CN111662325A - Method for preparing L-glufosinate-ammonium - Google Patents
Method for preparing L-glufosinate-ammonium Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- ONRKUGHFZWYUJP-UHFFFAOYSA-N methylphosphane dihydrochloride Chemical compound Cl.Cl.PC ONRKUGHFZWYUJP-UHFFFAOYSA-N 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 claims description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000006462 rearrangement reaction Methods 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 6
- IAJOBQBIJHVGMQ-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid Chemical compound CP(O)(=O)CCC(N)C(O)=O IAJOBQBIJHVGMQ-UHFFFAOYSA-N 0.000 description 12
- 239000005561 Glufosinate Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- -1 alkaline earth metal carbonates Chemical class 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005562 Glyphosate Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000010170 biological method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 2
- 229940097068 glyphosate Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 125000004114 N(2)-glutamino group Chemical group 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- 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
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- 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)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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 known as glufosinate-ammonium, having the chemical name 4- [ hydroxy (methyl) phosphono-yl]-L-homoalanine, the structural formula is shown as follows, and the molecular formula is C5H12NO4P, 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; melting point 214-216 ℃ CAS number 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 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 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 (250mL) are added into a 500mL three-necked flask, the mixture is heated to the internal temperature of 100 ℃ for reaction for 8 hours, MS (Mass Spectrometry) detects that raw materials disappear, the mixture is cooled to room temperature, 36% HCl (200mL, 2.36mol) is added dropwise, the mixture is heated and stirred to the internal temperature of 90 ℃ for reaction for 6 hours, the mixture is cooled to the room temperature, water is dried by spinning to obtain a white solid, the white solid is washed by ethanol (150mL x 3), and the white solid is dried to obtain 163.2g of 5- (2-hydroxyethyl) imidazolidine-2, 4-diketone, the yield is 96%, the ee value is 90% and the HPLC purity is 97.5%.
MS(ESI):m/z[M+H]+calcd for C5H9N2O3:145.06；found:146.3.
1H NMR(D2O,400MHz)：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).
13C NMR(D2O,400MHz)：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 100-200 ℃.
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 better catalytic effect, wherein the better catalyst is elementary iodine.
In the step (b), the catalyst is used in an amount of 1 to 10 wt% 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)2HCl or H2SO4。
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 (120mL) in a nitrogen atmosphere, adding 1.2g of granular iodine simple substance, heating to 150 ℃, and stirring for reaction until the raw materials react completely. 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 18 wt% aqueous HCl (39mL) and heated at reflux until the starting material disappeared. 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. Adding 36% HCl to adjust the pH value of the system to 5-6, distilling the solvent under reduced pressure, and then recrystallizing with ethanol to obtain 9.6g (ee value is 85%) of the target product L-glufosinate-ammonium with a molar yield of 95% based on the compound (4).
Example 2
The process of example 1 was followed while varying the type of base, the type of solvent and the reaction temperature in step (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 procedure 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 (10)
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 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.
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 or organic base, preferably triethylamine, diethylisopropylamine, n-butylamine, pyridine, picoline, more preferably triethylamine.
4. A method according to any one of claims 1-3, characterized in that: in the step (a), the reaction is carried out in a solvent selected from an ether solvent, an amide solvent, a halogenated alkane solvent or a benzene solvent, preferably any one or more selected from trimethylbenzene, xylene, toluene, tetrahydrofuran, N-dimethylformamide and 1, 2-dichloroethane.
5. The method according to any one of claims 1 to 4, characterized in that: in the step (a), the reaction temperature is-40 to 40 ℃, preferably-10 to-20 ℃.
6. A method according to claim 1 or 2, characterized in that: in the step (b), the reaction temperature is 100-200 ℃.
7. The method according to any one of claims 1,2 or 6, 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, and the elementary iodine is preferred.
8. The method according to any one of claims 1,2, 6 or 7, characterized in that: in step (b), the reaction is carried out in a benzene-based solvent, preferably any one or more of toluene, xylene and trimethylbenzene.
9. A compound represented by the formula (III) or a salt thereof, or a stereoisomer of the compound or a salt thereof
10. A compound of formula (IV) or a salt thereof, or a stereoisomer of the compound or a salt thereof
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| CN113480573A (en) * | 2021-06-21 | 2021-10-08 | 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 |
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