CN111662325B - Method for preparing L-glufosinate-ammonium - Google Patents
Method for preparing L-glufosinate-ammonium Download PDFInfo
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- CN111662325B CN111662325B CN202010138296.9A CN202010138296A CN111662325B CN 111662325 B CN111662325 B CN 111662325B CN 202010138296 A CN202010138296 A CN 202010138296A CN 111662325 B CN111662325 B CN 111662325B
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- 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 System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
Abstract
The invention relates to a method for preparing L-glufosinate-ammonium. Compared with the existing method, the method is a new route of chemical synthesis, has relatively simple steps, easily obtained raw materials and controllable cost, can obtain the L-glufosinate-ammonium product with high ee value without chiral catalysis, and has potential industrial application value.
Description
Technical Field
The invention relates to a method for preparing L-glufosinate-ammonium.
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. Glufosinate includes L-glufosinate-ammonium and racemic DL-type glufosinate-ammonium, wherein the herbicidal activity of L-glufosinate-ammonium is twice as high as that of racemic DL-type glufosinate-ammonium. The glufosinate preparation sold in the market at present is generally racemic DL-type glufosinate, and if the glufosinate product can be used in a pure chemical isomer form with an L-configuration, the using amount of the glufosinate can be reduced by about 50%, so that the glufosinate preparation has very important significance for improving atom economy, reducing use cost and relieving environmental pressure.
L-glufosinate-ammonium, also called glufosinate-ammonium, with the chemical name 4- [ hydroxy (methyl) phosphono- ] -phosphine]-L-homoalanine, the structural formula is shown as follows, and the molecular formula is C 5 H 12 NO 4 P, molecular weight 181.1; the refined glufosinate-ammonium is easy to dissolve in water, not easy to dissolve in an organic solvent and stable to light; the melting point is 214-216 ℃ and the CAS number is 35597-44-5. The glufosinate-ammonium is a broad-spectrum biocidal herbicide, has the advantages of high efficiency, low toxicity, easy degradation, safe and convenient use and the like, and has better weeding effect on annual and perennial dicotyledonous and gramineous weeds.
The existing preparation process of L-glufosinate-ammonium mainly comprises a chemical method and a biological method. The chemical synthesis of L-glufosinate-ammonium mainly comprises a chiral auxiliary agent induction method, a racemate resolution method, an asymmetric synthesis method and the like, but the methods face the problems of complex synthesis route, low yield or/and expensive chiral resolution reagent, and the high-efficiency industrial production or the large industrial application value is difficult to realize. The method for synthesizing the L-glufosinate-ammonium by the biological method mainly comprises a protease method, an amino acid dehydrogenase method, a transaminase method and the like, and the methods often have the defects of low optical purity of products, high separation difficulty or/and poor substrate tolerance and the like, and have relatively low industrial application value. Therefore, the development of the L-glufosinate-ammonium synthesis process which has the advantages of relatively simple steps, easily obtained raw materials, controllable cost and potential industrial application value has very important significance.
Disclosure of Invention
In order to solve the above problems, the present invention provides a process for producing L-glufosinate-ammonium (I) or a salt thereof,
the method comprises the following steps:
(a) Reacting a compound represented by the formula (II) or a salt thereof
Reacting with methyl phosphine dichloride to convert into a compound shown as a formula (III) or a salt thereof
(b) Subjecting the obtained compound represented by the formula (III) or a salt thereof to an Arbuzov rearrangement reaction to convert the compound into a compound represented by the formula (IV) or a salt thereof
And (c) a second step of,
(c) Subjecting the obtained compound of formula (IV) or a salt thereof to hydrolysis reaction to obtain a compound of formula (V) or a salt thereof
And the number of the first and second groups,
(d) Hydrolyzing the obtained compound represented by the formula (V) or a salt thereof to obtain a compound represented by the formula (I) or a salt thereof.
The compound (II) can be prepared according to the existing route, or can be prepared by a two-step reaction using L-homoserine with low cost as a starting material according to the following specific embodiment, with a yield of 90% or more, for example:
l-homoserine (140g, 1.18mol), urea (85.5g, 1.42mol), and water (250 mL) were charged into a 500mL three-necked flask, heated to an internal temperature of 100 ℃ for reaction for 8 hours, MS-detected starting materials were disappeared, cooled to room temperature, 36% HCl (200mL, 2.36mol) was added dropwise, heated with stirring to an internal temperature of 90 ℃ for reaction for 6 hours, cooled to room temperature, and water was spin-dried to obtain a white solid, and the white solid was washed with ethanol (150mL. Times.3) and dried to obtain 5- (2-hydroxyethyl) imidazolidine-2, 4-dione 163.2g, yield 96%, ee value 90%, and HPLC purity 97.5%.
MS(ESI):m/z[M+H]+calcd for C5H9N2O3:145.06；found:146.3.
1H NMR(D2O,400MHz)δ：4.22(dd,J＝8.0,4.0Hz,1H),3.72–3.50(m,2H),1.97(dtd,J＝14.4,6.0,4.8Hz,1H),1.87(dtd,J＝14.4,7.2,6.0Hz,1H).
13 C NMR(D 2 O,400MHz)δ：179.0,159.3,57.4,56.2,32.7.
In the step (a), the molar weight ratio of the compound represented by the formula (II) or a salt thereof to the methyl phosphine dichloride is not less than 2.
In the step (a), the aforementioned reaction may be carried out in the presence of an inorganic base or an organic base. The inorganic base may be selected from alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal hydrogencarbonates, alkaline earth metal hydrogencarbonates, alkali metal acetates or ammonia. In a specific embodiment, the organic base is selected from triethylamine, diethylisopropylamine, tri-n-butylamine, pyridine, picoline, and more preferably triethylamine.
In the step (a), the reaction may be carried out in a suitable solvent, and the solvent may be selected from an ether solvent, an amide solvent, a haloalkane solvent, or a benzene solvent. In a specific embodiment, the solvent is selected from the group consisting of trimethylbenzene, xylene, toluene, tetrahydrofuran, N-dimethylformamide, and 1, 2-dichloroethane, with trimethylbenzene being a more preferred solvent.
In the step (a), the temperature of the reaction is-40 to 40 ℃, preferably-10 to-20 ℃.
In the step (b), the temperature of the reaction is 100 to 200 ℃.
In the step (b), a catalyst may be additionally added to the reaction, and the catalyst is elementary iodine or an iodine-containing compound, for example, the reaction is carried out under the catalysis of elementary iodine, potassium iodide, sodium iodide, methyl iodide or ethyl iodide, and it is found that the inorganic catalyst has a relatively good catalytic effect, wherein the relatively good catalyst is elementary iodine.
In the step (b), the catalyst is used in an amount of 1 to 10wt% based on the compound represented by the formula (III) or a salt thereof.
In step (b), the aforementioned reaction is carried out in a benzene-based solvent, preferably any one or more of toluene, xylene and trimethylbenzene.
In step (c), the hydrolysis may be carried out using a mineral acid, in particular embodiments, selected from hydrochloric acid or sulfuric acid.
In step (d), hydrolysis with alkali or mineral acid may be employed. In a particular embodiment, the base or mineral acid is selected from NaOH, KOH, ba (OH) 2 HCl or H 2 SO 4 。
The present invention still further provides a compound represented by the formula (III) or a salt thereof, or a stereoisomer of the compound or a salt thereof
The present invention still further provides a compound of formula (IV) or a salt thereof, or a stereoisomer of the compound or a salt thereof
Compared with the existing L-glufosinate-ammonium synthesis route, the method is a new route for chemical synthesis, has relatively simple steps, easily obtained raw materials and controllable cost, can obtain the L-glufosinate-ammonium product with high ee value without chiral catalysis, and has potential industrial application value.
Detailed Description
Example 1
(1) Synthesis of Compound 2
Under a nitrogen atmosphere, 27.1g (ee value 90%) of the compound (1), 38.1g of triethylamine and 100mL of trimethylbenzene were added to a three-necked flask, the mixture was cooled to-20 ℃, 10g of methyl phosphine dichloride was added dropwise thereto, the mixture was stirred and reacted at-20 ℃, the reaction solution was monitored by Ms until the reaction of the raw materials was completed, and then trimethylbenzene and triethylamine were distilled off under reduced pressure to obtain 28.1g of a crude compound (2) in a molar yield of 90% based on the compound (1). The crude compound (2) was used in the next step without further purification.
(2) Synthesis of Compound 3
Dissolving the compound (2) in trimethylbenzene (120 mL) in a nitrogen atmosphere, adding 1.2g of granular iodine simple substance, heating to 150 ℃, and stirring for reaction until the raw materials are completely reacted. Trimethylbenzene was distilled off under reduced pressure and recrystallized from ethyl acetate to obtain 25.6g of the compound (3) in a yield of 91% by mole based on the compound (2).
(3) Synthesis of L-glufosinate-ammonium
Compound (3) was dissolved in 18wt% aqueous HCl (39 mL), and the mixture was heated under reflux until the disappearance of the starting material. The solvent was distilled off under reduced pressure and recrystallized twice from methanol to give compound (4) in a molar yield of 92.4% based on compound (3).
The mother liquors were combined and distilled under reduced pressure to recover compound (1).
11.5g of the compound (4) was dissolved in water, and 2.7g of sodium hydroxide was added thereto, followed by heating to reflux until the starting material disappeared. 36% of HCl was added to adjust the system pH to 5 to 6, the solvent was distilled off under reduced pressure, and then recrystallization was carried out with ethanol to obtain 9.6g (ee value: 85%) of the objective product L-glufosinate-ammonium in a molar yield of 95% based on the compound (4).
Example 2
The alkali type, solvent type and reaction temperature in step (1) were varied according to the procedure of example 1, and the results are shown in Table 1 below.
The molar yield in the table is the molar yield of the compound (2) based on the compound (1).
TABLE 1
Example 3
The catalyst type, solvent type and reaction temperature in step (2) were varied according to the method of example 1, and the results are shown in table 2 below.
The molar yield in the table is the molar yield of the compound (3) based on the compound (2).
TABLE 2
Claims (21)
1. A process for the preparation of L-glufosinate-ammonium (I) or a salt thereof,
the method is characterized in that: the method comprises the following steps:
(a) Reacting a compound represented by the formula (II) or a salt thereof
Reacting with methyl phosphine dichloride to convert into a compound shown as a formula (III) or a salt thereof
(b) Subjecting the obtained compound represented by the formula (III) or a salt thereof to an Arbuzov rearrangement reaction to convert the compound into a compound represented by the formula (IV) or a salt thereof
And the number of the first and second groups,
(c) Subjecting the obtained compound of formula (IV) or a salt thereof to hydrolysis reaction to obtain a compound of formula (V) or a salt thereof
And (c) a second step of,
(d) Hydrolyzing the obtained compound represented by the formula (V) or a salt thereof to obtain a compound represented by the formula (I) or a salt thereof.
2. A method according to claim 1, characterized in that: in the step (a), the molar weight ratio of the compound represented by the formula (II) or a salt thereof to the methyl phosphine dichloride is not less than 2.
3. A method according to claim 1 or 2, characterized in that: in step (a), the reaction is carried out in the presence of an inorganic base or an organic base.
4. A method according to claim 3, characterized in that: in step (a), the organic base is selected from triethylamine, diethylisopropylamine, n-butylamine, pyridine and picoline.
5. The method according to claim 4, characterized in that: in step (a), the organic base is selected from triethylamine.
6. A method according to claim 1 or 2, characterized in that: in the step (a), the reaction is carried out in a solvent, and the solvent is selected from an ether solvent, an amide solvent, a halogenated alkane solvent or a benzene solvent.
7. The method according to claim 6, characterized in that: in the step (a), the reaction is carried out in any one or more of trimethylbenzene, xylene, toluene, tetrahydrofuran, N-dimethylformamide and 1, 2-dichloroethane.
8. A method according to claim 3, characterized in that: in the step (a), the reaction is carried out in a solvent, and the solvent is selected from an ether solvent, an amide solvent, a halogenated alkane solvent or a benzene solvent.
9. The method of claim 8, wherein: in the step (a), the reaction is carried out in any one or more of trimethylbenzene, xylene, toluene, tetrahydrofuran, N-dimethylformamide and 1, 2-dichloroethane.
10. A method according to claim 1 or 2, characterized in that: in the step (a), the reaction temperature is-40 ℃.
11. A method according to claim 10, characterized in that: in the step (a), the temperature of the reaction is-10 to-20 ℃.
12. A method according to claim 1 or 2, characterized in that: in the step (b), the reaction temperature is 100-200 ℃.
13. A method according to claim 1 or 2, characterized in that: in the step (b), the reaction is carried out under the catalysis of elementary iodine, potassium iodide, sodium iodide, methyl iodide or ethyl iodide.
14. The method of claim 13, wherein: in the step (b), the reaction is carried out under the catalysis of iodine.
15. The method of claim 12, wherein: in the step (b), the reaction is carried out under the catalysis of elementary iodine, potassium iodide, sodium iodide, methyl iodide or ethyl iodide.
16. The method of claim 15, wherein: in the step (b), the reaction is carried out under the catalysis of iodine.
17. The method according to any one of claims 1,2, 14 to 16, characterized in that: in step (b), the reaction is carried out in a benzene-based solvent.
18. The method of claim 17, wherein: in the step (b), the reaction is carried out in any one or more of toluene, xylene and trimethylbenzene.
19. The method of claim 12, wherein: in step (b), the reaction is carried out in a benzene-based solvent.
20. The method of claim 13, wherein: in step (b), the reaction is carried out in a benzene-based solvent.
21. A method according to claim 19 or 20, characterized in that: in the step (b), the reaction is carried out in any one or more of toluene, xylene and trimethylbenzene.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA3163462C (en) * | 2020-10-14 | 2023-02-28 | Yongjiang Liu | Method for preparing l-glufosinate |
| CN113045604B (en) * | 2021-04-13 | 2023-03-17 | 河北威远生物化工有限公司 | Synthesis method of glufosinate-ammonium |
| EP4105335A1 (en) | 2021-06-16 | 2022-12-21 | Evonik Operations GmbH | Enzymatic method for the production of l-glufosinate p-alkyl esters |
| CN113480573B (en) * | 2021-06-21 | 2023-08-15 | 上海七洲紫岳生物科技有限公司 | Crystal form of L-glufosinate-ammonium, preparation method and application thereof |
| EP4151643A1 (en) | 2021-09-16 | 2023-03-22 | Evonik Operations GmbH | Improved process for production of phosphoesters of glufosinate precursors |
| AR127934A1 (en) | 2021-12-10 | 2024-03-13 | Basf Se | SYNTHESIS OF GLUFOSINATE THROUGH THE USE OF A HYDANTHOINASE-BASED PROCESS |
| WO2023105079A1 (en) | 2021-12-10 | 2023-06-15 | Basf Se | Enzymatic decarbamoylation of glufosinate derivatives |
| WO2023105078A1 (en) | 2021-12-10 | 2023-06-15 | Basf Se | Herbicidal activity of alkyl phosphinates |
| WO2023174511A1 (en) | 2022-03-14 | 2023-09-21 | Evonik Operations Gmbh | Enzymatic method for the production of l-glufosinate p-esters |
| WO2023222227A1 (en) | 2022-05-19 | 2023-11-23 | Evonik Operations Gmbh | Enzymatic method for producing l-glufosinate |
| WO2023222226A1 (en) | 2022-05-19 | 2023-11-23 | Evonik Operations Gmbh | Enzymatic method for producing l-glufosinate |
| WO2023232225A1 (en) | 2022-05-31 | 2023-12-07 | Evonik Operations Gmbh | Enzymatic method for the diastereoselective production of l-glufosinate p-esters |
| CN115246857B (en) * | 2022-09-22 | 2022-12-13 | 山东新和成氨基酸有限公司 | Preparation method of L-glufosinate-ammonium |
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