CN118146258A - Preparation method of glufosinate-ammonium - Google Patents
Preparation method of glufosinate-ammonium Download PDFInfo
- Publication number
- CN118146258A CN118146258A CN202410263342.6A CN202410263342A CN118146258A CN 118146258 A CN118146258 A CN 118146258A CN 202410263342 A CN202410263342 A CN 202410263342A CN 118146258 A CN118146258 A CN 118146258A
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- CN
- China
- Prior art keywords
- glufosinate
- ammonium
- formula
- hydrochloride
- compound
- Prior art date
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- 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 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 38
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000010533 azeotropic distillation Methods 0.000 claims abstract description 14
- 238000000926 separation method Methods 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 5
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 22
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 18
- 235000019441 ethanol Nutrition 0.000 claims description 15
- 230000002829 reductive effect Effects 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000011084 recovery Methods 0.000 abstract description 14
- 239000004009 herbicide Substances 0.000 abstract description 2
- 239000000575 pesticide Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 33
- 239000000047 product Substances 0.000 description 18
- -1 D-homoalanin-4-yl- (methyl) phosphonic acid Chemical compound 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 13
- 239000006227 byproduct Substances 0.000 description 12
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 11
- 239000002994 raw material Substances 0.000 description 11
- 239000005561 Glufosinate Substances 0.000 description 10
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 9
- 239000003513 alkali Substances 0.000 description 8
- 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 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000155 isotopic effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- IAJOBQBIJHVGMQ-SCSAIBSYSA-N (2R)-glufosinate Chemical compound C[P@@](O)(=O)CC[C@@H](N)C(O)=O IAJOBQBIJHVGMQ-SCSAIBSYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000003541 multi-stage reaction Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 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
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical group 0.000 description 2
- 229910001617 alkaline earth metal chloride Inorganic materials 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-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
- 230000001276 controlling effect Effects 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethylcyclohexane Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 150000004715 keto acids Chemical class 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- 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
- 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
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 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 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical class N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- 241001465754 Metazoa Species 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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 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
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- 238000006297 dehydration reaction Methods 0.000 description 1
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- 238000001514 detection method Methods 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- HDITUCONWLWUJR-UHFFFAOYSA-N diethylazanium;chloride Chemical compound [Cl-].CC[NH2+]CC HDITUCONWLWUJR-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
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- 235000013399 edible fruits Nutrition 0.000 description 1
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- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
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- 230000004151 fermentation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 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
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 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
- 238000002386 leaching Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- ONRKUGHFZWYUJP-UHFFFAOYSA-N methylphosphane dihydrochloride Chemical compound Cl.Cl.PC ONRKUGHFZWYUJP-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- REJGOFYVRVIODZ-UHFFFAOYSA-N phosphanium;chloride Chemical compound P.Cl REJGOFYVRVIODZ-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application belongs to the field of pesticide herbicides, and relates to a preparation method of glufosinate-ammonium. In particular to a method for preparing the glufosinate-ammonium from acidolysis solution containing the glufosinate-ammonium hydrochloride, which comprises the following steps: (1) Deacidifying acid hydrolysis solution containing the glufosinate-ammonium hydrochloride by adding absolute ethyl alcohol to carry out azeotropic distillation; (2) And adding diethylamine to adjust the pH of the system to 1.5-4.0, crystallizing, and carrying out solid-liquid separation to obtain the glufosinate-ammonium. The preparation method of the arginate-ammonium can obtain a high-quality target product with the content of more than 99 percent and the ee value of more than 99 percent, and the recovery rate can reach more than 99 percent.
Description
Technical Field
The application relates to the field of pesticide herbicides, in particular to a preparation method of glufosinate-ammonium.
Background
The glufosinate (Glufosinate) has the characteristics of wide weeding spectrum, high activity, low toxicity, easy degradation in soil, safety to crops, small drift, good environmental compatibility, quicker weeding 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-enantiomer, namely the smart glufosinate has activity, the smart glufosinate is easier to decompose in soil, the toxicity to human beings and animals is smaller, the environmental pressure can be greatly reduced, and the activity and the control effect on resistant weeds are better than those of the common glufosinate. Although most of the glufosinate-ammonium commercial products sold on the market today are still racemates thereof, with technological innovation and advancement, the entry of the L-enantiomer into the mainstream market is impermissible.
The existing method for synthesizing the glufosinate-ammonium mainly comprises a chemical method and a biological method. Among these chemical methods are asymmetric hydrogenation, chemical resolution and semi-synthetic methods.
The asymmetric hydrogenation method takes an intermediate keto acid PPO as a raw material, and under the action of a chiral catalyst and a ligand, the intermediate keto acid PPO and amine undergo a reductive amination reaction, and then deprotection is carried out to obtain the glufosinate-ammonium. The route is used as a method for industrially producing the refined glufosinate-ammonium at home and abroad, is developed and industrially applied by cooperation of Yongnong organisms and Ming Zhi fruit, has the advantages of mild reaction, high yield and the like, but is limited to further popularization and application due to the defects of unstable intermediate PPO, higher process cost and the like.
The chemical resolution method is to resolve racemized D, L-glufosinate or derivatives thereof by chiral resolution reagent, thereby preparing optically pure glufosinate. The specification of patent application publication No. 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 using a chiral base such as quinine and cinchonine to precipitate one of the diastereomeric salts. The method needs to use expensive chiral resolution reagent, has lower yield and has no obvious industrialization advantage.
The semisynthesis method uses amino acids obtained by fermentation as raw materials, for example: methionine, homoserine, etc., by a multi-step reaction.
The patent application specification with publication number of US5442088A discloses a method for obtaining the glufosinate-ammonium hydrochloride by carrying out Michaelis-Arbuzov reaction with methyl phosphodiester and finally hydrolyzing and refining by taking L-homoserine lactone derivative as raw material through ring-opening chlorination and esterification.
The multistep reaction process unit is convenient to operate, but the activity of chlorinated substrates of Michaelis-Arbuzov reaction raw materials is limited, the process can be 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 ee value of the L-enantiomer is reduced due to racemization of part of raw materials or products at the temperature.
Patent specification publication number 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 hydrolyzed to obtain the glufosinate-ammonium.
The method takes L-homoserine as a raw material, and synthesizes the L-homoserine through multi-step reactions such as cyclization, chlorination, esterification, protecting group protection and the like, and the reaction steps are longer. In addition, michaelis-Arbuzov reaction inevitably produces halogenated hydrocarbons, which are 3 types of carcinogens and have a damaging effect on ozone in the atmosphere.
Patent specification publication number CN116041387B discloses: the glufosinate is prepared by taking chlorohomoserine ester as a raw material and performing condensation cyclization, hydrolysis, refining and purification.
The novel process route is milder in reaction temperature than Michaelis-Arbuzov reaction due to different reaction mechanisms, the reaction temperature can be reduced by 30-80 ℃ compared with the Michaelis-Arbuzov reaction, and racemization of the L-enantiomer at high temperature can be reduced when the arginate is prepared due to the reaction temperature, so that the ee value of the L-enantiomer of a product is improved. Similarly, the process can avoid the halogenated hydrocarbon byproduct in Michaelis-Arbuzov reaction, save equipment and engineering investment for separating, purifying, collecting and the like of the byproduct, and avoid potential environmental and safety risks brought by the byproduct. However, the process has the defects in the aspects of separation and purification of crude products, and is difficult to simply, conveniently and efficiently realize the separation and purification of the products, ammonium chloride and organic amine salts, and further difficult to realize the continuity and automation of the separation and purification process.
The specification of the patent application publication CN117105976a discloses: separating and purifying ammonium glufosinate by electrodialysis, nanofiltration, dehydration and other steps of ammoniated solution (such as ammoniated solution of ammonium glufosinate hydrochloride). The method can obtain the high-content finished product glufosinate ammonium of the crude drug with high recovery rate, and can separate and recover the byproduct organic amine salt, thereby reducing the cost of raw materials and the emission of three wastes.
Patent specification publication number CN103827127B discloses: the method for preparing the glufosinate-ammonium by adding inorganic alkali into a methanol and water system to adjust the pH. The method adopts inorganic alkali such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium ethoxide, sodium methoxide and the like, and compared with the common method using NH 3 as alkali, the greatest difference is that byproduct salt is alkali metal or alkaline earth metal chloride instead of ammonium chloride. However, this process inevitably brings alkali metal or alkaline earth metal chlorides into the product and affects the product content.
The application aims to provide a method for preparing high-content high-ee-value glufosinate-ammonium by acidolysis solution containing glufosinate-ammonium hydrochloride with high recovery rate.
Disclosure of Invention
The application provides a method for preparing glufosinate-ammonium from acidolysis solution containing glufosinate-ammonium hydrochloride, which has the advantages of high recovery rate, high content of products, high ee value and the like.
The structure of the glufosinate-ammonium is shown as a formula (I):
According to the application, the compounds of formula (I) may be present as pure L-enantiomer or as mixtures of L, D-enantiomers. The L-enantiomer of the compound of formula (I) is preferably present in greater proportion in the enantiomeric mixture of the application, e.g., in one embodiment, the ee value of the compound of formula (I) may be 75% or more (e.g., 80% or more, 85% or more, 90% or more, 95% or more, 97% or more, 98% or more, 98.5% or more, 99% or more, 99.3% or more, 99.5% or more, 99.7% or more, 99.8% or more, 99.9% or more).
The application provides a method for preparing glufosinate-ammonium from acidolysis solution containing glufosinate-ammonium hydrochloride, which comprises the following steps:
(1) Deacidifying acid hydrolysis solution containing the glufosinate-ammonium hydrochloride by adding absolute ethyl alcohol to carry out azeotropic distillation;
(2) Adding diethylamine to regulate the pH value of the system to 1.5-4.0, crystallizing, and carrying out solid-liquid separation to obtain the refined glufosinate-ammonium shown in the formula (I).
In one embodiment, the acidolysis solution of the application further comprises diethylamine hydrochloride. The number of moles of diethylamine hydrochloride in the acidolysis solution is about equivalent to the number of moles of arginate-ammonium-phosphine hydrochloride, for example, the ratio of the number of moles of diethylamine hydrochloride to the number of moles of arginate-ammonium-phosphine hydrochloride is 0.9-1.2:1, preferably 1:1.
In one embodiment, the acidolysis solution disclosed by the application is prepared by adopting a method disclosed in patent specification with publication number CN 116041387B.
In one embodiment, the acidolysis solution is an acidolysis solution obtained by hydrolyzing a compound of formula (III) in hydrochloric acid; the hydrochloric acid is preferably 30-37% (mass concentration) hydrochloric acid. The hydrolysis may be carried out 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 ℃.
In one embodiment, the compound of formula (III) may be prepared by reacting a compound of formula (II) or a hydrochloride thereof with a compound of formula (V);
the step of preparing the compound of formula (III) 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, toluene, xylene, trimethylbenzene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, halogenated benzene or dihalobenzene), an alkane solvent (e.g., N-hexane, cyclohexane, N-heptane, methylcyclohexane, ethylcyclohexane), an ether solvent (e.g., tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, methylcycloamyl 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-based 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 reaction solution for preparing the compound of the formula (III) can be directly added with hydrochloric acid and then hydrolyzed by water phase to prepare acidolysis solution; or filtering out solid from the reaction solution, adding hydrochloric acid, and hydrolyzing the water phase to prepare acidolysis solution; or separating and purifying the compound of the formula (III), and then adding hydrochloric acid for hydrolysis to prepare acidolysis solution.
The amounts of the reactants used in the steps for preparing the compound of formula (III) 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 (II) to the compound of formula (V) may be 1:0.9-5, preferably 1:1.05-1.5. In one embodiment of the application, the reaction is preferably carried out at a temperature of 60-120 ℃ for 0.5-24 hours.
The acidolysis solution prepared according to the method of the present application, which already contains about equivalent amounts of diethylamine hydrochloride to the compound of formula (I), has a ratio of moles of diethylamine hydrochloride to moles of arginate-ammonium-phosphonate hydrochloride of 0.9-1.2:1, preferably 1:1; also contains a small amount of homoserine and other phosphorus-containing impurities.
In the step (1) of the application, in the later period of deacidification, as the water content is reduced, the system becomes viscous, the mass transfer and heat transfer of materials are blocked, and the residual acid water is difficult to directly remove, so the application utilizes the characteristic of azeotropy of an alcohol solvent and water, and the alcohol solvent is added after deacidification of water to carry out azeotropic distillation so as to realize that the system reaches different water contents after azeotropic distillation. Because the solubility of the glufosinate-ammonium in water is greater than that of the glufosinate-ammonium in an alcohol solvent, the recovery rate of the product is higher when the water content in the system is lower. In the selection of the alcohol solvent, ethanol is selected as the solvent, preferably absolute ethanol, because methanol and water cannot form an azeotrope, and the boiling point of the alcohol of C3 and above is relatively high, which is unfavorable for controlling the residue in the final product of the compound of formula (I).
In the step (1), the deacidification and water treatment process can be carried out under normal pressure or negative pressure; after deacidifying water, absolute ethyl alcohol with different weights can be added to continue azeotropic distillation so as to adjust the water content (weight) in the system to be different.
In one embodiment, in the step (1), the water content by weight of the system after azeotropic distillation is controlled to be within 10%, preferably within 5%, within 2%, more preferably within 1%, and within 0.5%; after azeotropic distillation, the weight of ethanol in the system is 2-10 times, preferably 3-6 times, the weight of the compound of formula (I).
In one embodiment, in the step (2), the amount of diethylamine varies according to the residual amount of acid water in the system, and may be 1.0 to 2.0 equivalents (for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 equivalents) of the molar amount of the arginate-ammonium-phosphonate hydrochloride in the acidolysis solution; regulating the pH value of the system to 1.5-4.0 by using diethylamine; preferably, the pH of the system is adjusted to 1.5-3.0, more preferably to 2.0-2.3. The amount of the glufosinate-ammonium hydrochloride in the acidolysis solution can be accurately measured by an external standard method.
In one embodiment, in the step (2), diethylamine is added to adjust the pH value of the system, and then the heat-preserving reaction is carried out; the incubation reaction is carried out at 0-90 ℃, preferably at 50-80 ℃; the reaction time is kept between 0.5 and 3 hours, preferably between 0.5 and 1 hour.
In one embodiment, in the step (2), the temperature of crystallization is 10 to 35 ℃, preferably 20 to 25 ℃, and the time of crystallization is 0.5 to 5 hours, preferably 0.5 to 1 hour. And (3) after crystallization, carrying out solid-liquid separation and drying to obtain the glufosinate-ammonium.
Since the acidolysis solution of the present application contains about the equivalent of diethylamine hydrochloride as that of glufosinate-ammonium hydrochloride, diethylamine is preferable as a base for adjusting the pH value, thereby obtaining a single byproduct diethylamine hydrochloride.
According to the application, the characteristic of larger solubility is utilized in absolute ethyl alcohol or ethyl alcohol containing a small amount of water (such as ethyl alcohol with the water content of less than 10%, less than 5%, less than 2%, less than 1% and less than 0.5%), the pH value is regulated to be close to the isoelectric point of the glufosinate-ammonium by controlling the different water contents of the system and using diethylamine as a base, so that the glufosinate-ammonium product with high content and high ee value is obtained with high recovery rate, and the residual diethylamine hydrochloride can be stably controlled within 0.1% (weight), so that the effect of completely removing the equivalent diethylamine hydrochloride in acidolysis solution is basically realized. The diethylamine hydrochloride byproduct dissolved in the mother solution is subjected to desolventizing, alkali regulating and free and rectification to obtain diethylamine, which can be recycled, and the raw material cost and the three-waste treatment cost are greatly reduced.
For the solubility of diethylamine hydrochloride in ethanol, see ：CRC handbook of chemistry and physics97th Edition by W.M.Haynes,David R.Lide,Thomas J.Bruno;International Standard Book Number-13:978-1-4987-5429-3(eBook–PDF). in pages 3-172 of the book, the compound numbered 3379 is described as DIETHYLAMINE HYDROCHLORIDE (660-68-4) with a solubility of: vs H 2 O, etOH. See page 3-1, where "vs" is defined as: "very soluble", i.e. "very soluble". In the regulations regarding solubility (same definition in USP) in the chinese pharmacopoeia 2010 edition two standard guide to the use, "very soluble" means that 1g (1 mL) of a solvent can be dissolved in less than 1mL of the solvent.
The applicant found through a great deal of experimental study that: the isoelectric point of the compound of the formula (I) is between pH=2.0 and 2.3, and when the pH is adjusted to the isoelectric point by adding alkali, the target product with high content can be obtained more easily with high recovery rate. If the pH is higher, for example ph=5-6, a certain proportion of the carboxyl groups in the compound of formula (I) will form salts with diethylamine, which will on the one hand reduce the recovery of the product and on the other hand will also cause a significant amount of diethylamine to remain in the final product. If the pH is adjusted to less than 1.5, the amino group in the compound of formula (I) will exist as the hydrochloride salt, which will also affect the recovery and content of the final product.
In addition, because the isoelectric point of homoserine is pi=5.6, at the pH=2.0-2.3, homoserine impurities in acidolysis solution exist in the form of hydrochloride, which is more beneficial to dissolving in mother liquor and improving the content of the compound shown as the formula (I) in the final product. The arginate-ammonium phosphine hydrochloride in the acidolysis solution contains a small amount of D-enantiomer, and when crystallization separation is carried out at the pH value of = 2.0-2.3, the D-glufosinate is easier to stay in the mother solution due to the difference of physicochemical properties of the L-glufosinate and the D-glufosinate, so that the ee value of a final product of the compound shown as the formula (I) is improved. In some embodiments, the ee value of the compounds of formula (I) in the acidolysis solution can reach 97.0%, and by the process of the application it is possible to obtain end products with an ee value of more than 98%, preferably more than 99%, more preferably more than 99.8%.
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. the application firstly uses absolute ethyl alcohol to realize azeotropic distillation for deacidification so as to realize that the system achieves different water contents after azeotropic distillation. When the water content is lower, the recovery rate of the product can be improved, and the generation of additional diethylamine hydrochloride by-product during the subsequent pH adjustment is avoided due to the more complete removal of the acid water.
2. The acidolysis solution of the application already contains diethylamine hydrochloride with equivalent weight as that of the glufosinate-ammonium hydrochloride, so diethylamine is used as alkali to adjust the pH value, thereby obtaining a single byproduct diethylamine hydrochloride. The byproduct can be subjected to desolventizing, alkali regulating and free, and rectifying to obtain diethylamine meeting national standards, and the diethylamine can be recycled in the synthesis of the formula (I), so that the raw material cost and the treatment cost of three wastes are greatly reduced.
3. According to the application, by utilizing the characteristic that diethylamine hydrochloride has larger solubility in ethanol, diethylamine is used as alkali to adjust the pH value to the isoelectric point of the smart glufosinate, and the byproduct diethylamine hydrochloride can be removed, meanwhile, the high-content product of the compound shown as the formula (I) can be obtained with high recovery rate, and the residual diethylamine hydrochloride can be stably controlled within 0.1%.
4. In an ethanol system, solid-liquid separation is carried out when the pH value is regulated to 2.0-2.3 of the isoelectric point of the glufosinate-ammonium, on one hand, because homoserine is in a hydrochloride state at the moment, the removal of homoserine is more facilitated, and the product content is improved; on the other hand, due to the difference in physicochemical properties of L-glufosinate and D-glufosinate, the D-enantiomer is more easily left in the mother liquor at this time, thereby increasing the ee value of the product compound of formula (I).
5. The preparation method can obtain a high-quality target product with the content of more than 98 percent and the ee value of more than 98 percent, and the recovery rate can reach more than 92 percent; the preparation method of the application can optimally obtain the high-quality target product with the content of more than 99 percent and the ee value of more than 99 percent, and the recovery rate can reach more than 99 percent.
Detailed Description
Unless otherwise indicated, the terms "spermatine", "spermatine hydrochloride", "glufosinate", "diethylamine hydrochloride", "acid", "compound of formula (N) (e.g. compound of formula (III)", etc. as used herein also encompass isotopic derivatives in which any one of the atoms of the compound is replaced by its isotopic atom, i.e. all agriculturally acceptable isotopic derivatives in which one or more of the atoms are replaced by an atom having the same atomic number as the one normally found in nature but a different atomic mass or mass number. Examples of isotopes suitable for inclusion in compounds of the application include isotopes of hydrogen, such as 2 H (D) and 3 H (T), isotopes of carbon, such as 11C、13 C and 14 C, isotopes of chlorine, such as 37 Cl, isotopes of fluorine, such as 18 F, isotopes of iodine, such as 123 I and 125 I, isotopes of nitrogen, such as 13 N and 15 N, isotopes of oxygen, such as 15O、17 O and 18 O, and isotopes of sulfur, such as 35 S. Isotopic derivatives can generally be prepared by conventional techniques known to those skilled in the art or by substituting a suitable isotopically labeled reagent for a previously used unlabeled reagent in a manner analogous to the processes appended herein.
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.
The technical solution of the present application will be clearly and completely described in the following examples, and it is obvious that the described examples are only some examples of the present application, but not all examples. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Example 1: preparation of acidolysis solution
1) Synthesis of Compound of formula (III)
Diethylamine (1031.52 g,14.103 mol) was added to 2600.0g of toluene, cooled to-5-5 ℃ under nitrogen protection, and methylphosphine dichloride (433.90 g,3.711 mol) was started to be added dropwise while keeping the system temperature at-5-5 ℃. After the dripping is finished, the temperature is kept for 0.5 hour, the temperature is slowly raised to 80-85 ℃ to obtain the compound of the formula (V), 1800.0g of toluene suspension of the compound of the formula (II) (600.0 g,2.969 mol) is added dropwise, the heat-insulating reaction is continued for 10 hours after the dripping is finished, nitrogen pressure filtration is carried out, the filter cake is washed twice by toluene, and the filtrate is combined to obtain the reaction solution of the compound of the formula (III), so that the reaction solution can be directly used for the next reaction.
2) Synthesis of acidolysis solution of formula (I)
Adding 1950.0g of 30% hydrochloric acid into the reaction solution of the compound shown in the formula (III), stirring for 0.5 hour, standing for layering, heating the water phase to 95-105 ℃ for reaction. After the reaction is finished, the external standard method is adopted for quantification, and the acidolysis solution with the formula (I) is measured to be: 614.39g (calculated as compound of formula (I)) of the hydrochloride of the compound of formula (I), 95.1% (calculated as compound of formula (II)), ee 97.0%; also contained were 374.23g of diethylamine hydrochloride and 17.68g of homoserine.
Example 2: preparation of Compounds of formula (I)
Taking acidolysis solution (containing 25.0g of compound shown in formula (I)) in the above example 1, decompressing and deacidifying, adding 200g of absolute ethyl alcohol for azeotropic distillation, measuring about 50g of residual ethyl alcohol in a system after distillation is finished, measuring that the water content in the system is 10.0%, adding diethylamine to regulate the pH value to 2.0, preserving heat for 1 hour at 60-70 ℃, cooling to room temperature for crystallization for 1 hour, carrying out suction filtration, leaching and drying to obtain the white solid compound shown in formula (I), wherein the recovery rate is 90.5%, the content is 98.1%, the ee value is 98.8%, and the diethylamine residue is lower than the detection limit.
Examples 3 to 20: preparation of formula (I)
The water content of the system after azeotropic distillation, the residual ethanol content, the pH value after diethylamine addition, the incubation temperature and other reaction conditions were changed according to the method of example 2, and the specific reaction conditions and results are shown in the following table:
The foregoing is only a preferred embodiment of the present application, but the scope of the present application is not limited thereto, and any person skilled in the art, who is within the scope of the present application, should make equivalent substitutions or modifications according to the technical scheme of the present application and the inventive concept thereof, and should be covered by the scope of the present application.
Claims (10)
1. A method for preparing glufosinate-ammonium from acidolysis solution containing glufosinate-ammonium hydrochloride, comprising the following steps:
(1) Deacidifying acid hydrolysis solution containing the glufosinate-ammonium hydrochloride by adding absolute ethyl alcohol to carry out azeotropic distillation;
(2) Adding diethylamine to adjust the pH of the system to 1.5-4.0, crystallizing, and carrying out solid-liquid separation to obtain the glufosinate-ammonium shown in the formula (I);
2. the method for preparing glufosinate-ammonium according to claim 1, wherein in the step (1), the acidolysis solution further comprises diethylamine hydrochloride.
3. The method for producing glufosinate-ammonium according to claim 2, wherein in the step (1), the ratio of the number of moles of diethylamine hydrochloride in the acidolysis solution to the number of moles of glufosinate-ammonium hydrochloride is 0.9-1.2:1.
4. A process for the preparation of glufosinate-ammonium according to any one of claims 1-3, wherein in step (2) diethylamine is added to adjust the pH of the system to 1.5-3.0, preferably to adjust the pH of the system to 2.0-2.3.
5. A process for the preparation of glufosinate-ammonium according to any one of claims 1-3 wherein in step (2) the incubation is performed after adjusting the pH of the system by adding diethylamine.
6. The process for the preparation of glufosinate-ammonium according to claim 5, wherein in step (2), the incubation reaction is carried out at 0-90 ℃, preferably at 50-80 ℃; the reaction time is kept between 0.5 and 3 hours, preferably between 0.5 and 1 hour.
7. A process for the preparation of glufosinate-ammonium according to any one of claims 1-3, wherein after azeotropic distillation in step (1) the water content by weight of the system is reduced to within 10%, preferably to within 1%, more preferably to within 0.5%.
8. A process for the preparation of glufosinate-ammonium according to any one of claims 1-3, wherein in step (1) the weight of ethanol in the system after azeotropic distillation is 2-10 times, preferably 3-6 times the weight of the compound of formula (I) in the system.
9. A process for the preparation of glufosinate-ammonium according to any one of claims 1-3, wherein in step (1), the acidolysis solution is an acidolysis solution obtained by hydrolysis of a compound of formula (III) in hydrochloric acid;
10. The process for the preparation of glufosinate-ammonium according to claim 9, wherein the compound of formula (III) is prepared by reacting a compound of formula (II) or its hydrochloride with a compound of formula (V);
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