CN115093339A - Synthetic method of L-glufosinate-ammonium intermediate - Google Patents
Synthetic method of L-glufosinate-ammonium intermediate Download PDFInfo
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- CN115093339A CN115093339A CN202210863447.6A CN202210863447A CN115093339A CN 115093339 A CN115093339 A CN 115093339A CN 202210863447 A CN202210863447 A CN 202210863447A CN 115093339 A CN115093339 A CN 115093339A
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- glufosinate
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- hydrogen chloride
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- 238000010189 synthetic method Methods 0.000 title claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 67
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 35
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000010438 heat treatment Methods 0.000 claims abstract description 23
- 238000004321 preservation Methods 0.000 claims abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 14
- 238000001816 cooling Methods 0.000 claims abstract description 13
- 238000005886 esterification reaction Methods 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000000926 separation method Methods 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 150000007513 acids Chemical class 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 230000002194 synthesizing effect Effects 0.000 claims description 17
- 239000012074 organic phase Substances 0.000 claims description 16
- 239000007789 gas Substances 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 claims 6
- XBKCXPRYTLOQKS-DFWYDOINSA-N [(3s)-2-oxooxolan-3-yl]azanium;chloride Chemical compound Cl.N[C@H]1CCOC1=O XBKCXPRYTLOQKS-DFWYDOINSA-N 0.000 abstract description 10
- 238000002425 crystallisation Methods 0.000 abstract 1
- 230000008025 crystallization Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 238000001308 synthesis method Methods 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- QJPWUUJVYOJNMH-UHFFFAOYSA-N alpha-amino-gamma-butyrolactone Natural products NC1CCOC1=O QJPWUUJVYOJNMH-UHFFFAOYSA-N 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 241000196324 Embryophyta Species 0.000 description 8
- -1 ammonium ions Chemical class 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 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 7
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 238000005660 chlorination reaction Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- QPOGJYQAKMZQQO-BYPYZUCNSA-N methyl (2S)-2-amino-4-chlorobutanoate Chemical compound COC([C@H](CCCl)N)=O QPOGJYQAKMZQQO-BYPYZUCNSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- HNXNVVLSHDIMHZ-YFKPBYRVSA-N CCOC(=O)[C@@H](N)CCCl Chemical compound CCOC(=O)[C@@H](N)CCCl HNXNVVLSHDIMHZ-YFKPBYRVSA-N 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229940125890 compound Ia Drugs 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- XBKCXPRYTLOQKS-UHFFFAOYSA-N (2-oxooxolan-3-yl)azanium;chloride Chemical compound Cl.NC1CCOC1=O XBKCXPRYTLOQKS-UHFFFAOYSA-N 0.000 description 2
- ZNUGAEVSKUIHIF-VKHMYHEASA-N (2S)-2-(bromoamino)-4-hydroxybutanoic acid Chemical compound BrN[C@@H](CCO)C(=O)O ZNUGAEVSKUIHIF-VKHMYHEASA-N 0.000 description 2
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- JIUHDQRXTPIQSV-VKHMYHEASA-N (2s)-2-amino-4-chlorobutanoic acid Chemical compound OC(=O)[C@@H](N)CCCl JIUHDQRXTPIQSV-VKHMYHEASA-N 0.000 description 1
- ANRLEQNQSYGXBB-DFWYDOINSA-N (2s)-2-amino-4-hydroxybutanoic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCO ANRLEQNQSYGXBB-DFWYDOINSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- OKIRBHVFJGXOIS-UHFFFAOYSA-N 1,2-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC=C1C(C)C OKIRBHVFJGXOIS-UHFFFAOYSA-N 0.000 description 1
- JIUHDQRXTPIQSV-UHFFFAOYSA-N 2-amino-4-chlorobutanoic acid Chemical compound OC(=O)C(N)CCCl JIUHDQRXTPIQSV-UHFFFAOYSA-N 0.000 description 1
- NGTMKIIZPMXFLA-UHFFFAOYSA-N 2-amino-4-chlorobutanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(N)CCCl NGTMKIIZPMXFLA-UHFFFAOYSA-N 0.000 description 1
- LMYNKFDVIZBWDF-UHFFFAOYSA-N 2-azaniumyl-4-bromobutanoate Chemical compound OC(=O)C(N)CCBr LMYNKFDVIZBWDF-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- MFRXFUDUWYXXFA-DFWYDOINSA-N Br.BrN[C@@H](CCO)C(=O)O Chemical compound Br.BrN[C@@H](CCO)C(=O)O MFRXFUDUWYXXFA-DFWYDOINSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 235000010823 Digitaria sanguinalis Nutrition 0.000 description 1
- 244000152970 Digitaria sanguinalis Species 0.000 description 1
- 239000005561 Glufosinate Substances 0.000 description 1
- QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical compound N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CNXHRBZWXVQQAI-UHFFFAOYSA-N NC(C(=O)[O-])CCP(=O)(OC)OO.[NH4+] Chemical compound NC(C(=O)[O-])CCP(=O)(OC)OO.[NH4+] CNXHRBZWXVQQAI-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Adding (S) -2-aminobutyrolactone hydrochloride into hydrochloric acid, introducing hydrogen chloride for heat preservation reaction under normal pressure or performing closed heating and heat preservation reaction, selectively introducing hydrogen chloride during the closed heating and heat preservation reaction, cooling for crystallization after the reaction is finished, performing solid-liquid separation or removing low-boiling-point substances under reduced pressure to obtain a compound (III), and directly adding the compound (III) into an alcohol R 1 -OH, adding hydrogen chloride and/or other protonic acids as catalysts to catalyze the esterification reaction, wherein R 1 Is a straight chain or branched chain alkyl of C1-C6; and carrying out post-treatment to obtain the target compound. The method has the advantages of mild reaction conditions, high yield, high enantiomeric excess rate and the like.
Description
Technical Field
The invention relates to the field of agricultural herbicides, and in particular relates to a synthetic method of an L-glufosinate-ammonium intermediate.
Background
Glufosinate-ammonium (Glufosinate-ammonium) is developed and produced by hester of germany (now bayer), and is a chemical name of 4- [ hydroxy (methyl) phosphono ] -DL-homoalanine ammonium salt, which is a glutamine synthesis inhibitor, a nonselective contact herbicide, and the action mechanism of the herbicide is to inhibit the activity of glutamine synthetase in plants, so that glutamine synthesis is hindered, nitrogen metabolism is disturbed, ammonium ions are accumulated, and the metabolism of the plants is disturbed, and the plants are killed.
The glufosinate-ammonium has the characteristics of wide herbicidal spectrum, high activity, low toxicity, easy degradation in soil, safety to crops, small drift, good environmental compatibility, quicker weed control and the like, and can prevent, kill and quickly kill over 100 annual and perennial broadleaf weeds and gramineous weeds such as digitaria sanguinalis, ryegrass and the like.
Common glufosinate is a mixture of two enantiomers, but only the L-isomer is active and is easily decomposed in soil and less toxic to humans and animals. Most of the commercial glufosinate-ammonium products on the market today are racemic mixtures. The dosage of the L-glufosinate-ammonium is reduced by half, the environmental pressure is greatly reduced, and the activity and the control effect on resistant weeds are better than those of common glufosinate-ammonium.
In the chemical synthesis of L-glufosinate-ammonium, there have been many reports and patents disclosing the synthesis of (S) -4-halo-2-aminobutyrate, an important intermediate thereof, and a salt thereof.
Patent specification publication No. CN 109369432B: under the catalysis of organic or inorganic sulfonic acid, (S) -2-aminobutyrolactone undergoes ring opening alcoholysis to obtain the corresponding S-homoserine ester, and then chlorination to obtain the target product.
Patent specification publication No. CN 110845347B: in an alcohol system, the 2-aminobutyrolactone hydrochloride and thionyl chloride are subjected to chlorination and esterification reactions to prepare 4-chloro-2-aminobutyrate hydrochloride. Although the raw materials are easy to obtain, the solubility of the 2-aminobutyrolactone hydrochloride in alcohol is poor, long time is needed for reaction and conversion due to poor mass transfer, chloralkane and equivalent sulfur dioxide are generated in the reaction, the economy is low, and the environment is not friendly.
Patent specification publication No. CN114163471A discloses: halogenated hydrocarbon or aromatic hydrocarbon is used as a solvent, and homoserine reacts with halogenated reagents such as dihalogenosulfoxide, phosphorus trihalide, phosphorus pentahalide and the like to obtain halogenated homoserine hydrochloride. The solubility of substrate homoserine in the solvent is extremely poor, and simultaneously, analysis on the reaction mechanism shows that carboxyl is easier to be halogenated into acyl halide, and intramolecular ring closure is easy to occur at the moment to obtain the 2-aminobutyrolactone ester salt. The process route is therefore not very practical.
Patent specification publication No. US5442088A discloses: heating 2-aminobutyrolactone protected by different amino groups in an alcohol solution to a preset temperature, and continuously introducing hydrogen chloride gas for several hours to prepare the amino-protected 4-chloro-2-aminobutyrate. Although the method can perform chlorination and esterification in one step, a large amount of hydrogen chloride needs to be introduced in the reaction process, and a large amount of chlorinated hydrocarbon is inevitably generated, and the substances are not only 3 kinds of carcinogens, but also can cause serious harm to the atmospheric environment, particularly the ozone layer.
In addition, there are a number of literature reports: homoserine or 2-aminobutyl lactone salt is heated in a hydrobromic acid glacial acetic acid solution for reaction to obtain bromohomoserine hydrobromide, and then is esterified to obtain 4-bromo-2-aminobutyrate and salts thereof [ Chemistry-A European Journal (2013),19(13), 4244-4248; chem.2008,73,1, 168-; chemical Communications (2019),55(54), 7860-. The methods need to use glacial acetic acid with large excess hydrobromic acid as a solvent, have high raw material cost, cannot perform the esterification reaction of the bromohomoserine directly in a glacial acetic acid system, and need to separate and purify the bromohomoserine from the glacial acetic acid system, and have difficult separation from the glacial acetic acid due to strong water solubility and low yield.
In recent years, with the increasing demand of glufosinate-ammonium, the L-type enantiomer has half the dosage and high biodegradation speed, can greatly reduce the influence on the environment, and has better activity and control effect on resistant weeds than DL-glufosinate-ammonium.
Therefore, the development of the synthetic method of the L-glufosinate-ammonium and the intermediate thereof, which has the advantages of mild reaction conditions, higher yield, lower cost and simple operation, has extremely important significance for reducing and enhancing the use amount of the herbicide.
Disclosure of Invention
When 2-aminobutyl lactone salt is used as a raw material and a thionyl chloride and alcohol system is adopted to prepare a target compound, a certain amount of byproduct hydrochloric ether and equivalent sulfur dioxide gas are inevitably generated, and the amount of three wastes is large; when the hydrogen chloride is introduced into an alcohol system for reaction, a certain amount of hydrochloric acid chloride gas can not be generated, and a large amount of hydrochloric acid as a byproduct is generated due to large consumption of the hydrogen chloride. In addition, the solubility of 2-aminobutyrolactone or homoserine in alcohol is low, and poor mass transfer also results in a substantial extension of the reaction time.
Aiming at the technical problems and the defects existing in the field, the invention provides a synthesis method of an L-glufosinate-ammonium intermediate, in particular to a synthesis method of (S) -4-chloro-2-aminobutyrate (I) and salts thereof, which takes (S) -2-aminobutyrolactone hydrochloride as a raw material, firstly performs chlorination in an aqueous phase system, and then performs esterification in alcohol under the action of catalytic amount of protonic acid. The method has the advantages of mild reaction conditions, high yield, high enantiomeric excess rate and the like, and can be further used for synthesizing the L-glufosinate-ammonium.
The specific technical scheme is as follows:
a synthetic method of an L-glufosinate-ammonium intermediate comprises the following reaction route:
the method specifically comprises the following steps:
(1) adding the compound (II) ((S) -2-aminobutyrolactone hydrochloride) into hydrochloric acid, introducing hydrogen chloride under normal pressure for heat preservation reaction, or heating in a closed manner for heat preservation reaction; hydrogen chloride can be selectively introduced in the process of the closed heating and heat preservation reaction;
(2) after the reaction in the step (1) is finished, cooling and crystallizing, and carrying out solid-liquid separation or decompression to remove low-boiling-point substances to obtain a compound (III) which is directly used in the step (3); preferably, the solid-liquid separation to obtain the compound (III) is directly used in the step (3);
(3) adding the compound (III) obtained in the step (2) into the alcohol R 1 Adding a catalytic amount of hydrogen chloride and/or other protonic acids into OH to catalyze the esterification reaction as a catalyst; the adding amount of the catalyst is 1 to 40 percent of the molar amount of the compound (III);
R 1 is a straight chain or branched chain alkyl of C1-C6;
(4) after post-treatment, the target compound (I) is obtained.
In a preferred embodiment, in the synthesis method of the L-glufosinate-ammonium intermediate, in the step (4), the post-treatment includes the following steps:
(i) and (3) esterification reaction post-treatment:
a. decompressing to remove low-boiling-point substances, and adding an organic solvent to obtain a mixture; or,
b. cooling, carrying out solid-liquid separation, and adding the obtained solid into a mixed solution of water and an organic solvent to obtain a mixture;
(ii) and (e) adjusting the pH of the mixture obtained in the step (I) to 6-9 (preferably 7-8), standing for layering, and carrying out vacuum distillation on the organic phase to obtain the target compound (I).
Further, in the step (i), the organic solvent is preferably at least one of toluene, (o, m, p) xylene, (meta, s) trimethylbenzene, ethylbenzene, (o, m, p) diethylbenzene, isopropylbenzene, (o, m, p) diisopropylbenzene, monohalobenzene, dihalobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, ethyl acetate, isopropyl acetate, and butyl acetate.
In the synthesis method of the L-glufosinate-ammonium intermediate, in the step (1), in the process of the closed heating and heat preservation reaction, the pressure of a reaction system is preferably 0.1-10.0 atm, and is more preferably 0.5-5.0 atm.
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (1), the temperature of the heat preservation reaction is preferably 50-130 ℃, and more preferably 90-110 ℃.
In the synthesis method of the L-glufosinate-ammonium intermediate, in the step (1), the molar ratio of the hydrochloric acid to the compound (II) is preferably 1-15: 1, and more preferably 1.5-4.5: 1 in terms of HCl.
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (1), the mass concentration of the hydrochloric acid is preferably 20-40%, and more preferably 30-36%.
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (1), the molar ratio of the introduced hydrogen chloride to the compound (II) is preferably 1-5: 1, and more preferably 1.5-3: 1.
The synthesis method of the L-glufosinate-ammonium intermediate comprises the step (3) of using alcohol R 1 -OH as solvent and reactant.
The synthesis method of the L-glufosinate-ammonium intermediate comprises the step (3) of R 1 Preferably methyl, ethyl or isopropyl.
The synthesis method of the L-glufosinate-ammonium intermediate comprises the step (3) of using alcohol R 1 The weight ratio of-OH to the compound (III) is preferably 0.8 to 10:1, more preferably 1 to 5: 1.
In the synthesis method of the L-glufosinate-ammonium intermediate, in the step (3), the hydrogen chloride can be added in the form of gas or solution.
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (3), the other protonic acid is preferably at least one of sulfuric acid, phosphoric acid, polyphosphoric acid and boric acid.
Further, in the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (3), the catalyst is preferably at least one of hydrogen chloride gas, sulfuric acid and phosphoric acid.
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (3), the addition amount of the catalyst is preferably 1-15% of the molar amount of the compound (III).
In the method for synthesizing the L-glufosinate-ammonium intermediate, in the step (3), the esterification reaction temperature is preferably 10-150 ℃, and more preferably 15-80 ℃.
In the technical scheme disclosed in the patent specification with the publication number of US5442088A, because hydrogen chloride is continuously introduced into alcohol to perform one-step chlorination and esterification reactions, the amino group of 2-aminobutyrolactone needs to be protected, otherwise, the reaction conversion is slow because the solubility of hydrochloride of 2-aminobutyrolactone in alcohol is extremely poor; meanwhile, amino protection means waste of raw materials related to the protecting group and increase of production cost; accordingly, the patented technology requires continuous introduction of a large amount of hydrogen chloride, and the treatment and disposal pressure of waste gas ethyl chloride and excessive hydrogen chloride gas is inevitably increased while the raw material cost is increased.
Compared with the prior art, the invention has the following beneficial effects:
1. the synthesis method can avoid the use of hydrogen bromide glacial acetic acid solution, also avoid the generation of mixed salt (hydrobromide and hydrochloride) during bromination, reduce the raw material cost and the treatment cost of byproduct salt, also can avoid the generation of byproduct chlorohydrocarbon and equivalent sulfur dioxide gas when a thionyl chloride and alcohol system is used, and reduce the amount of three wastes;
2. firstly, chlorination reaction is carried out in a water phase system, a compound (II) is directly added in a hydrochloride form without amino protection, then esterification reaction is carried out by catalytic amount of acid, and simultaneously the problem that a large amount of chlorinated hydrocarbon is generated due to continuous introduction of hydrogen chloride reaction in an alcohol system can be avoided, and the yield and the purity of a target product are improved;
3. by adopting the synthesis method, the single-batch yield of the target compound (I) can reach about 85 percent, on the basis, after the mother liquor in the first step is recycled, the comprehensive yield is 90-95 percent, meanwhile, the raw material and the product are not easy to racemize under the condition, and the ee value can be stabilized to be more than 98.5 percent;
4. the compound (III) can be directly used for the next reaction without purification after solid-liquid separation, thereby reducing the working procedures and the production cost.
In a word, the reaction raw materials are easy to obtain, the process is simple unit operation, the requirement on reaction equipment is low, the reaction condition is mild, the yield and the content are high, and the method is suitable for 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
The preparation method of the (S) -4-chloro-2-aminobutyric acid ethyl ester (Ia) comprises the following steps:
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (233.2g, 1.919mol, 2.2eq.) into a high-pressure kettle, heating and keeping the temperature at 95-100 ℃, reacting for 5 hours, wherein the highest pressure in the reaction kettle is 1.6atm, cooling and filtering to obtain 134.14g of a crude compound (III), the content of which is 97.1%, and the yield is 85.8%.
Adding the crude product of the compound (III) into ethanol (260g, 2w/w), slowly introducing hydrogen chloride (1.36g, 0.037mol, 0.05eq.) at 25-30 ℃, slowly heating to 50-55 ℃ after the introduction of the hydrogen chloride is finished, and reacting for 3 hours under the condition of heat preservation. And (3) after the reaction is finished, decompressing to remove low-boiling-point substances, adding 150g of deionized water and 150g of dichloromethane, uniformly stirring, adjusting the pH value to 7-8 by using ammonia water, standing for layering, extracting the water phase once by using dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ia, is 116.29g, the content is 98.5%, the yield is 92.4%, and the ee value is 99.2%.
Example 2
The preparation method of (S) -4-chloro-2-aminobutyric acid methyl ester (Ib):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (222.6g, 1.832mol, 2.1eq.) into an autoclave, heating and keeping the temperature at 95-100 ℃, reacting for 5 hours, wherein the highest pressure in the autoclave is 1.4atm, cooling and filtering to obtain 133.32g of crude compound (III), the content of which is 96.1%, and the yield of which is 84.4%.
Adding the crude product of the compound (III) into methanol (260g, 2w/w), slowly introducing hydrogen chloride (2.7g, 0.074mol, 0.1eq.) at 25-30 ℃, slowly heating to 50-55 ℃ after the introduction of the gas is finished, and reacting for 3 hours under the condition of heat preservation. And (3) after the reaction is finished, decompressing to remove low-boiling-point substances, adding 120g of deionized water and 120g of dichloromethane, uniformly stirring, adjusting the pH value to 7-8 by using ammonia water, standing for layering, extracting the water phase once by using dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ib, is 107.4g, the content is 98.1%, the yield is 94.4%, and the ee value is 98.5%.
Example 3
A preparation method of ethyl (S) -4-chloro-2-aminobutyric acid (Ia):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (212.04g, 1.745mol, 2.0eq.) into a reaction bottle, heating and keeping the temperature at 85-90 ℃, slowly introducing hydrogen chloride gas (about 63g), reacting for 2 hours, cooling, and performing suction filtration to obtain 113.98g of crude compound (III), wherein the content of the crude compound (III) is 93.5%, and the yield of the crude compound (III) is 70.2%.
Adding the crude compound (III) into ethanol (220g, 2w/w), slowly introducing hydrogen chloride (1.12g, 0.031mol and 0.05eq.) at 25-30 ℃, after the introduction of the hydrogen chloride is finished, slowly heating to 50-55 ℃, and keeping the temperature for reaction for 3 hours. And (3) after the reaction is finished, decompressing and removing low-boiling-point substances, adding 150g of deionized water and 150g of dichloromethane, uniformly stirring, adjusting the pH to 7-8 by using ammonia water, standing for layering, extracting the water phase once by using dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ia, is 97.26g, the content is 97.4%, the yield is 93.4%, and the ee value is 99.3%.
Example 4
Preparation method of (S) -4-chloro-2-aminobutyric acid methyl ester (Ib):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (212.04g, 1.745mol, 2.0eq.) into a reaction bottle, heating and keeping the temperature at 85-90 ℃, slowly introducing hydrogen chloride gas (about 80g), reacting for 2 hours, cooling, and performing suction filtration to obtain 117.44g of crude compound (III), wherein the content of the crude compound (III) is 94.1%, and the yield of the crude compound (III) is 72.8%.
Adding the crude compound (III) into methanol (240g, 2w/w), slowly introducing hydrogen chloride (1.16g, 0.032mol and 0.05eq.) at 25-30 ℃, after the gas introduction is finished, slowly heating to 50-55 ℃, and carrying out heat preservation reaction for 3 hours. And (3) after the reaction is finished, removing low-boiling-point substances under reduced pressure, adding 120g of deionized water and 120g of dichloromethane, uniformly stirring, adjusting the pH to 7-8 with ammonia water, standing for layering, extracting the water phase once with dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ib, is 101.13g, the content is 96.1%, the yield is 92.4%, and the ee value is 99.5%.
Example 5
A preparation method of ethyl (S) -4-chloro-2-aminobutyric acid (Ia):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (265.05g, 2.181mol, 2.5eq.) into an autoclave, heating and keeping the temperature at 95-100 ℃, reacting for 5 hours, wherein the highest pressure in the autoclave is 2.0atm, cooling, and filtering to obtain 137.02g of crude compound (III), the content of which is 96.5%, and the yield of which is 87.1%.
Adding the crude product of the compound (III) into ethanol (260g, 2w/w), slowly dropwise adding sulfuric acid (14.89g, 0.152mol and 0.2eq.) at 25-30 ℃, heating to 50-55 ℃ after dropwise adding, and keeping the temperature for reaction for 5 hours. And (3) after the reaction is finished, decompressing and removing low-boiling-point substances, adding 150g of deionized water and 150g of dichloromethane, uniformly stirring, adjusting the pH to 7-8 by using a sodium carbonate solution, standing for layering, extracting the water phase once by using dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ia, is 109.89g, the content is 97.8%, the yield is 85.4%, and the ee value is 99.1%.
Example 6
A process for the preparation of methyl (S) -4-chloro-2-aminobutyrate (Ib):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (264.0g, 2.172mol, 2.5eq.) into an autoclave, heating and keeping the temperature at 95-100 ℃, reacting for 5 hours, wherein the highest pressure in the autoclave is 2.0atm, cooling and filtering to obtain 138.59g of a crude compound (III), the content of which is 96.5%, and the yield is 88.1%.
Adding the crude product of the compound (III) into methanol (270g, 2w/w), slowly dropwise adding sulfuric acid (7.53g, 0.077mol and 0.1eq.) at 25-30 ℃, heating to 50-55 ℃ after dropwise adding, and reacting for 5 hours under heat preservation. And (3) after the reaction is finished, removing low-boiling-point substances under reduced pressure, adding 160g of deionized water and 160g of dichloromethane, uniformly stirring, adjusting the pH to 7-8 by using a sodium carbonate solution, standing for layering, extracting the water phase by using 120g of dichloromethane once, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and intermediate fractions, namely 115.76g of the target compound Ib, are collected, the content is 96.1%, the yield is 87.4%, and the ee value is 99.0%.
Example 7
A preparation method of ethyl (S) -4-chloro-2-aminobutyric acid (Ia):
putting (S) -2-aminobutyrolactone hydrochloride (120.0g, 0.872mol, 1.0eq.) and 30% hydrochloric acid (243.84g, 2.006mol, 2.3eq.) into an autoclave, heating and keeping the temperature to react at 95-100 ℃ for 5 hours, wherein the highest pressure in the autoclave is 1.7atm, cooling and filtering to obtain 131.48g of a crude compound (III), the content of which is 97.1%, and the yield of which is 84.1%.
Adding the crude compound (III) into ethanol (260g, 2w/w), slowly introducing hydrogen chloride (1.34g, 0.039mol and 0.05eq.) at 25-30 ℃, after the introduction of the hydrogen chloride is finished, slowly heating to 50-55 ℃, and keeping the temperature for reaction for 3 hours. And after the reaction is finished, cooling, suction filtering, adding the obtained filter cake into a mixed solution of 150g of deionized water and 150g of dichloromethane, uniformly stirring, adjusting the pH to 7-8 by using a sodium carbonate solution, standing for layering, extracting the water phase once by using dichloromethane, and combining the organic phases. The obtained organic phase is decompressed, desolventized and subjected to solvent recovery, then the reduced pressure distillation is carried out, and the collected middle fraction, namely the target compound Ia, is 112.33g, the content is 96.9%, the yield is 89.4%, and the ee value is 98.9%.
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 (10)
1. A synthetic method of an L-glufosinate-ammonium intermediate is characterized in that the reaction route is as follows:
the method specifically comprises the following steps:
(1) adding the compound (II) into hydrochloric acid, introducing hydrogen chloride under normal pressure for heat preservation reaction, or heating in a closed manner for heat preservation reaction; hydrogen chloride can be selectively introduced in the process of the closed heating and heat preservation reaction;
(2) after the reaction in the step (1) is finished, cooling and crystallizing, and carrying out solid-liquid separation or decompression to remove low-boiling-point substances to obtain a compound (III) which is directly used in the step (3);
(3) adding the compound (III) obtained in the step (2) into the alcohol R 1 Adding a catalytic amount of hydrogen chloride and/or other protonic acids into OH to catalyze the esterification reaction as a catalyst; the adding amount of the catalyst is 1 to 40 percent of the molar weight of the compound (III);
R 1 is a straight chain or branched chain alkyl of C1-C6;
(4) after post-treatment, the target compound (I) is obtained.
2. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in step (4), the post-treatment comprises the steps of:
(i) and (3) esterification reaction post-treatment:
a. decompressing to remove low-boiling-point substances, and adding an organic solvent to obtain a mixture; or,
b. cooling, carrying out solid-liquid separation, and adding the obtained solid into a mixed solution of water and an organic solvent to obtain a mixture;
(ii) and (e) adjusting the pH of the mixture obtained in the step (I) to 6-9, standing for layering, and carrying out vacuum distillation on the organic phase to obtain the target compound (I).
3. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in the step (1), the pressure of the reaction system is 0.1 to 10.0atm, preferably 0.5 to 5.0atm, during the closed heating and heat preservation reaction.
4. The method for synthesizing the L-glufosinate-ammonium intermediate according to claim 1, wherein in the step (1), the temperature of the heat preservation reaction is 50-130 ℃, preferably 90-110 ℃.
5. The method for synthesizing an L-glufosinate-ammonium intermediate according to claim 1, wherein in the step (1):
calculated by HCl, the molar ratio of the hydrochloric acid to the compound (II) is 1-15: 1, preferably 1.5-4.5: 1;
the mass concentration of the hydrochloric acid is 20-40%, preferably 30-36%;
the molar ratio of the introduced hydrogen chloride to the compound (II) is 1-5: 1, preferably 1.5-3: 1.
6. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in step (3), R is 1 Is methyl, ethyl or isopropyl.
7. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in step (3), the alcohol R 1 The weight ratio of-OH to the compound (III) is 0.8-10: 1, preferably 1-5: 1.
8. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in step (3):
the hydrogen chloride is added in the form of gas or solution;
the other protonic acid is at least one of sulfuric acid, phosphoric acid, polyphosphoric acid and boric acid.
9. The method for synthesizing an L-glufosinate-ammonium intermediate according to claim 1, wherein in the step (3), the catalyst is added in an amount of 1 to 15% by mole based on the compound (III).
10. The method for synthesizing an L-glufosinate intermediate according to claim 1, wherein in the step (3), the temperature of the esterification reaction is 10 to 150 ℃, preferably 15 to 80 ℃.
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