CN105837624A - Synthetic method of phosphinothricin - Google Patents
Synthetic method of phosphinothricin Download PDFInfo
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- CN105837624A CN105837624A CN201610331162.2A CN201610331162A CN105837624A CN 105837624 A CN105837624 A CN 105837624A CN 201610331162 A CN201610331162 A CN 201610331162A CN 105837624 A CN105837624 A CN 105837624A
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- Prior art keywords
- synthetic method
- phosphine oxamate
- reaction
- carbonyl
- phosphine
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 22
- IAJOBQBIJHVGMQ-UHFFFAOYSA-N Phosphinothricin Natural products CP(O)(=O)CCC(N)C(O)=O IAJOBQBIJHVGMQ-UHFFFAOYSA-N 0.000 title abstract 5
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- -1 methyl phosphorus dichloride compound Chemical class 0.000 claims abstract description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- WTEJQBARPJSNLZ-UHFFFAOYSA-N C(C(=O)N)(=O)O.P Chemical compound C(C(=O)N)(=O)O.P WTEJQBARPJSNLZ-UHFFFAOYSA-N 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 238000010792 warming Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 238000005352 clarification Methods 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- CDPKWOKGVUHZFR-UHFFFAOYSA-N dichloro(methyl)phosphane Chemical compound CP(Cl)Cl CDPKWOKGVUHZFR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 238000006845 Michael addition reaction Methods 0.000 claims description 3
- 238000004176 ammonification Methods 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006722 reduction reaction Methods 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 15
- SEJXNPFTEXQNOU-UHFFFAOYSA-N 2-(oxomethylidene)butanoic acid Chemical class CCC(=C=O)C(O)=O SEJXNPFTEXQNOU-UHFFFAOYSA-N 0.000 abstract description 3
- 238000001953 recrystallisation Methods 0.000 abstract description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 abstract description 2
- 150000003863 ammonium salts Chemical class 0.000 abstract description 2
- 230000009467 reduction Effects 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 238000007259 addition reaction Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WAXMRVDZHXIAHQ-UHFFFAOYSA-N COP(=O)(OO)CCC(C(=O)O)=C=O Chemical compound COP(=O)(OO)CCC(C(=O)O)=C=O WAXMRVDZHXIAHQ-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- NSSMTQDEWVTEKN-UHFFFAOYSA-N diethoxy(methyl)phosphane Chemical compound CCOP(C)OCC NSSMTQDEWVTEKN-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 231100000004 severe toxicity Toxicity 0.000 description 2
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-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 1
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 1
- HEGJOQDCIZEXLT-UHFFFAOYSA-N C(=O)=C(C(=O)OCC)C=C Chemical compound C(=O)=C(C(=O)OCC)C=C HEGJOQDCIZEXLT-UHFFFAOYSA-N 0.000 description 1
- ZTUVTQBAHLRCRV-UHFFFAOYSA-N COC(C(C=C)=C=O)=O Chemical compound COC(C(C=C)=C=O)=O ZTUVTQBAHLRCRV-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 238000007059 Strecker synthesis reaction Methods 0.000 description 1
- LUAMIGOADJTNQF-UHFFFAOYSA-N [Mg].[Cl-].C(=C)[N+]1=CNC=C1 Chemical compound [Mg].[Cl-].C(=C)[N+]1=CNC=C1 LUAMIGOADJTNQF-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical class C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- SWRNIYAQKATHDJ-UHFFFAOYSA-N dichloro(dichlorophosphanyl)phosphane Chemical compound ClP(Cl)P(Cl)Cl SWRNIYAQKATHDJ-UHFFFAOYSA-N 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 244000037671 genetically modified crops Species 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a synthetic method of phosphinothricin. According to the method, methyl phosphorus dichloride compound and 2-carbonyl-3-butenoic acid ester compound are subjected to addition reaction, so that carbonyl butyric acid derivative is obtained, and the carbonyl butyric acid derivative is subjected to ammoniation and reduction, so that a phosphinothricin compound can be obtained. The method can not only avoid using virulent cyanide, obviously shortens the reaction route, reduces the technical steps for synthesizing phosphinothricin, is convenient to operate, and does not need recrystallization to remove ammonium salt, but also is high in yield, low in cost, high in the purity of the prepared phosphinothricin, and particularly applicable to industrial production.
Description
Technical field
The invention belongs to chemosynthesis technical field, particularly to the synthesis side of a kind of herbicide phosphine oxamate
Method.
Background technology
Phosphine oxamate (Glufosinafe) is efficient, the low toxicity, non-developed at first by Hoechest company
Selective herbicide, trade name Basta, its molecular formula is: C5H12NO4P, its structure is:
Phosphine oxamate, as a kind of excellent herbicide, has efficiently, low toxicity and the feature such as non-selective,
Being the preferable herbicide of current transgenic resistance crop, its market demand is fast along with genetically modified crops
Speed develops and is greatly increased.More document is had to report the synthetic method of phosphine oxamate, Yan Hai both at home and abroad
Prosperous grade " synthetic method of phosphine oxamate " [" pesticide ", 2002, the 9th phase of volume 43, the page number:
46-48] literary composition reviews the most conventional several synthetic methods, mainly there is high-pressure catalytic to close
Cheng Fa, low temperature controlled syntheses method, smell and be combined to phosphine oxamate method, this special tired Ke Er (Strecker) reaction
Synthesis phosphine oxamate method, closely that (Michael) addition process and microbe fermentation method.Li Yiming etc. are " one
Plant the new method of synthesis phosphine oxamate " [" pesticide ", in January, 2012, the 1st phase of volume 51, the page number:
11-12] document summarizes main three routes that synthesis phosphine oxamate is used at present, route 1: with Asia
Phosphonic acids trimethyl is initiation material, by rearrangement, chlorination, grignard reaction, Michael addition, water
Solve 5 step reactions and obtain phosphine oxamate；Route 2: with diethyl methyl-phosphonite as raw material, with acrylic aldehyde
After there is rearrangement reaction, then obtain cyanamide derivant by Strecker reaction, after hydrolysis, obtain grass
Amine phosphine；Route 3: rearranged with diethyl methyl-phosphonite for raw material, replace, hydrolyze, smelling,
Decarboxylation, the reaction of ammonolysis 6 step obtain phosphine oxamate.Wherein the chemical synthesis process of route 2 is comparative maturity
Technique, Hoechst AG (DE) Frankfurt/Main 80, Federsl Republic of Germany one gives up self-employed tree cultivator industry Development Co., Ltd and announces in CN1267305A Patent
A kind of phosphine oxamate and the synthetic method of intermediate thereof, the method using above-mentioned route 2, by methylphosphine
Compound, such as diethyl methyl-phosphonite etc. and undersaturated ketone or aldehyde compound such as propylene
Aldehyde, reaction produces adduct, executes special rake (Strecker) reaction and final cyanamide water through follow-up
Solving, needing to use raw material during synthesizing amino cyanogen is NH3、NaCN、NH4C1, then
By cyanamide compound, hydrochloric acid or sodium hydroxide is used to hydrolyze the U.S. producing phosphine oxamate US6359162
Being synthesized also with Strecker in state's patent and obtain cyanamide compound, then hydrolysis obtains grass
Amine phosphine.Its technological reaction is as follows:
Route 2 course of reaction is short, and yield is of a relatively high, is current domestic synthesis phosphine oxamate comparative maturity
Technique, its have of both shortcoming: on the one hand be that cyanamide compound is used hydrochloric acid or hydrogen-oxygen
Change sodium and hydrolyze generation phosphine oxamate, substantial amounts of salt, the most mainly sodium chloride can be produced, cause in work
Industry also exists sodium chloride and product separating step in the middle of producing, and due to phosphine oxamate and sodium chloride dissolubility
Can there is similarity, the most all be dissolved in water so that physical separation step is not easy to, be the most all
Carrying out the sodium chloride in the middle of isolated product with methanol, this process occupies large number quipments, is doped in product
Methanol；On the other hand, the Cyanogran. of severe toxicity and concentrated hydrochloric acid is used can to produce the more three wastes, no
It is beneficial to environmental conservation.
Summary of the invention
In order to overcome the problems referred to above, it is an object of the invention to provide the synthetic method of a kind of phosphine oxamate, will
Methyl dichloro phosphorus species and 2-carbonyl-3-butenoic acid ester type compound carry out additive reaction, prepare
Carbonyl butanoic acid analog derivative, then through ammonification, reduction, i.e. can get phosphine oxamate compound.The method
It is possible not only to the cyanide avoiding using severe toxicity, hence it is evident that shorten reaction scheme so that synthesis phosphine oxamate
Processing step reduces, easy and simple to handle, it is not necessary to recrystallization goes out ammonium salt, and yield high cost is low, system
The phosphine oxamate purity obtained is higher, is particularly well-suited to industrialized production.
For achieving the above object, the present invention takes techniques below scheme: the synthetic method of a kind of phosphine oxamate,
Comprise the steps:
(1) the 2-carbonyl-3-butenoic acid ester type compound of acid binding agent Yu formula III is joined organic solvent
In, under the conditions of-20～20 DEG C, it is slowly added dropwise the methyl hypophosphorous acid compounds of Formula II, stirs 0.5-2h,
Carrying out Michael addition reaction, reaction adds basic hydrolysis after terminating, and is warming up to the 4-6h that refluxes, is down to
After room temperature, washing filtering, generate the alpha-carbonyl acid derivative of formula IV, reaction equation is as follows:
(2) the alpha-carbonyl acid derivative (IV) of gained in step (1) is taken in autoclave, to
Wherein add and be passed through ammonia under organic solvent, normal pressure, carry out ammonification, control reaction system pH, then
Add catalyst, be passed through hydrogen, be warming up to back flow reaction 4-6h, system has solid separate out, filter,
The phosphine oxamate of production I, reaction equation is as follows:
Optimizing further, step (1), step (2) described organic solvent are methanol or ethanol.
Optimizing further, R1 described in step (1) is the alkyl of 1-4 carbon atom of tool.
Optimizing further, described in step (1), acid binding agent is triethylamine, diethylamine, pyridine or ammonia
Gas.
Optimize further, in step (1), described methyl-phosphinic acid ester type compound and 2-carbonyl-3-
The mol ratio of butenoate compounds is 1:1-1.5.
Optimizing further, described in step (2), reaction system pH is 12 ± 0.5, and temperature is 0-20 DEG C.
Optimizing further, the catalyst of reduction reaction described in step (2) is that Pt/C, Pt/C add
Amount is the 1～20% of alpha-carbonyl acid derivative (IV) quality, and temperature is 40-100 DEG C.
Optimize further, also include the filter cake water dissolution of gained step (2), refilter,
Obtaining the filtrate of clarification, be added thereto to methanol, methanol, water consumption ratio are 1:5～20, stirring
Overnight.
Compared with prior art, provide the benefit that: 1), raw materials used oxalate diester, vinylimidazolium chloride
Magnesium is cheap, be easy to get, be readily synthesized, and three-step reaction total recovery is high, easy and simple to handle, is particularly suitable for industry
Produce；2), synthesized phosphine oxamate purity is high, it is not necessary to repeatedly recrystallization removes ammonia salt.
Detailed description of the invention
Illustrated embodiment is to preferably illustrate present disclosure, but is not the present invention
Content be only limitted to illustrated embodiment.So those of ordinary skill in the art are according to foregoing invention content
Embodiment is carried out nonessential improvement and adjustment, still falls within protection scope of the present invention.
Methyl dichloro phosphorus in patent of the present invention can be prepared by Phosphorous chloride. and methane reaction, specifically may be used
See the synthetic method of the dichloromethyl phosphine that Bayer AG proposes in US4521348, dichloromethyl
Change phosphine synthesis as follows:
Embodiment 1
The synthetic method of a kind of phosphine oxamate, comprises the steps:
1) 2-carbonyl-3-butenoic acid methyl ester 45.6g (0.4mol), acid binding agent triethylamine 60.6g are taken
(0.6mol) join in 50ml methanol solution, under the conditions of 0 DEG C, dropping methyl two the most wherein
Phosphorus chloride 47.5g (0.41mol), dropping 1h complete, and after low temperature stirring 1h, are added thereto to 1mol/l
Sodium hydrate aqueous solution 100ml, is warming up to the 5h that refluxes, and is down to room temperature and filters, and filter cake washes with water three times,
Obtain white solid 68.1g, productivity 93.8%；
2) 4-(methylhydroxy phosphono)-2-carbonyl-butanoic acid 54.0g (0.3mol) is taken in autoclave,
It is added thereto to methanol 300ml, 20 DEG C, be passed through ammonia under normal pressure to 0.5Mpa, controls reaction system
PH is 12, is then added thereto to the Pt/C of alpha-carbonyl acid derivative (IV) 5%, is passed through hydrogen
To 1Mpa, it is warming up to 60 DEG C of back flow reaction 5h, system has solid separate out, filter, by gained
Filter cake, with after 50ml water dissolution, refilters, and obtains the filtrate of clarification, is added thereto to 500ml first
Alcohol, is stirred overnight, and obtains white crystal 50.5g, yield 86.2%, and surveying purity with liquid phase normalization method is
98.1%.
Embodiment 2
The synthetic method of a kind of phosphine oxamate, comprises the steps:
1) 2-carbonyl-3-butenoic acid ethyl ester 51.2g (0.4mol), acid binding agent triethylamine 60.6g are taken
(0.6mol) join in 50ml methanol solution, under the conditions of-10 DEG C, drip methyl the most wherein
Phosphorus dichloride 47.5g (0.41mol), dropping 1h complete, and after low temperature stirring 1h, are added thereto to
1M sodium hydrate aqueous solution 100ml, is warming up to the 5h that refluxes, and is down to room temperature and filters, and filter cake washes with water
Three times, obtain white solid 64.8g, productivity 90.6%；
2) 4-(methylhydroxy phosphono)-2-carbonyl-butanoic acid 54.0g (0.3mol) is taken in autoclave,
It is added thereto under methanol 300ml, normal pressure be passed through ammonia and to 0.5Mpa, control reaction system pH is
12.5, then it is added thereto to the Pt/C of alpha-carbonyl acid derivative (IV) 10%, is passed through hydrogen extremely
1Mpa, is warming up to 80 DEG C of back flow reaction 5h, has solid to separate out in system, filters, by the filter of gained
Cake, with after 50ml water dissolution, refilters, and obtains the filtrate of clarification, is added thereto to 500ml methanol,
Being stirred overnight, obtain white crystal 50.9g, yield 85.6%, surveying purity with liquid phase normalization method is 98.4%.
Embodiment 3
The synthetic method of a kind of phosphine oxamate, comprises the steps:
1) the 2-carbonyl taken-3-butenoic acid ethyl ester 51.2g (0.4mol), acid binding agent triethylamine 60.6g
(0.6mol) join in 50ml ethanol solution, under the conditions of 10 DEG C, dropping methyl two the most wherein
Phosphorus chloride 47.5g (0.41mol), dropping 1h complete, and after low temperature stirring 1h, are added thereto to 1M hydrogen
Aqueous solution of sodium oxide 100ml, is warming up to the 5h that refluxes, and is down to room temperature and filters, and filter cake washes with water three times,
Obtain white solid 68.7g, productivity 94.6%；
2) 4-(methylhydroxy phosphono)-2-carbonyl-butanoic acid 54.0g (0.3mol) is taken in autoclave,
It is added thereto under methanol 300ml, normal pressure be passed through ammonia and to 0.5Mpa, control reaction system pH is
12.5, then it is added thereto to the Pt/C of alpha-carbonyl acid derivative (IV) 20%, is passed through hydrogen extremely
1Mpa, is warming up to 100 DEG C of back flow reaction 5h, has solid to separate out in system, filters, by the filter of gained
Cake, with after 50ml water dissolution, refilters, and obtains the filtrate of clarification, is added thereto to 500ml methanol,
Being stirred overnight, obtain white phosphine oxamate crystal 53.8g, yield 91.3%, HPLC purity is more than 99%,
Maximum list is miscellaneous is less than 0.1%.
Embodiment 4
The synthetic method of a kind of phosphine oxamate, comprises the steps:
The 2-carbonyl taken-3-butenoic acid ethyl ester 51.2g (0.4mol), acid binding agent pyridine 47.4g (0.6mol)
Join in 50ml ethanol solution, under the conditions of 10 DEG C, dropping methyl dichloro phosphorus 47.5g the most wherein
(0.41mol), dropping 1h completes, and after low temperature stirring 1h, is added thereto to 1M sodium hydroxide water
Solution 100ml, is warming up to the 5h that refluxes, and is down to room temperature and filters, and filter cake washes with water three times, obtains white
Solid 67.7g, productivity 94.2%；
2) 4-(methylhydroxy phosphono)-2-carbonyl-butanoic acid 54.0g (0.3mol) is taken in autoclave,
It is added thereto under methanol 300ml, normal pressure be passed through ammonia and to 0.5Mpa, control reaction system pH is
12.5, then it is added thereto to the Pt/C of alpha-carbonyl acid derivative (IV) 20%, is passed through hydrogen extremely
1Mpa, is warming up to 100 DEG C of back flow reaction 5h, has solid to separate out in system, filters, by the filter of gained
Cake, with after 50ml water dissolution, refilters, and obtains the filtrate of clarification, is added thereto to 500ml methanol,
Being stirred overnight, obtain white phosphine oxamate crystal 55.3g, yield 94.3%, HPLC purity is more than 99%,
Maximum list is miscellaneous is less than 0.1%.
Claims (8)
1. the synthetic method of a phosphine oxamate, it is characterised in that comprise the steps:
(1) the 2-carbonyl-3-butenoic acid ester type compound of acid binding agent Yu formula III is joined organic solvent
In, under the conditions of-20～20 DEG C, it is slowly added dropwise the methyl hypophosphorous acid compounds of Formula II, stirs 0.5-2h,
Carrying out Michael addition reaction, reaction adds basic hydrolysis after terminating, and is warming up to the 4-6h that refluxes, is down to
After room temperature, washing filtering, generate the alpha-carbonyl acid derivative of formula IV, reaction equation is as follows:
(2) the alpha-carbonyl acid derivative (IV) of gained in step (1) is taken in autoclave, to
Wherein add and be passed through ammonia under organic solvent, normal pressure, carry out ammonification, control reaction system pH, then
Add catalyst, be passed through hydrogen, be warming up to back flow reaction 4-6h, system has solid separate out, filter,
The phosphine oxamate of production I, reaction equation is as follows:
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that step (1),
Described in step (2), organic solvent is methanol or ethanol.
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that step (1)
Described in R1 be tool 1-4 carbon atom alkyl.
The synthetic method of phosphine oxamate the most according to claim 2, it is characterised in that step (1)
Described in acid binding agent be triethylamine, diethylamine, pyridine or ammonia.
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that in step
(1), in, described methyl dichloro phosphorus is 1 with the mol ratio of 2-carbonyl-3-butenoic acid ester type compound:
1-1.5。
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that step (2)
Described in reaction system pH be 12 ± 0.5, temperature is 0-20 DEG C.
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that step (2)
Described in the catalyst of reduction reaction be Pt/C, Pt/C addition be alpha-carbonyl acid derivative (IV)
The 1～20% of quality, temperature is 40-100 DEG C.
The synthetic method of phosphine oxamate the most according to claim 1, it is characterised in that also include
By step (2) by the filter cake water dissolution of gained, refilter, obtain the filtrate of clarification, wherein
Adding methanol, methanol, water consumption ratio are 1:5～20, are stirred overnight.
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| CN106632467B (en) * | 2016-12-15 | 2019-04-02 | 石家庄瑞凯化工有限公司 | A kind of synthetic method of glufosinate-ammonium ammonium salt |
| CN112552338A (en) * | 2020-12-10 | 2021-03-26 | 洪湖市一泰科技有限公司 | Comprehensive recycling method of phosphorus-containing composite salt as byproduct in organic phosphine production |
| CN115246857A (en) * | 2022-09-22 | 2022-10-28 | 山东新和成氨基酸有限公司 | Preparation method of L-glufosinate-ammonium |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106632467B (en) * | 2016-12-15 | 2019-04-02 | 石家庄瑞凯化工有限公司 | A kind of synthetic method of glufosinate-ammonium ammonium salt |
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| CN112552338A (en) * | 2020-12-10 | 2021-03-26 | 洪湖市一泰科技有限公司 | Comprehensive recycling method of phosphorus-containing composite salt as byproduct in organic phosphine production |
| CN112552338B (en) * | 2020-12-10 | 2021-07-27 | 洪湖市一泰科技有限公司 | Comprehensive recycling method of phosphorus-containing composite salt as byproduct in organic phosphine production |
| CN115246857A (en) * | 2022-09-22 | 2022-10-28 | 山东新和成氨基酸有限公司 | Preparation method of L-glufosinate-ammonium |
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