CN109879910A - A kind of preparation method of glufosinate-ammonium intermediate - Google Patents
A kind of preparation method of glufosinate-ammonium intermediate Download PDFInfo
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Abstract
The present invention relates to a kind of preparation methods of glufosinate-ammonium intermediate.To methylisothiouronium methylphosphite diester as starting material, Michael reaction occurs with methacrylaldehyde first, then product occurs Strecker with the ammonia spirit of third level natural division and ammonium chloride and react, obtain glufosinate-ammonium key intermediate glufosinate-ammonium cyanamide without processing.This method replaces Cymag compared to traditional synthetic method, using trimethyl silicane phosphorus, and toxicity is significantly smaller, increases operational safety, while nucleophilie nucleus ability is stronger, is conducive to the progress of reaction, yield with higher.
Description
Technical field
The present invention relates to the synthesis of organic compound, and in particular to a kind of preparation method of glufosinate-ammonium.
Background technique
Glufosinate-ammonium is to be succeeded in developing by Hirst company and (belong to Beyer Co., Ltd afterwards) eighties, and it is high to belong to hypophosphorous acid class
Effect, low toxicity, environment amenable non-conductive class steriland herbicide, are easy to degrade in the soil, to crop safety, are not easy to float
It moving, herbicidal spectrum is wide, and activity is high, and dosage is few, and it is small to environmental pressure, it is world's large-tonnage pesticide species.Especially current transgenosis
The fast development of technology, the plantation of transgenosis herbicide-tolerant crops are in the gesture to grow in intensity in recent years, and herbicide-tolerant uses big
Width increases.Glufosinate-ammonium is an outstanding steriland herbicide, is very suitable to do resistant gene, at present glufosinate-ammonium oneself become the world
The second largest genetically modified crops herbicide-tolerant, therefore the market prospects of the product are very wide.
Glufosinate-ammonium cyanamide is the key intermediate for synthesizing glufosinate-ammonium, the synthesis side reported at present about the intermediate
Method is that methylisothiouronium methylphosphite ester and methacrylaldehyde carry out addition reaction, then reacts to obtain glufosinate-ammonium with Cymag and ammonia/ammonium chloride
Intermediate glufosinate-ammonium cyanamide can use Cymag in this process, and Cymag has severe toxicity, and chance acid can generate hypertoxic, inflammable
Hydrogen cyanide gas.Micro hydrogen cyanide gas is slowly issued in humid air or carbon dioxide.
Summary of the invention
The present invention is in view of the foregoing drawbacks, it is therefore intended that finds a kind of smaller reagent that can substitute Cymag of toxicity, simultaneously
It can be improved reaction yield.
Thus the technical solution adopted by the present invention is that: selection third level natural division replace Cymag.
A kind of preparation method of glufosinate-ammonium intermediate, 1) with methylisothiouronium methylphosphite diester (1) for starting material, with methacrylaldehyde
(2) it reacts, obtains compound (3), reaction equation is as follows:
；
2) then obtained compound (3) is reacted again with the ammonia spirit of third level natural division (4) and ammonium chloride, is changed
It closes object (5), reaction equation:
。
It needs to carry out under inert gas protection in step (1), the ratio between the amount of methylisothiouronium methylphosphite diester and methacrylaldehyde substance
It is 1 ~ 2, wherein the alcohol reagent selected is methanol or ethyl alcohol.
Methacrylaldehyde and methylisothiouronium methylphosphite diester reaction temperature are 20 ~ 30 DEG C of room temperature in step (1), and the reaction time is 2 small
When.
In step (1), the ratio between amount of methylisothiouronium methylphosphite diester and methacrylaldehyde substance preferably 1:1.2, wherein the alcohol selected
Class reagent is methanol or ethyl alcohol, and dropping temperature is preferably 25 DEG C, and the reaction time is 2 hours, is needed in inert gas
Under the conditions of carry out.
Need to carry out under inert gas protection in step (2), the ratio between amount of compound 3 and third level natural division substance for 1 ~
2。
In step (2), reaction temperature is 20 ~ 30 DEG C, and the reaction time is 3 hours.
In step (2), the ratio between amount of compound 3 and third level natural division substance preferably 1:1.1, reaction temperature is 20 ~ 30
DEG C, the reaction time is 3 hours.
The technical effect that the present invention generates: this method replaces the Cymag that will use when preparing glufosinate-ammonium key intermediate
On behalf of third level natural division, the toxicity of third level natural division is far smaller than Cymag, reduces the risk of operation, is equally used as nucleophilic
The nucleophilie nucleus ability of reagent, third level natural division is stronger, is more advantageous to the progress of reaction, improves reaction yield.
Specific embodiment
In order to which the present invention is furture elucidated, a series of embodiments are given below, these embodiments be entirely it is illustrative, it
Only be used to the present invention specifically describe, be not construed as limitation of the present invention.
Embodiment 1
It is added 13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol in reaction flask, under nitrogen protection, 25 DEG C
It is lower that the 5.6 g methacrylaldehyde (0.1 moI) newly distilled are added dropwise, 2 hours are reacted at room temperature after being added dropwise.Then, it is evaporated under reduced pressure back
Receive ethyl alcohol and remaining acrylic acid.The hydrochloric acid of 10 g 5% is added at 25 DEG C into residue, the reaction was continued.After 2 hours,
Vacuum distillation removes the ethyl alcohol that hydrolysis generates, and obtains 15.4 g of phosphine aldehyde.15.4 obtained g phosphorus aldehyde are added into 4.9 g cyanidings dropwise
Sodium (0.1mol), 8 g ammonium chlorides (0.15mo1) 50 ml 25% ammonia spirit in, dropping temperature control 25 DEG C, drip
The reaction was continued after finishing 3 hours, and ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains among glufosinate-ammonium
16.8 g of body glufosinate-ammonium cyanamide, yield 88.9%.
Embodiment 2
It is added 13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol in reaction flask, under nitrogen protection, 25 DEG C
It is lower that the 5.6 g methacrylaldehyde (0.1 moI) newly distilled are added dropwise, 2 hours are reacted at room temperature after being added dropwise.Then, it is evaporated under reduced pressure back
Receive ethyl alcohol and remaining acrylic acid.The hydrochloric acid of 10 g 5% is added at 25 DEG C into residue, the reaction was continued.After 2 hours,
Vacuum distillation removes the ethyl alcohol that hydrolysis generates, and obtains 15.4 g of phosphine aldehyde.15.4 obtained g phosphorus aldehyde are added into 9.9 g front threes dropwise
Base silicon cyanogen (0.1mol), 8 g ammonium chlorides (0.15mo1) 50 ml 25% ammonia spirit in, dropping temperature control 25 DEG C, drop
The reaction was continued 3 hours after finishing are added, ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains glufosinate-ammonium
17 g of intermediate glufosinate-ammonium cyanamide, yield 89.5%.
Embodiment 3
It is added 13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol in reaction flask, under nitrogen protection, 25 DEG C
It is lower that the 6.7 g methacrylaldehyde (0.12 moI) newly distilled are added dropwise, 2 hours are reacted at room temperature after being added dropwise.Then, it is evaporated under reduced pressure back
Receive ethyl alcohol and remaining acrylic acid.The hydrochloric acid of 10 g 5% is added at 25 DEG C into residue, the reaction was continued.After 2 hours,
Vacuum distillation removes the ethyl alcohol that hydrolysis generates, and obtains 15.8 g of phosphine aldehyde.15.8 obtained g phosphorus aldehyde are added into 9.9 g front threes dropwise
Base silicon cyanogen (0.1mol), 8 g ammonium chlorides (0.15mo1) 50 ml 25% ammonia spirit in, dropping temperature control 25 DEG C, drop
The reaction was continued 3 hours after finishing are added, ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains glufosinate-ammonium
17.4 g of intermediate glufosinate-ammonium cyanamide, yield 91.6%.
Embodiment 4
It is added 13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol in reaction flask, under nitrogen protection, 25 DEG C
It is lower that the 6.7 g methacrylaldehyde (0.12 moI) newly distilled are added dropwise, 2 hours are reacted at room temperature after being added dropwise.Then, it is evaporated under reduced pressure back
Receive ethyl alcohol and remaining acrylic acid.The hydrochloric acid of 10 g 5% is added at 25 DEG C into residue, the reaction was continued.After 2 hours,
Vacuum distillation removes the ethyl alcohol that hydrolysis generates, and obtains 15.8 g of phosphine aldehyde.15.8 obtained g phosphorus aldehyde are added into 10.9 g tri- dropwise
Methyl silicon cyanogen (0.11mol), 8 g ammonium chlorides (0.15mo1) 50 ml 25% ammonia spirit in, dropping temperature control 25
DEG C, the reaction was continued after being added dropwise 3 hours, and ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains grass
17.9 g of ammonium phosphine intermediate glufosinate-ammonium cyanamide, yield 94.2%.
Embodiment 5
It is added 13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol in reaction flask, under nitrogen protection, 25 DEG C
It is lower that the 6.7 g methacrylaldehyde (0.12 moI) newly distilled are added dropwise, 2 hours are reacted at room temperature after being added dropwise.Then, it is evaporated under reduced pressure back
Receive ethyl alcohol and remaining acrylic acid.The hydrochloric acid of 10 g 5% is added at 25 DEG C into residue, the reaction was continued.After 2 hours,
Vacuum distillation removes the ethyl alcohol that hydrolysis generates, and obtains 15.8 g of phosphine aldehyde.15.8 obtained g phosphorus aldehyde are added into 11.9 g tri- dropwise
Methyl silicon cyanogen (0.12mol), 8 g ammonium chlorides (0.15mo1) 50 ml 25% ammonia spirit in, dropping temperature control 25
DEG C, the reaction was continued after being added dropwise 3 hours, and ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains grass
Ammonium phosphine intermediate glufosinate-ammonium cyanamide 17.8g, yield 93.7%.
Embodiment 6
13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol are added in reaction flask, new distillation is added dropwise at 40 DEG C
6.7 g methacrylaldehyde (0.12 moI), after being added dropwise react at room temperature 2 hours.Then, vacuum distillation recycling ethyl alcohol and residue
Acrylic acid.The hydrochloric acid of 10 g 5% is added at 40 DEG C into residue, the reaction was continued.After 2 hours, vacuum distillation is removed
The ethyl alcohol generated is hydrolyzed, 14.9 g of phosphine aldehyde is obtained.14.9 obtained g phosphorus aldehyde are added into 10.9 g third level natural divisions dropwise
In the ammonia spirit of 50 ml 25% of (0.11mol), 8 g ammonium chlorides (0.15mo1), dropping temperature controls 40 DEG C, drips
The reaction was continued after finishing 3 hours, and ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains among glufosinate-ammonium
15.1 g of body glufosinate-ammonium cyanamide, yield 79.4%.
Embodiment 7
13.6 g diethyl methyl-phosphonites (0.1mol) and 30 ml ethyl alcohol are added in reaction flask, new distillation is added dropwise at 0 DEG C
6.7 g methacrylaldehyde (0.12 moI), after being added dropwise react at room temperature 2 hours.Then, vacuum distillation recycling ethyl alcohol and residue
Acrylic acid.The hydrochloric acid of 10 g 5% is added at 0 DEG C into residue, the reaction was continued.After 2 hours, vacuum distillation is removed
The ethyl alcohol generated is hydrolyzed, 14.9 g of phosphine aldehyde is obtained.14.9 obtained g phosphorus aldehyde are added into 10.9 g third level natural divisions dropwise
In the ammonia spirit of 50 ml 25% of (0.11mol), 8 g ammonium chlorides (0.15mo1), dropping temperature controls 0 DEG C, is added dropwise
The reaction was continued afterwards 3 hours, and ethyl acetate extracts after reaction, merges organic phase, and vacuum distillation obtains glufosinate-ammonium intermediate
15.6 g of glufosinate-ammonium cyanamide, yield 82.1%.
Claims (5)
1. a kind of preparation method of glufosinate-ammonium intermediate, which comprises the following steps:
1) it reacts with methacrylaldehyde (2) for starting material with methylisothiouronium methylphosphite diester (1), obtains compound (3), reaction equation
It is as follows:
；
2) then obtained compound (3) is reacted again with the ammonia spirit of third level natural division (4) and ammonium chloride, is changed
It closes object (5), reaction equation:
。
2. the preparation method of glufosinate-ammonium intermediate according to claim 1, which is characterized in that step needs in (1) in inertia
It is carried out under gas shield, the ratio between amount of methylisothiouronium methylphosphite diester and methacrylaldehyde substance is 1 ~ 2, wherein the alcohol reagent selected is first
Alcohol or ethyl alcohol.
3. the preparation method of glufosinate-ammonium intermediate according to claim 1, which is characterized in that methacrylaldehyde and first in step (1)
Base diphosphite reaction temperature is 20 ~ 30 DEG C of room temperature, and the reaction time is 2 hours.
4. the preparation method of glufosinate-ammonium intermediate according to claim 1, which is characterized in that step needs in (2) in inertia
It is carried out under gas shield, the ratio between amount of compound 3 and third level natural division substance is 1 ~ 2.
5. the preparation method of glufosinate-ammonium intermediate according to claim 1, which is characterized in that in step (2), reaction temperature is
20 ~ 30 DEG C, the reaction time is 3 hours.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110590836A (en) * | 2019-09-30 | 2019-12-20 | 江苏七洲绿色化工股份有限公司 | Synthesis method of glufosinate-ammonium intermediate |
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| CN103030575A (en) * | 2013-01-04 | 2013-04-10 | 中国农业大学 | Double-cyano acidamide compound, and synthetic method and application of compound |
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2018
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| US4264532A (en) * | 1977-12-19 | 1981-04-28 | Takashi Tsuruoka | Process for preparing D,L-2-amino-4-methylphosphinobutyric acid |
| US4551526A (en) * | 1984-09-26 | 1985-11-05 | American Hospital Supply Corporation | Synthesis of alpha-aminonitriles |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110590836A (en) * | 2019-09-30 | 2019-12-20 | 江苏七洲绿色化工股份有限公司 | Synthesis method of glufosinate-ammonium intermediate |
| CN110590836B (en) * | 2019-09-30 | 2022-07-26 | 江苏七洲绿色化工股份有限公司 | Synthetic method of glufosinate-ammonium intermediate |
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