CN103288874B - Preparation method of glufosinate-ammonium and derivatives thereof - Google Patents
Preparation method of glufosinate-ammonium and derivatives thereof Download PDFInfo
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- CN103288874B CN103288874B CN201310180143.0A CN201310180143A CN103288874B CN 103288874 B CN103288874 B CN 103288874B CN 201310180143 A CN201310180143 A CN 201310180143A CN 103288874 B CN103288874 B CN 103288874B
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Abstract
The invention discloses a preparation method of glufosinate-ammonium and derivatives thereof. The method comprises the following steps: (1) by using a substituted hydantoin and methylphosphonate compounds as a raw material, adding alkali, carrying out nucleophilic substitution reaction at the reaction temperature of 20-100 DEG C in a reaction solvent to obtain a hydantoin derivative, and tracing product generation condition by high performance liquid chromatography in the reaction process to judge the reaction endpoint, wherein the molar ratio of the methylphosphonate compounds, substituted hydantoin and alkali is 1:(1.0-5.0):(1.0-4.0); (2) carrying out reflux reaction for prepared hydantoin derivative prepared and an inorganic acid in water for 30-60 hours; after reaction, adding ammonia water to adjust the pH of the liquor to 12; spirally distilling to remove the solvent; adding absolute methanol for reflux for 30-60 minutes; filtering; spirally drying the mother liquor; adding methanol for recrystallization to obtain pure glufosinate-ammonium shown in formula (I) or derivatives thereof, wherein the molar ratio of the hydantoin derivative and inorganic acid is 1.0:(4.0-9.0).
Description
Technical field
The present invention relates to the preparation method of a kind of careless ammonium phosphine and derivative thereof.
Background technology
Grass ammonium phosphine (glufosinate) is the novel steriland herbicide that Hirst company developed the eighties in last century, can be used for orchard, vineyard, bare place prevent and kill off 1 year and perennial dicotyledonous and gramineous weeds.The resistant gene of careless ammonium phosphine, has successfully imported in 20 various crop such as paddy rice, wheat, corn by resistant gene transfer, seed selection resistant crop varieties for target with careless ammonium phosphine by Hirst company.These genetically modified crops are not only generally planted at north America region, in recent years in Asia, Australia, the Countries such as Europe and area also start to promote, current careless ammonium phosphine consumption is only second to glyphosate, is second-biggest-in-the-world genetically modified crops herbicide-tolerant.Along with the high speed development of transgenic technology, the market outlook of careless ammonium phosphine are very good.
At present both at home and abroad about the technological line of careless ammonium phosphine is more, such as high-temperature catalytic synthesis method (EP0292918), bromination synthesis method (Yu Chuanming. agricultural chemicals, 2001,40 (4), 15), ultraviolet catalytic synthesis method (Li Yiming. agricultural chemicals, 2012,51 (1), 12) etc., although these routes can obtain careless ammonium phosphine, ubiquity route is long, complex operation, the shortcomings such as yield is low, are unsuitable for suitability for industrialized production.The operational path of current comparative maturity utilizes Strecker to react to prepare amino-nitrile, through the careless ammonium phosphine (US4264532, CN1267305A) of hydrolysis preparation.
This route reaction process is short, and yield is relatively high, but there is the following shortcoming: 1, reaction process uses highly toxic product sodium cyanide, and there is potential safety hazard in production process, environmental protection pressure is large; 2, with in acid hydrolysis, produce a large amount of ammonium chloride, refined product needs to carry out repeatedly recrystallization, and technique is loaded down with trivial details; 3, the key intermediate cyanamide compound boiling point in reaction process is high and without obvious uv-absorbing, is difficult to, with gas-chromatography and liquid chromatography tracing detection reaction process, be unfavorable for that production process carries out intermediate controlled.
Summary of the invention
The object of the invention is for overcoming above-mentioned the deficiencies in the prior art, the preparation method of a kind of careless ammonium phosphine and derivative thereof is provided.The present invention carries out nucleophilic substitution reaction with methyl-phosphorous acid ester derivative and substituted glycolylurea, then the method for the hydrolysis careless ammonium phosphine of preparation and derivative thereof.
For achieving the above object, the present invention adopts following technical proposals:
A preparation method for careless ammonium phosphine and derivative thereof, step is as follows:
(1) with the methyl-phosphorous acid ester compound shown in the substituted glycolylurea shown in formula (III) and formula (II) for raw material, add alkali, in reaction solvent, nucleophilic substitution reaction is carried out under 20 ~ 100 DEG C of temperature of reaction, obtain the hydantoin derivatives shown in formula (IV), reaction process is followed the tracks of product with high performance liquid chromatography and is generated situation to judge reaction end; The mol ratio of described methyl-phosphorous acid ester compound, substituted glycolylurea and alkali is 1:1.0 ~ 5.0:1.0 ~ 4.0;
Wherein, R
1for H, C
1~ C
8alkane, C
1~ C
8acyl group or benzyl; R
2for H ,-CH
3, (CH
3)
2cH-, (CH
3)
2cHCH
2-or CH
3cH
2cH (CH
3)-; X is chlorine, bromine or iodine;
(2) by the hydantoin derivatives shown in formula (IV) obtained for step (1) and mineral acid back flow reaction 30 ~ 60 hours in water, the pH=12 that ammoniacal liquor is adjusted to solution is added after reaction terminates, revolve and steam except desolventizing, add anhydrous methanol backflow 30 ~ 60 minutes, filter, mother liquor is spin-dried for, and obtains the sterling grass ammonium phosphine shown in formula (I) or its derivative after adding recrystallizing methanol; Wherein, the mol ratio of the hydantoin derivatives shown in formula (IV) and mineral acid is 1.0:4.0 ~ 9.0;
In described step (1), reaction solvent is alcohol, ketone or ether, and described alkali is sodium methylate, sodium ethylate, salt of wormwood or thanomin.
Described alcohol is methyl alcohol, ethanol, propyl alcohol or Virahol; Described ketone is acetone or butanone; Described ether is tetrahydrofuran (THF), ether or butyl ether.
In described step (1), the mol ratio of methyl-phosphorous acid ester compound, substituted glycolylurea and alkali is preferably 1:1.2:2.5.
In described step (1), temperature of reaction is preferably 60 DEG C.
In described step (2), mineral acid is hydrochloric acid, sulfuric acid or nitric acid.
In described step (2), mineral acid is preferably sulfuric acid, and the mol ratio of the hydantoin derivatives shown in sulfuric acid and formula (IV) is preferably 4:1.
In described step (2), return time is preferably 40 hours.
In the present invention, the methyl-phosphorous acid ester compound shown in formula (II) is reacted by methyl phosphinate compounds and dihalo thing to be prepared (Yu Chuanming, agricultural chemicals, 2001,40 (4), 15)
Substituted glycolylurea shown in formula (III) is reacted by amino acid and potassium cyanate and prepares (Read., J.Am.Chem.Soc., 1922,44,1746 ~ 1755)
The invention has the beneficial effects as follows, the present invention for raw material, obtains hydantoin derivatives through carrying out nucleophilic substitution reaction with substituted glycolylurea with methyl-phosphorous acid ester compound, reaction conditions is gentle, yield is higher, and reaction process is easy to detect, and avoids the use of severe poisonous chemicals sodium cyanide simultaneously; Just sterling grass ammonium phosphine and derivative thereof can be obtained without the need to repeatedly recrystallization after hydantoin derivatives hydrolysis.Reaction scheme is short, and reaction process is easy to detect, and product yield is high.
Embodiment
Below in conjunction with embodiment, the present invention will be further elaborated, should be noted that following explanation is only to explain the present invention, not limiting its content.
The preparation of embodiment 1:5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea
Glycolylurea 12.01g (0.12mol) is added in 250mL there-necked flask; sodium ethylate 10.2g (0.15mol); ethanol 90mL; stirring at room temperature 20min; until completely dissolved; drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol); dropwise, be warming up to 80 DEG C of reaction 5h, be cooled to room temperature; suction filtration removing solid; revolve and steam except desolventizing, add 100mL dissolve with ethanol and filter, after precipitation, obtain 5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea crude product 20.88g; yield: 89.2%, content: 86.4%.
1H NMR(D
2O,300MHz)δ:1.212～1.245(m,3H);1.513(d,J=13.6Hz,3H);1.672～1.910(m,4H);3.928～3.976(m,2H);4.182(t,J=5.4Hz,1H)。
The preparation of embodiment 2:5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea
Glycolylurea 12.01g (0.12mol) is added in 250mL there-necked flask; sodium ethylate 10.2g (0.15mol); ethanol 90mL; stirring at room temperature 20min; until completely dissolved; drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol); dropwise, be warming up to 40 DEG C of reaction 5h, be cooled to room temperature; suction filtration removing solid; revolve and steam except desolventizing, add 100mL dissolve with ethanol and filter, after precipitation, obtain 5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea crude product 13.68g; yield: 58.4%, content: 56.6%.
The preparation of embodiment 3:5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea
Glycolylurea 12.01g (0.12mol) is added in 250mL there-necked flask; sodium ethylate 10.2g (0.15mol); ethanol 90mL; stirring at room temperature 20min; until completely dissolved; drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol); dropwise, be warming up to 80 DEG C of reaction 3h, be cooled to room temperature; suction filtration removing solid; revolve and steam except desolventizing, add 100mL dissolve with ethanol and filter, after precipitation, obtain 5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea crude product 18.36g; yield: 78.4%, content: 76.6%.
The preparation of embodiment 4:5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea
Glycolylurea 12.01g (0.12mol) is added in 250mL there-necked flask; sodium ethylate 10.2g (0.15mol); tetrahydrofuran (THF) 90mL; stirring at room temperature 20min; until completely dissolved; drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol); dropwise, be warming up to 80 DEG C of reaction 5h, be cooled to room temperature; suction filtration removing solid; revolve and steam except desolventizing, add 100mL dissolve with ethanol and filter, after precipitation, obtain 5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea crude product 19.58g; yield: 83.6%, content: 78.3%
The preparation of embodiment 5:5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea
Glycolylurea 12.01g (0.12mol) is added in 250mL there-necked flask; sodium ethylate 10.2g (0.15mol); acetone 90mL; stirring at room temperature 20min; until completely dissolved; drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol); dropwise, be warming up to 60 DEG C of reaction 5h, be cooled to room temperature; suction filtration removing solid; revolve and steam except desolventizing, add 100mL dissolve with ethanol and filter, after precipitation, obtain 5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea crude product 18.76g; yield: 80.1%, content: 77.9%
The preparation of embodiment 6:5-(2-(methyl ethoxy phosphono) ethyl)-5-methyl hydantoin
5-methyl hydantoin 13.68g (0.12mol) is added in 250mL there-necked flask, sodium ethylate 10.2g (0.15mol), acetone 90mL, stirring at room temperature 20min, until completely dissolved, drip methyl-2-phosphonic acid ethyl bromide ethyl ester 21.4g (0.10mol), dropwise, be warming up to 60 DEG C of reaction 5h, be cooled to room temperature, suction filtration removing solid, revolve and steam except desolventizing, add 100mL dissolve with ethanol to filter, 5-(2-(methyl ethoxy phosphono) ethyl)-5-methyl hydantoin crude product 18.38g is obtained after precipitation, yield: 74.1%, content: 78.2%
Embodiment 7: the preparation of careless ammonium phosphine
5-(2-(methyl ethoxy phosphono) ethyl) glycolylurea 13.55g (0.05mol) prepared by embodiment 1 is added in 250mL there-necked flask; drip the sulfuric acid 49.02g (0.2mol) that mass concentration is 40%; dropwise; be heated to back flow reaction 50h; add the pH value to 12 of the ammoniacal liquor regulator solution of 25%; 65 DEG C revolve steaming desolvation; add anhydrous methanol backflow 0.5h; filter desalination; mother liquor is spin-dried for rear recrystallizing methanol and obtains sterling grass ammonium phosphine; yield: 8.6g, yield: 86.8%, content: 98.6%
Embodiment 8: the preparation of careless ammonium phosphine-derivatives
5-(2-(methyl ethoxy phosphono) ethyl)-5-methyl hydantoin 12.41g (0.05mol) prepared by embodiment 6 is added in 250mL there-necked flask, drip the sulfuric acid 49.02g (0.2mol) that mass concentration is 40%, dropwise, be heated to back flow reaction 50h, add the pH value to 12 of the ammoniacal liquor regulator solution of 25%, 65 DEG C revolve steaming desolvation, add anhydrous methanol backflow 0.5h, filter desalination, mother liquor is spin-dried for rear recrystallizing methanol and obtains sterling 4-[hydroxyl (methyl) phosphono]-2-methyl high lactamine 8.1g, yield: 76.4%, content: 96.6%.
Although above-mentioned, the specific embodiment of the present invention is described; but not limiting the scope of the invention; on the basis of technical scheme of the present invention, those skilled in the art do not need to pay various amendment or distortion that creative work can make still within protection scope of the present invention.
Claims (8)
1. a preparation method for careless ammonium phosphine and derivative thereof, it is characterized in that, step is as follows:
(1) with the methyl-phosphorous acid ester compound shown in the substituted glycolylurea shown in formula (III) and formula (II) for raw material, add alkali, in reaction solvent, nucleophilic substitution reaction is carried out under 20 ~ 100 DEG C of temperature of reaction, obtain the hydantoin derivatives shown in formula (IV), reaction process is followed the tracks of product with high performance liquid chromatography and is generated situation to judge reaction end; The mol ratio of described methyl-phosphorous acid ester compound, substituted glycolylurea and alkali is 1:1.0 ~ 5.0:1.0 ~ 4.0;
Wherein, R1 is the alkyl of H, C1 ~ C8, the acyl group of C1 ~ C8 or benzyl; R2 is H ,-CH3; X is chlorine, bromine or iodine;
(2) by the hydantoin derivatives shown in formula (IV) obtained for step (1) and mineral acid back flow reaction 30 ~ 60 hours in water, the pH=12 that ammoniacal liquor is adjusted to solution is added after reaction terminates, revolve and steam except desolventizing, add anhydrous methanol backflow 30 ~ 60 minutes, filter, mother liquor is spin-dried for, and obtains the sterling grass ammonium phosphine shown in formula (I) or its derivative after adding recrystallizing methanol; Wherein, the mol ratio of the hydantoin derivatives shown in formula (IV) and mineral acid is 1.0:4.0 ~ 9.0;
2. preparation method according to claim 1, is characterized in that, in described step (1), reaction solvent is alcohol, ketone or ether, and described alkali is sodium methylate, sodium ethylate, salt of wormwood or thanomin.
3. preparation method according to claim 2, is characterized in that, described alcohol is methyl alcohol, ethanol, propyl alcohol or Virahol; Described ketone is acetone or butanone; Described ether is tetrahydrofuran (THF), ether or butyl ether.
4. preparation method according to claim 1, is characterized in that, in described step (1), the mol ratio of methyl-phosphorous acid ester compound, substituted glycolylurea and alkali is 1:1.2:2.5.
5. preparation method according to claim 1, is characterized in that, in described step (1), temperature of reaction is 60 DEG C.
6. preparation method according to claim 1, is characterized in that, in described step (2), mineral acid is hydrochloric acid, sulfuric acid or nitric acid.
7. preparation method according to claim 1, is characterized in that, in described step (2), mineral acid is sulfuric acid, and the mol ratio of the hydantoin derivatives shown in sulfuric acid and formula (IV) is 4:1.
8. preparation method according to claim 1, is characterized in that, in described step (2), return time is 40 hours.
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| CN103880786B (en) * | 2014-03-18 | 2015-11-18 | 南京师范大学 | A kind of method reclaiming useful component in careless ammonium phosphine production process mixing solvent slop |
| CN109232644A (en) * | 2018-09-30 | 2019-01-18 | 武汉工程大学 | The synthetic method of glufosinate-ammonium |
| CN112574116B (en) * | 2019-09-29 | 2022-08-23 | 利尔化学股份有限公司 | Method for preparing glufosinate intermediate and analogue |
| CN113045604B (en) * | 2021-04-13 | 2023-03-17 | 河北威远生物化工有限公司 | Synthesis method of glufosinate-ammonium |
| CN113072579B (en) * | 2021-04-13 | 2022-09-27 | 河北威远生物化工有限公司 | Preparation method of glufosinate-ammonium |
| CN114805433B (en) * | 2021-05-13 | 2023-11-28 | 永农生物科学有限公司 | Crystalline forms of L-glufosinate-ammonium salt free of crystallization water and solid powders |
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| DE3142036A1 (en) * | 1981-10-23 | 1983-05-05 | Hoechst Ag, 6230 Frankfurt | Phosphorus-containing hydantoins, their preparation, and their use |
| CN102584893A (en) * | 2012-02-07 | 2012-07-18 | 浙江工业大学 | Preparation method for glufosinate |
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2013
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| US4168963A (en) * | 1976-05-17 | 1979-09-25 | Hoechst Aktiengesellschaft | Herbicidal agents |
| DE3142036A1 (en) * | 1981-10-23 | 1983-05-05 | Hoechst Ag, 6230 Frankfurt | Phosphorus-containing hydantoins, their preparation, and their use |
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