CN116478207A - Preparation method of glufosinate-ammonium - Google Patents
Preparation method of glufosinate-ammonium Download PDFInfo
- Publication number
- CN116478207A CN116478207A CN202310389331.8A CN202310389331A CN116478207A CN 116478207 A CN116478207 A CN 116478207A CN 202310389331 A CN202310389331 A CN 202310389331A CN 116478207 A CN116478207 A CN 116478207A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- alkyl
- cycloalkyl
- glufosinate
- 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 20
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 claims abstract description 16
- 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 15
- 239000005561 Glufosinate Substances 0.000 claims abstract description 12
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 4
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 34
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 29
- -1 cyano, amino Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 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 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 238000006467 substitution reaction Methods 0.000 claims description 10
- 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 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
- 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 230000008569 process Effects 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-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
- 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
- 150000001412 amines 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
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-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
- 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
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 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
- 150000008282 halocarbons Chemical class 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
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 230000006340 racemization Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000010276 construction Methods 0.000 abstract description 2
- 238000012423 maintenance Methods 0.000 abstract description 2
- 230000009257 reactivity Effects 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- CDPKWOKGVUHZFR-UHFFFAOYSA-N dichloro(methyl)phosphane Chemical compound CP(Cl)Cl CDPKWOKGVUHZFR-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 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
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 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
- 239000005562 Glyphosate Substances 0.000 description 2
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-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
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 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
- 125000003277 amino group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000005660 chlorination reaction Methods 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
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethylcyclohexane Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 2
- 229940097068 glyphosate Drugs 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 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
- 230000004060 metabolic process Effects 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 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
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- IVWWFWFVSWOTLP-YVZVNANGSA-N (3'as,4r,7'as)-2,2,2',2'-tetramethylspiro[1,3-dioxolane-4,6'-4,7a-dihydro-3ah-[1,3]dioxolo[4,5-c]pyran]-7'-one Chemical compound C([C@@H]1OC(O[C@@H]1C1=O)(C)C)O[C@]21COC(C)(C)O2 IVWWFWFVSWOTLP-YVZVNANGSA-N 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- OKIRBHVFJGXOIS-UHFFFAOYSA-N 1,2-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC=C1C(C)C OKIRBHVFJGXOIS-UHFFFAOYSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 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
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 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
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-L D-glucarate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O DSLZVSRJTYRBFB-LLEIAEIESA-L 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- QJPWUUJVYOJNMH-VKHMYHEASA-O L-homoserine lactone(1+) Chemical compound [NH3+][C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-O 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 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
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- UYQVCLAMCWIBKC-UHFFFAOYSA-N OOP(=O)(OC)CCC(N)C(=O)O Chemical compound OOP(=O)(OC)CCC(N)C(=O)O UYQVCLAMCWIBKC-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000009471 action Effects 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
- QJPWUUJVYOJNMH-UHFFFAOYSA-N alpha-amino-gamma-butyrolactone Natural products NC1CCOC1=O QJPWUUJVYOJNMH-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical group 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
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 239000006227 byproduct Substances 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
- 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
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- SWRNIYAQKATHDJ-UHFFFAOYSA-N dichloro(dichlorophosphanyl)phosphane Chemical compound ClP(Cl)P(Cl)Cl SWRNIYAQKATHDJ-UHFFFAOYSA-N 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
- 238000001035 drying Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 229960001078 lithium Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
- 230000007246 mechanism Effects 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
- 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
- 150000002894 organic compounds Chemical class 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
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 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
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application relates to a preparation method of glufosinate. Specifically, it relates to a process for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, which comprises reacting a compound of formula (II) with a compound of formula (III) and hydrolyzing the reaction product to obtain a compound of formula (I). According to the method, the substrate has higher reactivity, so that the construction condition of the P-C bond is milder, the reaction temperature is lower, racemization of the L-configuration at high temperature can be reduced, and the maintenance of the L-configuration during preparation of the L-glufosinate is improved.
Description
Technical Field
The application relates to the field of pesticide herbicides, in particular to a preparation method of glufosinate-ammonium.
Background
Glufosinate has the chemical name 4- [ hydroxy (methyl) phosphono ] -DL-homoalanine, which was developed and produced by helson corporation, germany. The herbicide is a glutamine synthesis inhibitor and a nonselective contact herbicide, and has the action mechanism of inhibiting glutamine synthetase activity in plants, so that glutamine synthesis is blocked, nitrogen metabolism is disturbed, ammonium ions are accumulated, thereby interfering with metabolism of the plants and leading the plants to die.
The glufosinate-ammonium molecule contains a chiral carbon and has two different configurations, namely L-glufosinate-ammonium and D-glufosinate-ammonium, wherein only L-isomer has herbicidal activity and is easy to decompose in soil, the glufosinate-ammonium molecule has low toxicity to human beings and animals, the environmental pressure can be greatly reduced, and the activity and the control effect on resistant weeds are better than those of common glufosinate-ammonium.
With the remarkable problems of paraquat inhibition and glyphosate resistance, the global glufosinate resistance gene is further widely introduced into tens of crops such as rice, wheat, corn, beet, tobacco, soybean, cotton, potato, tomato, rape and sugarcane, and the like, so that the substitution process of glufosinate for the other two is accelerated by the factors. Although most of the glufosinate commercial products sold on the market at present are racemates thereof, with technical innovation and progress, the L-glufosinate enters the mainstream market to be impossible.
The existing method for preparing chiral pure L-glufosinate mainly comprises a chemical method and a biological method. Wherein the chemical method comprises a chemical resolution method and a chemical synthesis method.
The chemical resolution method is to resolve racemic D, L-glufosinate or derivatives thereof synthesized by an external chemical method through chiral resolution reagents, thereby preparing optically pure L-glufosinate. Patent specification publication No. WO1995023805A1 discloses a method for obtaining single [ L ] -or [ D ] -homoalanin-4-yl- (methyl) phosphonic acid and salts thereof by resolution of one of the diastereoisomeric salts by salifying with a chiral base such as quinine and cinchonine and the like. The method needs to use expensive chiral resolution reagent, has lower yield and has no obvious industrialization advantage.
The preparation of L-glufosinate by chemical synthesis can be further subdivided into: adopts an asymmetric synthesis method and a total synthesis method which takes L-amino acid obtained by natural or fermentation as a raw material. The latter has more direct and simple synthetic route and good ee value maintenance than other methods because it does not need to construct chiral centers of amino acid structures, and is getting more and more attention from related enterprises and research institutions at home and abroad.
The patent specification with publication number US5442088A discloses a method for obtaining L-glufosinate-ammonium hydrochloride by using L-homoserine lactone or derivatives thereof as raw materials, performing ring-opening chlorination, esterification, condensation with methyl phosphite diester, 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 lower, the Arbuzov reaction can be performed at a higher temperature, meanwhile, the chlorinated alkane byproduct further reacts with methyl phosphite diester at a high temperature to increase the unit consumption, and in addition, the L-type ee value is reduced to a certain extent due to racemization of part of raw materials or products.
Patent specification publication No. CN113490671B discloses: amino protected or unprotected halogenated homoserine ester is taken as a raw material, condensed with methyl phosphonite monochloro ester 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 recent years, along with the problems of paraquat inhibition and glyphosate resistance, the demand of glufosinate is continuously increased, so that the development of the glufosinate synthesis method which has the advantages of mild reaction conditions, higher yield, lower cost and simple operation has extremely important significance for herbicide use reduction and synergy.
Disclosure of Invention
For the sake of brevity, the "compound of formula (N) (e.g., compound of formula (II)" described hereinafter may also encompass any optical isomer, geometric isomer, tautomer or mixture of isomers, or agriculturally acceptable salt of the compound of formula (N).
The term "optical isomer" means that when a compound has one or more chiral centers, each chiral center may exist in either the R configuration or the S configuration, and thus the various isomers constituted are optical isomers. Optical isomers include all diastereoisomers, enantiomers, meso, racemates or mixtures thereof. For example, the optical isomers may be separated by chiral chromatography columns or by chiral synthesis.
The term "geometric isomer" means that when a double bond is present in a compound, the compound may exist as cis, trans, E and Z isomers. Geometric isomers include cis, trans, E, Z, or mixtures thereof.
The term "tautomer" refers to an isomer that results from the rapid movement of an atom in a molecule at two positions. Those skilled in the art will appreciate that: tautomers can be transformed into each other, and in a certain state, an equilibrium state may be reached and coexist.
Unless otherwise indicated, references herein to "a compound of formula (N) (e.g., a compound of formula (II)", also encompass isotopically-labeled compounds wherein any one of the atoms in the compound is replaced by an isotopically-substituted atom thereof. That is, the present invention includes all agriculturally acceptable isotopically-labeled compounds of formula (N) wherein one or more atoms are replaced by an atom having the same atomic number but a different atomic mass or mass number than those typically found in nature.
Suitable for inclusion in the compounds of the inventionExamples of isotopes of (2) include isotopes of hydrogen, such as 2 H (D) and 3 isotopes of H (T), carbon, such as 11 C、 13 C and C 14 Isotopes of C, chlorine, such as 37 Isotopes of Cl, fluorine, such as 18 Isotopes of F, iodine, such as 123 I and 125 isotopes of I, nitrogen, such as 13 N and 15 isotopes of N, oxygen, such as 15 O、 17 O and 18 isotopes of O, and sulfur, such as 35 S。
Isotopically-labeled compounds of formula (N) can generally be prepared by conventional techniques known to those skilled in the art or by using an appropriate isotopically-labeled reagent in place of the non-labeled reagent previously used in a manner analogous to those described in the examples and preparations attached herein.
The compounds of formula (N) may be present in the form of agriculturally acceptable salts, for example, acid addition salts and/or base addition salts of the compounds of formula (N). As used herein, unless otherwise indicated, "agriculturally acceptable salts" include acid addition salts or base addition salts that may occur within the compounds of formula (N).
Agriculturally acceptable salts of the compound of formula (N) include acid addition salts and base addition salts thereof. Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include, but are not limited to: acetate, adipate, aspartate, benzoate, benzenesulfonate, bicarbonate/carbonate, bisulfate/sulfate, borate, camphorsulfonate, citrate, cyclohexylamine sulfonate, ethanedisulfonate, formate, fumarate, glucoheptonate, gluconate, glucuronate, hexafluorophosphate, 2- (4-hydroxybenzyl) benzoate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, 2-isethionate, lactate, malate, maleate, malonate, methanesulfonate, methylsulfate, napthalate, 2-naphthalenesulfonate, nicotinate, nitrate, orotate, oxalate, palmitate, phosphate/hydrogen phosphate/dihydrogen phosphate, pyroglutamate, glucarate, stearate, salicylate, tannate, tartrate, tosylate and trifluoroacetate. Suitable base addition salts are formed from bases which form non-toxic salts. Examples include, but are not limited to: ammonium salts, aluminum, arginine, calcium, choline, diethylamine, diethanolamine, glycine, lysine, magnesium, meglumine, ethanolamine, potassium, sodium, lithium, tromethamine and zinc salts. Semi-salts of acids and bases, such as hemisulfate and hemicalcium salts, may also be formed. Methods for preparing agriculturally acceptable salts of the compounds described herein are known to those skilled in the art.
Certain compounds of the invention may exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the compounds of formula (N), whether in solvated form or unsolvated form, are encompassed within the scope of the present invention.
Certain compounds of the present invention may exist in different crystalline or amorphous forms, and, regardless of the form in which they exist, the compounds of formula (N) are included within the scope of the present invention.
To avoid ambiguity, definitions are given below for terms used herein. Unless otherwise indicated, the terms used herein have the following meanings.
As used herein, the term "substituted" means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms in the group are independently replaced by a corresponding number of substituents.
As used herein, the term "independently" means that when the number of substituents exceeds one, the substituents may be the same or different.
As used herein, the term "optional" or "optionally" means that the event described may or may not occur. For example, a group "optionally substituted" means: the group may be unsubstituted or substituted.
As used herein, the term "heteroatom" represents oxygen (O), nitrogen (N), or S (O) m (wherein m may be 0, 1 or 2, i.e., sulfur atom S, or sulfoxide group SO, or sulfonyl group S (O) 2 )。
As used hereinThe term "alkyl" when used herein refers to saturated aliphatic hydrocarbons, including straight and branched chains. In some embodiments, the alkyl group has, for example, 1 to 6 or 1 to 3 carbon atoms. For example, the term "C 1 -C 6 Alkyl "refers to a straight or branched chain radical having 1 to 6 carbon atoms. The term "C 1 -C 6 Alkyl "includes the term" C "in its definition 1-6 Alkyl "," C 1 -C 3 Alkyl "and" C 1 -C 4 An alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, (R) -2-methylbutyl, (S) -2-methylbutyl, 3-methylbutyl, 2, 3-dimethylpropyl, 2, 3-dimethylbutyl, hexyl, and the like.
As used herein, the term "C 3 -C 6 Cycloalkyl "refers to cycloalkyl groups having 3 to 6 ring-forming carbon atoms. For example, C 3 -C 6 Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
As used herein, the term "n-membered heterocycloalkyl" refers to cycloalkyl having m ring-forming carbon atoms and (n-m) ring-forming heteroatoms selected from at least one of N, O and S. For example, ternary to hexacyclic heterocycloalkyl groups include, but are not limited to, oxetane, thietane, azetidine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, piperazine.
As used herein, the term "C 6 -C 10 Aryl "means aryl having an aromatic ring containing 6 to 10 carbon atoms, preferably phenyl.
As used herein, the term "n-membered heteroaryl" refers to a heteroaryl group having m carbon atoms forming an aromatic ring and (n-m) heteroatoms forming an aromatic ring, said heteroatoms being selected from at least one of N, O and S. For example, five to ten membered heteroaryl groups include, but are not limited to, pyrazine, pyrazole, pyrrole, furan, thiophene, thiazole, pyridine.
As used herein, the term "haloalkyl" means having oneAn alkyl group of one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). For example, the term "C 1 -C 6 Haloalkyl "means C having one or more halo substituents 1 -C 6 An alkyl group (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). As another example, the term "C 1 Haloalkyl "refers to a methyl group having 1, 2 or 3 halogen substituents. Examples of haloalkyl groups include: CF (compact flash) 3 、C 2 F 5 、CHF 2 、CH 2 F、CH 2 CF 3 、CH 2 Cl, and the like.
In this context, a range of numbers relating to the number of substituents, the number of carbon atoms, and the number of ring atoms represents a list of all integers within the range, and the range is merely a simplified representation. For example: "1-4 substituents" means 1, 2,3 or 4 substituents; "3-8 carbon atoms" means 3, 4, 5, 6, 7 or 8 carbon atoms. Accordingly, a range of numbers relating to the number of substituents, the number of carbon atoms, the number of ring atoms also encompasses any one of its subranges, and each subrange is also considered disclosed herein.
In 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:
1) Reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion with a compound of formula (III),
and
2) Hydrolyzing the reaction product of step 1) to obtain a compound of formula (I),
wherein,,
x is halogen;
y is-OR 3 or-N (R) 4 )(R 5 )；
Z is hydrogen or an amino protecting group;
R 1 and R is 2 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 1 And R is 2 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution;
R 3 and R is 6 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 7 And R is 8 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 HaloalkanesRadical, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution;
R 4 and R is 5 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 4 And R is 5 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution; and is also provided with
* For identifying chiral carbon atoms.
As used herein, "amino protecting group" refers to a protecting group that is applied to an amino group prior to reaction when the multifunctional organic compound is reacted in order to avoid the amino group from being affected by the reaction only at the desired group, and may be selected from a variety of amino protecting groups known in the art, and it is within the ability of one skilled in the art to adjust and select according to actual needs. In one embodiment of the present invention, the amino protecting group may be selected from one or more of the following: -C (O) R 7 、-C(O)OR 8 、-CH 2 R 9 and-SO 2 R 10 Wherein R is 7 、R 8 、R 9 And R is 10 Each independently selected from C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, C 6 -C 10 Aryl or five to ten membered heteroaryl. Preferably, the amino protecting group may be ethoxycarbonyl.
According to the invention, the compounds of formula (I) may exist in the form of a single enantiomer, for example, in one embodiment of the invention, the compounds of formula (I) may be pure L-glufosinate or D-glufosinate. In addition, the compounds of formula (I) may also be present in the form of mixtures of enantiomers, and the enantiomers may each be present in any proportion in the mixtures of enantiomers, for example, in one embodiment of the invention, mixtures of enantiomers of formula (I) in any proportion comprise 0.1:99.9 to 99.9:0.1L-glufosinate and D-glufosinate. However, since only L-glufosinate is active, the L-enantiomer of the compounds of formula (I) of the present invention may also preferably be present in greater proportions in enantiomeric mixtures, e.g., in one embodiment, mixtures of enantiomers of compounds of formula (I) in any ratio comprise 50:50 to 99.9:0.1 (e.g., 60:40, 70:30, 80:20, 90:10, 95:5 or 99:1, etc.) of L-glufosinate and D-glufosinate.
As a preferred embodiment of the compound of formula (II) and of the amino protecting group, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 And R is 10 Can each be independently selected from hydrogen, C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl, preferably hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl. 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 ternary to six membered heterocycloalkyl group may be selected from at least one of N, O and SCyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl on a heteroatom; c (C) 6 -C 10 Aryl may be selected from phenyl or naphthyl; and/or five to ten membered heteroaryl groups may be selected from pyrazinyl, pyrazolyl, pyrrolyl, furanyl, thienyl, thiazolyl or pyridyl.
As an alternative to the compounds of formula (II), R 1 、R 2 、R 3 、R 4 、R 5 And R is 6 Or may be each independently selected from-Si (R) 14 )(R 15 )(R 16 ) Wherein R is 14 、R 15 And R is 16 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five to ten membered heteroaryl, wherein the C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution.
Further, the preparation method of the first aspect of the present invention may further comprise a step of preparing the compound of formula (III). In one embodiment of the present invention, the compound of formula (III) may be prepared from a compound comprising formula (IV) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the A compound of formula (V) and a compound of formula (VII); compounds of formula (VI), formula (VII) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the Or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII),
wherein R is 1 、R 2 、R 6 And X is as previously defined.
In the step of preparing the compound of formula (III) as described above, the compound of formula (IV-VIII) used may be added as an initial reactant to the reaction system or may be further obtained by in situ reaction of other compounds. For example, the compound of formula (IV) may be obtained from the in situ reaction of a compound of formula (VI) with a compound of formula (VII); alternatively, the compound of formula (V) may be obtained by in situ reaction of a compound of formula (VI) with a compound of formula (VIII). Further, in the above-described various steps for producing the compound of formula (III), the order of addition of the respective raw materials is not limited at all, i.e., the respective raw materials may be added to the reaction system in any order.
According to the present invention, the step of preparing the compound of formula (III) 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 11 R 12 R 13 Wherein R is 11 、R 12 And R is 13 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 11 、R 12 And R is 13 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. It is notable that, since the compounds of the formula (VII) correspond to the abovementioned formula of the acid-binding agent, i.e.also to the requirements as acid-binding agent, in the case where the compounds of the formula (VII) have already been added to the reaction system, an excess amount can preferably be addedThe compounds of formula (VII) act as acid-binding agents present in the reaction. In a preferred embodiment of the present invention, the acid-binding agent may be selected from at least one of the compounds of formula (VII), ammonia, triethylamine, morpholine and piperidine in excess. In addition, the amounts of the respective reactants used in the reaction and the reaction conditions may be adjusted according to the actual needs and the knowledge of those skilled in the art. In one embodiment of the invention, the molar ratio of the composition to the acid-binding agent may be 1:0.01-5, preferably 1:0.1-1.5.
Further, step 1) may be performed in the absence of a solvent or an organic solvent. In one embodiment of the present invention, the organic solvent is selected from an aromatic hydrocarbon solvent (e.g., benzene, xylene, trimethylbenzene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, halogenated benzene or dihalobenzene), an alkane solvent (e.g., N-hexane, cyclohexane, N-heptane, methylcyclohexane, ethylcyclohexane), a halogenated hydrocarbon solvent (e.g., dichloromethane, dichloroethane, chloroform or carbon tetrachloride), an ether solvent (e.g., tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, methylcyclopentyl ether, ethylene glycol dimethyl ether, dioxane or diethylene glycol dimethyl ether), an ester solvent (e.g., ethyl acetate, isopropyl acetate or butyl acetate), an amide solvent (e.g., N-dimethylformamide, N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone or 1, 3-dimethyl-2-imidazolidinone) or a sulfur-containing solvent (e.g., dimethylsulfoxide or sulfolane), preferably, the organic solvent is selected from at least one of toluene and chlorobenzene. In another embodiment of the invention, the reaction of step 1) may be carried out at a temperature of-10-130 ℃ (e.g., -5 ℃,0 ℃, 5 ℃, 10 ℃, 20 ℃, 40 ℃, 60 ℃, 80 ℃, 100 ℃, 120 ℃, etc.) for 1-25 hours (e.g., 2h, 4h, 6h, 12h, 18h, 24h, etc.).
In addition, for step 2), the hydrolysis may be carried out directly under neutral conditions, i.e. the hydrolysis reaction may be carried out directly in the presence of water. In addition, the hydrolysis may also preferably be carried out in the presence of an acid or a base. More specifically, the acid may be selected from at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid, and acetic acid, preferably hydrochloric acid or sulfuric acid; the base may be selected from alkali or alkaline earth metal hydroxides, carbonates, bicarbonates or hydroxycarbonates, ammonia, organic bases, organic amines, preferably sodium hydroxide or triethylamine. In addition, in one embodiment of the present invention, the hydrolysis may be performed at a temperature of, for example, 30 to 140 ℃ (e.g., 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃, 110 ℃, 120 ℃, 130 ℃, etc.), preferably 60 to 110 ℃.
In a second aspect, the present application provides a composition comprising a compound of formula (IV) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the A compound of formula (V) and a compound of formula (VII); compounds of formula (VI), formula (VII) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the Or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII),
wherein R is 1 、R 2 、R 6 And X is as previously defined.
In a third aspect, the present application provides the use of the composition of the second aspect for the preparation of glufosinate-ammonium represented by formula (I) or a salt, enantiomer or mixture of enantiomers in any proportion thereof
Those skilled in the art will appreciate that the definitions and preferences described in one aspect of the present application apply equally to other aspects. It will be apparent to those skilled in the art that the embodiments of the various aspects of the present application may be combined in various ways without departing from the subject matter and concepts of the application, and such combinations are also included within the scope of the application.
According to research, compared with the prior art, the invention at least has the following beneficial effects:
1. the substrate has higher reactivity, so that the construction condition of the P-C bond is milder, the reaction temperature can be reduced by 30-70 ℃ compared with the former, and racemization of the L-configuration at high temperature can be reduced when the L-glufosinate is prepared, thereby improving the purity of the L-configuration of the product; and
2. the raw materials can be prepared and used in situ, and the synthesis and rectification purification procedures of methyl phosphodiester are omitted. Meanwhile, the preparation of the raw materials is simple and convenient, the parameter selection space is large and the fault tolerance rate is high when the phosphorus dichloride and the amine are selected to react.
Detailed Description
The invention is further illustrated by the following examples; but these examples do not limit the scope of the invention. All reactants used in each example were obtained commercially unless otherwise stated; the instruments and equipment used in the synthesis experiments and the product analysis and detection are all conventional instruments and equipment commonly used in organic synthesis.
Example 1: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (III-1)
Diethylamine (72.70 g,0.994mol,2.0 eq.) was added to 406.7g of toluene, cooled to-5 to 5 ℃ under nitrogen protection, methyl phosphorus dichloride (58.1 g,0.497mol,1.0 eq.) was started to be added dropwise while maintaining the system temperature at-5 to 5 ℃, and after the addition, an absolute ethanol solution (62.21 g) of diethylamine (38.17 g,0.522mol,1.05 eq.) was continuously added dropwise, the reaction was continued for 0.5 hours with heat preservation to give compound (III-1), and the salt was removed by filtration, and the filtrate was directly used for the next reaction.
m/z(ESI)164.13([M+1] + ，100％)； 31 P NMR(33MHz)δ：135.25ppm。
2) Synthesis of Compound (I-1)
Under the protection of nitrogen, the compound (II-1) (112.21 g, 0.470 mol,0.95 eq.) is added into the filtrate of the compound (III-1), and the temperature is slowly raised to 85-90 ℃ for reaction for 12 hours under heat preservation.
Adding 435.8g of 30% hydrochloric acid into the feed liquid, standing for layering, heating the water phase to 90-95 ℃ for reflux reaction. After the reaction is finished, the solution is distilled and desolventized under reduced pressure until the solution is dried, 435.8g 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 84.4g of the target product (I-1), the yield is 80.5%, the content is 98.0%, and the ee value is 97.0%.
m/z(ESI)182.07([M+1] + ，100％)；
31 P NMR(243MHz，D 2 O)δ：53.67；
1 H NMR(600MHz，D 2 O)δ：4.10(t，J＝6.1Hz，1H)，2.25-2.05(m，2H)，1.99-1.75(m，2H)，1.47(d，J＝14.1Hz，3H)；
13 C NMR(151MHz，D 2 O)δ：171.29，52.96(d，J＝16.6Hz)，25.25(d，J＝93.0Hz)，22.72(d，J＝2.6Hz)，13.61(d，J＝92.5Hz)。
Example 2: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (III-2)
Aniline (88.90 g,0.95 mol,2.0 eq.) is added to 390.6g toluene, cooled to-5 ℃ under nitrogen protection, methyl phosphorus dichloride (55.8 g,0.477mol,1.0 eq.) is added dropwise while maintaining the system temperature at-5 ℃, aniline (46.67 g,0.501mol,1.05 eq.) is continuously added dropwise after the dropwise addition of absolute ethanol solution (69.76 g), the reaction is continued for 0.5 hours under heat preservation to obtain compound (III-2), salt is removed by filtration, and the filtrate is directly used for the next reaction.
m/z(ESI)184.10([M+1] + ，100％)； 31 P NMR(33MHz)δ：112.50ppm。
2) Synthesis of Compound (I-1)
Under the protection of nitrogen, the compound (II-2) (77.47 g, 0.4638 mol,0.98 eq.) is added into the filtrate of the compound (III-2), and the temperature is slowly raised to 85-90 ℃ for reaction for 12 hours under heat preservation.
Adding 418.5g of 30% hydrochloric acid into the feed liquid, standing for layering, heating the water phase to 90-95 ℃ for reflux reaction. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 418.5g of absolute ethyl alcohol is added, the mixture is heated, refluxed, cooled, crystallized, filtered and dried to obtain a white solid, namely 79.1g of the target product (I-1), the yield is 75.5%, the content is 97.1%, and the ee value is 96.6%.
Example 3: synthesis of L-glufosinate hydrochloride (I-1)
1) Synthesis of Compound (III-3)
N-methylaniline (103.58 g,0.967mol,2.0 eq.) is added into 395.5g toluene, cooled to-5 ℃ under the protection of nitrogen, methyl phosphorus dichloride (56.5 g,0.483mol,1.0 eq.) is added dropwise while maintaining the system temperature at-5 ℃, after that, an absolute ethanol solution (77.76 g) of N-methylaniline (54.38 g,0.507mol,1.05 eq.) is continuously added dropwise, the reaction is kept for 0.5 hours, the compound (III-3) is obtained, and the salt is removed by filtration, and the filtrate is directly used for the next reaction.
m/z(ESI)198.13([M+1] + ，100％)； 31 P NMR(33MHz)δ：133.28ppm。
2) Synthesis of Compound (I-1)
Under the protection of nitrogen, the compound (II-2) (76.04 g,0.459mol,0.95 eq.) is added into the filtrate of the compound (III-3), and the temperature is slowly raised to 85-90 ℃ for reaction for 12 hours.
Adding 423.8g of 30% hydrochloric acid into the feed liquid, standing for layering, heating the water phase to 90-95 ℃ for reflux reaction. After the reaction is finished, the mixture is distilled under reduced pressure, desolventized and dried, 423.8g of absolute ethyl alcohol is added, the mixture is heated, refluxed, cooled, crystallized, filtered and dried to obtain white solid, namely 87.1g of the target product (I-1), the yield is 85.5%, 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-3)
N-methylaniline (104.86 g,0.979mol,2.0 eq.) is added into 400.4g toluene, cooled to-5 ℃ under the protection of nitrogen, methyl phosphorus dichloride (57.2 g, 0.4819 mol,1.0 eq.) is added dropwise while maintaining the system temperature at-5 ℃, after the dropwise addition, an absolute ethanol solution (78.19 g) of N-methylaniline (54.53 g,0.509mol,1.04 eq.) is continuously added dropwise, the reaction is kept for 0.5 hour, the compound (III-3) is obtained, and the salt is removed by filtration, and the filtrate is directly used for the next reaction.
2) Synthesis of Compound (I-1)
Under the protection of nitrogen, the compound (1I-3) (93.93 g, 0.460 mol,0.95 eq.) is added into the filtrate of the compound (III-3), and the temperature is slowly raised to 85-90 ℃ for heat preservation reaction for 12h.
Adding 429.0g of 30% hydrochloric acid into the feed liquid, standing for layering, heating the water phase to 90-95 ℃ for reflux reaction. After the reaction is finished, the solution is decompressed, distilled and desolventized to dryness, 429.0g of absolute ethyl alcohol is added, the mixture is heated, refluxed, cooled, crystallized, filtered and dried to obtain a white solid, namely 91.3g of the target product (I-1), the yield is 88.5%, the content is 98.0%, and the ee value is 97.1%.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Moreover, any combination of the various embodiments of the invention can be made without departing from the spirit of the invention, which should also be considered as disclosed herein.
Claims (10)
1. A process for preparing glufosinate-ammonium represented by formula (I) or a salt, enantiomer or a mixture of enantiomers in any proportion thereof, comprising the steps of:
1) Reacting a compound of formula (II) or a salt, enantiomer or mixture of enantiomers thereof in any proportion with a compound of formula (III),
and
2) Hydrolyzing the reaction product of step 1) to obtain a compound of formula (I),
wherein,,
x is halogen;
y is-OR 3 or-N (R) 4 )(R 5 )；
Z is hydrogen or an amino protecting group;
R 1 and R is 2 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl、C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 1 And R is 2 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution;
R 3 and R is 6 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;
R 4 and R is 5 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl, or R 4 And R is 5 Together with the N atom to which it is attached, form a three-to six-membered heterocycloalkyl, wherein said C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Cycloalkyl, ternary to six membered heterocycloalkyl, C 6 -C 10 Aryl or five-to ten-membered heteroaryl optionally substituted with halogen, carboxyl, hydroxyl, cyano, amino, nitro, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl substitution; and is also provided with
* For identifying chiral carbon atoms.
2. The method of claim 1, wherein the amino protecting group is selected from one or more of the following: -C (O) R 7 、-C(O)OR 8 、-CH 2 R 9 and-SO 2 R 10 Wherein R is 7 、R 8 、R 9 And R is 10 Each independently selected from C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, C 6 -C 10 Aryl or five to ten membered heteroaryl, preferably ethoxycarbonyl.
3. The process of claim 1, wherein the enantiomer of glufosinate is L-glufosinate or D-glufosinate, and/or the mixture of any ratio of enantiomers of glufosinate comprises 0.1:99.9 to 99.9: 0.1L-glufosinate and D-glufosinate, preferably 50:50 to 99.9: 0.1L-glufosinate and D-glufosinate.
4. The method according to claim 1 or 2, 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.
5. The method of claim 1 or 2, wherein the R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 And R is 10 Each independently selected from hydrogen, C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl or C 6 -C 10 Aryl, preferably hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl.
6. The method of claim 1, wherein the compound of formula (III) is prepared from a composition comprising: compounds of formula (IV) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the A compound of formula (V) and a compound of formula (VII); compounds of formula (VI), formula (VII) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the Or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII),
wherein R is 1 、R 2 、R 6 And X is as defined in claim 1.
7. The process according to claim 6, wherein the reaction is carried out in the presence of an acid-binding agent, preferably selected from NR 11 R 12 R 13 Wherein R is 11 、R 12 And R is 13 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 11 、R 12 And R is 13 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; and/or the molar ratio of the composition to the acid-binding agent is 1:0.01-5, preferably 1:0.1-1.5.
8. The process according to claim 1, wherein for step 1), the reaction is carried out in the absence of a solvent or an organic solvent, preferably the organic solvent is selected from at least one of an aromatic hydrocarbon solvent, an alkane solvent, a halogenated hydrocarbon solvent, an ether solvent, an ester solvent, an amide solvent and a sulfur-containing solvent, preferably at least one of toluene and chlorobenzene; more preferably, the reaction is carried out at a temperature of-10 to 130 ℃, preferably 30 to 95 ℃ for 1 to 25 hours; and/or the number of the groups of groups,
for step 2), the hydrolysis is carried out in the presence of an acid or base, preferably at least one acid selected from the group consisting 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 60-110 ℃ for 0.5-36 hours.
9. A composition comprising: compounds of formula (IV) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the A compound of formula (V) and a compound of formula (VII); compounds of formula (VI), formula (VII) and HOR 6 The method comprises the steps of carrying out a first treatment on the surface of the Or a compound of formula (VI), a compound of formula (VII) and a compound of formula (VIII),
wherein R is 1 、R 2 、R 6 And X is as defined in claim 1.
10. Use of the composition according to claim 9 for preparing glufosinate-ammonium represented by formula (I) or its salts, enantiomers or mixtures of enantiomers in any ratio
Wherein R is 1 、R 2 、R 6 X and X are as defined in claim 1.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310389331.8A CN116478207A (en) | 2023-04-12 | 2023-04-12 | Preparation method of glufosinate-ammonium |
| PCT/CN2024/087288 WO2024213059A1 (en) | 2023-04-12 | 2024-04-11 | Preparation method for glufosinate ammonium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310389331.8A CN116478207A (en) | 2023-04-12 | 2023-04-12 | Preparation method of glufosinate-ammonium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116478207A true CN116478207A (en) | 2023-07-25 |
Family
ID=87214845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310389331.8A Pending CN116478207A (en) | 2023-04-12 | 2023-04-12 | Preparation method of glufosinate-ammonium |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN116478207A (en) |
| WO (1) | WO2024213059A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024213059A1 (en) * | 2023-04-12 | 2024-10-17 | 宁夏永农生物科学有限公司 | Preparation method for glufosinate ammonium |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW353663B (en) * | 1991-04-06 | 1999-03-01 | Hoechst Ag | Process for the preparation of phosphorus-containing L-amino acids, their derivatives and intermediates for this process |
| CN111004280A (en) * | 2019-10-10 | 2020-04-14 | 利尔化学股份有限公司 | Continuous flow preparation method of diethyl methylphosphite |
| KR102515430B1 (en) * | 2020-01-20 | 2023-03-29 | 라이어 케이컬 씨오., 엘티디. | How to make glufosinate |
| CN113248537B (en) * | 2020-02-11 | 2023-06-06 | 利尔化学股份有限公司 | Preparation method of glufosinate-ammonium |
| AR126485A1 (en) * | 2021-07-20 | 2023-10-11 | Lier Chemical Co Ltd | PROCESS TO PREPARE GLUFOSINATE OR ANALOGUES OF THE SAME |
| CN115873033A (en) * | 2022-12-28 | 2023-03-31 | 永农生物科学有限公司 | Preparation method of glufosinate-ammonium |
| CN116478207A (en) * | 2023-04-12 | 2023-07-25 | 宁夏永农生物科学有限公司 | Preparation method of glufosinate-ammonium |
-
2023
- 2023-04-12 CN CN202310389331.8A patent/CN116478207A/en active Pending
-
2024
- 2024-04-11 WO PCT/CN2024/087288 patent/WO2024213059A1/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024213059A1 (en) * | 2023-04-12 | 2024-10-17 | 宁夏永农生物科学有限公司 | Preparation method for glufosinate ammonium |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024213059A1 (en) | 2024-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5524328B2 (en) | Pyrazolylacrylonitrile compound and use thereof | |
| WO2024213059A1 (en) | Preparation method for glufosinate ammonium | |
| US4297282A (en) | Resolution of mercaptopropionic acids | |
| TWI823808B (en) | Preparation method of glufosinate-ammonium | |
| 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 | |
| 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 | |
| CN115873033A (en) | Preparation method of glufosinate-ammonium | |
| KR890000480B1 (en) | Process and herbicidal compositions containing 3,5-dicarboxylic acid esters of 2,6-bis-(fluoroalkyl)tetrahydro-pyrans and piperidines | |
| EP0326766B1 (en) | 5-substituted ornithine derivatives | |
| CN117164621A (en) | Preparation method of glufosinate-ammonium | |
| Kondratyuk et al. | Reaction of diethyl 1-acylamino-2, 2-dichloroethenylphosphonates with amino acids esters | |
| EP4371992A1 (en) | Methods of preparing glufosinate | |
| US4411836A (en) | Racemization of an α-methyl-β-acylthiopropionic acid | |
| BR102023014787B1 (en) | GLUFOSINATE PREPARATION METHODS | |
| EP0705240B1 (en) | Novel processes for preparing (s)-4-amino-hepta-5,6-dienoic acid and intermediates thereof | |
| JP3972715B2 (en) | Method for producing sulfide derivatives | |
| JP2023180566A (en) | Method for producing ergothioneine derivative | |
| JP2006193439A (en) | New pyrrolidine compound | |
| JP4109446B2 (en) | Process for producing pure trans-2-[(α-methylbenzyl) amino] cyclopentanol as a diastereoisomer | |
| AU2013201895B2 (en) | Hypophosphorous acid derivatives and their therapeutical applications | |
| SU952104A3 (en) | Process for producing derivatives of interphenylene-9-thiaxo-12-azaprostanic acid | |
| HU179780B (en) | Process for preparing thiazolidine-carboxylic acid derivatives | |
| WO2013095307A1 (en) | New crystal salts of zofenopril, process for obtaining them and their use in therapy |
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 |