CN116375764A - Preparation method of glufosinate-ammonium - Google Patents
Preparation method of glufosinate-ammonium Download PDFInfo
- Publication number
- CN116375764A CN116375764A CN202310354575.2A CN202310354575A CN116375764A CN 116375764 A CN116375764 A CN 116375764A CN 202310354575 A CN202310354575 A CN 202310354575A CN 116375764 A CN116375764 A CN 116375764A
- Authority
- CN
- China
- Prior art keywords
- compound
- acid
- glufosinate
- reaction
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 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 claims abstract description 19
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
- 239000000203 mixture Substances 0.000 claims abstract description 68
- -1 alcohol compound Chemical class 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000006227 byproduct Substances 0.000 claims abstract description 25
- 239000005561 Glufosinate Substances 0.000 claims abstract description 18
- 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 claims abstract description 17
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 10
- 230000007062 hydrolysis Effects 0.000 claims abstract description 9
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 4
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 143
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 141
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 22
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical group CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 10
- 150000002989 phenols Chemical class 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- IAJOBQBIJHVGMQ-SCSAIBSYSA-N (2R)-glufosinate Chemical compound C[P@@](O)(=O)CC[C@@H](N)C(O)=O IAJOBQBIJHVGMQ-SCSAIBSYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 150000008282 halocarbons Chemical class 0.000 claims description 4
- 229940071870 hydroiodic acid Drugs 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 2
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 claims description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 2
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 2
- 150000002016 disaccharides Chemical class 0.000 claims description 2
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 150000002772 monosaccharides Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 150000005846 sugar alcohols Polymers 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 22
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000000926 separation method Methods 0.000 abstract description 6
- 238000011084 recovery Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 3
- 239000012467 final product Substances 0.000 abstract description 2
- 238000004064 recycling Methods 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 90
- 229910052757 nitrogen Inorganic materials 0.000 description 61
- 238000003786 synthesis reaction Methods 0.000 description 52
- 230000015572 biosynthetic process Effects 0.000 description 49
- 238000001816 cooling Methods 0.000 description 20
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- 235000019441 ethanol Nutrition 0.000 description 19
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 16
- 238000004321 preservation Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 239000012065 filter cake Substances 0.000 description 15
- ONRKUGHFZWYUJP-UHFFFAOYSA-N methylphosphane dihydrochloride Chemical compound Cl.Cl.PC ONRKUGHFZWYUJP-UHFFFAOYSA-N 0.000 description 15
- 238000011085 pressure filtration Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 238000005406 washing Methods 0.000 description 13
- 238000009835 boiling Methods 0.000 description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 230000006837 decompression Effects 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 239000012295 chemical reaction liquid Substances 0.000 description 8
- HNXNVVLSHDIMHZ-UHFFFAOYSA-N ethyl 2-amino-4-chlorobutanoate Chemical compound CCOC(=O)C(N)CCCl HNXNVVLSHDIMHZ-UHFFFAOYSA-N 0.000 description 8
- HNXNVVLSHDIMHZ-YFKPBYRVSA-N CCOC(=O)[C@@H](N)CCCl Chemical compound CCOC(=O)[C@@H](N)CCCl HNXNVVLSHDIMHZ-YFKPBYRVSA-N 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 230000002363 herbicidal effect Effects 0.000 description 6
- 239000004009 herbicide Substances 0.000 description 6
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000005562 Glyphosate Substances 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 4
- 229940097068 glyphosate Drugs 0.000 description 4
- 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 4
- 238000000967 suction filtration Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- QJYCYHVNBDXPFN-JEDNCBNOSA-N ethyl (2s)-2-amino-4-chlorobutanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CCCl QJYCYHVNBDXPFN-JEDNCBNOSA-N 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethylcyclohexane Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- IVWWFWFVSWOTLP-YVZVNANGSA-N (3'as,4r,7'as)-2,2,2',2'-tetramethylspiro[1,3-dioxolane-4,6'-4,7a-dihydro-3ah-[1,3]dioxolo[4,5-c]pyran]-7'-one Chemical compound C([C@@H]1OC(O[C@@H]1C1=O)(C)C)O[C@]21COC(C)(C)O2 IVWWFWFVSWOTLP-YVZVNANGSA-N 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 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
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-L D-glucarate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O DSLZVSRJTYRBFB-LLEIAEIESA-L 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000001602 Digitaria X umfolozi Nutrition 0.000 description 1
- 235000017898 Digitaria ciliaris Nutrition 0.000 description 1
- 235000005476 Digitaria cruciata Nutrition 0.000 description 1
- 235000006830 Digitaria didactyla Nutrition 0.000 description 1
- 235000005804 Digitaria eriantha ssp. eriantha Nutrition 0.000 description 1
- 235000010823 Digitaria sanguinalis Nutrition 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 244000025670 Eleusine indica Species 0.000 description 1
- 235000014716 Eleusine indica Nutrition 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical class OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- UYQVCLAMCWIBKC-UHFFFAOYSA-N OOP(=O)(OC)CCC(N)C(=O)O Chemical compound OOP(=O)(OC)CCC(N)C(=O)O UYQVCLAMCWIBKC-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- QJPWUUJVYOJNMH-UHFFFAOYSA-N alpha-amino-gamma-butyrolactone Natural products NC1CCOC1=O QJPWUUJVYOJNMH-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- MOFCYHDQWIZKMY-UHFFFAOYSA-N chloromethylphosphonic acid Chemical compound OP(O)(=O)CCl MOFCYHDQWIZKMY-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 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-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960001078 lithium Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- RXMBKOPBFXCPDD-UHFFFAOYSA-N methoxyphosphonamidous acid Chemical compound COP(N)O RXMBKOPBFXCPDD-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application relates to a preparation method of glufosinate. In particular to a method for preparing glufosinate represented by a formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion, which comprises the following steps: reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion with an alcohol compound or a phenol compound, and hydrolyzing the reaction product after separating by-products to obtain a compound of formula (I). The by-product can reach the recovery rate of more than 90% after being separated by a simple separation process, and the obtained by-product can be sold or further purified for recycling, thereby greatly reducing the cost of raw materials and reducing the emission of three wastes. In addition, the by-product can be separated and recovered before hydrolysis, so that the separation and purification difficulty of the final product is greatly reduced, the product yield is obviously improved, the content is slightly improved, and the ee value is maintained.
Description
Technical Field
The application relates to the field of pesticide herbicides, in particular to a preparation method of glufosinate-ammonium.
Background
Glufosinate was developed and produced by the germany helter company under the chemical name 4- [ hydroxy (methyl) phosphono ] -DL-homoalanine, and is a glutamine synthesis inhibitor and a nonselective contact herbicide. The action mechanism is to inhibit the activity of glutamine synthetase in plants, which leads to the inhibition of glutamine synthesis, nitrogen metabolism disorder and ammonium ion accumulation, thus interfering with the metabolism of plants and leading to the death of the plants.
The glufosinate has the characteristics of wide weed control spectrum, low toxicity, high activity, good environmental compatibility, small drift and the like, and can prevent and kill more than 100 annual and perennial broadleaf weeds and grassy weeds such as crabgrass, ryegrass and the like. The active action speed of the herbicide is slower than that of paraquat but better than that of glyphosate, and the herbicide is a nonselective herbicide which coexists with the glyphosate and the paraquat.
The glufosinate-ammonium molecule contains a chiral carbon and has two different configurations, namely L-glufosinate-ammonium and D-glufosinate-ammonium, wherein only L-isomer has herbicidal activity, is easier to decompose in soil, has low toxicity to human beings and animals, and can greatly reduce environmental stress, so that the activity and the control effect on resistant weeds are better than those of common glufosinate-ammonium.
In recent years, with the remarkable problems of paraquat inhibition and glyphosate resistance, the global glufosinate resistance gene is further introduced into tens of crops such as rice, wheat, corn, beet, tobacco, soybean, cotton, potato, tomato, rape and sugarcane, and the like, so that the substitution process of glufosinate for the other two is accelerated. Although most of the glufosinate commercial products sold on the market at present are racemates thereof, with technical innovation and progress, the L-glufosinate enters the mainstream market to be impossible.
The existing method for preparing chiral pure L-glufosinate mainly comprises a chemical method and a biological method. Wherein the chemical method comprises a chemical resolution method and a chemical synthesis method.
The preparation of L-glufosinate by chemical synthesis can be further subdivided into: adopts an asymmetric synthesis method and a total synthesis method which takes L-amino acid obtained by natural or fermentation as a raw material. The latter has high purity chiral center, so that the method has more convenient synthetic route and good ee value maintaining characteristic than other methods, and is more and more important for domestic and foreign enterprises and research institutions.
The patent specification with publication number of US5442088A discloses a method for obtaining L-glufosinate-ammonium hydrochloride by performing ring-opening chlorination, esterification and Michaelis-Arbuzov reaction on amino-protected L-homoserine lactone serving as a raw material and methyl phosphorous diester, and finally hydrolyzing and refining.
The multistep reaction process unit is convenient to operate, but the activity of chlorinated substrates of Michaelis-Arbuzov reaction raw materials is low, the process can be usually carried out at a high temperature, meanwhile, the chlorinated alkane byproducts and methyl phosphodiester are subjected to side reaction at a high temperature, so that the unit consumption is greatly increased, and in addition, the excessive value of L-type enantiomers is reduced due to racemization of part of raw materials or products.
Patent specification publication No. CN113490671B discloses: amino protected or unprotected halogenated homoserine ester is taken as a raw material, condensed with methyl phosphonite monochloro ester, cyclized by intramolecular Michaelis-Arbuzov reaction to obtain an intermediate, and then hydrolyzed to obtain the L-glufosinate-ammonium.
In the synthetic route, the Michaelis-Arbuzov reaction inevitably generates halogenated hydrocarbons, the small-molecule halogenated hydrocarbons are 3 types of carcinogens and have a destructive effect on ozone in the atmosphere, and in addition, diethyl methylphosphinate is still needed for in-situ preparation of monochloromethylphosphonate.
The patent with the application number of CN202310033931.0 provides a synthetic route for preparing glufosinate-ammonium by taking halogenated homoserine and derivatives thereof as raw materials, condensing, cyclization, hydrolysis and refining with methyl phosphoramidite and analogues thereof. The route can avoid halogenated hydrocarbon byproducts in Michaelis-Arbuzov reaction due to different reaction mechanisms, and the reaction temperature is reduced due to the improvement of the activity of a reaction substrate, so that the L-configuration content of a product is improved, but the hydrolysis process of the method brings ammonium salt and other byproducts which are unfavorable for the purification of the product and the improvement of the yield.
In recent years, with the problems of paraquat forbidden and glyphosate resistance, the demand of glufosinate is increased year by year, so that the development of the glufosinate synthesis method which has the advantages of mild reaction conditions, higher yield, lower cost and simple operation has extremely important significance for herbicide use reduction and synergy.
Disclosure of Invention
For the sake of brevity, the "compound of formula (N) (e.g., compound of formula (II)" described hereinafter may also encompass any optical isomer, geometric isomer, tautomer or mixture of isomers, or agriculturally acceptable salt of the compound of formula (N).
The term "optical isomer" means that when a compound has one or more chiral centers, each chiral center may exist in either the R configuration or the S configuration, and thus the various isomers constituted are optical isomers. Optical isomers include all diastereoisomers, enantiomers, meso, racemates or mixtures thereof. For example, the optical isomers may be separated by chiral chromatography columns or by chiral synthesis.
The term "geometric isomer" means that when a double bond is present in a compound, the compound may exist as cis, trans, E and Z isomers. Geometric isomers include cis, trans, E, Z, or mixtures thereof.
The term "tautomer" refers to an isomer that results from the rapid movement of an atom in a molecule at two positions. Those skilled in the art will appreciate that: tautomers can be transformed into each other, and in a certain state, an equilibrium state may be reached and coexist.
Unless otherwise indicated, references herein to "a compound of formula (N) (e.g., a compound of formula (II)", also encompass isotopically-labeled compounds wherein any one of the atoms in the compound is replaced by an isotopically-substituted atom thereof. That is, the present invention includes all agriculturally acceptable isotopically-labeled compounds of formula (N) wherein one or more atoms are replaced by an atom having the same atomic number but a different atomic mass or mass number than those typically found in nature.
Examples of isotopes suitable for inclusion in the compounds of the invention include isotopes of hydrogen, such as 2 H (D) and 3 isotopes of H (T), carbon, such as 11 C、 13 C and C 14 Isotopes of C, chlorine, such as 37 Isotopes of Cl, fluorine, such as 18 Isotopes of F, iodine, such as 123 I and 125 isotopes of I, nitrogen, such as 13 N and 15 isotopes of N, oxygen, such as 15 O、 17 O and 18 isotopes of O, and sulfur, such as 35 S。
Isotopically-labeled compounds of formula (N) can generally be prepared by conventional techniques known to those skilled in the art or by using an appropriate isotopically-labeled reagent in place of the non-labeled reagent previously used in a manner analogous to those described in the examples and preparations attached herein.
The compounds of formula (N) may be present in the form of agriculturally acceptable salts, for example, acid addition salts and/or base addition salts of the compounds of formula (N). As used herein, unless otherwise indicated, "agriculturally acceptable salts" include acid addition salts or base addition salts that may occur within the compounds of formula (N).
Agriculturally acceptable salts of the compound of formula (N) include acid addition salts and base addition salts thereof. Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include, but are not limited to: acetate, adipate, aspartate, benzoate, benzenesulfonate, bicarbonate/carbonate, bisulfate/sulfate, borate, camphorsulfonate, citrate, cyclohexylamine sulfonate, ethanedisulfonate, formate, fumarate, glucoheptonate, gluconate, glucuronate, hexafluorophosphate, 2- (4-hydroxybenzyl) benzoate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, 2-isethionate, lactate, malate, maleate, malonate, methanesulfonate, methylsulfate, napthalate, 2-naphthalenesulfonate, nicotinate, nitrate, orotate, oxalate, palmitate, phosphate/hydrogen phosphate/dihydrogen phosphate, pyroglutamate, glucarate, stearate, salicylate, tannate, tartrate, tosylate and trifluoroacetate. Suitable base addition salts are formed from bases which form non-toxic salts. Examples include, but are not limited to: ammonium salts, aluminum, arginine, calcium, choline, diethylamine, diethanolamine, glycine, lysine, magnesium, meglumine, ethanolamine, potassium, sodium, lithium, tromethamine and zinc salts. Semi-salts of acids and bases, such as hemisulfate and hemicalcium salts, may also be formed. Methods for preparing agriculturally acceptable salts of the compounds described herein are known to those skilled in the art.
Certain compounds of the invention may exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the compounds of formula (N), whether in solvated form or unsolvated form, are encompassed within the scope of the present invention.
Certain compounds of the present invention may exist in different crystalline or amorphous forms, and, regardless of the form in which they exist, the compounds of formula (N) are included within the scope of the present invention.
To avoid ambiguity, definitions are given below for terms used herein. Unless otherwise indicated, the terms used herein have the following meanings.
As used herein, the term "substituted" means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms in the group are independently replaced by a corresponding number of substituents.
As used herein, the term "independently" means that when the number of substituents exceeds one, the substituents may be the same or different.
As used herein, the term "optional" or "optionally" means that the event described may or may not occur. For example, a group "optionally substituted" means: the group may be unsubstituted or substituted.
As used herein, the term "heteroatom" represents oxygen (O), nitrogen (N), or S (O) m (wherein m may be 0, 1 or 2, i.e., sulfur atom S, or sulfoxide group SO, or sulfonyl group S (O) 2 )。
As used herein, the term "alkyl" refers to saturated aliphatic hydrocarbons, including straight and branched chains. In some embodiments, the alkyl group has, for example, 1 to 6 or 1 to 3 carbon atoms. For example, the term "C 1 -C 6 Alkyl "refers to a straight or branched chain radical having 1 to 6 carbon atoms. The term "C 1 -C 6 Alkyl "includes the term" C "in its definition 1-6 Alkyl "," C 1 -C 3 Alkyl "and" C 1 -C 4 An alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, (R) -2-methylbutyl, (S) -2-methylbutyl, 3-methylbutyl, 2, 3-dimethylpropyl, 2, 3-dimethylbutyl, hexyl, and the like.
As used herein, the term "C 3 -C 6 Cycloalkyl "refers to cycloalkyl groups having 3 to 6 ring-forming carbon atoms. For example, C 3 -C 6 Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
As used herein, the term "n-membered heterocycloalkyl" refers to cycloalkyl having m ring-forming carbon atoms and (n-m) ring-forming heteroatoms selected from at least one of N, O and S. For example, ternary to hexacyclic heterocycloalkyl groups include, but are not limited to, oxetane, thietane, azetidine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, piperazine.
As used herein, the term "C 6 -C 10 Aryl "means aryl having an aromatic ring containing 6 to 10 carbon atoms, preferably phenyl.
As used herein, the term "n-membered heteroaryl" refers to a heteroaryl group having m carbon atoms forming an aromatic ring and (n-m) heteroatoms forming an aromatic ring, said heteroatoms being selected from at least one of N, O and S. For example, five to ten membered heteroaryl groups include, but are not limited to, pyrazine, pyrazole, pyrrole, furan, thiophene, thiazole, pyridine.
As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). For example, the term "C 1 -C 6 Haloalkyl "means C having one or more halo substituents 1 -C 6 An alkyl group (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). As another example, the term "C 1 Haloalkyl "refers to a methyl group having 1, 2 or 3 halogen substituents. Examples of haloalkyl groups include: CF (compact flash) 3 、C 2 F 5 、CHF 2 、CH 2 F、CH 2 CF 3 、CH 2 Cl, and the like.
In this context, a range of numbers relating to the number of substituents, the number of carbon atoms, and the number of ring atoms represents a list of all integers within the range, and the range is merely a simplified representation. For example: "1-4 substituents" means 1, 2, 3 or 4 substituents; "3-8 carbon atoms" means 3, 4, 5, 6, 7 or 8 carbon atoms. Accordingly, a range of numbers relating to the number of substituents, the number of carbon atoms, the number of ring atoms also encompasses any one of its subranges, and each subrange is also considered disclosed herein.
In view of the above technical problems and the shortcomings in the art, the present invention provides a method for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, comprising the steps of:
1) Reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion with an alcohol compound or a phenolic compound,
and
2) Separating the reaction product of step 1) into byproducts, hydrolyzing to obtain a compound of formula (I),
wherein,,
x is halogen;
y is-OR 3 or-N (R) 4 )(R 5 )；
R 1 And R is 2 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 1 And R is 2 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution;
R 3 、R 4 and R is 5 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 4 And R is 5 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution; and is also provided with
* For identifying chiral carbon atoms.
According to the invention, the compounds of formula (I) may exist in the form of a single enantiomer, for example, in one embodiment of the invention, the compounds of formula (I) may be pure L-glufosinate or D-glufosinate. In addition, the compounds of formula (I) may also be present in the form of mixtures of enantiomers, and the enantiomers may each be present in any proportion in the mixture of enantiomers, for example, in one embodiment of the invention, a mixture of enantiomers of formula (I) in any proportion comprises 0.1:99.9 to 99.9: 0.1L-glufosinate and D-glufosinate. However, since only L-glufosinate is active, the L-enantiomer of the compounds of formula (I) of the present invention may also preferably be present in greater proportion in the enantiomeric mixture, e.g., in one embodiment, a mixture of any proportion of enantiomers of the compounds of formula (I) comprises 50:50 to 99.9:0.1 L-glufosinate and D-glufosinate (e.g., 60:40, 70:30, 80:20, 90:10, 95:5, 96:4, 97:3, 98:2, or 99:1, etc.).
As a preferred embodiment of the compounds of formula (II), R 1 、R 2 、R 3 、R 4 And R is 5 Can each be independently selected from hydrogen, C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl, preferably hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. More preferably, in the compound of formula (II), X is selected from chlorine, R 1 And R is 2 Independently selected from hydrogen, methyl, ethyl OR phenyl, Y is selected from OR 4 And R is 4 Selected from hydrogen, methyl, ethyl or isopropyl. Additionally, in a preferred embodiment, as used herein, halogen may be selected from fluorine, chlorine or bromine; c (C) 1 -C 6 The alkyl group may be selected from methyl, ethyl, propyl or isopropyl; c (C) 2 -C 6 Alkenyl groups may be selected from ethenyl, propenyl, 1-butenyl, 2-butenyl or isobutenyl; c (C) 2 -C 6 Alkynyl groups may be selected from ethynyl, propynyl, 1-butynyl or 2-butynyl; c (C) 3 -C 6 Cycloalkyl groups may be selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; the three-to six-membered heterocycloalkyl group may be selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl containing at least one heteroatom in N, O and S; c (C) 6 -C 10 Aryl may be selected from phenyl or naphthyl; and/or five to ten membered heteroaryl groups may be selected from pyrazinyl, pyrazolyl, pyrrolyl, furanyl, thienyl, thiazolyl or pyridyl.
As an alternative to the compounds of formula (II), R 1 、R 2 、R 3 、R 4 And R is 5 Or may be each independently selected from-Si (R) 8 )(R 9 )(R 10 ) Wherein R is 8 、R 9 And R is 10 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five to ten membered heteroaryl, wherein the C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution.
Further, the preparation method of the present invention may further comprise a step of preparing the compound of formula (II). More specifically, the steps of the process for the preparation of the compound of formula (II) may be carried out by steps as described in another patent application CN202310033931.0 by the applicant, the entire content of which is incorporated herein by reference.
In addition, the alcohol compound or phenol compound used in step 1) may be an alcohol compound or phenol compound commonly known in the art, and is not particularly limited. In one embodiment of the present invention, the alcohol compound may be a monohydric or polyhydric alcohol (e.g., dihydric, trihydric, etc.), or may be a monosaccharide, disaccharide, or polysaccharide compound (e.g., glucose, sucrose, starch, etc.); preferably, the alcohol compound can be glucose or R 6 (OH) n A compound of formula wherein R 6 Selected from C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl, and n is any integer from 1 to 3; more preferably, the alcohol compound may be methanol, ethanol, isopropanol, ethylene glycol, glycerol, or glucose. In another embodiment of the present invention, the phenolic compound may be a compound selected from the group consisting of R 7 (OH) m A compound of formula wherein R 7 Selected from C 6 -C 10 Aryl or five to ten membered heteroaryl, and m is any integer from 1 to 3; preferably, the phenolic compound is represented by R 7 (OH) m A compound of formula wherein R 7 Is phenyl, and m is any integer from 1 to 3; more preferably, the phenolic compound is phenol.
In the above step 1), the amounts of each reactant and the reaction conditions in the step of reacting the compound of formula (II) with the alcohol or phenol compound as described above may be adjusted according to actual needs and knowledge of those skilled in the art. In one embodiment of the invention, the molar ratio of the compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion to the alcohol compound or phenolic compound is 1:0.5-100, preferably 1:2-20 (e.g., 1:3, 1:4, 1:5, 1:8, 1:10, 1:12, 1:15, 1:18, or 1:20, etc.). In another embodiment of the present invention, the reaction may be carried out at a temperature of 20-130 ℃ (e.g., 30 ℃, 40 ℃, 50 ℃, 60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 90 ℃, 100 ℃, 110 ℃, 120 ℃, etc.), preferably 60-80 ℃, and the reaction time may be 1-20 hours (e.g., 2 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 18 hours, 20 hours, etc.).
In the above step 1), the reaction of the compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion with the alcohol compound or phenol compound may be carried out optionally in the presence of an acid, wherein the acid may preferably be at least one of hydrogen chloride, hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid and acetic acid, and may further preferably be hydrogen chloride, hydrochloric acid or sulfuric acid. In a more preferred embodiment, the molar ratio of the compound of formula (II) to the hydrogen ions in the acid is 1:0.1-10 (e.g., 1:0.1, 1:0.2, 1:0.5, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:5, or 1:10, etc.), preferably 1:0.9-2. That is, depending on the stoichiometry, the molar amount of acid used can be adjusted accordingly.
The above step 1) may be performed in the absence of a solvent or an organic solvent. In one embodiment of the present invention, the organic solvent is selected from an aromatic hydrocarbon solvent (e.g., benzene, xylene, trimethylbenzene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, halogenated benzene or dihalobenzene), an alkane solvent (e.g., N-hexane, cyclohexane, N-heptane, methylcyclohexane, ethylcyclohexane), a halogenated hydrocarbon solvent (e.g., dichloromethane, dichloroethane, chloroform or carbon tetrachloride), an ether solvent (e.g., tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, methylcyclopentyl ether, ethylene glycol dimethyl ether, dioxane or diethylene glycol dimethyl ether), an ester solvent (e.g., ethyl acetate, isopropyl acetate or butyl acetate), an amide solvent (e.g., N-dimethylformamide, N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone or 1, 3-dimethyl-2-imidazolidinone) or a sulfur-containing solvent (e.g., dimethylsulfoxide or sulfolane), preferably, the organic solvent is selected from at least one of toluene and chlorobenzene.
Further, in the above step (1), after the completion of the reaction of the compound of the formula (II) with the alcohol or phenol compound, a by-product, for example, HN (R) is optionally separated, such as removal of low boiling substances or solid-liquid separation 1 )(R 2 ) Or the salt thereof can be recycled after recovery treatment, and the filtrate can be directly used for the next reaction. Thus, in one embodiment of the present invention, the byproduct HN (R) 1 )(R 2 ) Or a salt thereof, is preferably recycled.
In step 2), the hydrolysis may be carried out directly under neutral conditions, i.e. the hydrolysis reaction may be carried out directly in the presence of water. In addition, the hydrolysis may also preferably be carried out in the presence of an acid or a base. More specifically, the acid may be selected from at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid, and acetic acid, preferably hydrochloric acid or sulfuric acid; the base may be selected from alkali or alkaline earth metal hydroxides, carbonates, bicarbonates or hydroxycarbonates, ammonia, organic bases, organic amines, preferably sodium hydroxide or triethylamine. In addition, in one embodiment of the present invention, the hydrolysis may be performed at a temperature of, for example, 30 to 140 ℃ (e.g., 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃, 110 ℃, 120 ℃, 130 ℃, etc.), preferably 70 to 110 ℃.
Those skilled in the art will appreciate that the definitions and preferences described in one aspect of the present application apply equally to other aspects. It will be apparent to those skilled in the art that the embodiments of the various aspects of the present application may be combined in various ways without departing from the subject matter and concepts of the application, and such combinations are also included within the scope of the application.
According to research, compared with the prior art, the invention at least has the following beneficial effects:
1. by-product HN (R) 1 )(R 2 ) Or the salt thereof can obtain the recovery rate of more than 90 percent after separation and recovery, and the obtained byproducts can be sold or further purified for recycling, thereby greatly reducing the cost of raw materials and reducing the emission of three wastes; and
2. the separation and recovery of the byproducts can be carried out before the hydrolysis, so that the separation and purification difficulty of the final product is greatly reduced, the product yield is obviously improved, the content is slightly improved, and the ee value is maintained.
Detailed Description
The invention is further illustrated by the following examples; but these examples do not limit the scope of the invention. All reactants used in each example were obtained commercially unless otherwise stated; the instruments and equipment used in the synthesis experiments and the product analysis and detection are all conventional instruments and equipment commonly used in organic synthesis.
Example 1: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (67.77 g,0.927mol,2.12 eq.) was added to 255.5g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (51.1 g,0.437mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (69.78 g, 0.426 mol,0.96 eq) is added into 209.4g of toluene, diethylamine (30.82 g, 0.426 mol,0.96 eq.) is added, and after stirring uniformly, the above prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, and the reaction is carried out after the addition is completed for 2 hours. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-1) reaction solution, wherein the compound (II-1) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Ethanol (97.06 g,2.107mol,4.82 eq.) is added into the reaction solution of the compound (II-1), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 383.3g of 30 percent hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 383.3g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 83.6g of the target product (I-1), the yield is 89.5%, the content is 98.2%, and the ee is 97.4%.
Example 2: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (68.01 g,0.930mol,2.14 eq.) was added to 254.0g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (50.80 g,0.435mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (69.09 g,0.417mol,0.96 eq.) is added into 207.3g toluene, diethylamine (30.51 g,0.417mol,0.96 eq.) is added, after stirring evenly, the above prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, and the reaction is carried out after the addition for 2 hours. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-1) reaction solution, wherein the compound (II-1) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
To the reaction solution of the above compound (II-1), 112.82g of an ethanol solution containing hydrogen chloride (16.73 g,0.459mol,1.06 eq.) was added and heated to 70-80℃for reaction for 5 hours. Removing low-boiling substances under reduced pressure, cooling to normal temperature, filtering to obtain byproduct salt, adding 381.0g of 30% hydrochloric acid into filtrate, stirring for 0.5 hr, standing for layering, heating to 95-105deg.C, and reacting. After the reaction, the mixture is decompressed, desolventized and dried, 381.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 84.4g of the target product (I-1), the yield is 91.4%, the content is 98.3%, and the ee is 97.5%.
Example 3: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (68.63 g,0.938mol,2.13 eq.) was added to 257.5g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (51.5 g,0.441mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, adding (2S) -2-amino-4-ethyl chlorobutyrate [ CAS No.:777033-03-1] (69.53 g,0.420mol,0.95 eq.) into 208.6g toluene, adding diethylamine (30.70 g,0.420mol,0.95 eq.) into the mixture, stirring the mixture uniformly, adding the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution under ice bath cooling, controlling the internal temperature of the system to be 5-10 ℃, keeping the temperature after the addition for 2 hours, and slowly heating the mixture to 80-85 ℃ for keeping the temperature for reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-1) reaction solution, wherein the compound (II-1) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Phenol (79.02 g, 0.84mol, 1.91 eq.) is added into the reaction solution of the compound (II-1), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 386.3g of 30% hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 386.3g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain a white solid, namely 79.5g of the target product (I-1), the yield is 85.4%, the content is 98.1%, and the ee is 97.4%.
Comparative example 1: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (66.08 g, 0.254 mol,2.1 eq.) was added to 251.5g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (50.30 g,0.430mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (67.69 g, 0.09 mol,0.95 eq.) is added into 203.1g of toluene, diethylamine (29.89 g, 0.09 mol,0.95 eq.) is added, and after stirring uniformly, the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, the reaction is carried out after the addition for 2 hours, and the temperature is slowly raised to 80-85 ℃ for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-1) solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
377.3g of 30% hydrochloric acid was added to the solution of the above compound (II-1), and the aqueous phase was heated to 95-105℃to react. After the reaction, the mixture is distilled under reduced pressure to remove the solvent until the mixture is dried, 377.3g of absolute ethyl alcohol is added, the mixture is heated to reflux for dissolving, cooled for crystallization, filtered and dried to obtain white solid, namely 74.4g of the target product (I-1), the yield is 81.8%, the content is 97.8%, and the ee is 97.2%.
Example 4: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (137.20 g,1.876mol,4.25 eq.) was added to 258.0g toluene, cooled to-5-5 ℃ under nitrogen, and methylphosphine dichloride (51.6 g,0.441mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the completion of the dropwise addition, the temperature was kept for 0.5 hour, the temperature was slowly raised to an internal temperature of 80-85 ℃, 255.3g of toluene suspension of (2S) -2-amino-4-chlorobutyric acid ethyl ester hydrochloride [ CAS No.:162955-16-0] (85.09 g,0.421mol,0.95 eq) was added dropwise, the thermal insulation reaction was continued for 10 hours after the completion of the dropwise addition, nitrogen pressure filtration was continued, the filter cake was washed twice with toluene, and the filtrate was combined to obtain a compound (II-1) reaction solution, which could be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Ethanol (96.99 g,2.105mol,4.77 eq.) is added into the reaction solution of the compound (II-1), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, the low-boiling substances and byproducts are removed under reduced pressure, 387.0g of 30% hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 387.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed and dissolved, cooled, crystallized, filtered and dried to obtain white solid, namely 84.3g of target product (I-1), the yield is 90.2%, the content is 98.0%, and the ee is 97.3%.
Example 5: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (133.48 g, 1.435 mol,4.2 eq.) was added to 254.0g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (50.8 g,0.435mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the completion of the dropwise addition, the temperature was kept for 0.5 hour, the temperature was gradually raised to 80-85℃and a suspension of (2S) -ethyl 2-amino-4-chlorobutyrate hydrochloride [ CAS No.:162955-16-0] (84.30 g,0.417mol,0.96 eq) in 252.9g of toluene was added dropwise, and the dropwise addition was continued for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-1) reaction solution, wherein the compound (II-1) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Adding 112.82g of ethanol solution prepared to contain hydrogen chloride (16.73 g,0.459mol,1.06 eq.) into the reaction solution of the compound (II-1), heating to 70-80 ℃ for reaction for 5 hours, decompressing to remove low-boiling substances, cooling to normal temperature, suction filtering to obtain byproduct salt, adding 381.0g of 30% hydrochloric acid into filtrate, stirring for 0.5 hour, standing for layering, heating to 95-105 ℃ by water phase, and reacting. After the reaction, the mixture is decompressed, desolventized and dried, 381.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 86.3g of the target product (I-1), the yield is 93.4%, the content is 98.2%, and the ee is 97.2%.
Comparative example 2: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (128.51 g,1.757mol,4.1 eq.) was added to 250.5g toluene, cooled to-5-5 ℃ under nitrogen, and methylphosphine dichloride (50.10 g, 0.428 mol,1.0 eq.) was started to drop while maintaining the system temperature at-5-5 ℃. After the completion of the dropwise addition, the temperature was kept for 0.5 hour, the temperature was slowly raised to an internal temperature of 80-85 ℃, and a suspension of 246.8g of toluene (2S) -2-amino-4-chlorobutyric acid ethyl ester hydrochloride [ CAS No.:162955-16-0] (82.407 mol,0.95 eq) was added dropwise, the dropwise addition was continued for 10 hours after the completion of the thermal insulation reaction, the nitrogen pressure filtration was carried out, the filter cake was washed twice with toluene, and the filtrate was combined to obtain a reaction solution of the compound (II-1) which could be directly used for the next reaction.
2) Synthesis of Compound (I-1)
375.8g of 30% hydrochloric acid is added into the reaction solution of the compound (II-1), the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95-105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 375.8g of absolute ethyl alcohol is added, the mixture is heated, refluxed and dissolved, cooled, crystallized, filtered and dried to obtain a white solid, namely 77.9g of the target product (I-1), the yield is 85.4%, the content is 97.1%, and the ee is 97.0%.
Example 6: synthesis of DL-glufosinate hydrochloride (I-2)
1) Synthesis of Compound (II-2)
Diethylamine (73.67 g,1.007mol,2.3 eq.) was added to 256.0g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (51.20 g,0.438mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl 2-amino-4-chlorobutyrate [ CAS No.:806595-35-7] (71.30 g,0.430mol,0.98 eq.) is added into 213.9g of toluene, diethylamine (31.49 g,0.430mol,0.98 eq.) is added, and after stirring uniformly, the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, the reaction is carried out after the addition, the temperature is kept for 2 hours, and the temperature is slowly raised to 80-85 ℃ for heat preservation reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-2) reaction solution, wherein the compound (II-2) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-2)
Ethanol (99.17 g,2.152mol,4.92 eq.) is added into the reaction solution of the compound (II-2), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 384.0g of 30% hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction is finished, decompression and desolventizing are carried out until the reaction is finished, 384.0g of absolute ethyl alcohol is added, heating, refluxing and clearing are carried out, cooling crystallization is carried out, suction filtration and drying are carried out, and white solid is obtained, namely 85.4g of target product (I-2), the yield is 89.8%, and the content is 98.5%.
Example 7: synthesis of DL-glufosinate hydrochloride (I-2)
1) Synthesis of Compound (II-2)
Diethylamine (72.95 g,0.997mol,2.3 eq.) was added to 253.5g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (50.7 g, 0.433 mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl 2-amino-4-chlorobutyrate [ CAS No.:806595-35-7] (70.67 g,0.427mol,0.98 eq.) is added into 212.0g of toluene, diethylamine (31.21 g,0.427mol,0.98 eq.) is added, and after stirring uniformly, the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, the reaction is carried out after the addition is carried out for 2 hours, and the temperature is slowly raised to 80-85 ℃ for heat preservation reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-2) reaction solution, wherein the compound (II-2) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-2)
To the reaction solution of the above compound (II-2), 116.19g of an ethanol solution containing hydrogen chloride (17.89 g,0.491mol,1.13 eq.) was added, and the mixture was heated to 70-80℃for reaction for 5 hours. Removing low-boiling substances under reduced pressure, cooling to normal temperature, filtering to obtain byproduct salt, adding 380.3g of 30% hydrochloric acid into filtrate, stirring for 0.5 hr, standing for layering, heating to 95-105deg.C, and reacting. After the reaction is finished, decompression and desolventizing are carried out until the reaction is finished, 380.3g of absolute ethyl alcohol is added, heating, refluxing and clearing are carried out, cooling crystallization is carried out, suction filtration and drying are carried out, thus obtaining the white solid which is 87.9g of the target product (I-2), the yield is 93.3%, and the content is 98.6%.
Example 8: synthesis of DL-glufosinate hydrochloride (I-2)
1) Synthesis of Compound (II-2)
Diethylamine (72.59 g,0.992mol,2.24 eq.) was added to 259.0g toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (51.80 g,0.443mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl 2-amino-4-chlorobutyrate (CAS No.:806595-35-7] (72.65 g,0.439mol,0.99 eq.) is added into 218.0g of toluene, diethylamine (32.08 g,0.439mol,0.99 eq.) is added, after stirring uniformly, the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, the reaction is carried out after the addition is carried out for 2 hours, and the temperature is slowly raised to 80-85 ℃ for heat preservation reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-2) reaction solution, wherein the compound (II-2) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-2)
Glycerol (81.61 g,0.886mol,2.0 eq.) is added into the reaction solution of the compound (II-2), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 388.5g of 30 percent hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction is finished, decompression and desolventizing are carried out until the reaction is finished, 388.5g of absolute ethyl alcohol is added, heating, refluxing and clearing are carried out, cooling crystallization is carried out, suction filtration and drying are carried out, thus obtaining 82.7g of target product (I-2), the yield is 85.3%, and the content is 98.4%.
Comparative example 3: synthesis of DL-glufosinate hydrochloride (I-2)
1) Synthesis of Compound (II-2)
Diethylamine (69.37 g,0.948mol,2.2 eq.) was added to 252.0g toluene and cooled to-5-5 ℃ under nitrogen, and methyl phosphine dichloride (50.4 g,0.431mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the reaction is carried out for 0.5 hour under the condition of heat preservation, and N, N-diethyl-methyl phosphoramidite monochloro [ CAS No. 40467-94-5] reaction liquid is obtained for standby.
Under the protection of nitrogen, ethyl 2-amino-4-chlorobutyrate (CAS No.:806595-35-7] (69.97 g, 0.428 mol,0.98 eq.) is added into 209.9g of toluene, diethylamine (30.90 g, 0.428 mol,0.98 eq.) is added, and after stirring uniformly, the prepared N, N-diethyl-methylphosphinamide monochloro reaction solution is added under ice bath cooling, the internal temperature of the system is controlled to be 5-10 ℃, the reaction is carried out after the addition is carried out for 2 hours, and the temperature is slowly raised to 80-85 ℃ for heat preservation reaction for 10 hours. And (3) carrying out pressure filtration by using nitrogen, washing a filter cake twice by using toluene, and combining filtrate to obtain a compound (II-2) reaction solution, wherein the compound (II-2) reaction solution can be directly used for the next reaction.
2) Synthesis of Compound (I-2)
378.0g of 30% hydrochloric acid is added into the reaction solution of the compound (II-2), stirred for 0.5 hour, then the mixture is stood for layering, and the mixture is heated to 95-105 ℃ to react. After the reaction is finished, decompression and desolventizing are carried out until the reaction is finished, 378.0g of absolute ethyl alcohol is added, heating, refluxing and clearing are carried out, cooling crystallization is carried out, suction filtration and drying are carried out, thus obtaining a white solid which is 76.3g of the target product (I-2), the yield is 81.7%, and the content is 98.4%.
Example 9: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-3)
N-methylaniline (96.21 g,0.898mol,2.05 eq.) was added to 358.4g toluene, cooled to-5-5℃under nitrogen protection, and methylphosphine dichloride (51.20 g,0.438mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the mixture is reacted for 0.5 hour by heat preservation, and N-methyl-N-phenyl-methyl phosphoramidite monochloro [ CAS No. 91275-60-4] is obtained for standby.
Ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (71.23 g,0.430mol,0.98 eq) was added to 356.1g of toluene under nitrogen protection, N-methylaniline (46.09 g,0.430mol,0.98 eq) was added, and after stirring uniformly, the above-mentioned pre-prepared N-methyl-N-phenyl-methylphosphinamide monochloro reaction solution was added under ice bath cooling, the internal temperature of the system was controlled at 5-10℃and the reaction was continued for 2 hours. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by nitrogen, washing a filter cake twice by toluene, and combining filtrate to obtain a compound (II-3) reaction solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Ethanol (99.06 g,2.150mol,4.91 eq.) is added into the reaction solution of the compound (II-3), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 384.0g of 30 percent hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 384.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 78.4g of the target product (I-1), the yield is 82.1%, the content is 98.0%, and the ee is 97.1%.
Example 10: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-3)
N-methylaniline (99.13 g,0.925mol,2.1 eq.) was added to 360.5g toluene, cooled to-5-5℃under nitrogen protection, and methylphosphine dichloride (51.50 g,0.441mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the mixture is reacted for 0.5 hour by heat preservation, and N-methyl-N-phenyl-methyl phosphoramidite monochloro [ CAS No. 91275-60-4] is obtained for standby.
Ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (72.23 g,0.436mol,0.99 eq) was added to 361.1g of toluene under nitrogen protection, N-methylaniline (49.07 g,0.458mol,1.04 eq.) was added, and after stirring uniformly, the above-mentioned pre-prepared N-methyl-N-phenyl-methylphosphinamide monochloro reaction solution was added under ice bath cooling, the internal temperature of the system was controlled at 5-10℃and the reaction was allowed to stand for 2 hours after the addition. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by nitrogen, washing a filter cake twice by toluene, and combining filtrate to obtain a compound (II-3) reaction solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
118.0g of an ethanol solution containing hydrogen chloride (17.49 g,0.480mol,1.09 eq.) was added to the reaction solution of the above compound (II-3), and the mixture was heated to 70 to 80℃to react for 5 hours. Removing low-boiling substances under reduced pressure, cooling to normal temperature, filtering to obtain byproduct salt, adding 386.3g of 30% hydrochloric acid into filtrate, stirring for 0.5 hr, standing for layering, heating to 95-105deg.C, and reacting. After the reaction, the mixture is decompressed, desolventized and dried, 386.3g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 82.9g of the target product (I-1), the yield is 85.8%, the content is 98.2%, and the ee is 97.2%.
Example 11: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-3)
N-methylaniline (94.52 g,0.882mol,2.03 eq.) was added to 355.6g toluene and the temperature was reduced to-5-5℃under nitrogen, and methylphosphine dichloride (50.80 g,0.435mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the mixture is reacted for 0.5 hour by heat preservation, and N-methyl-N-phenyl-methyl phosphoramidite monochloro [ CAS No. 91275-60-4] is obtained for standby.
Under the protection of nitrogen, ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (69.81 g, 0.426 mol,0.97 eq) was added to 349.0g of toluene, N-methylaniline (47.42 g, 0.447 mol,1.02 eq) was added, and after stirring uniformly, the above-mentioned pre-prepared N-methyl-N-phenyl-methylphosphinamide monochloro reaction solution was added under ice bath cooling, the internal temperature of the system was controlled at 5-10℃and the reaction was carried out for 2 hours after the addition. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by nitrogen, washing a filter cake twice by toluene, and combining filtrate to obtain a compound (II-3) reaction solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
Glucose (51.70 g,0.478mol,1.1 eq.) is added into the reaction solution of the compound (II-3), the mixture is heated to 70 to 80 ℃ for reaction for 5 hours, after the low-boiling substances and byproducts are removed by decompression, 381.0g of 30% hydrochloric acid is added, the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95 to 105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 381.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed, dissolved and cleared, cooled, crystallized, filtered and dried to obtain white solid, namely 71.9g of the target product (I-1), the yield is 76.7%, the content is 97.8%, and the ee is 96.9%.
Comparative example 4: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-3)
N-methylaniline (94.14 g,0.878mol,2.05 eq.) was added to 350.7g of toluene, cooled to-5-5℃under nitrogen protection, and methylphosphine dichloride (50.10 g, 0.428 mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5-5 ℃. After the dripping, the mixture is reacted for 0.5 hour by heat preservation, and N-methyl-N-phenyl-methyl phosphoramidite monochloro [ CAS No. 91275-60-4] is obtained for standby.
Ethyl (2S) -2-amino-4-chlorobutyrate [ CAS No.:777033-03-1] (69.55 g,0.420mol,0.98 eq.) was added to 347.8g of toluene under nitrogen protection, N-methylaniline (45.00 g,0.420mol,0.98 eq.) was added, and after stirring uniformly, the above-mentioned pre-prepared N-methyl-N-phenyl-methylphosphinamide monochloro reaction solution was added under ice bath cooling, the internal temperature of the system was controlled at 5-10℃and the reaction was continued for 2 hours. Slowly heating to 80-85 ℃ and preserving heat for reaction for 10 hours. And (3) carrying out pressure filtration by nitrogen, washing a filter cake twice by toluene, and combining filtrate to obtain a compound (II-3) reaction solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
375.8g of 30% hydrochloric acid is added into the reaction solution of the compound (II-3), the mixture is stirred for 0.5 hour and then is stood for layering, and the water phase is heated to 95-105 ℃ for reaction. After the reaction, the mixture is decompressed, desolventized and dried, 375.8g of absolute ethyl alcohol is added, the mixture is heated, refluxed and dissolved, cooled, crystallized, filtered and dried to obtain white solid, namely 67.9g of the target product (I-1), the yield is 72.5%, the content is 97.5%, and the ee is 96.8%.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Moreover, any combination of the various embodiments of the invention can be made without departing from the spirit of the invention, which should also be considered as disclosed herein.
Claims (10)
1. A process for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, comprising the steps of:
1) Reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion with an alcohol compound or a phenolic compound,
and
2) Separating the reaction product of step 1) into byproducts, hydrolyzing to obtain a compound of formula (I),
Wherein,,
x is halogen;
y is-OR 3 or-N (R) 4 )(R 5 )；
R 1 And R is 2 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 1 And R is 2 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution;
R 3 、R 4 and R is 5 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 4 And R is 5 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution; and is also provided with
* For identifying chiral carbon atoms.
2. The process of claim 1, wherein the enantiomer of glufosinate is L-glufosinate or D-glufosinate, and/or the mixture of any ratio of enantiomers of glufosinate comprises 0.1:99.9 to 99.9: 0.1L-glufosinate and D-glufosinate, preferably 50:50 to 99.9: 0.1L-glufosinate and D-glufosinate.
3. The method of claim 1, wherein,
halogen is selected from fluorine, chlorine or bromine;
C 1 -C 6 alkyl is selected from methyl, ethyl, propyl or isopropyl;
C 2 -C 6 alkenyl is selected from ethenyl, propenyl, 1-butenyl, 2-butenyl or isobutenyl;
C 2 -C 6 alkynyl is selected from ethynyl, propynyl, 1-butynyl or 2-butynyl;
C 3 -C 6 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
the three-to six-membered heterocycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl containing at least one heteroatom in N, O and S;
C 6 -C 10 aryl is selected from phenyl or naphthyl; and/or
The five-membered to ten-membered heteroaryl is selected from pyrazinyl, pyrazolyl, pyrrolyl, furyl, thienyl, thiazolyl or pyridyl.
4. The method of claim 1, wherein the R 1 、R 2 、R 3 、R 4 And R is 5 Each independently selected from hydrogen, C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl, preferably hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
5. The method of claim 1, wherein the alcohol compound is a monohydric or polyhydric alcohol, or is a monosaccharide, disaccharide, or polysaccharideA saccharide compound; preferably, the alcohol compound is glucose or R 6 (OH) n A compound of formula wherein R 6 Selected from C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl, and n is any integer from 1 to 3; more preferably, the alcohol compound is methanol, ethanol, isopropanol, ethylene glycol, glycerol or glucose.
6. The method of claim 1, wherein the phenolic compound is selected from the group consisting of R 7 (OH) m A compound of formula wherein R 7 Selected from C 6 -C 10 Aryl or five to ten membered heteroaryl, and m is any integer from 1 to 3; preferably, the phenolic compound is represented by R 7 (OH) m A compound of formula wherein R 7 Is phenyl, and m is any integer from 1 to 3; more preferably, the phenolic compound is phenol.
7. The process according to claim 1, wherein for step 1), the molar ratio of the compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion to the alcohol compound or phenolic compound is 1:0.5-100, preferably 1:2-20 parts; and/or the reaction is carried out in the absence of a solvent or an organic solvent, preferably the organic solvent is selected from an aromatic hydrocarbon solvent, an alkane solvent, a halogenated hydrocarbon solvent, an ether solvent, an ester solvent, an amide solvent or a sulfur-containing solvent, preferably the organic solvent is selected from at least one of toluene and chlorobenzene.
8. The process according to claim 1, wherein step 1) is carried out in the presence of an acid, preferably at least one of hydrogen chloride, hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid and acetic acid, and further preferably hydrogen chloride, hydrochloric acid or sulfuric acid, more preferably the molar ratio of the compound of formula (II) to the hydrogen ions in the acid is 1:0.1-10, preferably 1:0.9-2.
9. The process according to claim 1, wherein step 1) is carried out at a temperature of 20-130 ℃, preferably 60-80 ℃; and/or the hydrolysis in step 2) is carried out at a temperature of 30-140 ℃, preferably 70-110 ℃.
10. The process according to claim 1, wherein the hydrolysis is carried out in the presence of an acid or base, preferably the acid is selected from at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid and acetic acid, more preferably hydrochloric acid or sulfuric acid, and/or the base is selected from alkali metal or alkaline earth metal hydroxides, carbonates, bicarbonates or hydroxycarbonates, aqueous ammonia, organic bases or organic amines, more preferably sodium hydroxide or triethylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310354575.2A CN116375764A (en) | 2023-04-05 | 2023-04-05 | Preparation method of glufosinate-ammonium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310354575.2A CN116375764A (en) | 2023-04-05 | 2023-04-05 | Preparation method of glufosinate-ammonium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116375764A true CN116375764A (en) | 2023-07-04 |
Family
ID=86967080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310354575.2A Pending CN116375764A (en) | 2023-04-05 | 2023-04-05 | Preparation method of glufosinate-ammonium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116375764A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024104419A1 (en) * | 2022-11-17 | 2024-05-23 | 永农生物科学有限公司 | Preparation method for glufosinate-ammonium |
-
2023
- 2023-04-05 CN CN202310354575.2A patent/CN116375764A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024104419A1 (en) * | 2022-11-17 | 2024-05-23 | 永农生物科学有限公司 | Preparation method for glufosinate-ammonium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO331372B1 (en) | Process for the preparation of combretastatin | |
| CN116375764A (en) | Preparation method of glufosinate-ammonium | |
| US4297282A (en) | Resolution of mercaptopropionic acids | |
| TWI823808B (en) | Preparation method of glufosinate-ammonium | |
| EP0002925A1 (en) | Preparation of herbicidal 2-(4-(pyridyl-2-oxy)-phenoxy)- propionic acid derivatives and compounds thus obtained | |
| CA2241414A1 (en) | Thiol derivatives with metallopeptidase inhibitory activity | |
| US4325886A (en) | Optical resolution of acylthiopropionic acid | |
| CN116478207A (en) | Preparation method of glufosinate-ammonium | |
| Zygmunt et al. | Stereoselective synthesis of 2-amino-1-hydroxy-3-phenylpropylphosphonic acid | |
| LU82699A1 (en) | HERBICIDE COMPOSITIONS CONTAINING DIPHENYL ETHER AS ACTIVE INGREDIENT | |
| CA1327804C (en) | Process for the minimization of racemization in the preparation of optically active ((aryloxy)phenoxy)proprionates herbicides | |
| CN117164621A (en) | Preparation method of glufosinate-ammonium | |
| US7205433B2 (en) | Crystal of amino acid ester salt and process for producing the same | |
| JP2009518380A (en) | Preparation of 2-chloroethoxy-acetic acid-N, N-dimethylamide | |
| CN115873033A (en) | Preparation method of glufosinate-ammonium | |
| US4411836A (en) | Racemization of an α-methyl-β-acylthiopropionic acid | |
| EP4371992A1 (en) | Methods of preparing glufosinate | |
| US5591859A (en) | Process for the production of 2-cyanoiminothiazolidine | |
| US20080119441A1 (en) | Phosphonic Acid Derivatives and the Treating Agents of Diseases Related Hyperphosphatemia | |
| KR101023455B1 (en) | Method for Preparing Racemic or Optically Active ??Glycerophosphoryl choline | |
| JP4109446B2 (en) | Process for producing pure trans-2-[(α-methylbenzyl) amino] cyclopentanol as a diastereoisomer | |
| FR2485013A1 (en) | PROCESS FOR PRODUCING 3- (N-ARYL-N-ACYLAMINO) -GAMMA-BUTYROTHIOLATES AND PRODUCTS OBTAINED | |
| KR20080097708A (en) | Process for preparation of sarpogrelate hcl salt | |
| CN111732568A (en) | Synthesis method of 4-methoxycarbonyl-2-methylthiophene-3-sulfonyl chloride | |
| FR2482099A1 (en) | MERCAPTOACYLDIHYDROPYRAZOLE CARBOXYLIC ACID DERIVATIVES WITH ANTI-HYPERTENSIVE ACTION |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |