliphatic hydrocarbons such as dichloromethane or chloroform, aromatic hydrocarbons such as benzene, toluene or xylene, halogenated aromatic hydrocarbons such as chlorobenzene or o-dichlorobenzene, or ethers such as methyl tert-butyl ether.
The product obtained crystallizes, optionally after concentration of the extractant by evaporation, and can be isolated by filtration or the extractant can be completely or substantially completely removed and, if desired, the residue purified, for example by recrystallization.
In the step (d), the rearrangement reaction is an Arbuzov rearrangement reaction. This reaction is also known as the Michaelis-Arbuzov reaction. The rearrangement reaction can be carried out by adding elemental iodine, for example, as is well known to those skilled in the art.
Further, in the step (d), the reaction temperature is 60 to 200 ℃.
Further, in the aforementioned step (d), the reaction is carried out under catalysis of a lewis acid.
Further, in the step (d), the reaction temperature is 20 to 200 ℃.
The invention provides a method for preparing glufosinate-ammonium, which is characterized in that a compound shown in a formula (I) is prepared according to the method, the compound shown in the formula (I) and diethyl methylphosphite undergo Arbuzov rearrangement reaction, and glufosinate-ammonium is obtained through hydrolysis reaction.
The aforementioned hydrolysis reaction is carried out in the presence of an acid or a base.
The invention provides a preparation method of a glufosinate-ammonium hydantoin intermediate and analogues thereof, the hydantoin intermediate is used for preparing glufosinate-ammonium, the problems of high cost, low efficiency and the like in the prior art can be solved, and the preparation method has a cost advantage.
Unless stated to the contrary, the following terms used in the specification and claims have the following meanings.
The term "alkyl" refers to a saturated aliphatic hydrocarbon group, including straight and branched chain groups of 1 to 18 carbon atoms. Alkyl groups having 1 to 6 carbon atoms are preferred, such as methyl, ethyl, propyl, 2-propyl, n-butyl, isobutyl, tert-butyl, pentyl and the like. The alkyl group may be substituted or unsubstituted, and when substituted, the substituent may be halogen, nitro, sulfonyl, etheroxy, etherthio, ester, thioester, or cyano.
The term "alkenyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond. Such as ethenyl, 1-propenyl, 2-propenyl, 1-, 2-or 3-butenyl, and the like. The alkenyl group may be substituted or unsubstituted, and when substituted, the substituent may be halogen, nitro, sulfonyl, etheroxy, etherthio, ester, thioester, or cyano.
The term "aryl" refers to a group having at least one aromatic ring structure. The aryl group is preferably a phenyl group or a benzyl group. Phenyl and benzyl groups may be substituted or unsubstituted.
The term "amino protecting group" refers to a group that can be attached to a nitrogen atom on an amino group to protect the amino group from reaction and which can be easily removed in a subsequent reaction. Suitable amino protecting groups include, but are not limited to, the following:
a carbamate group of the formula-C (O) O-R, wherein R is, for example, methyl, ethyl, tert-butyl, benzyl, phenethyl, CH 2 ＝CH-CH 2 -, etc.; amide groups of the formula-c (o) -R ', wherein R' is, for example, methyl, ethyl, phenyl, trifluoromethyl, and the like; formula-SO 2 The N-sulfonyl derivative-group of-R ', wherein R' is, for example, tolyl, phenyl, trifluoromethyl, 2,5,7, 8-pentamethylchroman-6-yl-, 2,3, 6-trimethyl-4-methoxybenzene, and the like.
C 1 -C 4 Alkyl groups are linear or branched, saturated hydrocarbon chains containing from 1 to 4 carbon atoms. It may be a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl group.
Detailed Description
All of the features disclosed in this specification, or all of the steps in any method or process so disclosed, may be combined in any combination, except combinations of features and/or steps that are mutually exclusive.
Any feature disclosed in this specification may be replaced by alternative features serving equivalent or similar purposes, unless expressly stated otherwise. That is, unless expressly stated otherwise, each feature is only an example of a generic series of equivalent or similar features.
Example 1
Figure GDA0002764510590000061
Adding L-methionine (149.2g, 1mol), urea (72.1g, 1.2mol) and water (500mL) into a 250mL three-necked flask, reacting at 100 ℃ for 10h, naturally cooling to room temperature, carrying out water spin-drying in the reaction system to obtain a white solid, washing with methanol (100mL x 3), and drying to obtain 180.7g of (S) -4- (methylthio) -2-ureidobutyric acid solid with the purity of 95% and the yield of 94%.
Example 2
Figure GDA0002764510590000071
Adding (S) -4- (methylthio) -2-ureidobutyric acid (19.2g, 100mmol), ethanol (100mL) and water (100mL) into a 250mL three-necked bottle, dropwise adding dimethyl sulfate (15.2g, 120mmol), reacting at room temperature for 5h, adding 18% HCl (35mL, 210mmol) after raw materials disappear, refluxing for 2h, spin-drying the solvent to obtain a white solid or a viscous substance, washing with ethanol (100mL x 3), and drying to obtain 12.8g of 1- (2-oxo-tetrahydrofuran-3-yl) urea white solid with the purity of 95% and the yield of 89%.
Example 3
Figure GDA0002764510590000072
1- (2-oxotetrahydrofuran-3-yl) urea (35g,243mmol) and 100mL of water were added to a 250mL three-necked flask, and reacted at 100 ℃ for 8 hours, cooled to room temperature, the water was dried by spinning, and then slurried with 100mL of methanol, filtered by suction, and dried to obtain 32.9g of 5- (2-hydroxyethyl) imidazolidine-2, 4-dione as a white solid in 94% yield and 99% HPLC purity as a racemic mixture.
Example 4
Figure GDA0002764510590000073
Adding 5- (2-hydroxyethyl) imidazolidine-2, 4-dione (12g, 83.2mmol) and a 48% hydrobromic acid acetic acid solution (34mL, 50g, 300mmol) into a 250mL sealed tube, sealing and pressing, reacting at 90 ℃ for 10h, naturally cooling to room temperature, spin-drying a solvent in a reaction system, recrystallizing with ethyl acetate, filtering by suction, and drying to obtain a white solid product, namely 14.6g of 5- (2-bromoethyl) imidazolidine-2, 4-dione, wherein the yield is 85% and the HPLC purity is 96.5%.
Example 5
Figure GDA0002764510590000081
Adding 5- (2-hydroxyethyl) imidazolidine-2, 4-dione (20g, 138.8mmol) and a 48% hydrobromic acid acetic acid solution (34mL, 50g, 300mmol) into a 250mL sealed tube, sealing the tube, reacting at 100 ℃ for 10 hours, naturally cooling to room temperature, spin-drying a solvent in a reaction system, recrystallizing with ethyl acetate, performing suction filtration and drying to obtain a white solid product, namely 20.3g of 5- (2-chloroethyl) imidazolidine-2, 4-dione, wherein the yield is 90%, and the HPLC purity is 98%.
Product structure analysis data are as follows:
1 H NMR(DMSO-d6,400MHz)δ：10.69(s,1H),8.05(s,1H),4.19–4.11(m,1H),3.92–3.65(m,2H),2.16(dtd,J＝14.8,7.6,4.8Hz,1H),2.01(ddt,J＝14.4,8.4,6.0Hz,1H).
example 6
Figure GDA0002764510590000082
Diethyl methylphosphonite (20.5g,150.1mmol), 5- (2-bromoethyl) imidazolidine-2, 4-dione (25.7g,125mmol) and 20mL of toluene were added to a 250mL three-necked flask, replaced with argon gas three times, stirred, heated to 100 ℃ to react for 5 hours, and the solvent and unreacted raw materials were removed by desolventization under reduced pressure to obtain 25.2g of a pale yellow viscous liquid with a yield of 86.0% and an HPLC purity of 97%.
Product structure analysis data are as follows:
1 H NMR(DMSO-d6,400MHz)δ：1.20(t,J＝7.0Hz,3H),1.40(d,J＝13.7Hz,3H),1.64(dq,J＝15.2,7.6Hz,4H),3.93–3.89(m,2H),4.07(t,J＝5.6Hz,1H),8.05(s,1H),10.75(s,1H).
example 7
Figure GDA0002764510590000091
Diethyl methylphosphonite (20.5g,150.1mmol), 5- (2-chloroethyl) imidazolidine-2, 4-dione (20.3g,125mmol) and chlorobenzene 20mL were added into a 250mL three-necked flask, and the mixture was replaced with argon three times, stirred, heated to 140 ℃ to react for 20 hours, and the solvent and unreacted raw materials were removed by desolvation under reduced pressure to obtain 23.1g of light yellow viscous liquid with a yield of 79% and a HPLC purity of 96%.
Example 8
Figure GDA0002764510590000092
Diethyl methylphosphonite (20.5g,150.1mmol), 5- (2-chloroethyl) imidazolidine-2, 4-dione (20.3g,125mmol), TBAB (2.1g, 6.25mmol) and chlorobenzene (20mL) were added to a 250mL three-necked flask, and replaced with argon three times, followed by stirring, heating to 140 ℃ to react for 8 hours, and after removing the solvent and unreacted starting materials by desolvation under reduced pressure, 24.0g of a pale yellow viscous liquid was obtained, with a yield of 82% and a HPLC purity of 96.5%.
Example 9
Figure GDA0002764510590000093
The product from example 6 (24g,102.5mmol), 36% HCl (40mL) was added to a sealed tube, the reaction was allowed to warm to 130 ℃ for 40h, desolventizing under reduced pressure gave a pale yellow viscous liquid, ethanol (20mL) was added and stirred at room temperature for 3h, a large amount of white solid appeared, suction filtered, washed with ethanol (20mL x 3), dried to give 17.6g of glufosinate-ammonium in 95% yield and 98.7% HPLC purity.
Example 10
Figure GDA0002764510590000101
A250 mL three-necked flask was charged with the product from example 8 (24g,102.5mmol), water 100mL, Ba (OH) 2 ·8H 2 O (31.6g,100mmol) was heated under reflux for 30 h. Addition of H 2 SO 4 Adjusting the pH value to 5-6, filtering, adjusting the pH value of filtrate to 12 by using ammonia water, adding A after rotary evaporation and desolventizationRecrystallizing the alcohol, filtering, drying to obtain 17.8g of glufosinate-ammonium, wherein the yield is 96 percent, and the HPLC purity is 98.5 percent.
The invention is not limited to the foregoing embodiments. The invention extends to any novel feature or any novel combination of features disclosed in this specification and any novel method or process steps or any novel combination of features disclosed.

Claims (10)

1. A process for the preparation of glufosinate-ammonium hydantoin intermediates of formula (I) and analogues thereof:
Figure FDA0003780206660000011
or a salt thereof, characterized in that: the method comprises the following steps:
(a) reacting a compound of formula (II)
Figure FDA0003780206660000012
Or a salt thereof
With compounds of the formula (III)
Figure FDA0003780206660000013
Reaction to give the compound of formula (IV)
Figure FDA0003780206660000014
Or a salt thereof;
(b) converting the resulting compound of formula (IV) to a compound of formula (V)
Figure FDA0003780206660000015
Or a salt thereof;
the step (b) comprises the steps of: 19.2g of a compound shown in a formula (IV), 100mL of ethanol and 100mL of water, 15.2g of dimethyl sulfate is dropwise added, the reaction is carried out for 5 hours at room temperature, after the raw materials disappear, 35mL of 18% HCl is added for refluxing for 2 hours, the solvent is dried by spinning to obtain a white solid or a viscous substance, and the white solid or the viscous substance is washed by 100mL of ethanol multiplied by 3 and dried;
(c) reacting 35g of the compound shown in the formula (V) with 100mL of water at 100 ℃ for 8h, cooling to room temperature, spin-drying the water, pulping with 100mL of methanol, filtering, and drying; reacting the resulting compound with a halogenating agent to provide a compound of formula (I), or a salt thereof;
wherein:
hal is a halogen atom;
y is O;
R 1 is hydrogen;
R 2 is hydrogen.
2. A process for preparing glufosinate intermediates of formula (VI) and analogues thereof:
Figure FDA0003780206660000021
or a salt thereof, characterized in that: the method comprises the following steps:
obtaining a compound of formula (I) according to the process of claim 1
Figure FDA0003780206660000022
Or a salt thereof;
(d) reacting the resulting compound of formula (I), with a compound of formula (VII) without removing the amino protecting group or without removing the amino protection
Figure FDA0003780206660000023
(ii) conversion to a compound of formula (VI), or a salt thereof, by a rearrangement reaction;
wherein:
hal is a halogen atom;
y is O;
R 1 is hydrogen;
R 2 is hydrogen;
R 3 is R 6 Or R 7 ；
R 4 Is an alkyl or aryl group;
R 5 is hydrogen or R 1 ；
R 6 And R 7 Each independently hydrogen, alkyl, alkenyl or aryl.
3. The method of claim 2, wherein:
the R is 4 Is C 1 -C 6 An alkyl group; and/or the presence of a gas in the gas,
the R is 6 Is C 1 -C 6 An alkyl group; and/or the presence of a gas in the gas,
the R is 7 Is C 1 -C 6 An alkyl group.
4. The method of claim 3, wherein: the R is 4 Is methyl.
5. The method of claim 3, wherein: the R is 6 Is ethyl.
6. The method of claim 3, wherein: the R is 7 Is ethyl.
7. The method according to claim 1 or 2, characterized in that: in the step (c), the halogenating agent is a hydrohalic acid.
8. The method of claim 2, wherein: said step (d) is carried out under any one of the following conditions or any combination of the following conditions:
the rearrangement reaction is an Arbuzov rearrangement reaction; and the combination of (a) and (b),
the reaction temperature is 60-200 ℃; and the combination of (a) and (b),
the reaction is carried out under the catalysis of Lewis acid.
9. The method of claim 8, wherein: in the step (d), the reaction temperature is 20-200 ℃ under the catalysis of Lewis acid.
10. A method for preparing glufosinate-ammonium, characterized in that the compound of formula (I) is prepared according to the method of claim 1, the compound of formula (I) and diethyl methylphosphite undergo an Arbuzov rearrangement reaction, and then undergo a hydrolysis reaction to obtain glufosinate-ammonium.
CN202010996969.4A 2019-09-29 2020-09-21 Preparation method of glufosinate intermediate and analogue Active CN112574117B (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN2019109379887 2019-09-29
CN201910938251 2019-09-29
CN201910937988 2019-09-29
CN2019109382517 2019-09-29

Publications (2)

Publication Number Publication Date
CN112574117A CN112574117A (en) 2021-03-30
CN112574117B true CN112574117B (en) 2022-09-20

Family

ID=75120181

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010996969.4A Active CN112574117B (en) 2019-09-29 2020-09-21 Preparation method of glufosinate intermediate and analogue

Country Status (1)

Country Link
CN (1) CN112574117B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2022407771A1 (en) * 2021-12-10 2024-06-20 Basf Se Enzymatic decarbamoylation of glufosinate derivatives
CA3240053A1 (en) * 2021-12-10 2023-06-15 Klaus Ditrich Synthesis of glufosinate using a hydantoinase-based process
WO2023232225A1 (en) * 2022-05-31 2023-12-07 Evonik Operations Gmbh Enzymatic method for the diastereoselective production of l-glufosinate p-esters

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101481336A (en) * 2009-01-19 2009-07-15 南昌大学 Preparation of N-carbamoyl-aminoglutaric acid and sodium salt thereof
CN103980163B (en) * 2014-05-30 2015-07-08 南京工业大学 Method for continuously synthesizing N-carbamylglutamic acid by using micro-channel reactor

Also Published As

Publication number Publication date
CN112574117A (en) 2021-03-30

Similar Documents

Publication Publication Date Title
CN112574117B (en) Preparation method of glufosinate intermediate and analogue
CN113490671B (en) Preparation method of glufosinate-ammonium
CN111662324B (en) Method for preparing L-glufosinate-ammonium
CN114585631A (en) Process for preparing L-glufosinate intermediates
WO2014049512A2 (en) Novel process for preparation of azilsartan medoxomil
CN113402424A (en) Synthetic method of cyanoacrylate compound
CN101412733B (en) Preparation of N-alkyl thiophosphoryl triamide by one-pot method
CN112574120A (en) Method for preparing chlorohydantoin derivative
CN112574119B (en) Process for preparing hydantoin derivatives
CN112574116B (en) Method for preparing glufosinate intermediate and analogue
CN112574118B (en) Process for preparing glufosinate-hydantoin intermediates and analogues
US6320057B1 (en) Intermediates for the preparation of 2-imidazoline-5-ones
CA3200300A1 (en) Preparation method for glufosinate-ammonium
Stanoeva et al. Synthesis and Plant Growth Regulating Activity of New Triazolo-and Pyrazolopyrimidine Derivatives Of Aminomethyl, Aminoalkyloxymethyl Dimethylphosphine Oxides and (Aminomethane) Phosphonic Acid Esters
CN115279746A (en) Process for preparing arthropodicidal anthranilamide compounds
CN104829592B (en) The synthetic method of 4 piperidyl 1H pyrroles, 3 Carbox amide hydrochloride
CN112679437B (en) Process for preparing chlorohydantoin derivatives
KR870000523B1 (en) Process for preparing pyrazole herbicide
KR960001477B1 (en) Improved process for the preparation of benzo(chalcogeno)
JPS5888396A (en) Manufacture of aminomethylphosphonic acid
Vasilevskii et al. Synthesis of new fungicidal biphenyl derivatives of 4, 5-dichloroisothiazole-3-carboxylic acid
Ivonin et al. Phosphorylation of 5‐substituted furfurals
CN111606902A (en) Ester pyrazole bithiazole amine compound and preparation method and application thereof
RU2300527C1 (en) Method for preparing n-substituted derivatives of 4,6-dimethyl-3-cyanopyridyl-2-sulfonylamides
CN117510537A (en) Preparation method of L-glufosinate or salt thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant