CN109232644A - The synthetic method of glufosinate-ammonium - Google Patents
The synthetic method of glufosinate-ammonium Download PDFInfo
- Publication number
- CN109232644A CN109232644A CN201811159960.7A CN201811159960A CN109232644A CN 109232644 A CN109232644 A CN 109232644A CN 201811159960 A CN201811159960 A CN 201811159960A CN 109232644 A CN109232644 A CN 109232644A
- Authority
- CN
- China
- Prior art keywords
- butyrolacton
- gamma
- glufosinate
- ammonium
- bromine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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 System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
Abstract
The present invention relates to a kind of synthetic methods of glufosinate-ammonium; it include that single bromine replaces; amination, amido protecting, chlorination open loop; A Erbuzuofu reaction; acidification hydrolization ammonification, single bromine substitution are that gamma-butyrolacton I replaces through catalyst and the single bromines of bromine generation α, and vacuum distillation obtains pure intermediate II α-bromo- gamma-butyrolacton; wherein, the catalyst is phosphorus tribromide；The amination is the bromo- gamma-butyrolacton II of α-and ammonium hydroxide generation ammoxidation, and then plus hydrochloric acid reflux obtains III alpha-amido of intermediate-gamma-butyrolacton hydrochloride.The beneficial effects of the present invention are: 1) using cheap gamma-butyrolacton as raw material, it is acted on bromine and single bromine substitution occurs, then carry out ammoxidation with ammonium hydroxide, used raw material is cheap and easily-available, reaction condition is mild, simple to operation, highly-safe, amplification production is feasible, and reaction yield is high, product purity is high, greatly reduces cost, is suitble to industrialized production.
Description
Technical field
The present invention relates to technical field of pesticide, in particular to a kind of synthetic method of glufosinate-ammonium.
Background technique
Glufosinate-ammonium (glufosinate-ammonium), chemical name are 4- [hydroxyl (methyl) phosphono] third ammonia of-DL-
Acid, structure are as follows:
Glufosinate-ammonium (glufosinate) is a kind of high-efficiency low-toxicity broad-spectrum touch-out type organic phosphates herbicide, it be earliest by
Hirst company (belongs to Bayer AG's development and production) afterwards.It is a kind of glutamine synthetase inhibitor, leads to plant
Interior nitrogen metabolism disorder, the excess accumulation of ammonia, chloroplaset disintegrate, and inhibit its photosynthesis so as to cause Plant death.In those early years, conspicuous
Si Te company has successfully imported the resistant gene of glufosinate-ammonium in 20 various crop such as rice, wheat, corn.Glufosinate-ammonium is only second to
Glyphosate becomes second-biggest-in-the-world genetically modified crops herbicide-tolerant.Glufosinate-ammonium toxicity is low, safer, is easy to drop in the soil
Solution, to crop safety, environmental pressure is small.The market prospects of glufosinate-ammonium are very good.
The primary synthetic methods of glufosinate-ammonium are Si Chuikefa in industrial production at present, while being also the tradition side of comparative maturity
After methylisothiouronium methylphosphite ester and methacrylaldehyde addition Strecker reaction, hydrolysis, the grass for obtaining high-purity after purification occur for method
Ammonium phosphine.But its route of synthesis is long, and the hypertoxic raw material such as Cymag has been used in raw material, has been unfavorable for environmental protection, and produce
Raw three-protection design is more complicated, at high cost.
Therefore low raw-material cost is provided, the method for short, conducive to environmental protection preparation glufosinate-ammonium reaction time has important meaning
Justice.
There is document to be reported for the first time using gamma-butyrolacton as raw material at present, through oximate, restores, amido protecting, chlorination open loop, with
Methylisothiouronium methylphosphite diethylester, which carries out arbuzov reaction, can be obtained the higher glufosinate-ammonium of purity, and reaction yield is high, have certain
Industrialization potential.But potassium tert-butoxide and isobutyl nitrite that its oximation reaction uses, expensive cost are very high and not
It is easy to get, reduction reaction is related to hydrogen and Pd/C catalyst, and at high cost and safety is defective.Its synthetic route is as follows:
Summary of the invention
The present invention provides a kind of method for preparing glufosinate-ammonium, and using cheap gamma-butyrolacton as raw material, reaction yield is higher,
Product purity is high, mild condition and simple and convenient, and safety is good, meets green chemical industry trend, is suitable for industrialized production.
The technical proposal adopted by the invention to solve the above technical problems is that: the synthetic method of glufosinate-ammonium includes single bromine
Replace, amination, amido protecting, chlorination open loop, A Erbuzuofu reaction, acidification hydrolization ammonification, single bromine substitution is γ-
Butyrolactone I occurs α single bromines through catalyst and bromine and replaces, and vacuum distillation (b.p.120~125 DEG C/1.6kPa) obtains pure
Intermediate II α-bromo- gamma-butyrolacton, wherein the catalyst is phosphorus tribromide；The amination is the bromo- gamma-butyrolacton of α-
II occurs ammoxidation with ammonium hydroxide, and then plus hydrochloric acid reflux obtains III alpha-amido of intermediate-gamma-butyrolacton hydrochloride.
According to the above scheme: the amido protecting is III alpha-amido of intermediate-gamma-butyrolacton hydrochloride for will obtaining molten
In the presence of agent, suitable alkali is added, reacts to obtain intermediate IV (2- oxo-tetrahydrofuran -3- base) amino first with alcoxyl dicarbonyl chloride
Acetoacetic ester.
According to the above scheme: the chlorination open loop is intermediate IV (2- oxo-tetrahydrofuran -3- base) amino that will be obtained
Ethyl formate reacts to obtain the chloro- 2- ethoxycarbonylamino ethyl butyrate of V 4- of intermediate with the HCl ethanol solution of saturation；Described
A Erbuzuofu reaction is the chloro- 2- ethoxycarbonylamino ethyl butyrate of V 4- of intermediate and methylisothiouronium methylphosphite diethylester that will be obtained
It is reacted by Arbuzov, obtains VI 4- ethyoxyl -4- methyl phosphono -2- ethoxycarbonylamino ethyl butyrate of intermediate；It is described
Acidification hydrolization ammonification be the VI 4- ethyoxyl -4- methyl phosphono -2- ethoxycarbonylamino ethyl butyrate of intermediate that will be obtained
Hydrochloric acid hydrolysis is first passed through, then plus ammonium hydroxide reacts to obtain product glufosinate-ammonium ammonium salt.
According to the above scheme: the molar ratio of the bromine and gamma-butyrolacton is 1-2:1.
According to the above scheme: the molar ratio of the bromine and gamma-butyrolacton is 2:1.
According to the above scheme: the molar ratio of the intermediate II and ammonium hydroxide is 1:3-9, the molar ratio of intermediate II and hydrochloric acid
For 1:1-2.5.
According to the above scheme: the molar ratio of the intermediate II and ammonium hydroxide is 1:6, and the molar ratio of intermediate II and hydrochloric acid is
1:1.5。
According to the above scheme: the alkali is Na2CO3Or triethylamine.
According to the above scheme: the alcoxyl dicarbonyl chloride is appointing in ethyl chloroformate, methylchloroformate and carbobenzoxy chloride
It anticipates one kind.
According to the above scheme: the solvent is methylene chloride and one of water and the mixed liquor of tetrahydrofuran.
Reaction equation according to the present invention are as follows:
Wherein R1For the alkyl or Bn of C1-C2.
The beneficial effects of the present invention are:
1) it using cheap gamma-butyrolacton as raw material, is acted on bromine and single bromine substitution occurs, then carry out amination with ammonium hydroxide
Reaction, used raw material is cheap and easily-available, and reaction condition is mild, simple to operation, highly-safe, and amplification production is feasible, and anti-
High income is answered, product purity is high, greatly reduces cost, is suitble to industrialized production；
2) present invention use cheap and easily-available bromine as bromine source, selectively single bromine substitution reaction yield 88% or more,
Product purity is high after vacuum distillation, and gamma-butyrolacton is both raw material and solvent in bromo-reaction, after reducing costs and reducing
The step of processing；
3) ammoxidation of the present invention generates III alpha-amido of intermediate-gamma-butyrolacton hydrochloride mild condition, and reaction is received
Rate is 70% or more, and post-processing is simple and to obtain product purity very high；
4) present invention has used the mixed solvent body of tetrahydrofuran and water in the reaction that amido protecting generates intermediate IV
System, and select to use inorganic base system, reaction yield is 85% or more；
5) present invention selects the ethanol solution of saturation HCl in the reaction that chlorination open loop generates intermediate V, and the system is green
Colour circle is protected, and yield is 65% or more.
Detailed description of the invention
Fig. 1 is V compound 4-chloro -2- ethoxycarbonylamino ethyl butyrate of formula prepared by the present invention1H-NMR figure；
Fig. 2 is formula VII compound 2- amino -4- (hydroxymethyl phosphono) butyric acid prepared by the present invention1H-NMR figure；
Fig. 3 is formula VII compound 2- amino -4- (hydroxymethyl phosphono) butyric acid prepared by the present invention13C-NMR figure；
Fig. 4 is formula VII compound 2- amino -4- (hydroxymethyl phosphono) butyric acid prepared by the present invention31P-NMR figure.
Specific embodiment
The present invention is further described in detail below by specific embodiment:
Embodiment 1: intermediate II α-bromo- gamma-butyrolacton preparation method:
Under ice bath, 330mL bromine is slowly added dropwise into the mixture of 500g gamma-butyrolacton and 31g red phosphorus in there-necked flask,
70 DEG C are then heated to, continues that 330mL bromine is added dropwise.After being added dropwise, it is warming up to 80 DEG C of reaction 3h.Stopping is heated to cooling down,
It is persistently blown into air, the hydrogen bromide of excessive bromine and generation is blown away.Then it is warming up to 80 DEG C again, 100mL water is slowly added dropwise,
Equal reactions add 700mL water after mitigating, and flow back 4h.It is layered after cooling, water layer is extracted with dichloromethane, and merges organic layer, nothing
Water magnesium sulfate is dry.Decompression obtains crude product (b.p.120~125 DEG C/1.6kPa) after boiling off solvent, after vacuum distillation purification,
Obtain pale yellow oily liquid 850g, yield 88.7%.
Embodiment 2: intermediate II α-bromo- gamma-butyrolacton preparation method:
Under ice bath, 330mL bromine is slowly added dropwise into the mixture of 500g gamma-butyrolacton and 31g red phosphorus in there-necked flask,
70 DEG C are then heated to, continues that 250mL bromine is added dropwise.After being added dropwise, it is warming up to 80 DEG C of reaction 3h.Stopping is heated to cooling down,
It is persistently blown into air, the hydrogen bromide of excessive bromine and generation is blown away.Then it is warming up to 80 DEG C again, 100mL water is slowly added dropwise,
Equal reactions add 750mL water after mitigating, and flow back 4h.It is layered after cooling, water layer is extracted with dichloromethane, and merges organic layer, nothing
Water magnesium sulfate is dry.Decompression obtains crude product after boiling off solvent, and vacuum distillation purification obtains pale yellow oily liquid 760g, yield
80%.
Embodiment 3: intermediate II α-bromo- gamma-butyrolacton preparation method:
Under ice bath, 330mL bromine is slowly added dropwise into the mixture of 500g gamma-butyrolacton and 31g red phosphorus in there-necked flask,
70 DEG C are then heated to, continues that 150mL bromine is added dropwise.After being added dropwise, it is warming up to 80 DEG C of reaction 3h.Stopping is heated to cooling down,
It is persistently blown into air, the hydrogen bromide of excessive bromine and generation is blown away.Then it is warming up to 80 DEG C again, 100mL water is slowly added dropwise,
Equal reactions add 750mL water after mitigating, and flow back 4h.It is layered after cooling, water layer is extracted with dichloromethane, and merges organic layer, nothing
Water magnesium sulfate is dry.Decompression obtains crude product after boiling off solvent, and vacuum distillation purification obtains pale yellow oily liquid 610g, yield
64.2%.
1H NMR(600MHz,CDCl3)δ:4.48(td,1H),4.41(ddd,2H),2.84–2.74(m,1H),2.47
(ddt,1H).
In embodiment 1, the bromine of addition and the equivalent proportion of gamma-butyrolacton are 2, finally obtain pale yellow oily liquid
850g, yield is up to 88.7%；In embodiment 2, the bromine of addition and the equivalent proportion of gamma-butyrolacton are 1.8, are finally obtained faint yellow
Oily liquids 760g, yield is up to 80%；In embodiment 3, the bromine of addition and the equivalent proportion of gamma-butyrolacton are 1.5, are finally obtained
Pale yellow oily liquid 610g, yield is up to 64.2%.Therefore when the equivalent proportion of the bromine and gamma-butyrolacton that are added is 2, yield reaches
88.7%, effect is best.
Embodiment 4: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, (similarly hereinafter) bromination product of the embodiment 1 of 50g is slowly added drop-wise to 136mL 25wt%'s
In ammonium hydroxide, after reacting 48h, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid, flow back 1h at 110 DEG C, and suction filtration obtains 39.4g
White solid, yield 50.3%.
Embodiment 5: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, the bromination product of 50g is slowly added drop-wise in the ammonium hydroxide of 270mL 25wt%, reacts 48h
Afterwards, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid, flow back 1h at 110 DEG C, and suction filtration obtains the white solid of 48.25g, receives
Rate 70.6%.
Embodiment 6: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, the bromination product of 50g is slowly added drop-wise in the ammonium hydroxide of 46mL 25wt%, reacts 48h
Afterwards, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid, flow back 1h at 110 DEG C, and suction filtration obtains the white solid of 18.5g, yield
10.2%.
In embodiment 4, when the equivalent proportion of ammonium hydroxide and the bromo- gamma-butyrolacton of α-is 3eq, it is solid to obtain III white of product Intermediate
Body has a 39.4g, and yield is up to 50.3%；In embodiment 5, when the equivalent proportion of ammonium hydroxide and the bromo- gamma-butyrolacton of α-is 6eq, product is obtained
III white solid of intermediate has a 48.25g, and yield is up to 70.6%；In embodiment 6, the equivalent proportion of ammonium hydroxide and the bromo- gamma-butyrolacton of α-
When for 1eq, obtaining III white solid of product Intermediate has 18.5g, and yield is up to 10.2%. therefore when ammonium hydroxide and the bromo- gamma-butyrolacton of α-
Equivalent proportion be 6eq when, for yield up to 70.6%, effect is best.
Embodiment 7: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, the bromination product of 50g is slowly added drop-wise in the ammonium hydroxide of 270mL 25wt%, reacts 48h
Afterwards, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid 26mL, flow back 1h at 110 DEG C, and the white that suction filtration obtains 40.96g is solid
Body, yield 42.8%.
Embodiment 8: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, the bromination product of 50g is slowly added drop-wise in the ammonium hydroxide of 270mL 25wt%, reacts 48h
Afterwards, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid 39mL, flow back 1h at 110 DEG C, and suction filtration obtains the white solid of 46g, receives
Rate 68.3%.
Embodiment 9: III alpha-amido of intermediate-gamma-butyrolacton hydrochloride preparation method:
Under condition of ice bath, the bromination product of 50g is slowly added drop-wise in the ammonium hydroxide of 270mL 25wt%, reacts 48h
Afterwards, vacuum distillation removes solvent, and subsequent enriching hydrochloric acid 65mL, flow back 1h at 110 DEG C, and the white that suction filtration obtains 36.17g is solid
Body, yield 40.3%.1H NMR(600MHz,DMSO)δ8.89(s,2H),4.46–4.25(m,3H),2.59–2.52(m,1H),
2.36–2.26(m,1H).
In embodiment 7, when the equivalent proportion of hydrochloric acid and the bromo- gamma-butyrolacton of α-is 1, III white solid of product Intermediate is obtained
There are 40.96g, yield 42.8%；In embodiment 8, when the equivalent proportion of hydrochloric acid and the bromo- gamma-butyrolacton of α-is 1.5, product is obtained
III white solid of intermediate has 46g, yield 68.3%；In embodiment 9, the equivalent proportion of hydrochloric acid and the bromo- gamma-butyrolacton of α-is
When 2.0, obtaining III white solid of product Intermediate has 36.17g, yield 40.3%；Therefore when hydrochloric acid and the bromo- gamma-butyrolacton of α-
Equivalent proportion be 1.5eq when, obtaining III white solid of product Intermediate has 46g, and yield 68.3%, effect is best.
Embodiment 10: the preparation method of intermediate IV:
Under condition of ice bath, amination product as white solid 20g is taken to mix with 100mL tetrahydrofuran and 200mL water, toward it
Middle addition sodium carbonate, then after reaction half an hour is slowly added dropwise into the ethyl chloroformate of 19g, the reaction was continued after restoring to room temperature
2h, vacuum distillation remove solvent, adjust pH to acidity, are extracted with dichloromethane to obtain thick IV compound of formula, have solid after cooling
It is precipitated, suction filtration obtains colourless oil liquid 13.08g.Yield is 87%.1H NMR(600MHz,CDCl3)δ:5.20(s,1H),
4.47–4.12(m,5H),2.79(s,1H),2.27–2.15(m,1H),1.60(s,2H),0.87(s,1H).
Embodiment 11: the preparation method of intermediate IV:
Under condition of ice bath, takes amination product as white solid 20g to mix with tetrahydrofuran and water, be charged with carbonic acid
Sodium, then after reaction half an hour is slowly added dropwise into the benzyl chloroformate of 30g, the reaction was continued after restoring to room temperature 2h, decompression are steamed
Solvent is removed in distillation, adjusts pH to acidity, is extracted with dichloromethane to obtain thick IV compound of formula, there is solid precipitation after cooling, take out
Filter obtains product colourless oil liquid 13.54g, yield 90%.1H NMR(600MHz,CDCl3) δ: 7.36~7.25 (m,
5H), 5.34 (s, 1H), 5.13 (s, 2H), 4.48~4.21 (m, 3H), 2.80~2.75 (m, 1H), 2.27~2.18 (m, 1H)
Embodiment 12: the preparation method of intermediate IV:
Under condition of ice bath, amination product as white solid 20g is taken to mix with 100mL tetrahydrofuran and 200mL water, toward it
Middle addition sodium carbonate, then after reaction half an hour is slowly added dropwise into the methylchloroformate of 16.5g, continue after restoring to room temperature anti-
2h is answered, vacuum distillation removes solvent, adjusts pH to acidity, is extracted with dichloromethane to obtain thick IV compound of formula, have after cooling
Solid is precipitated, and suction filtration obtains colourless oil liquid 9.0g.Two step yields are 60%.1H NMR(600MHz,CDCl3)δ:5.52(s,
1H), 4.49~4.23 (m, 3H), 3.71 (s, 3H), 2.79~2.70 (m, 1H), 2.28-2.21 (m, 1H)
Embodiment 13: the preparation method of intermediate IV:
Under condition of ice bath, amination product as white solid 20g is taken to be added to the CH of the triethylamine containing 20mL2Cl2
(300mL), then after reaction half an hour is slowly added dropwise into the benzyl chloroformate of 30g, the reaction was continued after restoring to room temperature 2h subtract
Solvent is distilled off in pressure, adjusts pH to acidity, is extracted with dichloromethane to obtain thick IV compound of formula, there is solid analysis after cooling
Out, it filters and obtains product colourless oil liquid 3.0g.Two step yields are 20%.
Embodiment 14: the preparation method of intermediate V:
IV compound of 10g formula is taken, is added in the pressure pipe of 200ml, then by the HCl ethanol solution of the saturation of 150mL
It is added thereto, after being warming up to 65 DEG C of reaction 12h, rotates alcohol solvent therein, a small amount of water is added, extract with ethyl acetate
It takes three times, after spinning off solvent, then uses petroleum ether, obtain colourless oil liquid 8.12g i.e. V compound of formula, yield and exist
60% or more.1H NMR(400MHz,CDCl3)δ:5.29(s,1H),4.47(s,1H),4.27–4.18(m,2H),4.13(d,
2H), 3.60 (t, 2H), 2.34 (s, 1H), 2.16 (s, 1H), 1.32-1.23 (m, 6H),1H-NMR is as shown in Figure 1.
Embodiment 15: the preparation method of intermediate VI:
10.0g such as the intermediate of formula V 4 is taken to mix in 150mL dry toluene with 6.9g methylisothiouronium methylphosphite diethylester, nitrogen
Under gas shielded, back flow reaction 10h.Vacuum distillation removal toluene and superfluous methylisothiouronium methylphosphite diethylester, residue are dissolved in acetic acid second
After ester, salt water washing 3 times, organic layer is dry, and vacuum distillation removal solvent obtains 5 yield of intermediate of 9.6g such as formula VI
75.87%.1HNMR(400MHz,DMSO-d6) δ: 7.49 (s, 1H), 4.17-3.97 (m, 6H), 2.14~1.91 (m, 2H),
1.65–1.07(m,13H).
Embodiment 16: the preparation method of VII product of formula:
The intermediate for weighing 10.0g such as formula VI is added in 100mL 6mol/L HCl solution, and flow back 8h.Again with 28% ammonia
PH value is transferred to 9 by water, is continued the 6h that flows back, after vacuum distillation, with recrystallizing methanol, is obtained white glufosinate-ammonium crystal 5.2g, yield
80.96%.1H NMR(400MHz,D2O) δ: 3.67 (dd, 1H), 2.04~1.87 (m, 2H), 1.58-1.41 (m, 2H), 1.14
(d,3H).13C NMR(101MHz,D2O)δ:172.3,53.7(d,JC-P=14.1Hz), 25.9 (d, JC-P=92.0Hz), 23.2
(d,JC-P=2.3Hz), 14.1 (d, JC-P=93.2Hz)31P NMR(162MHz,D2O) δ: 49.04,1H-NMR is as shown in Figure 2
,13C-NMR as shown in figure 3,31P-NMR is as shown in Figure 4.
Although the embodiments of the present invention have been disclosed as above, but its is not only in the description and the implementation listed
With it can be fully applied to various fields suitable for the present invention, for those skilled in the art, can be easily
Realize other modification, therefore without departing from the general concept defined in the claims and the equivalent scope, the present invention is simultaneously unlimited
In specific details and embodiment shown and described herein.
Claims (10)
1. the synthetic method of glufosinate-ammonium includes that single bromine replaces, amination, amido protecting, chlorination open loop, A Erbuzuofu reaction
With acidification hydrolization ammonification, single bromine substitution is that gamma-butyrolacton I replaces through catalyst and the single bromines of bromine generation α, and decompression is steamed
It evaporates to obtain pure intermediate II α-bromo- gamma-butyrolacton, wherein the catalyst is phosphorus tribromide；The amination is α-
With ammonium hydroxide ammoxidation occurs for bromo- gamma-butyrolacton II, and then plus hydrochloric acid reflux obtains III alpha-amido of intermediate-gamma-butyrolacton
Hydrochloride.
2. the synthetic method of glufosinate-ammonium according to claim 1, it is characterised in that: the amido protecting will obtain
In the presence of solvent, suitable alkali is added in III alpha-amido of intermediate-gamma-butyrolacton hydrochloride, reacts to obtain with alcoxyl dicarbonyl chloride
Intermediate IV (2- oxo-tetrahydrofuran -3- base) urethanes.
3. the synthetic method of glufosinate-ammonium according to claim 1, it is characterised in that:
The chlorination open loop is (2- oxo-tetrahydrofuran -3- base) urethanes of intermediate IV that will be obtained and saturation
HCl ethanol solution reacts to obtain the chloro- 2- ethoxycarbonylamino ethyl butyrate of V 4- of intermediate；
The A Erbuzuofu reaction is that the chloro- 2- ethoxycarbonylamino ethyl butyrate of V 4- of intermediate that will be obtained and methyl are sub-
Diethyl phosphate is reacted by Arbuzov, obtains VI 4- ethyoxyl -4- methyl phosphono -2- ethoxycarbonylamino fourth of intermediate
Acetoacetic ester；
The acidification hydrolization ammonification is the VI 4- ethyoxyl -4- methyl phosphono -2- ethoxycarbonylamino of intermediate that will be obtained
Ethyl butyrate first passes through hydrochloric acid hydrolysis, and then plus ammonium hydroxide reacts to obtain product glufosinate-ammonium ammonium salt.
4. the synthetic method of glufosinate-ammonium according to claim 1, it is characterised in that: the bromine and gamma-butyrolacton
Molar ratio is 1-2:1.
5. the synthetic method of glufosinate-ammonium according to claim 4, it is characterised in that: the bromine and gamma-butyrolacton
Molar ratio is 2:1.
6. the synthetic method of glufosinate-ammonium according to claim 1, it is characterised in that: the intermediate II and ammonium hydroxide is rubbed
, than being 1:3-9, the molar ratio of intermediate II and hydrochloric acid is 1:1-2.5 for you.
7. the synthetic method of glufosinate-ammonium according to claim 6, it is characterised in that: the intermediate II and ammonium hydroxide is rubbed
, than being 1:6, the molar ratio of intermediate II and hydrochloric acid is 1:1.5 for you.
8. the synthetic method of glufosinate-ammonium according to claim 2, it is characterised in that: the alkali is Na2CO3Or triethylamine.
9. the synthetic method of glufosinate-ammonium according to claim 2, it is characterised in that: the alcoxyl dicarbonyl chloride is chloro-carbonic acid
Any one in ethyl ester, methylchloroformate and carbobenzoxy chloride.
10. the synthetic method of glufosinate-ammonium according to claim 2, it is characterised in that: the solvent is methylene chloride, with
And one of water and the mixed liquor of tetrahydrofuran.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811159960.7A CN109232644A (en) | 2018-09-30 | 2018-09-30 | The synthetic method of glufosinate-ammonium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811159960.7A CN109232644A (en) | 2018-09-30 | 2018-09-30 | The synthetic method of glufosinate-ammonium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109232644A true CN109232644A (en) | 2019-01-18 |
Family
ID=65054779
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811159960.7A Pending CN109232644A (en) | 2018-09-30 | 2018-09-30 | The synthetic method of glufosinate-ammonium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109232644A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109912649A (en) * | 2019-04-11 | 2019-06-21 | 利尔化学股份有限公司 | The synthetic method of L-glufosinate-ammonium intermediate |
| CN110204517A (en) * | 2019-07-12 | 2019-09-06 | 利尔化学股份有限公司 | A kind of preparation method of (S)-(2- oxo-tetrahydrofuran -3- base) carbamate |
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
| WO2021143712A1 (en) * | 2020-01-13 | 2021-07-22 | 利尔化学股份有限公司 | Method for preparing l-glufosinate-ammonium intermediate |
| WO2021143713A1 (en) * | 2020-01-13 | 2021-07-22 | 利尔化学股份有限公司 | Method for preparing intermediate of l-glufosinate-ammonium |
| WO2021147894A1 (en) * | 2020-01-20 | 2021-07-29 | 利尔化学股份有限公司 | Preparation method for glufosinate ammonium |
| CN114181177A (en) * | 2021-11-25 | 2022-03-15 | 烟台泽湃新材料科技有限公司 | Production method of novel alpha-bromo-gamma-butyrolactone |
| CN114736119A (en) * | 2022-05-09 | 2022-07-12 | 迈奇化学股份有限公司 | One-step preparation method of ethyl 4-bromobutyrate |
| WO2022264043A1 (en) * | 2021-06-15 | 2022-12-22 | Upl Limited | One pot process for preparation of a chiral amino acid |
| WO2022264168A1 (en) * | 2021-06-17 | 2022-12-22 | Chandrasekhar Dayal Mudaliar | A process for preparation of an intermediate of l-glufosinate |
| WO2023001131A1 (en) * | 2021-07-20 | 2023-01-26 | 利尔化学股份有限公司 | Preparation method for glufosinate-ammonium |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0508296A1 (en) * | 1991-04-06 | 1992-10-14 | Hoechst Schering AgrEvo GmbH | Process for the preparation of phosphorus containing L-amino acids, their derivatives and intermediates for this process |
| CN103288874A (en) * | 2013-05-15 | 2013-09-11 | 山东省农药研究所 | Preparation method of glufosinate-ammonium and derivatives thereof |
| CN105906591A (en) * | 2016-04-22 | 2016-08-31 | 中国药科大学 | Synthesis method of 2-amino-gamma-butyrolactone hydrochloride |
| CN106045947A (en) * | 2016-06-23 | 2016-10-26 | 李建中 | Method for synthesizing L-glufosinate-ammonium intermediate (S)-3-amino-gamma-butyrolactone hydrochloride, and application of method |
-
2018
- 2018-09-30 CN CN201811159960.7A patent/CN109232644A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0508296A1 (en) * | 1991-04-06 | 1992-10-14 | Hoechst Schering AgrEvo GmbH | Process for the preparation of phosphorus containing L-amino acids, their derivatives and intermediates for this process |
| CN103288874A (en) * | 2013-05-15 | 2013-09-11 | 山东省农药研究所 | Preparation method of glufosinate-ammonium and derivatives thereof |
| CN105906591A (en) * | 2016-04-22 | 2016-08-31 | 中国药科大学 | Synthesis method of 2-amino-gamma-butyrolactone hydrochloride |
| CN106045947A (en) * | 2016-06-23 | 2016-10-26 | 李建中 | Method for synthesizing L-glufosinate-ammonium intermediate (S)-3-amino-gamma-butyrolactone hydrochloride, and application of method |
Non-Patent Citations (2)
| Title |
|---|
| 任旭康: "海因衍生物与5-氯水杨酸的合成研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
| 肖伟等: "草铵膦合成工艺的改进研究", 《现代农药》 * |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109912649A (en) * | 2019-04-11 | 2019-06-21 | 利尔化学股份有限公司 | The synthetic method of L-glufosinate-ammonium intermediate |
| CN110204517A (en) * | 2019-07-12 | 2019-09-06 | 利尔化学股份有限公司 | A kind of preparation method of (S)-(2- oxo-tetrahydrofuran -3- base) carbamate |
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
| CN114555612A (en) * | 2020-01-13 | 2022-05-27 | 利尔化学股份有限公司 | Method for preparing L-glufosinate-ammonium intermediate |
| WO2021143712A1 (en) * | 2020-01-13 | 2021-07-22 | 利尔化学股份有限公司 | Method for preparing l-glufosinate-ammonium intermediate |
| WO2021143713A1 (en) * | 2020-01-13 | 2021-07-22 | 利尔化学股份有限公司 | Method for preparing intermediate of l-glufosinate-ammonium |
| CN114585631A (en) * | 2020-01-13 | 2022-06-03 | 利尔化学股份有限公司 | Process for preparing L-glufosinate intermediates |
| KR102515430B1 (en) | 2020-01-20 | 2023-03-29 | 라이어 케이컬 씨오., 엘티디. | How to make glufosinate |
| CN113490671A (en) * | 2020-01-20 | 2021-10-08 | 利尔化学股份有限公司 | Preparation method of glufosinate-ammonium |
| KR20220113365A (en) * | 2020-01-20 | 2022-08-12 | 라이어 케이컬 씨오., 엘티디. | Method for the preparation of ammonium glufosinate |
| WO2021147894A1 (en) * | 2020-01-20 | 2021-07-29 | 利尔化学股份有限公司 | Preparation method for glufosinate ammonium |
| US11680077B2 (en) | 2020-01-20 | 2023-06-20 | Lier Chemical Co., Ltd. | Preparation method for glufosinate |
| WO2022264043A1 (en) * | 2021-06-15 | 2022-12-22 | Upl Limited | One pot process for preparation of a chiral amino acid |
| WO2022264168A1 (en) * | 2021-06-17 | 2022-12-22 | Chandrasekhar Dayal Mudaliar | A process for preparation of an intermediate of l-glufosinate |
| WO2023001131A1 (en) * | 2021-07-20 | 2023-01-26 | 利尔化学股份有限公司 | Preparation method for glufosinate-ammonium |
| KR20230079459A (en) * | 2021-07-20 | 2023-06-07 | 라이어 케이컬 씨오., 엘티디. | Method for producing glufosinate |
| KR102631796B1 (en) | 2021-07-20 | 2024-01-30 | 라이어 케이컬 씨오., 엘티디. | Method for producing glufosinate |
| CN114181177A (en) * | 2021-11-25 | 2022-03-15 | 烟台泽湃新材料科技有限公司 | Production method of novel alpha-bromo-gamma-butyrolactone |
| CN114736119A (en) * | 2022-05-09 | 2022-07-12 | 迈奇化学股份有限公司 | One-step preparation method of ethyl 4-bromobutyrate |
| CN114736119B (en) * | 2022-05-09 | 2024-02-06 | 迈奇化学股份有限公司 | One-step preparation method of ethyl 4-bromobutyrate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109232644A (en) | The synthetic method of glufosinate-ammonium | |
| Kimura et al. | Phosphodiester hydrolysis by a New Zinc (II) macrocyclic tetraamine complex with an alcohol pendant: elucidation of the roles of Ser-102 and Zinc (II) in Alkaline Phosphatase | |
| CN102584893B (en) | Preparation method for glufosinate | |
| IE59310B1 (en) | Substituted alpha-amino acids, their preparation and pharmaceutical compositions containing them | |
| CN103374030B (en) | A kind ofly prepare the careless method of ammonium phosphine and the preparation method of intermediate thereof | |
| CN101798292A (en) | Method for preparing novel Bc1-2 protein inhibitor derived from ABT-263 | |
| CN114805314A (en) | Synthesis method of Ensaitevir | |
| KR20110139274A (en) | Methods for the preparation of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid and precursors thereof | |
| US4654429A (en) | Process for the preparation of a glyphosate product | |
| CN108101942A (en) | Half fumaric acid tenofovir Chinese mugwort draws the synthetic method of potential impurity in the production of phenol amine | |
| CA1215999A (en) | Method for preparation of n-phosphonomethylglycine | |
| JPH09309891A (en) | Production of monoalkyl phosphonite | |
| CN100410235C (en) | Capsicine chemical synthesis and purification method | |
| CN103588812B (en) | A kind of method preparing careless ammonium phosphine | |
| CN106256819A (en) | A kind of synthetic method of (4S) N Boc 4 methoxy L proline amine salt | |
| CN106946724B (en) | The synthetic method of monoamine base inhibitor class intermediate 2- acetylaminohydroxyphenylarsonic acid 2- benzyl malonic acid mono ethyl ester | |
| US5990307A (en) | Process for the preparation of [2-((8.9)-Dioxo-2,6-Diazabicyclo [5.2.0]-Non-1(7)-en-2yl) Ethyl]Phosphonic acid | |
| CN110330422B (en) | Preparation method of 2, 6-diethyl-4-methylphenylacetic acid | |
| CN108033892A (en) | A kind of preparation method of N- alkyl iminodiacetics acid | |
| US4617415A (en) | α-Substituted N-phosphonomethyliminodiacetic acid | |
| WO2016202232A1 (en) | Synthesis method for (4s)-n-boc-4-methoxy methyl-l-proline amine salt | |
| CN109879910A (en) | A kind of preparation method of glufosinate-ammonium intermediate | |
| EP1000072B1 (en) | Process for the preparation of [2-((8,9)- dioxo-2,6-diazabicyclo [5.2.0]-non-1(7)-en-2-yl)-ethyl] phosphonic acid | |
| CN105037239B (en) | A kind of preparation method of the acetic acid of 4 chloro-indole 3 | |
| CA2013919A1 (en) | Unsaturated aminodicarboxylic acid derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190118 |
|
| RJ01 | Rejection of invention patent application after publication |