CN108484666B - 一种精草铵膦的合成方法 - Google Patents
一种精草铵膦的合成方法 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
- reaction
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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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Abstract
本发明属于有机化合物合成技术领域,具体涉及一种精草铵膦的合成方法。本发明所述合成精草铵膦的方法,以L‑3,6‑双(2‑卤乙基)‑2,5‑二酮哌嗪和甲基亚磷酸单酯为原料进行合成,通过烷基化反应合成了中间体式(Ⅲ)所示化合物,再经水解反应制得精草铵膦。由于L‑3,6‑双(2‑卤乙基)‑2,5‑二酮哌嗪原料含有手性碳中心,可经过简单反应即制备所需构象的精草铵膦,使得整个合成过程简单易行,且由于原料易得有助于降低生产成本;并且反应中使用了烷基化催化剂,以促进了反应进行,提高了产物的收率,有益于工业化生产。
Description
技术领域
本发明属于有机化合物合成技术领域,具体涉及一种精草铵膦的合成方法,特别涉及一种以L-3,6-双(2-卤乙基)-2,5-二酮哌嗪为原料合成精草铵膦的方法。
背景技术
草铵膦是由赫斯特公司于80年代开发成功的一种广谱有机磷触杀型除草剂,草铵膦是一种谷氨酰胺合成抑制剂,其内吸作用不强,与早期的草甘膦杀根不同,草铵膦先杀叶,再通过植物蒸腾作用可以在植物木质部进行传导,其速效性间于百草枯和草甘膦之间,是一种非选择性触杀除草剂。草铵膦包括L-草铵膦和外消旋DL-型草铵膦,其中,L-草铵膦的除草活性为外消旋DL-型草铵膦的两倍。目前市场上销售的草铵膦制剂一般都是外消旋DL-型草铵膦,如果草铵膦产品能以L-构型的纯化学异构体形式予以使用,可使草铵膦的使用量降低50%左右,这对于提高原子经济性、降低使用成本、减轻环境压力都具有十分重要的意义。
L-草铵膦,又称精草铵膦,化学名称为4-[羟基(甲基)膦酰基]-L-高丙氨酸(结构式如下),分子式为C5H12NO4P,分子量181.1;精草铵膦易溶于水,不易溶于有机溶剂,且对光稳定;熔点为214-216℃,CAS号35597-44-5。精草铵膦是一种广谱灭生性除草剂,具有高效、低毒、易降解、使用安全方便等优点,一年生、多年生的双子叶和禾本科杂草具有较好的除草效果。
精草铵膦最初发现是源于生物农药除草剂双丙氨膦在植物体内的活性代谢物。双丙氨膦是从链霉菌发酵液中分离到的高效低毒生物除草剂,科研人员研究了双丙氨膦的除草机理,发现其本身并无除草活性,而是在植物体内降解成具有除草活性的精草铵膦,精草铵膦再通过抑制植物体内的谷氨酰胺合成,导致铵离子的累积进而破坏光合层,使杂草死亡。
目前国内外有较多的文献报道了精草铵膦的制备方法,主要有三种方法:其一为生物发酵法合成,其二为通过化学法合成,其三是以DL-草铵膦的前体为底物,通过酶的选择性分获得。目前研究较多是采用化学合成法制备精草铵膦。董文凯等在《化学法合成精草铵膦的研究进展》【《现代农药》,2016年,第15卷第5期,页码:26-29】一文中综述了化学法制备精草铵膦的几种方法,即手性辅助试剂法、天然氨基酸手性源法、以及不对称催化法。
关于精草铵膦的化学合成,国内外已有一些文献报道,如J.Org.Chem.1991,56(5),1783-1788;WO2006104120A1等,其合成过程如下:
但上述方法中,一方面工艺步骤繁琐、中间体纯化难,而且该工艺中使用了昂贵手性配体磷和铑催化剂,导致总收率低,不利于工业化。
另有毛明珍等在中国专利CN105131032A中的报道,采用手性季铵盐相转移(辛可尼丁手性季铵盐衍生物)催化剂来构建精草铵膦分子结构中的手性中心,其合成路线如下:
但该方法中,不仅原料不易得使得生产成本较高,并且手性季铵盐相转移催化剂价格较高,且最终产物ee值较低,远不能达到目前已有的原药标准。
闫立单等在中国专利CN105218579A中报道了以4-(羟基-(甲基)氧膦基)-2-乙酰氧基丁氰为原料,经过水解、氧化、氨化加氢合成精草铵膦,其合成路线如下:
但是在该方法中,涉及的氧化、加氢步骤分别采用了采用贵金属钌、铑做催化剂,导致成本高昂,且工业实施难度较大。
李旭坤等在CN 106083922A中提到,以天然氨基酸L-蛋氨酸为起始物料,经过环合先得到(S)-3-氨基-γ-丁内酯盐酸盐,再经保护、开环、阿布佐夫、水解等反应,可得到ee值93.5%的精草铵膦,总收率达到69.2%,其合成路线如下:
但是该方法中,使用了含硫原料L-蛋氨酸,导致工艺中含硫三废多,且中间体(S)-3-氨基-γ-丁内酯盐酸盐需要用酰氯保护氨基,才能顺利进行后续反应,增加了工艺成本。
可见,开发一种收率高、成本低、操作简单的合成精草铵膦的方法具有重要的工业意义。
发明内容
为此,本发明所要解决的技术问题在于提供一种精草铵膦的合成方法,以解决现有技术中精草铵膦合成工艺存在操作复杂、成本高且收率较低的问题。
为解决上述技术问题,本发明所述的一种精草铵膦的合成方法,包括如下步骤:
(1)以式(II)所示L-3,6-双(2-卤乙基)-2,5-二酮哌嗪和甲基亚磷酸单酯为原料,置于有机溶剂中,在碱及催化剂存在下,经烷基化反应得到式(Ⅲ)所示化合物;
(2)取式(Ⅲ)所示化合物溶于酸中,加热进行水解反应,并于反应结束后脱除溶剂,并加入醇进行溶解,然后加入环氧烷烃进行转化反应,制得所需精草铵膦(Ⅰ);
所述步骤(1)中:
所述L-3,6-双(2-卤乙基)-2,5-二酮哌嗪中,X选自Cl、Br、I、OSO2CH3、OSO2C6H3或OSO2C7H8;
所述甲基亚磷酸单酯中,R选自-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2CH2CH2CH3或-CH2C6H5。
所述步骤(1)中:
所述溶剂选自四氢呋喃、甲基四氢呋喃、乙二醇二甲醚、二氧六环、二乙二醇二甲醚、二甲基亚砜、N、N-二甲基甲酰胺或N、N-二乙基甲酰胺;
所述碱选自醇锂、醇钠、醇钾、烷基锂、氨基锂、有机胺锂、碱金属的氢盐或碱土金属的氢盐;
所述催化剂选自碘的碱金属、碱土金属、过渡金属的盐,或者是以碘为负离子的铵盐或季铵盐。
更具体的,所述碱选自甲醇锂、乙醇锂、异丙醇锂、叔丁醇锂、甲醇钠、乙醇钠、异丙醇钠、甲醇钾、乙醇钾、异丙醇钾、叔丁醇钾、甲基锂、乙基锂、丙基锂、异丙基锂、丁基锂、叔丁基锂、仲丁基锂、2-(乙基己基)锂、二乙胺基锂、二异丙胺基锂、双三甲基硅基胺基锂、氢化锂、氢化钠、氢化钾或氢化钙;
所述催化剂选自碘化锂、碘化钠、碘化钾、碘化铯、碘化铵、四甲基碘化铵、四乙基碘化铵、四正丙基碘化铵、四正丁基碘化铵、四正己基碘化铵、苄基三甲基碘化铵或苄基三乙基碘化铵。
所述步骤(1)中,所述L-3,6-双(2-卤乙基)-2,5-二酮哌嗪、甲基亚磷酸单乙酯、有机溶剂、碱和催化剂的摩尔比为1:2-10:1-200:2-10:0.01-0.2。
所述步骤(1)中,所述烷基化反应的温度为-80~100℃。
所述步骤(1)中,还包括对式(Ⅲ)所示化合物进行纯化的步骤,具体包括:取反应液过滤去除所述有机溶剂,剩余物加入水和萃取剂进行萃取,脱除所述萃取剂,得到式(Ⅲ)所示化合物。
所述萃取剂选自二氯甲烷、二氯乙烷、氯仿、四氯化碳、苯、甲苯、二甲苯、乙酸乙酯、乙酸丁酯、乙酸叔丁酯、***、异丙醚、甲基叔丁基醚或正丁醚。
所述步骤(2)中:
所述酸为盐酸、硫酸或氢溴酸;
所述醇为甲醇、乙醇或异丙醇;
所述环氧烷烃为环氧乙烷、环氧丙烷或环氧氯丙烷。
所述步骤(2)中,所述式(Ⅲ)所示化合物、酸、环氧烷烃的摩尔比为1:1-100:1-5。
所述步骤(2)中,所述水解反应的温度为50-160℃,所述转化反应的温度为0-50℃。
本发明所述合成精草铵膦的方法,以L-3,6-双(2-卤乙基)-2,5-二酮哌嗪和甲基亚磷酸单酯为原料进行合成,通过烷基化反应合成了中间体式(Ⅲ)所示化合物,再经水解反应制得精草铵膦。由于L-3,6-双(2-卤乙基)-2,5-二酮哌嗪原料含有手性碳中心,可经过简单反应即制备所需构象的精草铵膦,使得整个合成过程简单易行,且由于原料易得有助于降低生产成本;并且反应中使用了烷基化催化剂,以促进了反应进行,提高了产物的收率,有益于工业化生产。
附图说明
为了使本发明的内容更容易被清楚的理解,下面根据本发明的具体实施例并结合附图,对本发明作进一步详细的说明,其中,
图1为实施例1中制得精草铵膦的ee值测定液相谱图;
图2为实施例1中制得精草铵膦的核磁共振波谱图(1H-NMR);
图3为实施例1中制得精草铵膦的ESI质谱图;
图4为实施例1中制得精草铵膦的红外谱图。
具体实施方式
本发明下述各实施例中合成精草铵膦的步骤按照如下路线图进行:
其中,X选自Cl、Br、I、OSO2CH3、OSO2C6H3或OSO2C7H8;
R选自-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2CH2CH2CH3或-CH2C6H5。
下述各实施例中,对于目标产物精草铵膦的ee值的测定,采用现有技术中已知的高效液相色谱法进行测定,具体测定方法及条件包括:
色谱柱:SUMICHIRAL OA-5000L,5μm,150mm×4.6mm(I.D.);
流动相:2mM硫酸铜水溶液:乙腈=1000:3;
柱温:30℃;
流速:1mL/min;
检测波长:UV220nm;
柱温:30℃。
实施例1
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向1L四口烧瓶中加入L-3,6-双(2-溴乙基)-2,5-二酮哌嗪65.6g(0.2mol)、甲基亚磷酸单丁酯65.2g(0.48mol)、新鲜四氢呋喃300ml、碘化钠0.9g(0.006mol),搅拌均匀后,降温至-50℃,并缓慢滴入正丁基锂己烷溶液268ml(0.4mol),滴加完后搅拌2h,随后升温至室温,继续搅拌反应20h,过滤;收集滤液减压浓缩以除去所述有机溶剂,收集剩余物,并加入水(200ml)、二氯甲烷(100mL×3次)进行萃取分层;随后合并有机相,并回收溶剂二氯甲烷,得到60.1g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率为73.5%;
(2)精草铵膦的合成:将上述得到的式(Ⅲ)所示化合物60.1g(0.147mol)加入至500mL四口烧瓶中,并加入浓盐酸300ml,于110℃进行回流反应20h,减压脱除溶剂,得到精草铵膦盐酸盐;随后加95%的乙醇150ml,于室温下加入环氧丙烷23.4g(0.4mol),搅拌反应3h,过滤,得到所需的精草铵膦49.8g,计算本步骤产率为93.6%,按照前述方法测定产物的ee值为92.9%。
本实施例中制得终产物的ee值测定液相谱图见图1所示,核磁共振波谱图(1H-NMR)见图2所示,其ESI质谱图见图3所示,其红外谱图见图4所示。可见,本发明所述方法制得产物结构正确。
经计算,本实施例中目标产物精草铵膦的总产率为68.8%。
实施例2
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向500ml四口烧瓶中加入L-3,6-双(2-溴乙基)-2,5-二酮哌嗪20g(0.06mol)、甲基亚磷酸单乙酯16.2g(0.15mol)、新鲜乙二醇二甲醚150ml、碘化钠0.3g(0.002mol),搅拌均匀,并降温至-10℃,分批加入乙醇钠8.6g(0.126mol),加完后,搅拌4h,反应升至室温,继续搅拌20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、乙酸乙酯(50mL×3次)萃取分层,合并有机相,回收溶剂乙酸乙酯,得到11.8g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率为56.4%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
实施例3
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向500ml四口烧瓶中加入L-3,6-双(2-氯乙基)-2,5-二酮哌嗪23.9g(0.1mol)、甲基亚磷酸单丁酯32.6g(0.24mol)、新鲜四氢呋喃180ml、碘化钠0.6g(0.004mol),搅拌均匀,降温至-50℃,缓慢滴入正丁基锂己烷溶液134ml(0.2mol),滴加完,搅拌2h,升至室温,继续搅拌反应20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、甲基叔丁基醚(80mL×3次)萃取分层;合并有机相,回收溶剂甲基叔丁基醚,得到27.9g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率68.5%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
实施例4
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向500ml四口烧瓶中加入L-3,6-双(2-溴乙基)-2,5-二酮哌嗪30g(0.09mol)、甲基亚磷酸单异丙酯28.0g(0.23mol)、新鲜乙二醇二甲醚200ml、碘化钠0.3g(0.002mol),搅拌均匀,降温至-10℃,分批加入异丙醇钠15.3g(0.186mol),加完后,搅拌6h,反应升至室温,继续搅拌20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、二氯甲烷(80mL×3次)萃取分层,合并有机相,回收溶剂二氯甲烷,得到17.0g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率48.6%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
实施例5
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向500ml四口烧瓶中加入L-3,6-双(2-溴乙基)-2,5-二酮哌嗪15g(0.045mol)、甲基亚磷酸单丁酯15.3g(0.113mol)、新鲜四氢呋喃150ml、碘化钠0.3g(0.002mol),搅拌均匀,降温至-10℃,分批加入氢化钠3.6g(含量60%,0.09mol),加完后,搅拌6h,反应升至室温,继续搅拌20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、二氯甲烷(50mL×3次)萃取分层,合并有机相,回收溶剂二氯甲烷,得到11.4g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率61.8%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
实施例6
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向500ml四口烧瓶中加入L-3,6-双(2-溴乙基)-2,5-二酮哌嗪20g(0.06mol)、甲基亚磷酸单丁酯20.4g(0.15mol)、新鲜四氢呋喃150ml,搅拌均匀,降温至-50℃,缓慢滴入正丁基锂己烷溶液85ml(0.126mol),滴加完,搅拌2h,升至室温,继续搅拌反应20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、二氯甲烷(50mL×3次)萃取分层;合并有机相,回收溶剂二氯甲烷,得到16.2g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率65.7%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
实施例7
本实施例所述精草铵膦的合成方法包括如下步骤:
(1)式(Ⅲ)所示化合物的合成:在氮气保护下,向1L四口烧瓶中加入L-3,6-双(2-甲磺酰基氧基乙基)-2,5-二酮哌嗪35.8g(0.1mol)、甲基亚磷酸单丁酯34g(0.25mol)、新鲜四氢呋喃400ml,搅拌均匀,降温至-50℃,缓慢滴入正丁基锂己烷溶液137ml(0.206mol),滴加完,搅拌2h,升至室温,继续搅拌反应20h,过滤;滤液减压浓缩除去溶剂,剩余物中加入水(100ml)、二氯甲烷(80mL×3次)萃取分层;合并有机相,回收溶剂二氯甲烷,得到17.9g油状物,即为所需的式(Ⅲ)所示化合物,计算其产率43.8%;
(2)精草铵膦的合成:同实施例1中步骤(2)。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
2.根据权利要求1所述的精草铵膦的合成方法,其特征在于:
所述L-3,6-双(2-卤乙基)-2,5-二酮哌嗪中,X选自Cl、Br或I;
所述甲基亚磷酸单酯中,R选自-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-CH2 CH2CH2CH3或-CH2C6H5。
3.根据权利要求2所述的精草铵膦的合成方法,其特征在于,所述步骤(1)中:
所述溶剂选自四氢呋喃、甲基四氢呋喃、乙二醇二甲醚、二氧六环、二乙二醇二甲醚、二甲基亚砜、N、N-二甲基甲酰胺或N、N-二乙基甲酰胺;
所述碱选自醇锂、醇钠、醇钾、烷基锂、氨基锂、有机胺锂、碱金属的氢盐或碱土金属的氢盐。
4.根据权利要求3所述的精草铵膦的合成方法,其特征在于:所述步骤(1)中,所述L-3,6-双(2-卤乙基)-2,5-二酮哌嗪、甲基亚磷酸单乙酯、有机溶剂、碱和催化剂的摩尔比为1:2-10:1-200:2-10:0.01-0.2。
5.根据权利要求4所述的精草铵膦的合成方法,其特征在于:所述步骤(1)中,所述烷基化反应的温度为-80~100℃。
6.根据权利要求5所述的精草铵膦的合成方法,其特征在于:所述步骤(1)中,还包括对式(Ⅲ)所示化合物进行纯化的步骤,具体包括:取反应液过滤,收集滤液减压浓缩以除去所述有机溶剂,剩余物加入水和萃取剂进行萃取,脱除所述萃取剂,得到式(Ⅲ)所示化合物。
7.根据权利要求6所述的精草铵膦的合成方法,其特征在于,所述萃取剂选自二氯甲烷、二氯乙烷、氯仿、四氯化碳、苯、甲苯、二甲苯、乙酸乙酯、乙酸丁酯、乙酸叔丁酯、***、异丙醚、甲基叔丁基醚或正丁醚。
8.根据权利要求1-7任一项所述的精草铵膦的合成方法,其特征在于,所述步骤(2)中:
所述酸为盐酸、硫酸或氢溴酸;
所述醇为甲醇、乙醇或异丙醇;
所述环氧烷烃为环氧乙烷、环氧丙烷或环氧氯丙烷。
9.根据权利要求8所述的精草铵膦的合成方法,其特征在于,所述步骤(2)中,所述式(Ⅲ)所示化合物、酸、环氧烷烃的摩尔比为1:1-100:1-5。
10.根据权利要求9所述的精草铵膦的合成方法,其特征在于,所述步骤(2)中,所述水解反应的温度为50-160℃,所述转化反应的温度为0-50℃。
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