CN108484666B - Synthetic method of refined glufosinate-ammonium - Google Patents
Synthetic method of refined glufosinate-ammonium Download PDFInfo
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- CN108484666B CN108484666B CN201810525453.4A CN201810525453A CN108484666B CN 108484666 B CN108484666 B CN 108484666B CN 201810525453 A CN201810525453 A CN 201810525453A CN 108484666 B CN108484666 B CN 108484666B
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- ammonium
- glufosinate
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 4
- 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 title description 58
- 238000000034 method Methods 0.000 claims abstract description 43
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims abstract description 6
- ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 claims abstract 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 18
- -1 transition metal salt Chemical class 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 10
- 238000001308 synthesis method Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- IXLIDZMVNVBMIT-UHFFFAOYSA-N ethyl methyl hydrogen phosphite Chemical compound CCOP(O)OC IXLIDZMVNVBMIT-UHFFFAOYSA-N 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 2
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical class [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 24
- 230000015572 biosynthetic process Effects 0.000 abstract description 22
- 230000008569 process Effects 0.000 abstract description 7
- 230000009286 beneficial effect Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000029936 alkylation Effects 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 241000196324 Embryophyta Species 0.000 description 7
- 239000005561 Glufosinate Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 230000002363 herbicidal effect Effects 0.000 description 6
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- FSVWUQGXSDGXAR-ZBHICJROSA-N (3S)-3,6-bis(2-bromoethyl)piperazine-2,5-dione Chemical compound BrCC[C@H]1C(NC(C(N1)=O)CCBr)=O FSVWUQGXSDGXAR-ZBHICJROSA-N 0.000 description 5
- OJYIPVKINQFIME-UHFFFAOYSA-N CCCCOP(C)(O)O Chemical compound CCCCOP(C)(O)O OJYIPVKINQFIME-UHFFFAOYSA-N 0.000 description 5
- 239000004009 herbicide Substances 0.000 description 5
- 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 4
- ANUZKYYBDVLEEI-UHFFFAOYSA-N butane;hexane;lithium Chemical compound [Li]CCCC.CCCCCC ANUZKYYBDVLEEI-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000009333 weeding Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- MZYONVUDAOYDKV-DFWYDOINSA-N (4s)-4-aminooxolan-2-one;hydrochloride Chemical compound Cl.N[C@@H]1COC(=O)C1 MZYONVUDAOYDKV-DFWYDOINSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 239000005562 Glyphosate Substances 0.000 description 2
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 229930195722 L-methionine Natural products 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation 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
- 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
- 238000002329 infrared spectrum Methods 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical group [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 229960004452 methionine Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- JMGFLAMAHONTEW-UHFFFAOYSA-N (3-acetyloxy-3-cyanopropyl)-methylphosphinic acid Chemical compound CC(=O)OC(C#N)CCP(C)(O)=O JMGFLAMAHONTEW-UHFFFAOYSA-N 0.000 description 1
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- NVLPDIRQWJSXLZ-UHFFFAOYSA-N 3-hydroxypyridine-4-carbaldehyde Chemical compound OC1=CN=CC=C1C=O NVLPDIRQWJSXLZ-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- CMNQIVHHHBBVSC-UHFFFAOYSA-N 5-hydroxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=C1C=CC=C2O CMNQIVHHHBBVSC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- LRRJQNMXIDXNIM-UHFFFAOYSA-M benzyl(trimethyl)azanium;iodide Chemical compound [I-].C[N+](C)(C)CC1=CC=CC=C1 LRRJQNMXIDXNIM-UHFFFAOYSA-M 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000853 biopesticidal effect Effects 0.000 description 1
- XQPRBTXUXXVTKB-UHFFFAOYSA-M caesium iodide Chemical compound [I-].[Cs+] XQPRBTXUXXVTKB-UHFFFAOYSA-M 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- BLHLJVCOVBYQQS-UHFFFAOYSA-N ethyllithium Chemical compound [Li]CC BLHLJVCOVBYQQS-UHFFFAOYSA-N 0.000 description 1
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical group [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 1
- HAUKUGBTJXWQMF-UHFFFAOYSA-N lithium;propan-2-olate Chemical compound [Li+].CC(C)[O-] HAUKUGBTJXWQMF-UHFFFAOYSA-N 0.000 description 1
- SZAVVKVUMPLRRS-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].C[CH-]C SZAVVKVUMPLRRS-UHFFFAOYSA-N 0.000 description 1
- XBEREOHJDYAKDA-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].CC[CH2-] XBEREOHJDYAKDA-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- YIZNYMADIRZRAL-UHFFFAOYSA-N methyl(propan-2-yloxy)phosphinous acid Chemical compound CC(C)OP(C)O YIZNYMADIRZRAL-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 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
- 239000000575 pesticide Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000243 photosynthetic effect Effects 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- UQFSVBXCNGCBBW-UHFFFAOYSA-M tetraethylammonium iodide Chemical compound [I-].CC[N+](CC)(CC)CC UQFSVBXCNGCBBW-UHFFFAOYSA-M 0.000 description 1
- RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 description 1
- GKXDJYKZFZVASJ-UHFFFAOYSA-M tetrapropylazanium;iodide Chemical compound [I-].CCC[N+](CCC)(CCC)CCC GKXDJYKZFZVASJ-UHFFFAOYSA-M 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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Abstract
The invention belongs to the technical field of organic compound synthesis, and particularly relates to a synthetic method of glufosinate-ammonium. The method for synthesizing the refined glufosinate-ammonium takes L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine and methyl phosphite monoester as raw materials to synthesize, compounds shown as an intermediate formula (III) are synthesized through alkylation reaction, and then the refined glufosinate-ammonium is prepared through hydrolysis reaction. Because the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine raw material contains a chiral carbon center, the refined glufosinate-ammonium with the required conformation can be prepared through simple reaction, the whole synthesis process is simple and easy to implement, and the raw material is easy to obtain, thereby being beneficial to reducing the production cost; and an alkylation catalyst is used in the reaction to promote the reaction, improve the yield of the product and be beneficial to industrial production.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for synthesizing refined glufosinate-ammonium, in particular to a method for synthesizing refined glufosinate-ammonium by taking L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine as a raw material.
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 (structural formula shown below), 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.
Glufosinate-ammonium was originally found to originate from the active metabolite of the biopesticide herbicide bialaphos in plants. Bialaphos is a high-efficiency low-toxicity biological herbicide separated from streptomyces fermentation liquor, researchers study the weeding mechanism of bialaphos, find that the bialaphos has no weeding activity, but is degraded into glufosinate-ammonium with weeding activity in plants, and the glufosinate-ammonium can cause the accumulation of ammonium ions by inhibiting the synthesis of glutamine in the plants, so that the photosynthetic layer is damaged, and weeds can die.
At present, a plurality of documents at home and abroad report the preparation method of the refined glufosinate-ammonium, and the preparation method mainly comprises three methods: the first is synthesized by a biological fermentation method, the second is synthesized by a chemical method, and the third is obtained by taking a precursor of DL-glufosinate-ammonium as a substrate and selectively separating by enzyme. At present, the chemical synthesis method is adopted to prepare the refined glufosinate-ammonium for more research. Progress of research on the synthesis of glufosinate-ammonium by chemical methods in Dongwei Kai et al (modern pesticide, 2016, Vol.15, No. 5, page number: 26-29 several methods for chemically preparing glufosinate-ammonium are reviewed in the text, namely chiral auxiliary reagent method, natural amino acid chiral source method, and asymmetric catalysis method.
Regarding the chemical synthesis of glufosinate-ammonium, some literature reports are available at home and abroad, such as J.org.chem.1991, 56(5), 1783-1788; WO2006104120A1 et al, the synthesis process is as follows:
however, in the above method, on one hand, the process steps are complicated, the intermediate is difficult to purify, and the process uses expensive chiral ligands of phosphorus and rhodium catalyst, which results in low total yield and is not beneficial to industrialization.
In addition, the reports of maomingzhen et al in chinese patent CN105131032A, chiral quaternary ammonium salt phase transfer (cinchonidine chiral quaternary ammonium salt derivative) catalyst is used to construct the chiral center in the molecular structure of glufosinate-ammonium, and the synthetic route is as follows:
however, in the method, not only are the raw materials not easily available and the production cost is high, but also the chiral quaternary ammonium salt phase transfer catalyst is high in price, and the ee value of the final product is low, so that the final product can not reach the existing original drug standard.
Yan Li et al reported in CN105218579A that 4- (hydroxy- (methyl) phosphinyl) -2-acetoxy-butyronitrile as raw material is hydrolyzed, oxidized, aminated and hydrogenated to synthesize refined glufosinate-ammonium, and the synthetic route is as follows:
however, in the method, the oxidation and hydrogenation steps are respectively carried out by using noble metals ruthenium and rhodium as catalysts, so that the cost is high and the industrial implementation difficulty is high.
Li Xunkun et al, in CN 106083922A, mention that natural amino acid L-methionine is used as a starting material, and (S) -3-amino-gamma-butyrolactone hydrochloride is obtained through cyclization, and then through protection, ring opening, Abuzov, hydrolysis and other reactions, refined glufosinate-ammonium with ee value of 93.5% can be obtained, the total yield reaches 69.2%, and the synthetic route is as follows:
however, in the method, the sulfur-containing raw material L-methionine is used, so that the process has more sulfur-containing three wastes, and the intermediate (S) -3-amino-gamma-butyrolactone hydrochloride can smoothly perform subsequent reaction only by protecting amino with acyl chloride, thereby increasing the process cost.
Therefore, the development of the method for synthesizing the refined glufosinate-ammonium, which has the advantages of high yield, low cost and simple operation, has important industrial significance.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide a method for synthesizing refined glufosinate-ammonium, so as to solve the problems of complex operation, high cost and low yield of the synthetic process of the refined glufosinate-ammonium in the prior art.
In order to solve the technical problems, the synthesis method of the refined glufosinate-ammonium comprises the following steps:
(1) taking L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine shown in a formula (II) and methyl phosphite monoester as raw materials, placing the raw materials in an organic solvent, and carrying out alkylation reaction in the presence of alkali and a catalyst to obtain a compound shown in a formula (III);
(2) dissolving a compound shown as a formula (III) in acid, heating for hydrolysis reaction, removing a solvent after the reaction is finished, adding alcohol for dissolution, and then adding alkylene oxide for conversion reaction to obtain the required glufosinate-ammonium (I);
in the step (1):
in the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine, X is selected from Cl, Br, I and OSO2CH3、OSO2C6H3Or OSO2C7H8；
In the methyl phosphite monoester, R is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2CH2CH2CH3or-CH2C6H5。
In the step (1):
the solvent is selected from tetrahydrofuran, methyltetrahydrofuran, ethylene glycol dimethyl ether, dioxane, diethylene glycol dimethyl ether, dimethyl sulfoxide, N, N-dimethylformamide or N, N-diethylformamide;
the base is selected from lithium alkoxide, sodium alkoxide, potassium alkoxide, alkyl lithium, lithium amide, organic amine lithium, alkali metal hydrogen salt or alkali earth metal hydrogen salt;
the catalyst is selected from alkali metal, alkaline earth metal and transition metal salt of iodine, or ammonium salt or quaternary ammonium salt taking iodine as negative ion.
More specifically, the base is selected from lithium methoxide, lithium ethoxide, lithium isopropoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium isopropoxide, potassium methoxide, potassium ethoxide, potassium isopropoxide, potassium tert-butoxide, methyllithium, ethyllithium, propyllithium, isopropyllithium, butyllithium, tert-butyllithium, sec-butyllithium, 2- (ethylhexyl) lithium, diethylaminolithium, diisopropylaminolithium, bistrimethylsilylaminolithium, lithium hydride, sodium hydride, potassium hydride or calcium hydride;
the catalyst is selected from lithium iodide, sodium iodide, potassium iodide, cesium iodide, ammonium iodide, tetramethylammonium iodide, tetraethylammonium iodide, tetra-n-propylammonium iodide, tetra-n-butylammonium iodide, tetra-n-hexylammonium iodide, benzyltrimethylammonium iodide or benzyltriethylammonium iodide.
In the step (1), the molar ratio of the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine, the methyl ethyl phosphite, the organic solvent, the base and the catalyst is 1: 2-10: 1-200: 2-10: 0.01-0.2.
In the step (1), the temperature of the alkylation reaction is-80-100 ℃.
In the step (1), a step of purifying the compound represented by the formula (iii) is further included, and specifically includes: and (3) filtering the reaction liquid to remove the organic solvent, adding water and an extracting agent into the remainder for extraction, and removing the extracting agent to obtain the compound shown in the formula (III).
The extractant is selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, ethyl acetate, butyl acetate, tert-butyl acetate, diethyl ether, isopropyl ether, methyl tert-butyl ether or n-butyl ether.
In the step (2):
the acid is hydrochloric acid, sulfuric acid or hydrobromic acid;
the alcohol is methanol, ethanol or isopropanol;
the alkylene oxide is ethylene oxide, propylene oxide or epichlorohydrin.
In the step (2), the molar ratio of the compound represented by the formula (III), the acid and the alkylene oxide is 1: 1-100: 1-5.
In the step (2), the temperature of the hydrolysis reaction is 50-160 ℃, and the temperature of the conversion reaction is 0-50 ℃.
The method for synthesizing the refined glufosinate-ammonium takes L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine and methyl phosphite monoester as raw materials to synthesize, compounds shown as an intermediate formula (III) are synthesized through alkylation reaction, and then the refined glufosinate-ammonium is prepared through hydrolysis reaction. Because the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine raw material contains a chiral carbon center, the refined glufosinate-ammonium with the required conformation can be prepared through simple reaction, the whole synthesis process is simple and easy to implement, and the raw material is easy to obtain, thereby being beneficial to reducing the production cost; and an alkylation catalyst is used in the reaction to promote the reaction, improve the yield of the product and be beneficial to industrial production.
Drawings
In order that the present disclosure may be more readily and clearly understood, the following detailed description of the present disclosure is provided in connection with specific embodiments thereof and the accompanying drawings, in which,
FIG. 1 is a liquid phase spectrum of ee value measurement of glufosinate-ammonium prepared in example 1;
FIG. 2 is a nuclear magnetic resonance spectrum (1H-NMR) of glufosinate-ammonium prepared in example 1;
FIG. 3 is an ESI mass spectrum of glufosinate-ammonium prepared in example 1;
FIG. 4 is an IR spectrum of glufosinate-ammonium prepared in example 1.
Detailed Description
The steps for synthesizing refined glufosinate-ammonium in the following examples are carried out according to the following scheme:
wherein X is selected from Cl, Br, I, OSO2CH3、OSO2C6H3Or OSO2C7H8；
R is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2CH2CH2CH3or-CH2C6H5。
In the following examples, the ee value of the target product, glufosinate-ammonium, was determined by high performance liquid chromatography known in the art, and the specific determination method and conditions included:
a chromatographic column: SUMICHIRAL OA-5000L, 5 μm, 150mm × 4.6mm (I.D.);
mobile phase: 2mM copper sulfate aqueous solution: acetonitrile 1000: 3;
column temperature: 30 ℃;
flow rate: 1 mL/min;
detection wavelength: UV220 nm;
column temperature: at 30 ℃.
Example 1
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): adding 65.6g (0.2mol) of L-3, 6-bis (2-bromoethyl) -2, 5-diketopiperazine, 65.2g (0.48mol) of monobutyl methylphosphite, 300ml of fresh tetrahydrofuran and 0.9g (0.006mol) of sodium iodide into a 1L four-neck flask under the protection of nitrogen, uniformly stirring, cooling to-50 ℃, slowly dropping 268ml (0.4mol) of n-butyl lithium hexane solution, stirring for 2h after dropping, then heating to room temperature, continuously stirring for reaction for 20h, and filtering; the filtrate was collected and concentrated under reduced pressure to remove the organic solvent, and the residue was collected and extracted with water (200mL), methylene chloride (100mL × 3 times) to separate layers; the organic phases were then combined and the solvent dichloromethane was recovered to give 60.1g of an oil, a calculated yield of 73.5%, of the desired compound of formula (III);
(2) synthesis of refined glufosinate-ammonium: adding 60.1g (0.147mol) of the compound shown in the formula (III) into a 500mL four-neck flask, adding 300mL of concentrated hydrochloric acid, carrying out reflux reaction at 110 ℃ for 20h, and removing the solvent under reduced pressure to obtain refined glufosinate-ammonium hydrochloride; 150ml of 95% ethanol was added, 23.4g (0.4mol) of propylene oxide was added thereto at room temperature, and the reaction was stirred for 3 hours, followed by filtration to obtain 49.8g of the desired glufosinate-ammonium in a calculated yield of 93.6% in this step and an ee value of 92.9% of the product as determined by the method described above.
The liquid chromatogram obtained in the final product obtained in this example is shown in FIG. 1, the nuclear magnetic resonance (1H-NMR) spectrum is shown in FIG. 2, the ESI mass spectrum is shown in FIG. 3, and the infrared spectrum is shown in FIG. 4. Therefore, the product prepared by the method has correct structure.
The total yield of the target product, glufosinate-ammonium, in this example was calculated to be 68.8%.
Example 2
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): under the protection of nitrogen, 20g (0.06mol) of L-3, 6-bis (2-bromoethyl) -2, 5-diketopiperazine, 16.2g (0.15mol) of methyl ethyl phosphite, 150ml of fresh ethylene glycol dimethyl ether and 0.3g (0.002mol) of sodium iodide are added into a 500ml four-neck flask, the mixture is uniformly stirred, the temperature is reduced to-10 ℃, 8.6g (0.126mol) of sodium ethoxide is added in batches, after the addition is finished, the mixture is stirred for 4 hours, the reaction is heated to the room temperature, the stirring is continued for 20 hours, and the filtration is carried out; concentrating the filtrate under reduced pressure to remove solvent, adding water (100mL) and ethyl acetate (50mL multiplied by 3 times) into the residue, extracting and layering, combining organic phases, recovering the solvent ethyl acetate to obtain 11.8g of oily matter, namely the required compound shown in the formula (III), and calculating the yield to be 56.4%;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
Example 3
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): adding 23.9g (0.1mol) of L-3, 6-bis (2-chloroethyl) -2, 5-diketopiperazine, 32.6g (0.24mol) of monobutyl methylphosphite, 180ml of fresh tetrahydrofuran and 0.6g (0.004mol) of sodium iodide into a 500ml four-neck flask under the protection of nitrogen, uniformly stirring, cooling to-50 ℃, slowly dropping 134ml (0.2mol) of n-butyl lithium hexane solution, stirring for 2h, heating to room temperature, continuously stirring for reaction for 20h, and filtering; concentrating the filtrate under reduced pressure to remove solvent, adding water (100mL) and methyl tert-butyl ether (80mL × 3 times) into the residue, and extracting for layering; the organic phases were combined and the solvent methyl t-butyl ether was recovered to give 27.9g of an oil, which was the desired compound of formula (III) in 68.5% calculated yield;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
Example 4
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): under the protection of nitrogen, 30g (0.09mol) of L-3, 6-bis (2-bromoethyl) -2, 5-diketopiperazine, 28.0g (0.23mol) of monoisopropyl methylphosphonite, 200ml of fresh ethylene glycol dimethyl ether and 0.3g (0.002mol) of sodium iodide are added into a 500ml four-neck flask, the mixture is uniformly stirred, the temperature is reduced to-10 ℃, 15.3g (0.186mol) of sodium isopropoxide is added in batches, after the addition is finished, the mixture is stirred for 6 hours, the reaction is heated to the room temperature, the stirring is continued for 20 hours, and the filtration is carried out; concentrating the filtrate under reduced pressure to remove solvent, adding water (100mL) and dichloromethane (80mL multiplied by 3 times) into the residue, extracting and layering, combining organic phases, recovering solvent dichloromethane to obtain 17.0g of oily matter, namely the required compound shown in the formula (III), and calculating the yield to be 48.6%;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
Example 5
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): under the protection of nitrogen, 15g (0.045mol) of L-3, 6-bis (2-bromoethyl) -2, 5-diketopiperazine, 15.3g (0.113mol) of monobutyl methylphosphite, 150ml of fresh tetrahydrofuran and 0.3g (0.002mol) of sodium iodide are added into a 500ml four-neck flask, the mixture is uniformly stirred, the temperature is reduced to-10 ℃, 3.6g (with the content of 60 percent and the content of 0.09mol) of sodium hydride are added in batches, after the addition is finished, the mixture is stirred for 6 hours, the reaction is heated to the room temperature, the mixture is continuously stirred for 20 hours, and the filtration is carried out; concentrating the filtrate under reduced pressure to remove the solvent, adding water (100mL) and dichloromethane (50mL multiplied by 3 times) into the residue, extracting and layering, combining the organic phases, recovering the solvent dichloromethane to obtain 11.4g of oily matter, namely the required compound shown in the formula (III), and calculating the yield to be 61.8%;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
Example 6
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): under the protection of nitrogen, adding 20g (0.06mol) of L-3, 6-bis (2-bromoethyl) -2, 5-diketopiperazine, 20.4g (0.15mol) of monobutyl methylphosphite and 150ml of fresh tetrahydrofuran into a 500ml four-neck flask, uniformly stirring, cooling to-50 ℃, slowly dropping 85ml (0.126mol) of n-butyl lithium hexane solution, stirring for 2h, raising the temperature to room temperature, continuously stirring for reaction for 20h, and filtering; the filtrate was concentrated under reduced pressure to remove the solvent, and the residue was extracted with water (100mL) and methylene chloride (50mL × 3 times) to separate layers; the organic phases were combined and the solvent dichloromethane was recovered to give 16.2g of an oil, which was the desired compound of formula (III) in 65.7% yield;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
Example 7
The synthesis method of glufosinate-ammonium comprises the following steps:
(1) synthesis of a compound of formula (iii): adding 35.8g (0.1mol) of L-3, 6-bis (2-methylsulfonyloxyethyl) -2, 5-diketopiperazine, 34g (0.25mol) of monobutyl methylphosphite and 400ml of fresh tetrahydrofuran into a 1L four-neck flask under the protection of nitrogen, uniformly stirring, cooling to-50 ℃, slowly dropping 137ml (0.206mol) of n-butyl lithium hexane solution, stirring for 2h, raising the temperature to room temperature, continuously stirring for reaction for 20h, and filtering; the filtrate was concentrated under reduced pressure to remove the solvent, and the residue was extracted with water (100mL) and methylene chloride (80 mL. times.3 times) to separate layers; the organic phases were combined and the solvent dichloromethane was recovered to give 17.9g of an oil, which was the desired compound of formula (III) in 43.8% yield;
(2) synthesis of refined glufosinate-ammonium: the same procedure as in step (2) of example 1.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (10)
1. A synthetic method of refined glufosinate-ammonium is characterized by comprising the following steps:
(1) taking L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine shown in a formula (II) and methyl phosphite monoester as raw materials, placing the raw materials in an organic solvent, and carrying out alkylation reaction in the presence of alkali and a catalyst to obtain a compound shown in a formula (III);
the catalyst is selected from alkali metal, alkaline earth metal and transition metal salt of iodine, or ammonium salt or quaternary ammonium salt taking iodine as negative ion;
(2) dissolving a compound shown as a formula (III) in acid, heating for hydrolysis reaction, removing a solvent after the reaction is finished, adding alcohol for dissolution, and then adding alkylene oxide for conversion reaction to obtain the required glufosinate-ammonium (I);
2. the method for synthesizing glufosinate-ammonium according to claim 1, characterized in that:
in the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine, X is selected from Cl, Br or I;
in the methyl phosphite monoester, R is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2 CH2CH2CH3or-CH2C6H5。
3. A synthesis method of glufosinate-ammonium according to claim 2, characterized in that in step (1):
the solvent is selected from tetrahydrofuran, methyltetrahydrofuran, ethylene glycol dimethyl ether, dioxane, diethylene glycol dimethyl ether, dimethyl sulfoxide, N, N-dimethylformamide or N, N-diethylformamide;
the base is selected from the group consisting of lithium alkoxides, sodium alkoxides, potassium alkoxides, alkyl lithium, lithium amides, lithium organic amines, alkali metal hydrogen salts, and alkaline earth metal hydrogen salts.
4. The method for synthesizing glufosinate-ammonium according to claim 3, characterized in that: in the step (1), the molar ratio of the L-3, 6-bis (2-haloethyl) -2, 5-diketopiperazine, the methyl ethyl phosphite, the organic solvent, the base and the catalyst is 1: 2-10: 1-200: 2-10: 0.01-0.2.
5. The method for synthesizing glufosinate-ammonium according to claim 4, characterized in that: in the step (1), the temperature of the alkylation reaction is-80-100 ℃.
6. The method for synthesizing glufosinate-ammonium according to claim 5, characterized in that: in the step (1), a step of purifying the compound represented by the formula (iii) is further included, and specifically includes: and (3) filtering the reaction solution, collecting filtrate, concentrating under reduced pressure to remove the organic solvent, adding water and an extracting agent into the residue for extraction, and removing the extracting agent to obtain the compound shown in the formula (III).
7. The method for synthesizing glufosinate-ammonium according to claim 6, wherein the extractant is selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, ethyl acetate, butyl acetate, tert-butyl acetate, diethyl ether, isopropyl ether, methyl tert-butyl ether or n-butyl ether.
8. A synthesis method of glufosinate-ammonium according to any of the claims 1-7, characterized in that in step (2):
the acid is hydrochloric acid, sulfuric acid or hydrobromic acid;
the alcohol is methanol, ethanol or isopropanol;
the alkylene oxide is ethylene oxide, propylene oxide or epichlorohydrin.
9. The method for synthesizing glufosinate-ammonium according to claim 8, wherein in the step (2), the molar ratio of the compound represented by the formula (III), the acid and the alkylene oxide is 1: 1-100: 1-5.
10. The method for synthesizing glufosinate-ammonium according to claim 9, wherein in the step (2), the temperature of the hydrolysis reaction is 50-160 ℃ and the temperature of the conversion reaction is 0-50 ℃.
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| CN111574559A (en) * | 2020-04-30 | 2020-08-25 | 河北威远生物化工有限公司 | Post-treatment method of L-glufosinate-ammonium enzyme hydrolysate |
| CN115160173B (en) * | 2022-09-01 | 2022-12-02 | 烟台海川化学制品有限公司 | Preparation method of N epsilon-lauroyl lysine |
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