CN114989213A - Preparation method of L-glufosinate-ammonium or salt thereof - Google Patents
Preparation method of L-glufosinate-ammonium or salt thereof Download PDFInfo
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- CN114989213A CN114989213A CN202210639489.1A CN202210639489A CN114989213A CN 114989213 A CN114989213 A CN 114989213A CN 202210639489 A CN202210639489 A CN 202210639489A CN 114989213 A CN114989213 A CN 114989213A
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- 150000003839 salts Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 239000000376 reactant Substances 0.000 claims abstract description 11
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- RQVLGLPAZTUBKX-VKHMYHEASA-N L-vinylglycine Chemical group C=C[C@H](N)C(O)=O RQVLGLPAZTUBKX-VKHMYHEASA-N 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 25
- 239000003999 initiator Substances 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- 150000003254 radicals Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 5
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- WPPLKRDOKPISSC-UHFFFAOYSA-N pentyl 2,2-dimethylpropaneperoxoate Chemical compound CCCCCOOC(=O)C(C)(C)C WPPLKRDOKPISSC-UHFFFAOYSA-N 0.000 claims description 3
- OPQYOFWUFGEMRZ-UHFFFAOYSA-N tert-butyl 2,2-dimethylpropaneperoxoate Chemical compound CC(C)(C)OOC(=O)C(C)(C)C OPQYOFWUFGEMRZ-UHFFFAOYSA-N 0.000 claims description 3
- AQKYLAIZOGOPAW-UHFFFAOYSA-N 2-methylbutan-2-yl 2,2-dimethylpropaneperoxoate Chemical compound CCC(C)(C)OOC(=O)C(C)(C)C AQKYLAIZOGOPAW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- NMOALOSNPWTWRH-UHFFFAOYSA-N tert-butyl 7,7-dimethyloctaneperoxoate Chemical compound CC(C)(C)CCCCCC(=O)OOC(C)(C)C NMOALOSNPWTWRH-UHFFFAOYSA-N 0.000 claims description 2
- QEQBMZQFDDDTPN-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy benzenecarboperoxoate Chemical compound CC(C)(C)OOOC(=O)C1=CC=CC=C1 QEQBMZQFDDDTPN-UHFFFAOYSA-N 0.000 claims 1
- ZIDNXYVJSYJXPE-UHFFFAOYSA-N 2-methylbutan-2-yl 7,7-dimethyloctaneperoxoate Chemical compound CCC(C)(C)OOC(=O)CCCCCC(C)(C)C ZIDNXYVJSYJXPE-UHFFFAOYSA-N 0.000 claims 1
- 150000002978 peroxides Chemical class 0.000 claims 1
- 239000002994 raw material Substances 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 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 9
- HGXJDMCMYLEZMJ-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy 2,2-dimethylpropaneperoxoate Chemical compound CC(C)(C)OOOC(=O)C(C)(C)C HGXJDMCMYLEZMJ-UHFFFAOYSA-N 0.000 description 8
- 229940126214 compound 3 Drugs 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 229940125782 compound 2 Drugs 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- -1 tert-butyl peroxypivalate free radical Chemical class 0.000 description 4
- 239000005561 Glufosinate Substances 0.000 description 3
- 239000005562 Glyphosate Substances 0.000 description 3
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 3
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 3
- 229940097068 glyphosate Drugs 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010170 biological method Methods 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 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 2
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 2
- RAWISQFSQWIXCW-UHFFFAOYSA-N 2-methylbutan-2-yl 2,2-dimethyloctaneperoxoate Chemical compound CCCCCCC(C)(C)C(=O)OOC(C)(C)CC RAWISQFSQWIXCW-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- UYQVCLAMCWIBKC-UHFFFAOYSA-N OOP(=O)(OC)CCC(N)C(=O)O Chemical compound OOP(=O)(OC)CCC(N)C(=O)O UYQVCLAMCWIBKC-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 231100000674 Phytotoxicity Toxicity 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- GINJFDRNADDBIN-FXQIFTODSA-N bilanafos Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCP(C)(O)=O GINJFDRNADDBIN-FXQIFTODSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 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
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)
Abstract
The invention discloses a preparation method of L-glufosinate-ammonium or salt thereof, which comprises the following steps: reacting the reactant X with a compound with a structure shown as a formula (III), and performing hydrolysis reaction on the obtained product to obtain the L-glufosinate-ammonium or the salt thereof no matter whether the intermediate is separated or not. The reactant X is (S) -2-amino-3-butenoic acid and/or derivatives thereof, and is specifically selected from at least one of compounds with the structures shown as formulas (II-1), (II-2) or (II-3).
R 1 Is H, Ac, -CO 2 Me or-CO 2 Et，R 2 Is H or C1-C5 alkyl, R 3 Is NH 4 Or C1-C5 alkyl.
Description
Technical Field
The invention relates to the technical field of pesticide synthesis, and particularly relates to a preparation method of L-glufosinate-ammonium or salt thereof.
Background
Glufosinate (also known as bialaphos, glufosinate, trade names including baustda, bushattan, etc., known as phosphinothricin, and chemical name 2-amino-4- [ hydroxy (methyl) phosphono ] butanoic acid) is a herbicide resistant to the second largest transgenic crop in the world.
Glufosinate, a class of phosphonic acid herbicides, is a glutamine synthetase inhibitor, a non-selective (biocidal) contact-type herbicide.
At present, three herbicides in the world are paraquat, glyphosate and glufosinate-ammonium respectively.
Due to the long-term use of glyphosate, a large amount of weeds generate resistance, and the glyphosate tends to lose efficacy; due to its virulent characteristics, paraquat is forbidden or restricted in more and more countries worldwide; at present, the glufosinate-ammonium has excellent weeding performance and small phytotoxicity side effect although the yield is small, and therefore the glufosinate-ammonium has great market potential in a future period.
The glufosinate-ammonium has two optical isomers, namely L-glufosinate-ammonium and D-glufosinate-ammonium, but only L-type glufosinate-ammonium has herbicidal activity, is easy to decompose in soil, has low toxicity to human and animals, has a wide herbicidal spectrum, and has low destructive power to the environment.
At present, the preparation method 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 biological method for synthesizing the L-glufosinate-ammonium mainly comprises a protease method, an enzyme-catalyzed D/L conversion method and the like, and the methods often have the defects of high purification difficulty, poor substrate tolerance and the like.
Patent specification No. CN111793085A discloses a chemical method for preparing L-glufosinate, but since the raw material (formula II) is difficult to be dissolved in common organic solvents and is itself a dimer, both double bonds need to react until the reaction is complete, so a higher reaction temperature (above 90 ℃ to have a considerable yield) is required, but the high temperature easily causes racemization of the raw material, and is not conducive to obtaining L-glufosinate with high ee value, so this method is not suitable for industrial production:
further, it is found from the detailed embodiment of the above patent art that the use of t-butyl peroxypivalate as an initiator in the reaction system is not optimal and the yield is not the highest. In fact, even the same initiator may show significant effect difference in different reaction systems, which needs to be determined after experimental exploration.
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
Aiming at the technical problems, the invention provides a preparation method of L-glufosinate-ammonium or salt thereof, which adopts brand-new reaction raw materials, can obtain considerable yield and ee value at lower temperature (such as 75 ℃), reduces reaction temperature and energy consumption, improves operation safety and production efficiency, and is very suitable for industrial practical application.
A method for preparing L-glufosinate-ammonium or a salt thereof, wherein the structure of the L-glufosinate-ammonium is shown as the following formula (I):
the preparation method comprises the following steps:
1) reacting the reactant X with a compound having the structure shown in the following formula (III):
in the formula (III), R 3 Is NH 4 Or C1-C5 alkyl;
the reactant X is (S) -2-amino-3-butenoic acid and/or derivatives thereof, and is specifically selected from at least one of compounds with the following structures (II-1), (II-2) or (II-3):
in the formula (II-1), R 1 Is H, Ac, -CO 2 Me or-CO 2 Et，R 2 H or C1-C5 alkyl;
2) whether the intermediate is separated or not, the product obtained in the step 1) is subjected to hydrolysis reaction to obtain the L-glufosinate-ammonium or the salt thereof.
The compound with the structure shown as the formula (II-1) can be prepared according to the method described in the literature (such as org. biomol. chem.2015, Volume 13, Issue 48, Pages 11602-11606); the compounds represented by the formulae (II-2) and (II-3) can be prepared from the compounds represented by the formula (II-1) by the methods described in references such as Angewandte Chemie, International Edition (2018),57(35), 11389-9493 and Synlett (2018),29(7), 943-948.
In a preferred embodiment, in the preparation method of L-glufosinate-ammonium or salt thereof, in the step 1), R 1 Is H, R 2 Is H, R 3 Is C1-C5 alkyl.
In the preparation method of the L-glufosinate-ammonium or the salt thereof, in the step 1), the reaction temperature is preferably 50-150 ℃, more preferably 75-110 ℃, and relatively high yield and ee value can be obtained.
In a preferred embodiment, in the preparation method of L-glufosinate-ammonium or a salt thereof, in the step 1), the molar ratio of the reactant X to the compound represented by the formula (III) is 1: 1-8.
The process for the preparation of L-glufosinate-ammonium or a salt thereof according to step 1), wherein the reaction is preferably carried out in the presence of at least one free-radical initiator;
the free radical initiator is selected from dibenzoyl peroxide and a compound with the structure shown as the following formula (IV);
in the formula (IV):
R 4 is methyl, ethyl, 2-dimethylpropyl or phenyl;
R 5 is H, phenyl or C1-C10 alkane, preferably phenyl or C1-C6 alkane, more preferably phenyl or C1-C4 alkane.
Further, the radical initiator is preferably selected from dibenzoyl peroxide, tert-butyl peroxypivalate, amyl peroxypivalate, tert-butyl peroxyneodecanoate, 1,3, 3-tetramethyl tert-butyl peroxyneodecanoate, tert-amyl peroxypivalate, 1,3, 3-tetramethyl butyl peroxy2-ethylacetate, tert-amyl peroxyneodecanoate, 1-dimethyl-3-hydroxybutyl peroxyneoheptanoate, and tert-butyl peroxybenzoate.
Further, the radical initiator is preferably selected from dibenzoyl peroxide, tert-butyl peroxypivalate, amyl peroxypivalate, 1-dimethyl-3-hydroxybutyl peroxypivalate, and tert-butyl peroxybenzoate.
Most preferably, the free radical initiator is t-butyl peroxypivalate.
The research of the invention finds that the final yield of the L-glufosinate-ammonium or the salt thereof can reach not less than 89% and the ee value is not less than 98% under the condition that the reactant X exists in the tert-butyl peroxypivalate free radical initiator and the reaction temperature is 75 ℃, the reaction condition is milder and safer, and the yield and the ee value of the product are higher.
In a preferred embodiment, in the method for preparing L-glufosinate-ammonium or the salt thereof, the molar ratio of the reactant X to the radical initiator is 1-200: 1.
In a preferred embodiment, in the method for preparing L-glufosinate-ammonium or the salt thereof, in the step 2), the hydrolysis reaction is performed in the presence of an inorganic acid and/or an organic acid.
The inorganic acid is preferably hydrochloric acid, sulfuric acid and/or phosphoric acid.
In a preferred embodiment, in the preparation method of L-glufosinate-ammonium or a salt thereof, in the step 2), the temperature of the hydrolysis reaction is 20 to 130 ℃.
Compared with the prior art, the invention has the main advantages that:
the preparation method of the L-glufosinate-ammonium or the salt thereof has the advantages of easily obtained raw materials, mild conditions, high yield, high ee value, convenient continuous operation and easy industrial production.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The following examples are conducted under conditions not specified, usually according to conventional conditions, or according to conditions recommended by the manufacturer.
Example 1
(1) Synthesis of Compound 1
Under the protection of nitrogen, compound 2(10.1g,1.0eq) and compound 3(27.2g,2.0eq) were added to a reaction flask, stirred for 10 minutes, heated to 75 ℃, and initiator tert-butyl peroxypivalate (1g,0.05eq) was slowly added dropwise, the reaction was continued at this temperature until GC showed disappearance of the starting compound 2, and excess starting compound 3 was distilled off under reduced pressure to give the intermediate crude compound 1(24.3g), with a yield of about 96.3% and an ee value of 98%, and the next step was carried out without purification.
Other common initiators (0.05eq) were screened as described above and the results are shown in Table 1.
TABLE 1
| Initiator | Yield (%) | ee value (%) |
| Diphenyl formyl peroxide | 85 | 99 |
| Perneoheptanoic acid 1, 1-dimethyl-3-hydroxybutyl ester | 90 | 92 |
| Peroxybenzoic acid tert-butyl ester | 80 | 85 |
| Peroxypivalic acid amyl ester | 93 | 95 |
| Azobisisobutyronitrile (AIBN) | 54 | 80 |
It can be seen that in the preparation of compound 1 of the present invention, the most preferred initiator is tert-butyl peroxypivalate, and the product yield and ee value are relatively best.
(2) Synthesis of L-glufosinate-ammonium
And (3) dissolving the crude product in 30% industrial hydrochloric acid (50g,4eq), heating and refluxing for about 10 hours, wherein LC shows that the raw material completely reacts, evaporating excess acid water under reduced pressure, adding ethanol for recrystallization to obtain 19.8g of L-glufosinate-ammonium hydrochloride, and after mother liquor is recycled, the total yield of two steps is about 93%, and the ee value is 98%.
Example 2
(1) Synthesis of Compound 4
Adding the compound 5(12.7g,1.0eq) and the compound 3(27.2g,2.0eq) into a reaction flask under the protection of nitrogen, stirring for 10 minutes, heating to 75 ℃, slowly adding an initiator tert-butyl peroxypivalate (1g,0.05eq) dropwise, continuing to react at the temperature until GC shows that the raw material compound 5 disappears, and distilling under reduced pressure to remove the excessive raw material compound 3 to obtain an intermediate crude product compound 4(26.0g), wherein the yield is about 92 percent, the ee is 99 percent, and the next operation can be directly carried out without purification.
(2) Synthesis of L-glufosinate-ammonium
And (3) dissolving the crude product in 30% industrial hydrochloric acid (50g,4eq), heating and refluxing for about 15 hours, wherein LC shows that the raw material completely reacts, evaporating excess acid water under reduced pressure, adding ethanol for recrystallization to obtain 18.3g of L-glufosinate-ammonium hydrochloride, and after mother liquor is recycled, the total yield of the two steps is about 89%, and the ee value is 99%.
Example 3
(1) Synthesis of Compound 6
Adding the compound 7(12.6g,1.0eq) and the compound 3(27.2g,2.0eq) into a reaction flask under the protection of nitrogen, stirring for 10 minutes, heating to 75 ℃, slowly adding an initiator tert-butyl peroxypivalate (1g,0.05eq) dropwise, continuing to react at the temperature until GC shows that the raw material compound 7 disappears, and distilling under reduced pressure to remove the excessive raw material compound 3 to obtain an intermediate crude product compound 6(26.2g), wherein the yield is about 93 percent, the ee is 99 percent, and the next operation can be directly carried out without purification.
(2) Synthesis of L-glufosinate-ammonium
And (3) dissolving the crude product in 30% industrial hydrochloric acid (50g,4eq), heating and refluxing for about 15 hours, wherein LC shows that the raw material completely reacts, evaporating excess acid water under reduced pressure, adding ethanol for recrystallization to obtain 18.8g of L-glufosinate-ammonium hydrochloride, and after mother liquor is recycled, the total yield of two steps is about 91%, and the ee value is 99%.
Example 4
(1) Synthesis of Compound 1
Under the protection of nitrogen, adding a compound 2(10.1g,1.0eq) and a compound 3(27.2g,2.0eq) into a reaction bottle, stirring for 10 minutes, heating to 110 ℃, slowly adding an initiator tert-butyl peroxypivalate (1g,0.05eq) dropwise, continuing to react at the temperature until GC shows that the raw material compound 2 disappears, and distilling under reduced pressure to remove the excessive raw material compound 3 to obtain an intermediate crude product compound 1(24.0g), wherein the yield is about 90%, the ee is 91%, and the next operation is directly carried out without purification.
(2) Synthesis of L-glufosinate-ammonium
And (3) dissolving the crude product in 30% industrial hydrochloric acid (50g,4eq), heating and refluxing for about 10 hours, wherein LC shows that the raw materials completely react, evaporating excess acid water under reduced pressure, adding ethanol for recrystallization to obtain 16.6g of L-glufosinate-ammonium hydrochloride, and after mother liquor is recovered and reused, the total yield of the two steps is about 85%, and the ee value is 90%.
Example 5
(1) Synthesis of Compound 8
Under the protection of nitrogen, compound 2(10.1g,1.0eq) and compound 9(21.6g,2.0eq) were added to a reaction flask, stirred for 10 minutes, heated to 75 ℃, and initiator tert-butyl peroxypivalate (1g,0.05eq) was slowly added dropwise, the reaction was continued at this temperature until GC showed disappearance of starting compound 2, and excess starting compound 9 was distilled off under reduced pressure to give intermediate crude compound 8(24.0g), with a yield of about 91% and ee of 96%, which was directly subjected to the next step without purification.
(2) Synthesis of L-glufosinate-ammonium
And (3) dissolving the crude product in 30% industrial hydrochloric acid (50g,4eq), heating and refluxing for about 10 hours, wherein LC shows that the raw materials completely react, evaporating excess acid water under reduced pressure, adding ethanol for recrystallization to obtain 17.1g of L-glufosinate-ammonium hydrochloride, and after mother liquor is recycled, the total yield of the two steps is about 89%, and the ee value is 98%.
Furthermore, it should be understood that various changes or modifications can be made by those skilled in the art after reading the above description of the present invention, and equivalents also fall within the scope of the invention defined by the appended claims.
Claims (9)
1. A method for preparing L-glufosinate-ammonium or a salt thereof, wherein the structure of the L-glufosinate-ammonium is shown as the following formula (I):
the preparation method is characterized by comprising the following steps:
1) reacting the reactant X with a compound having the structure shown in the following formula (III):
in the formula (III), R 3 Is NH 4 Or C1-C5 alkyl;
the reactant X is (S) -2-amino-3-butenoic acid and/or derivatives thereof, and is specifically selected from at least one of compounds with the following structures (II-1), (II-2) or (II-3):
in the formula (II-1), R 1 Is H, Ac, -CO 2 Me or-CO 2 Et，R 2 H or C1-C5 alkyl;
2) whether the intermediate is separated or not, the product obtained in the step 1) is subjected to hydrolysis reaction to obtain the L-glufosinate-ammonium or the salt thereof.
2. The method according to claim 1, wherein the reaction temperature in step 1) is 50 to 150 ℃.
3. The preparation method of claim 1, wherein in the step 1), the molar ratio of the reactant X to the compound having the structure shown in the formula (III) is 1: 1-8.
4. The process according to any one of claims 1 to 3, wherein in step 1), the reaction is carried out in the presence of at least one radical initiator;
the free radical initiator is selected from dibenzoyl peroxide and a compound with the structure shown as the following formula (IV);
in the formula (IV):
R 4 is methyl, ethyl, 2-dimethylpropyl or phenyl;
R 5 is H, phenyl or C1-C10 alkane.
5. The method according to claim 4, wherein the radical initiator is selected from the group consisting of dibenzoyl peroxide, t-butyl peroxypivalate, amyl peroxypivalate, t-butyl peroxyneodecanoate, 1,3, 3-tetramethyl t-butyl peroxyneodecanoate, t-amyl peroxypivalate, 1,3, 3-tetramethyl butyl 2-ethyl acetate peroxide, t-amyl peroxyneodecanoate, 1-dimethyl-3-hydroxybutyl peroxyneoheptanoate, and t-butyl peroxybenzoate.
6. The method according to claim 4, wherein the molar ratio of the reactant X to the radical initiator is 1 to 200: 1.
7. The method according to claim 1, wherein the hydrolysis reaction is carried out in the presence of an inorganic acid and/or an organic acid in the step 2).
8. The method according to claim 7, wherein the inorganic acid is hydrochloric acid, sulfuric acid and/or phosphoric acid.
9. The method according to claim 1 or 7, wherein the hydrolysis reaction is carried out at a temperature of 20 to 130 ℃ in the step 2).
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5530142A (en) * | 1988-05-27 | 1996-06-25 | Hoechst Aktiengesellschaft | Process for the preparation of phosphorus-containing L-amino acids and their esters and N-derivatives |
| CN102399240A (en) * | 2011-12-27 | 2012-04-04 | 江苏优士化学有限公司 | Improved synthesis method for glufosinate and analogue thereof |
| CN110386950A (en) * | 2019-07-18 | 2019-10-29 | 石家庄瑞凯化工有限公司 | A kind of synthetic method of glufosinate-ammonium ammonium salt |
| CN111793085A (en) * | 2019-04-04 | 2020-10-20 | 利尔化学股份有限公司 | Method for preparing L-glufosinate-ammonium |
| CN113264958A (en) * | 2014-05-13 | 2021-08-17 | 拜耳作物科学股份公司 | Process for preparing phosphorus-containing cyanohydrins |
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2022
- 2022-06-07 CN CN202210639489.1A patent/CN114989213A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5530142A (en) * | 1988-05-27 | 1996-06-25 | Hoechst Aktiengesellschaft | Process for the preparation of phosphorus-containing L-amino acids and their esters and N-derivatives |
| CN102399240A (en) * | 2011-12-27 | 2012-04-04 | 江苏优士化学有限公司 | Improved synthesis method for glufosinate and analogue thereof |
| CN113264958A (en) * | 2014-05-13 | 2021-08-17 | 拜耳作物科学股份公司 | Process for preparing phosphorus-containing cyanohydrins |
| CN111793085A (en) * | 2019-04-04 | 2020-10-20 | 利尔化学股份有限公司 | Method for preparing L-glufosinate-ammonium |
| CN110386950A (en) * | 2019-07-18 | 2019-10-29 | 石家庄瑞凯化工有限公司 | A kind of synthetic method of glufosinate-ammonium ammonium salt |
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