CN117164621A - Preparation method of glufosinate-ammonium - Google Patents
Preparation method of glufosinate-ammonium Download PDFInfo
- Publication number
- CN117164621A CN117164621A CN202311125758.3A CN202311125758A CN117164621A CN 117164621 A CN117164621 A CN 117164621A CN 202311125758 A CN202311125758 A CN 202311125758A CN 117164621 A CN117164621 A CN 117164621A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- vii
- salt
- reaction
- 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 15
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 252
- 238000006243 chemical reaction Methods 0.000 claims abstract description 85
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 31
- 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 25
- 239000005561 Glufosinate Substances 0.000 claims abstract description 12
- 150000008282 halocarbons Chemical class 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- -1 cyano, amino Chemical group 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical group CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 230000008569 process Effects 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
- 239000002585 base Substances 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([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
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- 238000006467 substitution reaction Methods 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 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
- 229910021529 ammonia Inorganic materials 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
- 229910052801 chlorine Inorganic materials 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229910001854 alkali hydroxide Inorganic materials 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
- 229910000147 aluminium phosphate Inorganic materials 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
- 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
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 229940071870 hydroiodic acid Drugs 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 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
- 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
- 239000002994 raw material Substances 0.000 abstract description 14
- 239000000047 product Substances 0.000 abstract description 11
- 239000006227 byproduct Substances 0.000 abstract description 9
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical class OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 abstract description 6
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 4
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 abstract description 3
- 239000012298 atmosphere Substances 0.000 abstract description 3
- 230000007246 mechanism Effects 0.000 abstract description 2
- 150000004714 phosphonium salts Chemical group 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 44
- 238000003786 synthesis reaction Methods 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- ONRKUGHFZWYUJP-UHFFFAOYSA-N methylphosphane dihydrochloride Chemical compound Cl.Cl.PC ONRKUGHFZWYUJP-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 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
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000011065 in-situ storage 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
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 2
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- 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
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-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
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 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
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000004009 herbicide Substances 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
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000003541 multi-stage reaction 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000002689 soil 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
- 125000006273 (C1-C3) alkyl group Chemical group 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
- SIFCJBSEPSZGIK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]oxybutanoic acid Chemical compound CP(O)(=O)OCCC(N)C(O)=O SIFCJBSEPSZGIK-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
- 239000004475 Arginine Substances 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
- 235000001258 Cinchona calisaya Nutrition 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
- 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
- 240000003176 Digitaria ciliaris Species 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
- 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
- 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
- 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
- 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
- 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
- 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
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-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
- 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
- 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
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 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
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit 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
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000007805 chemical reaction reactant Substances 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-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
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 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
- 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
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 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
- 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
- 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
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-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
- 239000012452 mother liquor Substances 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
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000006239 protecting group Chemical group 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
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000011160 research 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
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate 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
- 230000002194 synthesizing effect Effects 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Landscapes
- 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: the compound of formula (II) is hydrolyzed to give the compound of formula (I). The method of the application uses halogenated homoserine as a raw material to prepare a five-membered ring intermediate, further obtains a quaternary phosphonium salt intermediate, and finally hydrolyzes to obtain a target product. Because of different reaction mechanisms, halogenated hydrocarbon byproducts in Michaelis-Arbuzov reaction can be avoided, the damage of the halogenated hydrocarbon byproducts to ozone in the atmosphere is prevented, equipment and engineering investment for separating, purifying, collecting and the like of the byproducts are omitted correspondingly, and potential environmental and safety risks brought by the byproducts are avoided.
Description
Technical Field
The application relates to the field of pesticide herbicides, in particular to a preparation method of glufosinate-ammonium.
Background
The glufosinate has the characteristics of wide weed control spectrum, high activity, low toxicity, easy degradation in soil, safety to crops, small drift, good environmental compatibility, quicker weed control and the like, and can prevent and kill more than 100 annual and perennial broadleaf weeds and grassy weeds such as crabgrass, ryegrass and the like.
The common glufosinate is a mixture of two enantiomers, but only the L-isomer has activity, and is easy to decompose in soil, has low toxicity to human beings and animals, can greatly reduce environmental pressure, and has better activity and better control effect on resistant weeds than the common glufosinate. Although most of the glufosinate-ammonium commercial products sold on the market at present are racemates thereof, the entry of the L-isomer into the mainstream market is impermissible with technical innovation and progress.
The existing method for synthesizing 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 chemical resolution method is to split racemic D, L-glufosinate or derivatives thereof synthesized by a chemical method through chiral resolution reagents, thereby preparing optically pure L-glufosinate. Patent specification publication WO1995023805A1 discloses a process for obtaining [ L ] -or [ D ] -homoalanin-4-yl- (methyl) phosphonic acid and salts thereof from the racemisation of D, L-homoalanin-4-yl- (methyl) phosphonic acid by precipitation of one of the diastereomeric salts with a chiral base such as quinine and cinchonine. The method needs to use expensive chiral resolution reagent, has lower yield and has no obvious industrialization advantage.
The chemical synthesis method synthesizes the L-glufosinate-ammonium by natural chiral amino acid or asymmetric method.
The patent specification with publication number of US5442088A discloses a method for obtaining L-glufosinate-ammonium hydrochloride by performing ring-opening chlorination, esterification and Arbuzov reaction with methyl phosphodiester as raw materials, and finally hydrolyzing and refining.
The multistep reaction process unit is convenient to operate, but the activity of the chlorinated substrate of the Arbuzov reaction raw material is limited, the Arbuzov reaction raw material is usually carried out at a higher temperature (130-140 ℃ or higher), meanwhile, the chlorinated alkane byproduct further generates side reaction with methyl phosphite diester at a high temperature, so that the unit consumption is greatly increased, and in addition, the excessive value of the L-type enantiomer is reduced due to racemization of part of raw materials or products at the temperature.
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 to obtain an intermediate, and then hydrolyzed to obtain the L-glufosinate.
The method takes homoserine as a raw material, and synthesizes the homoserine through multi-step reactions such as cyclization, chlorination, esterification, protecting group protection and the like, and the reaction steps are long. In addition, the Arbuzov reaction inevitably produces halogenated hydrocarbons, which are class 3 carcinogens and have a damaging effect on ozone in the atmosphere.
In recent years, with the continuous increase of the demand of the glufosinate, the development of the glufosinate synthesis method which has mild reaction conditions, higher yield, lower cost and simple operation has extremely important significance for the use reduction and synergy of herbicides.
Disclosure of Invention
For the sake of brevity, the "compound of formula (N) (e.g., compound of formula (III)" 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 (III)", 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 application 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 application 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 application 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 application.
Certain compounds of the present application 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 application.
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, 1-6 or 1-3 carbon atomsAnd (5) a seed. 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.
Based on the present inventors' publication No. CN116041387A, further studies by the present inventors have found that when the reaction starting material is particularly halogenated homoserine (rather than halogenated homoserine ester), a novel reaction route is provided, and the present application has been completed based on this finding.
In a first aspect, the present application provides 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:
hydrolyzing the compound of formula (II) to obtain the compound of formula (I),
wherein,
X 1 is halogen; and is also provided with
* For identifying chiral carbon atoms.
According to the application, the compounds of formula (I) may exist in the form of a single enantiomer, for example, in one embodiment of the application, 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 application, 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 application 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 or 99:1, etc.).
In the preparation process of the first aspect of the present application, the hydrolysis of the compound of formula (II) 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 application, 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 ℃.
Further, the preparation method of the first aspect of the present application may further comprise a step of preparing the compound of formula (III).
In one embodiment of the present application, the compound of formula (II) may be prepared by reacting a compound of formula (IV) or a salt thereof
Is prepared by reaction with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein,
X 2 is halogen; and is also provided with
R 1 、R 2 、R 3 And R is 4 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.
As a preferred embodiment of the compounds of the formula (V-VII), R 1 、R 2 、R 3 And R is 4 Can be each independently selected fromHydrogen, 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. 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 the formula (V-VII), R 1 、R 2 、R 3 And R is 4 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.
In the step of preparing the compound of formula (II) as described above, the compound of formula (V), the compound of formula (VI) and/or the compound of formula (VII) used may be added as an initial reactant to the reaction system or may be obtained by in situ reaction of other compounds. For example, the compound of formula (V) may be prepared from a compound of formula (VII) and a compound of formula (VIII) NHR 1 R 2 Obtained by in situ reaction or by in situ reaction of a compound of formula (VI) and a compound of formula (VII); compounds of formula (VI) (where R 3 And R is 4 Can respectively correspond to R 1 And R is 2 ) Can be obtained by in situ reaction of a compound of formula (VII) with a compound of formula (VIII). As an alternative to the preparation of the compounds of formula (II), the compounds of formula (II) may also be obtained by reacting a compound of formula (IV) or a salt thereof with a compound of formula (VII) and a compound of formula (VIII). Further, in the above-described various steps for producing the compound of formula (II), the order of feeding the respective raw materials is not limited at all, i.e., the respective raw materials may be fed into the reaction system in any order.
According to the present application, the step of preparing the compound of formula (II) as described above may preferably be performed in the presence of an acid-binding agent. In particular, the acid binding agent may be selected from NR 5 R 6 R 7 Wherein R is 5 、R 6 And R is 7 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 5 、R 6 And R is 7 Any two of which together with the N atom to which they are attached form a ternary to hexa-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 group、C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution.
In addition, due to the compound NHR of formula (VIII) 1 R 2 The general formula of the acid-binding agent described above, i.e. also the requirement as acid-binding agent, is met, so that it is possible to choose to add an excess of the compound of the formula (VIII) as acid-binding agent which is preferably present in the reaction. In a preferred embodiment of the present application, the acid-binding agent may be selected from at least one of the compounds of formula (VIII), ammonia, triethylamine, morpholine and piperidine in excess.
Further, the step of preparing the compound of formula (II) as described above may be performed in the absence of a solvent or an organic solvent. In one embodiment of the present application, 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.
The amounts of the reactants used in the steps for preparing the compound of formula (II) and the reaction conditions as described above may be adjusted according to the actual needs and the knowledge of those skilled in the art. In one embodiment of the present application, the molar ratio of the compound of formula (IV) or a salt thereof, the sum of the compound of formula (V) and the compound of formula (VI) and the compound of formula (VII), and the acid-binding agent may be 1:0.9-5:0.9-5, preferably 1:1.05-1.5:1.05-1.5. In another embodiment of the application, the reaction may be carried out at a temperature of-20 to 20 ℃ (e.g., -10 ℃, -5 ℃,0 ℃, 5 ℃, 10 ℃, or 15 ℃, etc.) for 1 to 15 hours (e.g., 2 hours, 4 hours, 6 hours, or 12 hours, etc.), and then at a temperature of 20 to 120 ℃ (e.g., 30 ℃, 45 ℃, 60 ℃, 75 ℃, 90 ℃, or 105 ℃, etc.) for 0.5 to 24 hours (e.g., 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, or 18 hours, etc.).
As an alternative to preparing the compound of formula (II), the compound of formula (II) may also be prepared by a process comprising the steps of:
1) Allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
to obtain a compound of formula (III),
2) Preparing a compound of formula (II) by reacting a compound of formula (III),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 And is as defined previously.
In this alternative, the starting materials are essentially the same as in the previous schemes, except that it is clear that the compound of formula (III) is obtained as an intermediate for the subsequent reaction. Therefore, the selection of the reaction raw materials, the reaction system, the reaction conditions, etc. in this alternative scheme can refer to the scheme for preparing the compound of formula (II) described above, and will not be described herein again to avoid unnecessary redundancy. Taking reaction conditions as an example, the reaction of step 1) may be carried out at a temperature of-20 to 20℃for 1 to 15 hours; the reaction of step 2) is carried out at a temperature of 20-120℃for 0.5-24 hours.
In a second aspect, the present application provides a compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion thereof,
wherein X is 1 And is as defined previously.
Preferably, the compound of formula (II) may be prepared with reference to the first aspect of the application.
In a third aspect, the present application provides a process for the preparation of a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising the steps of:
allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 And is as defined previouslyMeaning.
In a fourth aspect, the present application provides a process for preparing a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
the compound of formula (II) is prepared by the reaction of the compound of formula (III),
wherein X is 1 And is as defined previously.
In a fifth aspect, the present application provides a compound of formula (III) or a salt, enantiomer or mixture of enantiomers in any proportion thereof,
wherein X is 1 And is as defined previously.
Preferably, the compound of formula (III) may be prepared with reference to the first aspect of the application.
In a sixth aspect, the present application provides a process for preparing a compound of formula (III) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 And is as defined previously.
In a seventh aspect, the present application provides a process for preparing a compound of formula (III) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
allowing a compound of formula (IV) or a salt thereof
With a compound of formula (VII) and a compound of formula (VIII),
wherein X is 1 、X 2 、R 1 、R 2 And is as defined previously.
Those skilled in the art will appreciate that the definitions and preferences described in one aspect of the application apply equally to other aspects. It will be apparent to those skilled in the art that embodiments of the various aspects of the application may be combined in various ways without departing from the subject matter and concepts of the application, and such combinations are included within the scope of the application.
According to research, compared with the prior art, the application at least has the following beneficial effects:
1. and (3) preparing a five-membered ring intermediate by using halogenated homoserine as a raw material, further obtaining a quaternary phosphonium salt intermediate, and finally hydrolyzing to obtain a target product. The process can avoid the halogenated hydrocarbon byproducts in Michaelis-Arbuzov reaction due to different reaction mechanisms, the halogenated hydrocarbon byproducts are usually chloroethane and chloromethane, are all 3 types of cancerogens and have destructive effect on ozone in the atmosphere, correspondingly, the equipment and engineering investment for separating, purifying, collecting and the like of the byproducts are saved, and the potential environmental and safety risks brought by the byproducts are avoided;
2. the esterification step of halogenated homoserine is omitted, and the strategy of carboxylic acid cyclization is utilized to protect amino and carboxyl simultaneously, and can be used for the construction of subsequent C-P bonds; and
3. the raw material source is simplified, the methyl phosphine dichloride is directly used as the raw material, the methyl phosphorous diester is not required to be used as an intermediate, and the raw material cost is reduced.
Detailed Description
The application is further illustrated by the following examples; but these examples do not limit the scope of the application. 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 (III-1)
Diethylamine (128.51 g,1.757mol,4.1 eq.) was added to 350g toluene and cooled to-5 to 5 ℃ under nitrogen protection, and methylphosphine dichloride (50.1 g,0.429mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5 to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction solution of the compound (VI-1). To this reaction solution, compound (IV-1) (70.84 g,0.407mol,0.95 eq.) was slowly added while controlling the internal temperature of the reaction solution at 10 to 20℃and the reaction was carried out at a temperature of 2 hours after the addition, to obtain a reaction solution of compound (III-1).
m/z(ESI)182.11([M+1] + ,100％)； 31 P NMR(33MHz)δ:137.14ppm。
2) Synthesis of Compound (II-1)
And (3) continuously and slowly heating the reaction solution of the compound (III-1) to 80-85 ℃, preserving heat for reaction for 10 hours, cooling to normal temperature, carrying out suction filtration and washing to obtain a solution of the compound (II-1), and directly using the solution for the next reaction.
m/z(ESI)146.14([M-Cl] + ,100％)； 31 P NMR(33MHz)δ:103.21ppm。
3) Synthesis of Compound (I-1)
To the above compound (II-1) solution, 375g of 30% hydrochloric acid was added, and the mixture was heated to 95-105℃for reaction. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 375g of absolute ethyl alcohol is added, the mixture is heated and refluxed, cooled and crystallized, and the white solid is obtained after suction filtration and drying, namely 79.5g of the target product (I-1), the yield is 87.5%, the content is 97.5%, and the ee value is 97.5%.
m/z(ESI)182.05([M+1] + ,100％)；
31 P NMR(243MHz,D 2 O)δ:53.79；
1 H NMR(600MHz,D 2 O)δ:4.10(t,J＝6.1Hz,1H),2.27–2.04(m,2H),1.98–1.77(m,2H),1.49(d,J＝14.1Hz,3H)；
13 C NMR(151MHz,D 2 O)δ:171.49,52.93(d,J＝16.5Hz),25.35(d,J＝93.4Hz),22.75(d,J＝2.6Hz),13.65(d,J＝92.6Hz)。
Example 2: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (III-1)
Diethylamine (66.21 g, 0.015 mol,2.1 eq.) was added to 350g toluene, cooled to-5 to 5 ℃ under nitrogen protection, and methylphosphine dichloride (50.4 g,0.431mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5 to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction liquid of the compound (V-1). To this reaction solution, a mixture of a preformed compound (IV-1) (72.02 g,0.414mol,0.96 eq.) and diethylamine (62.05 g,0.848mol,1.97 eq.) and 150g of toluene was slowly added while controlling the internal temperature of the reaction solution to 10 to 20℃and the reaction was continued for 2 hours after the addition, to obtain a reaction solution of the compound (III-1).
2) Synthesis of Compound (II-1)
And (3) continuously and slowly heating the reaction solution of the compound (III-1) to 80-85 ℃, preserving heat for reaction for 10 hours, cooling to normal temperature, carrying out suction filtration and washing to obtain a solution of the compound (II-1), and directly using the solution for the next reaction.
3) Synthesis of Compound (I-1)
To the above compound (II-1) solution, 378g of 30% hydrochloric acid was added, and the mixture was heated to 95 to 105℃to react. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 378g of absolute ethyl alcohol is added, the mixture is heated and refluxed, cooled and crystallized, and the white solid is obtained after suction filtration and drying, namely 76.7g of the target product (I-1), the yield is 82.2%, the content is 96.5%, and the ee value is 96.4%.
Example 3: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
Diethylamine (129.53 g,1.771mol,4.1 eq.) was added to 250g toluene, cooled to-5 to 5 ℃ under nitrogen protection, and methylphosphine dichloride (50.5 g,0.432mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5 to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction solution of the compound (VI-1).
The reaction solution is slowly heated to 80-85 ℃, and mixed solution of compound (IV-1) (72.16 g,0.415mol,0.96 eq.) and toluene 150g is added dropwise, the reaction is carried out for 10 hours after the dripping, the reaction solution is cooled to normal temperature, filtered and washed to obtain compound (II-1) solution, and the compound (II-1) solution can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
To the above compound (II-1) solution, 378g of 30% hydrochloric acid was added, and the mixture was heated to 95 to 105℃to react. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 378g of absolute ethyl alcohol is added, the mixture is heated and refluxed, cooled and crystallized, and the white solid is obtained after suction filtration and drying, namely 83.5g of the target product (I-1), the yield is 91.1%, the content is 98.1%, and the ee value is 97.2%.
Example 4: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (III-1)
N-methylaniline (188.58 g,1.760mol,4.05 eq.) was added to 500g toluene, cooled to-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℃to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction solution of the compound (VI-2). To this reaction solution, compound (IV-1) (72.59 g,0.417mol,0.96 eq.) was slowly added while controlling the internal temperature of the reaction solution at 10 to 20℃and the reaction was continued for 2 hours after the addition to give compound (III-1).
2) Synthesis of Compound (II-1)
And (3) continuously and slowly heating the reaction solution of the compound (III-1) to 80-85 ℃, preserving heat for reaction for 12 hours, cooling to normal temperature, carrying out suction filtration, washing, and combining the washing solution and mother liquor to obtain a compound (II-1) solution which can be directly used for the next reaction.
3) Synthesis of Compound (I-1)
To the above compound (II-1) solution, 381g of 30% hydrochloric acid was added, and the mixture was heated to 95 to 105℃for reaction. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 381g of absolute ethyl alcohol is added, the mixture is heated, refluxed, cooled, crystallized, filtered and dried to obtain a white solid, namely 76.7g of the target product (I-1), the yield is 81.5%, the content is 96.5%, and the ee value is 97.0%.
Example 5: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (II-1)
N-methylaniline (193.54 g,1.806mol,4.1 eq.) was added to 515g toluene, cooled to-5℃under nitrogen, and methylphosphine dichloride (51.5 g,0.441mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5℃to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction solution of the compound (VI-2).
The reaction solution is slowly heated to 80-85 ℃, mixed solution of compound (IV-1) (75.12 g,0.432mol,0.98 eq.) and toluene 150g is added dropwise, the reaction is carried out for 12 hours after the dropwise addition, the reaction solution is cooled to normal temperature, and the solution is filtered and washed to obtain compound (II-1) solution which can be directly used for the next reaction.
2) Synthesis of Compound (I-1)
To the above compound (II-1) solution, 386g of 30% hydrochloric acid was added, and the mixture was heated to 95-105℃for reaction. After the reaction is finished, the solution is decompressed, distilled and desolventized to dryness, 386g of absolute ethyl alcohol is added, the mixture is heated, refluxed, cooled, crystallized, filtered and dried to obtain white solid, namely 82.8g of the target product (I-1), the yield is 86.3%, the content is 97.9%, and the ee value is 97.5%.
Example 6: synthesis of DL-glufosinate hydrochloride (I-2)
1) Synthesis of Compound (III-2)
Diethylamine (129.79 g,1.775mol,4.1 eq.) was added to 354g toluene, cooled to-5 to 5 ℃ under nitrogen protection, and methylphosphine dichloride (50.6 g,0.433mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5 to 5 ℃. After the dripping, the reaction is carried out for 0.5 hour at a constant temperature to obtain the reaction solution of the compound (VI-1). To this reaction solution, compound (IV-2) (71.55 g,0.411mol,0.95 eq.) was slowly added while controlling the internal temperature of the reaction solution at 10 to 20℃and the reaction was carried out at a temperature of 2 hours after the addition, to obtain a reaction solution of compound (III-2).
2) Synthesis of Compound (II-2)
And (3) continuously and slowly heating the reaction solution of the compound (III-2) to 80-85 ℃, preserving heat for reaction for 10 hours, cooling to normal temperature, carrying out suction filtration and washing to obtain a solution of the compound (II-1), and directly using the solution for the next reaction.
3) Synthesis of Compound (I-2)
To the above compound (II-2) solution, 380g of 30% hydrochloric acid was added, and the mixture was heated to 95-105℃to react. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 380g of absolute ethyl alcohol is added, the mixture is heated and refluxed, cooled and crystallized, and the white solid is obtained after suction filtration and drying, namely 81.1g of the target product (I-1), the yield is 88.7%, and the content is 97.8%.
The preferred embodiments of the present application have been described in detail above, but the present application 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 application within the scope of the technical concept of the present application, and all the simple modifications belong to the protection scope of the present application.
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 application can be made without departing from the spirit of the application, which should also be considered as disclosed herein.
Claims (15)
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:
hydrolyzing the compound of formula (II) to obtain the compound of formula (I),
wherein,
X 1 is halogen; and is also provided with
* For identifying chiral carbon atoms.
2. 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, preferably hydrochloric acid or sulfuric acid; and/or the base is selected from the group consisting of alkali or alkaline earth metal hydroxides, carbonates, bicarbonates or hydroxycarbonates, ammonia, organic bases or organic amines, preferably sodium hydroxide or triethylamine; more preferably, the hydrolysis is carried out at a temperature of 30-140 ℃, preferably 70-110 ℃.
3. The method of claim 1, wherein the enantiomer of glufosinate is L-glufosinate or D-glufosinate; and/or the mixture of enantiomers of glufosinate-ammonium in any ratio 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.
4. The method of claim 1, wherein the compound of formula (II) is prepared by reacting a compound of formula (IV)
Is prepared by reaction with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein,
X 2 is halogen; and is also provided with
R 1 、R 2 、R 3 And R is 4 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.
5. The method of claim 4, 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.
6. The method of claim 4, wherein the R 1 、R 2 、R 3 And R is 4 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.
7. The process according to claim 4, wherein the reaction is carried out in the presence of an acid-binding agent, preferably selected from the group consisting of NR 5 R 6 R 7 Wherein R is 5 、R 6 And R is 7 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 5 、R 6 And R is 7 Any two of which together with the N atom to which they are attached form a ternary to hexa-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; more preferably, the molar ratio of the compound of formula (IV) or salt thereof, the sum of the amounts of the compound of formula (V), (VI), (VII) and the acid binding agent is 1:0.9-5:0.9-5, preferably 1:1.05-1.5:1.05-1.5.
8. The process according to claim 4, wherein 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, more preferably the organic solvent is selected from at least one of toluene and chlorobenzene; more preferably, the reaction is carried out at a temperature of-20 to 20 ℃ for 1 to 15 hours, and then at a temperature of 20 to 120 ℃ for 0.5 to 24 hours.
9. The process according to claim 1, wherein the compound of formula (II) is prepared by a process comprising the steps of:
1) Allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
to obtain a compound of formula (III),
2) Preparing a compound of formula (II) by reacting a compound of formula (III),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 And as defined in any one of claims 1 to 6,
preferably, wherein the reaction of step 1) is carried out at a temperature of-20 to 20 ℃ for 1 to 15 hours and/or the reaction of step 2) is carried out at a temperature of 20 to 120 ℃ for 0.5 to 24 hours.
10. A compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion,
wherein X is 1 As defined in claim 1,
preferably, the compound of formula (II) or a salt, enantiomer or mixture of enantiomers in any proportion thereof is prepared by a step in a process according to any one of claims 4-9.
11. A process for preparing a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising the steps of:
allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 As defined in any one of claims 1 to 6.
12. A process for preparing a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
the compound of formula (II) is prepared by the reaction of the compound of formula (III),
wherein X is 1 And is as defined in claim 1.
13. A compound of formula (III) or a salt, enantiomer or mixture of enantiomers in any proportion,
wherein X is 1 As defined in claim 1,
preferably, the compound of formula (III) or a salt, enantiomer or mixture of enantiomers thereof in any proportion is prepared by a step in a process according to claim 9.
14. A process for preparing a compound of formula (III) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
allowing a compound of formula (IV) or a salt thereof
React with any one of the following: a compound of formula (V); a compound of formula (VI); a compound of formula (V) and a compound of formula (VI); a compound of formula (V) and a compound of formula (VII); a compound of formula (VI) and a compound of formula (VII); or a compound of formula (V), a compound of formula (VI) and a compound of formula (VII),
wherein X is 1 、X 2 、R 1 、R 2 、R 3 、R 4 As defined in any one of claims 1 to 6.
15. A process for preparing a compound of formula (III) or a salt, enantiomer or mixture of enantiomers thereof in any proportion, comprising:
allowing a compound of formula (IV) or a salt thereof
With a compound of formula (VII) and a compound of formula (VIII),
wherein X is 1 、X 2 、R 1 、R 2 As claimed in claims 1 to 6Any one of the definitions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311125758.3A CN117164621A (en) | 2023-09-01 | 2023-09-01 | Preparation method of glufosinate-ammonium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311125758.3A CN117164621A (en) | 2023-09-01 | 2023-09-01 | Preparation method of glufosinate-ammonium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117164621A true CN117164621A (en) | 2023-12-05 |
Family
ID=88931244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311125758.3A Pending CN117164621A (en) | 2023-09-01 | 2023-09-01 | Preparation method of glufosinate-ammonium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117164621A (en) |
-
2023
- 2023-09-01 CN CN202311125758.3A patent/CN117164621A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN116789695B (en) | Preparation method of glufosinate-ammonium | |
| ES2528716T3 (en) | Procedure for the preparation of pyridine derivatives | |
| KR20110139274A (en) | Methods for the preparation of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid and precursors thereof | |
| WO2008078482A1 (en) | Process for producing intermediate of asenapine synthesis | |
| SE452610B (en) | SETTING DIVERSE RACEMIC CIS-1,2-CYCLOPROPANDICARBOXYLIC ACID DERIVATIVES | |
| DK171843B1 (en) | Analogous Process for Preparation of Oxazaphosphorin-4-Thioalkanesulfonic Acids and Neutral Salts thereof | |
| CN116375764A (en) | Preparation method of glufosinate-ammonium | |
| CN117164621A (en) | Preparation method of glufosinate-ammonium | |
| CN116478207A (en) | Preparation method of glufosinate-ammonium | |
| CN115873033A (en) | Preparation method of glufosinate-ammonium | |
| JP4278859B2 (en) | Method for producing oxaazaphosphorin-2-amine | |
| EP4371992A1 (en) | Methods of preparing glufosinate | |
| EP1581475B1 (en) | Synthesis of (r) and (s)-aminocarnitine and derivatives thereof from d-and l-aspartic acid | |
| BR102023014787B1 (en) | GLUFOSINATE PREPARATION METHODS | |
| JPH01168675A (en) | Production of 1,3-dialkylpyrazole-5-carboxylic acid esters | |
| JP3677786B2 (en) | Method for producing aryloxypropionic acid | |
| JP2023180566A (en) | Method for producing ergothioneine derivative | |
| JP2006193439A (en) | New pyrrolidine compound | |
| 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 | |
| Gimalova et al. | Reaction of 5-Allyl-2, 3, 5-trichloro-4, 4-dimethoxycyclopent-2-en-1-one with amino acids | |
| KR100343551B1 (en) | Process for preparing 4-alkoxycarbonyl-5-chloropyrazole derivatives | |
| JP5092317B2 (en) | Method for producing 3-imino-2,3-dihydropyridazine-2-acetic acid compound | |
| CN111732568A (en) | Synthesis method of 4-methoxycarbonyl-2-methylthiophene-3-sulfonyl chloride | |
| DE3439347A1 (en) | METHOD FOR PRODUCING ORGANIC PHOSPHORIC ACID ESTERS |
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 |