CN116135864A - Simple and efficient preparation method of L-glufosinate-ammonium - Google Patents
Simple and efficient preparation method of L-glufosinate-ammonium Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 32
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- UTZAXPKCGJZGLB-UHFFFAOYSA-N diethyl methyl phosphite Chemical compound CCOP(OC)OCC UTZAXPKCGJZGLB-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 6
- 238000004176 ammonification Methods 0.000 claims abstract description 5
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 3
- 238000007146 photocatalysis Methods 0.000 claims abstract description 3
- 230000001699 photocatalysis Effects 0.000 claims abstract description 3
- 239000011941 photocatalyst Substances 0.000 claims description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- 239000010949 copper Substances 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000012434 nucleophilic reagent Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- ZOMQCVKHGOMNER-UHFFFAOYSA-N 2,4,5,6-tetrakis(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical group C(#N)C1=C(C(=C(C(=C1N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)C#N)N(C1=CC=CC=C1)C1=CC=CC=C1 ZOMQCVKHGOMNER-UHFFFAOYSA-N 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- UDJSNDZZNASIPD-UHFFFAOYSA-N 2,4,5,6-tetrakis(9H-carbazol-1-yl)benzene-1,3-dicarbonitrile Chemical compound C1(=CC=CC=2C3=CC=CC=C3NC1=2)C1=C(C(=C(C(=C1C#N)C1=CC=CC=2C3=CC=CC=C3NC1=2)C#N)C1=CC=CC=2C3=CC=CC=C3NC1=2)C1=CC=CC=2C3=CC=CC=C3NC1=2 UDJSNDZZNASIPD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 10
- 238000009776 industrial production Methods 0.000 abstract description 6
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- AQTUACKQXJNHFQ-LURJTMIESA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCC(O)=O AQTUACKQXJNHFQ-LURJTMIESA-N 0.000 description 7
- 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 description 7
- 239000000047 product Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000005561 Glufosinate Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- 238000006845 Michael addition reaction Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- CEMZBWPSKYISTN-RXMQYKEDSA-N methyl (2r)-2-amino-3-methylbutanoate Chemical compound COC(=O)[C@H](N)C(C)C CEMZBWPSKYISTN-RXMQYKEDSA-N 0.000 description 2
- -1 methyl-butylene phosphite Chemical compound 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000005954 phosphonylation reaction Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 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 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 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 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000001457 gas chromatography time-of-flight mass spectrometry Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003643 water by type Substances 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
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- 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 invention discloses a simple and efficient method for preparing L-glufosinate-ammonium, which comprises the following steps a-b-c in a synthetic route:
Description
Technical Field
The invention relates to a simple and efficient method for preparing L-glufosinate-ammonium, and belongs to the technical field of organic synthesis.
Background
The glufosinate-ammonium is used as a low-toxicity, high-efficiency and broad-spectrum nonselective organophosphorus herbicide, and has wider and wider market prospect along with the gradual market return of paraquat worldwide, so that the preparation process of the glufosinate-ammonium is also receiving more and more attention from fine chemical industry and research institutions.
The industrial process for the production of glufosinate mainly comprises the thermal cracking-ACA process [ (a) US4336206[ P ],1982.06.22; (b) US4549995[ P ],1985.10.29; (c) US4599207[ P ],1986.07.08] and Strecker process [ US4510102[ P ],1985.04.09], which only give a racemic mixture of glufosinate-ammonium, which contains 2 isomers of L-and D-form, but of which only the L-form has herbicidal activity. The use of L-glufosinate for weeding can not only reduce the dosage by half, improve the economy and reduce the environmental pressure, but also have better activity and weeding performance than the glufosinate of racemate [ Li Jianing, zhao Jingnan, meng Qingwei ] the research progress of the glufosinate preparation process [ J ]. Pesticide, 2020,59 (12): 859-866]. Although a number of different chemical methods have been developed for the selective synthesis of L-glufosinate, the cost of producing large-scale pure L-isomers is still significantly higher than the cost of racemic mixtures [ Pest Manag. Sci.2018,74,2265-2276].
The preparation method of the L-glufosinate can be mainly divided into four methods of a dynamic kinetic resolution method, a chiral raw material method, a chiral auxiliary method and an asymmetric catalysis method.
L-glufosinate can be obtained through direct chiral resolution of racemic glufosinate, but the theoretical yield is only 50% at most, D-configuration can be racemized through dynamic kinetic resolution, and the reaction yield is improved. Synthetic [ J ] modern pesticides, 2019,18 (2): 21-23] of Knorr [ US5767309[ P ],1998.06.16] and Zhang Dayong [ Wang Zhijian, zhang Dayong ] L-glufosinate are prepared to obtain high-purity L-glufosinate with higher yield by using (-) -quinine and chiral Ni catalyst respectively, but the method reported by Knorr requires higher equipment cost, and the method reported by Zhang Dayong uses expensive chiral prosthetic group, which is not suitable for industrial production.
It has been reported that L-glutamic acid [ Tetrahedron 1992,48,8263-8270], L-methionine [ chip. Chem. Lett.2006,17,177-179], L-aspartic acid [ Tetrahedron Lett.1992,33,2669-2672] and the like are used as chiral raw materials to prepare a high-purity L-glufosinate product, wherein the method using glutamic acid as the raw material requires an elimination reaction under palladium or copper catalysis, and then a free radical addition reaction with methyl-butylene phosphite under the initiation of a free radical initiator. In addition, the methods have low total reaction yield and complicated reaction steps, and are not easy to realize industrialization.
The use of D-valine methyl ester [ Tetrahedron Lett.1987,28,1255-1258] and (S) -2-hydroxy-3-pinone [ Bull. Chem. Sol. Jpn.1987,60,1761-1766] as chiral auxiliary for the preparation of L-glufosinate has been reported. However, when D-valine methyl ester is used as a chiral auxiliary, the reaction is required to be carried out at a low temperature of-78 ℃, and the reaction is difficult to achieve industrially and is only suitable for preparing L-glufosinate in a laboratory; the E.e. value of the L-glufosinate-ammonium product obtained by using (S) -2-hydroxy-3-pinone as a chiral auxiliary is lower, the raw material structure is complex, the cost is higher, and industrialization is not easy to realize.
Asymmetric catalytic processes include asymmetric catalytic hydrogenation processes [ (a) j.org.chem.1991,56,1783-1788; (b) WO2006104120[ P],2006.10.05]Asymmetric Strecker method [ WO2008035687[ P ]],2008.03.27]And asymmetric Michael addition [ ZL201510450698.1[ P ]],2015.12.09]Three kinds. Wherein, chiral ligand used by the asymmetric catalytic hydrogenation method is expensive; using the asymmetric Strecker method (CH 3 ) 3 SiCN raw materials are high in cost and also need to react at low temperature; the total yield and the e.e. value of the asymmetric Michael addition method are not high, and the asymmetric Michael addition method is difficult to be applied to industrialization.
In view of the above, the current method for preparing L-glufosinate is either long in route and complicated in operation, or has severe reaction conditions, or adopts expensive raw materials or reagents, and is not suitable for industrial production as a whole, so that it is necessary to develop a simple and efficient method for preparing L-glufosinate, which is suitable for industrial production.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a simple and efficient method for preparing L-glufosinate-ammonium, which is suitable for industrial production.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a simple and efficient method for preparing L-glufosinate-ammonium comprises the following steps a-b-c in a synthetic route:
the step a is carried out by reacting a compound of formula 1 (i.e., N-t-butoxycarbonyl-L-glutamic acid-1-methyl ester) with N-hydroxyphthalimide
Carrying out condensation reaction in the presence of a condensing agent and a catalyst to obtain a compound of a formula 2; said step b is prepared from compound of formula 2 and diethylmethylphosphite +.>
Decarboxylation phosphonoation reaction is carried out under the photocatalysis condition to obtain the compound of the formula 3; and step c is to sequentially perform acid hydrolysis reaction and ammonification reaction on the compound shown in the formula 3 to obtain the L-glufosinate-ammonium.
In one embodiment, the operations of step a comprise: the compound of formula 1 is combined with N-hydroxyphthalimide in an organic solvent, preferably dichloromethane DCM
The condensation reaction is carried out at room temperature in the presence of a condensing agent (preferably dicyclohexylcarbodiimide, DCC, or the like) and a catalyst (preferably 4-dimethylaminopyridine, DMAP, or the like) to give the compound of formula 2.
In a preferred embodiment, in step a, the molar ratio of the compound of formula 1 to N-hydroxyphthalimide is 1 (1-2), and the molar ratio of the compound of formula 1 to condensing agent is 1 (1-2).
In a preferred embodiment, in step a, dicyclohexylcarbodiimide (i.e., DCC) is used as the condensing agent, and 4-dimethylaminopyridine (i.e., DMAP) is used as the catalyst.
In one embodiment, the operations of step b comprise: the compound of formula 2 is reacted with diethyl methylphosphite in an organic solvent, preferably chlorobenzene
Under light irradiation in the presence of a photocatalyst, a nucleophile or under light irradiation of a photocatalyst, a metal catalyst, a nucleophileDecarboxylation phosphonylation reaction is carried out at room temperature in the presence of light irradiation to obtain the compound of the formula 3.
In a preferred embodiment, in the step b, the light irradiation is blue light irradiation.
In a preferred embodiment, in step b, the molar ratio of the compound of formula 2 to diethylmethylphosphite is 1 (1-5); the mol ratio of the compound of formula 2 to the nucleophilic reagent is 1 (1-3).
In a preferred embodiment, in step b, the amount of the photocatalyst is 1 to 5mol% based on the compound of formula 2, and the amount of the metal catalyst is 0 to 30mol% (when the amount of the metal catalyst is 0, this means that no metal catalyst is added during the reaction).
In a preferred embodiment, in step b, the photocatalyst is 1,2,3, 5-tetra (diphenylamino) -4, 6-dicyanobenzene (i.e., 4 DPAIPN) or 1,2,3, 5-tetra (carbazolyl) -4, 6-dicyanobenzene (i.e., 4 CzIPN), and the metal catalyst is copper catalyst (preferably Cu (OAc) 2 ) And the nucleophilic reagent is PhCOOLi.
In one embodiment, the operations of step c comprise: the compound of formula 3 is firstly hydrolyzed in acidic aqueous solution (preferably hydrochloric acid aqueous solution) to obtain hydrolysis product, and then the hydrolysis product is ammoniated with ammonia water to obtain L-glufosinate-ammonium.
In the invention, the compound (N-t-butoxycarbonyl-L-glutamic acid-1-methyl ester) of the formula 1 can be directly used as a commercial product or can be self-made, and the preparation method comprises the following steps:
the method comprises the steps of firstly, reacting L-glutamic acid with di-tert-butyl dicarbonate (namely, boc anhydride) in the presence of alkali (preferably triethylamine) to obtain N-tert-butoxycarbonyl-L-glutamic acid; the obtained N-tert-butoxycarbonyl-L-glutamic acid is reacted with acetic anhydride to obtain an anhydride product, and the obtained anhydride product is reacted with sodium methoxide to obtain the compound of formula 1.
In one embodiment, the molar ratio of L-glutamic acid to di-tert-butyl dicarbonate to alkali is 1 (1-1.5) (1.5-2.5).
In one embodiment, in the process of preparing the compound of formula 1 from N-t-butoxycarbonyl-L-glutamic acid, the molar ratio of N-t-butoxycarbonyl-L-glutamic acid to acetic anhydride to sodium methoxide is 1 (3-10): 1.5-2.5.
Compared with the prior art, the invention has the following remarkable beneficial effects:
the invention takes N-tert-butoxycarbonyl-L-glutamic acid-1-methyl ester (compound of formula 1) as a raw material, and prepares the L-glufosinate-ammonium through condensation reaction, decarboxylation phosphonoation reaction, hydrolysis and ammonification reaction.
Detailed Description
The technical scheme of the invention is further and fully described in the following by combining specific embodiments.
In this example, all solvents or reagents are commercial reagents except for the specific descriptions; 1 H NMR, 13 C NMR, 31 p NMR was performed on Bruke-400M, agilent-400M, varian-400M and Bruker-500M nuclear magnetic resonance apparatus; EI-MS was measured on instrument Waters Premier GC-TOF MS; flash column chromatography using silica gel (200-300 mesh) produced by tobacco plant; the color development modes of the TLC plate are an ultraviolet lamp, an iodine cylinder, bromocresol green and phosphomolybdic acid.
Example 1: preparation of N-Boc-L-glutamic acid
L-glutamic acid (2.59 g,17.6 mmol) was added to the reaction flask, then a mixed solvent of DMF and water (volume ratio of DMF to water: 3:2, 40 mL) was added to obtain a suspension, triethylamine (4.90 mL,35.3mmol,2.0 equiv.) was then slowly added thereto, stirring was carried out at room temperature for 10 minutes to obtain a clear solution, then di-tert-butyl dicarbonate (3.92 g,17.9mmol,1.02 equiv.) was added to the clear solution, stirring was carried out at room temperature for 1 hour, and the reaction was terminatedThe solvent was removed from the reaction solution under high vacuum, the resulting residue was dissolved in ethyl acetate (115 mL) and the solution was washed with 1M HCl (12 mL), the aqueous layer was saturated with NaCl and extracted with ethyl acetate (60 mL), the organic phases were combined, and then the combined organic phases were washed with water (60 mL), brine (2X 60 mL), and with anhydrous Na, respectively 2 SO 4 Drying, filtration and removal of the organic solvent under reduced pressure gave 3.79g of N-t-butoxycarbonyl-L-glutamic acid (white solid, yield: 87%).
Tested:
1 H NMR(400MHz,CDCl 3 )δ5.28–5.18(m,1H),4.46–4.35(m,1H),2.59–2.47(m,2H),2.31–2.12(m,2H),1.45(s,9H)；
13 C NMR(126MHz,CDCl 3 )δ179.0,177.8,155.3,80.6,52.5,29.4,28.4,27.0。
example 2: preparation of Compound of formula 1 (N-t-Butoxycarbonyl-L-glutamic acid-1-methyl ester)
N-t-Butoxycarbonyl-L-glutamic acid (1.20 g,5.0 mmol) and acetic anhydride (5.0 mL,50mmol,10 equiv.) are added to a reaction flask, the resulting mixture is stirred at 55deg.C for 15 min, toluene (30.0 mL) is then added, the solvent is then removed by rotary evaporation under reduced pressure, the trace AcOH is then removed by vacuum drying over KOH, the residue is then dissolved in MeOH (15 mL) and NaOMe (413 mg,10mmol,2.0 equiv.) is added, the reaction is refluxed for 2 hours, the reaction is terminated, the reaction solution is diluted with water, acidified to pH=1 with 12M HCl and extracted with EtOAc (2X 5.0 mL), the organic layer is combined, anhydrous 2 SO 4 Drying, filtration and removal of the organic solvent under reduced pressure gave 914mg of the compound of formula 1 (white solid, yield: 70%).
Tested:
1 H NMR(400MHz,CDCl 3 )δ5.19(s,1H),4.41–4.29(m,1H),3.74(dd,J＝3.3,2.1Hz,3H),2.55–2.36(m,2H),2.17(s,1H),1.94(dt,J＝14.7,7.5Hz,1H),1.43(dd,J＝3.3,2.1Hz,9H)；
13 C NMR(126MHz,CDCl 3 )δ178.1,172.8,155.6,80.4,52.8,52.6,30.1,28.4,27.8。
example 3: preparation of Compounds of formula 2
To a reaction flask were added the compound of formula 1 (5.23 g,20 mmol), N-hydroxyphthalimide (3.59 g,22mmol,1.1 equiv.), DCC (4.54 g,22mol,1.1 equiv.), DMAP (244 mg,2.0mmol,0.1 equiv.) and 100mL of DCM, and the resulting mixed solution was stirred at room temperature for 12 hours, monitored by TLC plates, after completion of the reaction, the reaction system mixture was filtered through silica gel (200-300 mesh), eluted with 3X 100mL of DCM, followed by removal of the solvent by rotary evaporation under reduced pressure, and the residue was separated by column chromatography (PE: EA=2:1) to give 6.71g of the compound of formula 2 (white solid, yield: 76%).
Tested:
1 H NMR(400MHz,CDCl 3 )δ7.87(ddd,J＝5.2,3.0,1.8Hz,2H),7.78(qt,J＝5.1,2.5Hz,2H),5.21(d,J＝8.3Hz,1H),4.47–4.33(m,1H),3.76(d,J＝1.7Hz,3H),2.87–2.66(m,2H),2.39–2.25(m,1H),2.16–2.02(m,1H),1.43(d,J＝1.7Hz,9H)；
13 C NMR(126MHz,CDCl 3 )δ172.3,169.0,161.9,155.5,135.0,129.0,124.2,80.4,52.8,52.7,28.4,27.8,27.5。
example 4.1: preparation of compound of formula 3 under conditions of 4DPAIPN as photocatalyst, metallic copper catalyst and blue light irradiation
To a Schlenk tube was added the compound of formula 2 (406 mg,1.0 mmol), cu (OAc) in this order 2 (45 mg,0.25mmol,25 mol%), photocatalyst 4DPAIPN (8 mg,0.01mmol,1 mol%) and PhCOOLi (256 mg,2.0mmol,2.0 equiv.) followed by pumping the Schlenk tube through the double-row tube three times with argonAfter 30 seconds or more each time, diethyl methylphosphite (450. Mu.L, 3.0mmol,3.0 equiv.) and PhCl (10 mL) were sequentially added under an argon atmosphere, then the Schlenk tube was sealed and irradiated under an 18W blue light lamp at a distance of about 5 cm, and the reaction was stirred at room temperature for 12 hours, monitored by TLC during the reaction, and after the completion of the reaction, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (60 mL), brine (2X 60 mL), and then with anhydrous Na 2 SO 4 Drying, filtration, removal of the organic solvent under reduced pressure, and finally isolation by flash column chromatography (DCM: meoh=100:1) afforded 230mg of the compound of formula 3 (colorless oil, yield: 71%).
Tested:
1 H NMR(400MHz,CDCl 3 )δ5.41(d,J＝5.7Hz,1H),4.24(q,J＝7.4,6.4Hz,1H),4.02–3.90(m,2H),3.66(s,3H),2.04(q,J＝10.9,7.9Hz,1H),1.92–1.77(m,1H),1.77–1.59(m,2H),1.37(d,J＝17.7Hz,12H),1.23(td,J＝7.0,1.7Hz,3H)；
13 C NMR(126MHz,CDCl 3 )δ172.4,155.4,80.0,60.2(t,J＝5.0Hz),53.6(d,J＝16.0Hz),52.4,28.2,25.8(dd,J＝94.7,10.3Hz),25.2(d,J＝11.9Hz),16.6(d,J＝4.9Hz),13.9(dd,J＝92.2,7.4Hz)；
31 P NMR(162MHz,CDCl 3 )δ53.77；
EI-MS:m/z(rel intensity)324([M+H] + 100),323([M] + 22),264(15),250(31),57(38)；
HRMS calcd for C 13 H 27 O 6 NP[M+H]324.1571,found:324.1569。
example 4.2: preparation of compound of formula 3 under conditions of 4CzIPN as photocatalyst, no addition of metallic copper catalyst and blue light irradiation
To a Schlenk tube was added the compound of formula 2 (406 mg,1.0 mmol), the photocatalyst 4CzIPN (16 mg,0.02mmol,2 mol%) and PhCOOLi (256 mg,2.0mmol,2.0 e)quino.) the Schlenk tube was then purged with argon three times through double tubing for 30 seconds or more each time, then diethyl methylphosphite (450 μl,3.0mmol,3.0 equiv.) and PhCl (10 mL) were sequentially added under argon atmosphere, then the Schlenk tube was sealed and exposed to an 18W blue light lamp at about 5 cm from the blue light lamp, stirred at room temperature for 12 hours, monitored by TLC during the reaction, after the reaction was completed, the reaction mixture was diluted with ethyl acetate (50 mL) and then washed with water (60 mL), brine (2×60 mL), respectively, then with anhydrous Na 2 SO 4 Drying, filtration, removal of the organic solvent under reduced pressure, and finally isolation by flash column chromatography (DCM: meoh=100:1) afforded 249mg of the compound of formula 3 (colorless oil, yield: 77%).
Example 4.3: preparation of compound of formula 3 under the conditions of 4CzIPN photocatalyst, no addition of metallic copper catalyst and ultraviolet irradiation
The compound of formula 2 (406 mg,1.0 mmol), the photocatalyst 4CzIPN (8 mg,0.01mmol,1 mol%) and PhCOOLi (256 mg,2.0mmol,2.0 equiv.) were sequentially added to a Schlenk tube, then the Schlenk tube was purged with argon three times through a double-row tube for 30 seconds or more each time, then diethyl methylphosphite (450 μl,3.0mmol,3.0 equiv.) and PhCl (10 mL) were sequentially added under an argon atmosphere, then the Schlenk tube was sealed and irradiated under an 18W uv lamp for about 5 cm from the uv lamp, stirred at room temperature for 12 hours, monitored by TLC during the reaction, after the reaction, the reaction mixture was diluted with ethyl acetate (50 mL), then washed with water (60 mL), brine (2×60 mL), respectively, then with anhydrous Na 2 SO 4 Drying, filtration, removal of the organic solvent under reduced pressure, and finally isolation by flash column chromatography (DCM: meoh=100:1) afforded 210mg of the compound of formula 3 (colorless oil, yield: 65%).
Combining examples 4.1-4.3 it can be seen that when a compound of formula 2 is prepared with diethylmethylphosphite: the price of the photocatalyst is far more than that of the metallic copper catalyst, and the existence of the metallic copper catalyst can effectively reduce the dosage of the photocatalyst without affecting the reaction yield, so the preparation cost can be effectively reduced; in addition, blue light irradiation can effectively improve reaction yield than ultraviolet light irradiation.
Example 5: preparation of L-glufosinate
To a reaction flask was added the compound of formula 3 (323 mg,1.0 mmol) and 6M HCl (10 mL), followed by heating and refluxing for 12 hours, the reaction was completed, after cooling to room temperature, the reaction mixture was extracted with DCM (2×60 mL), the organic phase was discarded, the aqueous phase was distilled off by high vacuum to remove the solvent, aqueous ammonia was added to the residue and adjusted to ph=9, and then the solvent was removed again under high vacuum to give crude L-glufosinate, and the obtained crude was recrystallized from methanol to give 178mg of L-glufosinate (white solid, yield: 90%).
Tested:
1 H NMR(400MHz,D 2 O)δ3.83(t,J＝5.9Hz,1H),2.14–2.03(m,2H),1.77–1.52(m,2H),1.28(d,J＝13.5Hz,3H)；
13 C NMR(126MHz,D 2 O)δ173.8,55.5,26.9(d,J＝91.2Hz),24.1,15.0(d,J＝92.7Hz)；
31 P NMR(162MHz,D 2 O)δ42.21；
[α]D 27 ＝+16.2(c 1.00,H 2 O)。
specific optical rotation value [ alpha ] of L-glufosinate prepared by the invention]D 27 ＝+16.2(c 1.00,H 2 O), and literature [ sci.rep.1973,13,42 ]]Reported specific optical rotation value [ alpha ] of pure L-glufosinate]D 23 ＝+17(c 1.00,H 2 O) are similar, which indicates that the purity of the L-glufosinate-ammonium product prepared by the invention is higher.
In summary, the invention takes N-t-butoxycarbonyl-L-glutamic acid-1-methyl ester (compound of formula 1) as a raw material, and L-glufosinate can be prepared through simple condensation reaction, decarboxylation phosphonylation reaction, hydrolysis and ammonification reaction, and the invention has the advantages of simple operation, easily obtained raw materials, low cost, mild reaction conditions, suitability for industrial production and the like, and has important significance for industrial application of the L-glufosinate.
Finally, it is pointed out here that: the above is only a part of the preferred embodiments of the present invention and should not be construed as limiting the scope of the present invention, and some insubstantial modifications and adaptations of the present invention based on the foregoing are within the scope of the present invention.
Claims (10)
1. A simple and efficient method for preparing L-glufosinate-ammonium is characterized by comprising the following steps a-b-c in a synthetic route:
the step a is that a compound of formula 1 and N-hydroxyphthalimide are subjected to condensation reaction in the presence of a condensing agent and a catalyst to obtain a compound of formula 2; step b is that the compound of formula 2 and methyl diethyl phosphite are subjected to decarboxylation and phosphonoation reaction under the photocatalysis condition to obtain the compound of formula 3; and step c is to sequentially perform acid hydrolysis reaction and ammonification reaction on the compound shown in the formula 3 to obtain the L-glufosinate-ammonium.
2. The method of claim 1, wherein the operation of step a comprises: the compound of formula 1 is subjected to condensation reaction with N-hydroxyphthalimide in an organic solvent in the presence of a condensing agent and a catalyst at room temperature to obtain the compound of formula 2.
3. The preparation method according to claim 2, characterized in that: in the step a, the molar ratio of the compound of formula 1 to N-hydroxyphthalimide is 1 (1-2), and the molar ratio of the compound of formula 1 to condensing agent is 1 (1-2).
4. The preparation method according to claim 2, characterized in that: in the step a, dicyclohexylcarbodiimide is used as the condensing agent, and 4-dimethylaminopyridine is used as the catalyst.
5. The method of claim 1, wherein the operation of step b comprises: the compound of the formula 2 and diethyl methylphosphite are subjected to decarboxylation and phosphonoation reaction in an organic solvent in the presence of a photocatalyst and a nucleophilic reagent and under light irradiation or in the presence of a photocatalyst, a metal catalyst and a nucleophilic reagent and under light irradiation at room temperature to obtain the compound of the formula 3.
6. The method of manufacturing according to claim 5, wherein: in the step b, the light irradiation is blue light irradiation.
7. The method of manufacturing according to claim 5, wherein: in the step b, the molar ratio of the compound of formula 2 to the diethyl methylphosphite is 1 (1-5); the mol ratio of the compound of formula 2 to the nucleophilic reagent is 1 (1-3).
8. The method of manufacturing according to claim 5, wherein: in the step b, the photocatalyst is 1,2,3, 5-tetra (diphenylamino) -4, 6-dicyanobenzene or 1,2,3, 5-tetra (carbazolyl) -4, 6-dicyanobenzene, the metal catalyst is copper catalyst, and the nucleophilic reagent is PhCOOLi.
9. The method of claim 1, wherein the operation of step c comprises: the compound of formula 3 is firstly hydrolyzed in acidic aqueous solution to obtain hydrolysis product, and then the hydrolysis product is ammoniated with ammonia water to obtain L-glufosinate-ammonium.
10. The method of manufacturing according to claim 9, wherein: the acidic aqueous solution is hydrochloric acid aqueous solution.
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