CN107963993A - A kind of preparation method of high-purity ethiprole - Google Patents
A kind of preparation method of high-purity ethiprole Download PDFInfo
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- CN107963993A CN107963993A CN201810013328.5A CN201810013328A CN107963993A CN 107963993 A CN107963993 A CN 107963993A CN 201810013328 A CN201810013328 A CN 201810013328A CN 107963993 A CN107963993 A CN 107963993A
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- ethiprole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of preparation method of high-purity ethiprole：Under the conditions of micro-vacuum, trifluoromethyl thionyl chloride, 5 amino, 3 cyano group 1 are sequentially added into reaction kettle（2,6 dichloro-4,4 trifluoromethyls）Pyrazoles, catalyst trimethyl benzyl ammonia chloride and solvent dichloroethanes, at 35 ~ 45 DEG C react 1 ~ 2 it is small when after, again add trifluoromethyl thionyl chloride, finish continue insulation reaction 9 ~ 12 it is small when after, reaction solution is added to the water, stratification, centrifugal filtration, filtrate is distilled to recover dichloroethanes recovery, and filter cake A adds in the mixed solvent, is warming up to 85 ~ 90 DEG C, stirring is to after being completely dissolved, crystallisation by cooling, is then centrifuged for separating, filter cake B drying ethiproles.The technique that the present invention prepares ethiprole is simple, easily operated, purifies ethiprole using the method for mixed solvent recrystallization, gained ethiprole yield, purity are high, and product cut size is evenly distributed.
Description
Technical field
The invention belongs to pesticide synthesis technical field, and in particular to a kind of preparation method of high-purity ethiprole.
Background technology
Ethiprole is that French Luo Na-Rhone-Poulenc developed in 1987~1989 years, is stepped in China within 1992
Note, by open up for many years should, have evolved into an interesting efficient pesticides.Ethiprole passes through γ-aminobutyric acid
The path of the chloride channel interference chlorion of adjusting, destroys the activity of normal central nervous system and is made in the case of sufficient dosage
Into individual death.Due to this unique mechanism of action, make ethiprole that there is the distinguishing feature different from common insecticides.By
Many experimental results prove that the insecticide is to including pests such as Semiptera, Lepidoptera, Thysanoptera, coleopteras and to ring penta 2
The pest that alkenes, chrysanthemum esters, carbamate insecticides develop immunity to drugs all has high sensitiveness, while has concurrently long-acting
Property (lasting period is generally 2~4 weeks, for up to 6 weeks), (dosage is low, and per hectare only needs tens grams of active ingredients just for high activity
Controllable pierce-suck type or pests with chewing mouthparts), environment friendly, finally, ethiprole is to many germs (such as pythium spp, Bai Ye
Blight bacterium) there is inhibitory action, and plant growth can be promoted.
The synthetic route of ethiprole mainly has following two：1. compound 5- amino -1- (2,6- dichlor-4-trifluoromethyls
Phenyl) -3- cyano pyrazoles, react generation compound 5- amino -1- (2,6- bis- chloro- 4- fluoroforms with trifluoromethyl sulphur chlorine first
Base phenyl) -3- cyano group -4- trifluoromethylthio pyrazoles, the latter aoxidizes to obtain product fluorine with hydrogen peroxide or metachloroperbenzoic acid again
Worm nitrile.In the route, trifluoromethyl sulphur chlorine toxicity is very high, and is gas, thus in commercial Application to operating condition requirement compared with
It is high.
Compound 5- amino -1- 2. (2,6- dichlor-4-trifluoromethyl phenyl) -3- cyano pyrazoles-first and sodium sulfocynanate
Progress thiocyanation reaction, generation 5- amino -1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- cyano group -4- thiocyanogens pyrazoles -, after
Person is condensed-two sulphur of generation 5- amino -1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- cyano pyrazole -4- bases under alkaline condition
Compound, disulphide under the existence condition of alkalescent and reducing agent, with bromotrifluoromethane react to obtain 5- amino -1- (2,
6- dichlor-4-trifluoromethyls phenyl) -3- cyano group -4- trifluoromethylthio pyrazoles, last oxidized step (hydrogen peroxide or m-chloro
Benzoyl hydroperoxide) obtain ethiprole.The route is the route industrially used at present, but operating procedure is longer, overall yield
Have much room for improvement.
Therefore, a kind of ethiprole preparation method easy to operate, product purity high income is developed to ask as urgently to be resolved hurrily
Topic.
The content of the invention
The present invention provides a kind of preparation method of ethiprole, and technique is simple, equipment is conventional, and product yield and purity is high, fits
Close industrialized production.
The technical proposal for solving the technical problem of the invention is：
Under the conditions of micro-vacuum, sequentially added into reaction kettle trifluoromethyl thionyl chloride, 5- Amino 3 cyanos -1- (2,
6- dichlor-4-trifluoromethyls phenyl) pyrazoles, catalyst trimethyl benzyl ammonia chloride and solvent dichloroethanes, at 35~45 DEG C
Reaction 1~2 it is small when after, again add trifluoromethyl thionyl chloride, finish continue insulation reaction 9~12 it is small when after, by reaction solution
It is added to the water, stratification, centrifugal filtration, filtrate is distilled to recover dichloroethanes recovery, and filter cake A adds mixed solvent
In, 85~90 DEG C are warming up to, is stirred to after being completely dissolved, crystallisation by cooling, is then centrifuged for separating, filter cake B drying ethiproles.
Under conditions of micro-vacuum, the product HCl gases in continuous extraction, contribute to being smoothed out for reaction, carry
The yield and speed of height reaction.Trifluoromethyl thionyl chloride is added portionwise, is disposably to add trifluoromethyl sulfurous in order to prevent
Acyl chlorides is run away with HCl gases, it is ensured that reaction yield.
Dichloroethanes has reaction raw materials good dissolubility as solvent, and byproduct hydrogen chloride gas is insoluble in molten
In agent dichloroethanes, hydrochloric acid will not be formed in reaction solution, so as to ensure that pH solves 5~7 in follow-up washing process.In addition, two
Chloroethanes can be preferably dissolved in atent solvent (such as hexane, benzene-like compounds), easy to be removed from product.
Preferably, the specific vacuum of the micro-vacuum is -0.1~-0.05Mpa.
Preferably, the trifluoromethyl thionyl chloride, 5- Amino 3 cyanos -1- (2,6- dichlor-4-trifluoromethyls
Phenyl) pyrazoles, trimethyl benzyl ammonia chloride and dichloroethanes mass ratio be 2.2~2.5：4.3~4.7：0.1：15~20.
Preferably, the filter cake A and the mass ratio of mixed solvent are 1：4~6.The dosage of mixed solvent is to recrystallization
Effect there is large effect, the dosage of mixed solvent is too low, it is impossible to which the ethiprole being completely dissolved in filter cake A, causes product
Loss；The dosage of mixed solvent is excessive, then during crystallisation by cooling, the speed that ethiprole separates out crystallization is excessively slow, even results in part fluorine
Worm nitrile cannot be fully crystallized precipitation, and product yield reduces.
Preferably, the mixed solvent is 1 by volume ratio：4~5 butyl acetate and toluene composition.
Preferably, the mixed solvent is 1 by volume ratio：2~4 n-hexane and toluene composition.
Recrystallization solvent is required to dissolved impurity, at high temperature at the same time can dissolved product, when the temperature decreases, ethiprole
Product separates out separation, and impurity remains dissolved in the mixed solvent.Due to ethiprole still have in toluene in lower temperature it is certain
Dissolubility, it is therefore desirable to other solvents (butyl acetate or n-hexane) are added, so that ethiprole is at low temperature in solvent
In dissolubility reduce, make its it is as much as possible separate out crystallization, increase the yield of product.In addition, recrystallized using mixed solvent
The ethiprole particle diameter of gained evenly, purity higher.
Mixed solvent is made of toluene and butyl acetate or toluene and n-hexane form, the effect of the content of toluene to crystallization
Fruit also has considerable influence, is mainly manifested in：The too high levels of toluene, then under low temperature ethiprole still have in the mixed solvent it is higher
Solubility, product yield reduce；The content of toluene is too low, then the effect unobvious of mixed solvent, and ethiprole yield is not high, and grain
Footpath skewness.
Preferably, the drying temperature of the filter cake B is 110~130 DEG C, when drying time is 8~12 small.
Preferably, the specific method of the crystallisation by cooling is：Be cooled to 0~5 DEG C, and keep the temperature standing 2~5 it is small when.
The temperature of decrease temperature crystalline has considerable influence to the purifying process of ethiprole, is mainly manifested in：Crystallization temperature is too low, then crystallization speed
Spend soon, formation crystal size is uneven, and the yield of ethiprole is not high；Crystallization temperature is excessive, then crystallization rate is excessively slow, influences to give birth to
Produce efficiency.
Beneficial effects of the present invention are：
1st, the present invention prepare ethiprole technique it is simple, it is easily operated, using mixed solvent recrystallize method purified fluorine
Worm nitrile, gained ethiprole yield, purity are high, and product cut size is evenly distributed.
2nd, organic solvent used in the present invention energy recovery, meets environmentally protective production requirement.
Embodiment
With reference to specific embodiment, the present invention is further described, but it is specific real not limit the invention to these
Apply mode.
Embodiment 1
Under the conditions of vacuum is the micro-vacuum of -0.1Mpa, 120kg trifluoromethyl thionyl is sequentially added into reaction kettle
Chlorine, 450kg 5- Amino 3 cyanos -1- (2,6- dichlor-4-trifluoromethyls phenyl) pyrazoles, 10kg catalyst trimethyl benzyl chlorine
Change ammonium and 1900kg solvent dichloroethanes, reacted at 40 DEG C 1.5 it is small when after, add 120kg trifluoromethyl thionyl chlorides, add
Enter follow-up continuous insulation reaction 10 it is small when after, reaction solution is added in 1000kg water, stratification, centrifugal filtration, filtrate distills back
Dichloroethanes recovery is received, 560kg filter cakes A is obtained and adds in 560kg butyl acetates and 2240kg toluene, be warming up to 85 DEG C,
Stirring to after being completely dissolved, be cooled to 0 DEG C, and keep the temperature standing 3 it is small when be then centrifuged for separating, filter cake B drying 450kg fluorine worms
Nitrile, the purity of ethiprole is 98% after measured, yield 88.4%.
Embodiment 2
Under the conditions of vacuum is the micro-vacuum of -0.08Mpa, 110kg trifluoromethyl sulfurous is sequentially added into reaction kettle
Acyl chlorides, 470kg 5- Amino 3 cyanos -1- (2,6- dichlor-4-trifluoromethyls phenyl) pyrazoles, 10kg catalyst trimethyl benzyls
Ammonium chloride and 1500kg solvent dichloroethanes, at 35 DEG C react 2 it is small when after, add 110kg trifluoromethyl thionyl chlorides, add
Enter follow-up continuous insulation reaction 9 it is small when after, by reaction solution add 1000kg water in, stratification, centrifugal filtration, filtrate be distilled to recover
Dichloroethanes recovery, obtains 548kg filter cakes A and adds in 360kg butyl acetates and 1832kg toluene, be warming up to 88 DEG C, stir
Mix to after being completely dissolved, be cooled to 2 DEG C, and keep the temperature standing 2 it is small when be then centrifuged for separating, filter cake B drying 443kg fluorine worms
Nitrile, the purity of ethiprole is 97.6% after measured, yield 90.3%.
Embodiment 3
Under the conditions of vacuum is the micro-vacuum of -0.05Mpa, 125kg trifluoromethyl sulfurous is sequentially added into reaction kettle
Acyl chlorides, 430kg 5- Amino 3 cyanos -1- (2,6- dichlor-4-trifluoromethyls phenyl) pyrazoles, 10kg catalyst trimethyl benzyls
Ammonium chloride and 2000kg solvent dichloroethanes, at 45 DEG C react 1 it is small when after, add 125kg trifluoromethyl thionyl chlorides, add
Enter follow-up continuous insulation reaction 12 it is small when after, reaction solution is added in 1000kg water, stratification, centrifugal filtration, filtrate distills back
Dichloroethanes recovery is received, 578kg filter cakes A is obtained and adds 867kg n-hexanes and 2601kg toluene, is warming up to 90 DEG C, stirring
To after being completely dissolved, be cooled to 5 DEG C, and keep the temperature standing 5 it is small when be then centrifuged for separating, filter cake B drying 458kg ethiproles,
The purity of ethiprole is 98.2% after measured, yield 89.7%.
Comparative example 1
Using operation same as Example 1 and raw material rate of charge, the difference is that the solvent of recrystallization selects equal quality
Toluene, is not mixed solvent, the purity of gained ethiprole is 92.1%, yield 76.8%.
Comparative example 2
Using operation same as Example 1 and raw material rate of charge, the difference is that the solvent of recrystallization uses 560kg ethanol
With 2240kg toluene, the purity of gained ethiprole is 90.7%, yield 78.3%.
Comparative example 3
Using operation same as Example 3 and raw material rate of charge, the difference is that the solvent of recrystallization uses 867kg positive penta
Alkane and 2601kg toluene, the purity of gained ethiprole is 91.4%, yield 76.9%.
In conclusion analysis is found：The made ethiprole purity of mixed solvent of the present invention and yield highest.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should all be included in the protection scope of the present invention.
Claims (8)
1. a kind of preparation method of high-purity ethiprole, it is characterised in that the preparation method is specially：In micro-vacuum condition
Under, trifluoromethyl thionyl chloride, 5- Amino 3 cyanos -1- are sequentially added into reaction kettle（2,6- dichlor-4-trifluoromethyl benzene
Base）Pyrazoles, catalyst trimethyl benzyl ammonia chloride and solvent dichloroethanes, at 35 ~ 45 DEG C react 1 ~ 2 it is small when after, again plus
Enter trifluoromethyl thionyl chloride, finish continue insulation reaction 9 ~ 12 it is small when after, reaction solution is added to the water, stratification, centrifuge
Filtering, filtrate are distilled to recover dichloroethanes recovery, and filter cake A adds in the mixed solvent, are warming up to 85 ~ 90 DEG C, stirring is extremely
After being completely dissolved, crystallisation by cooling, is then centrifuged for separating, filter cake B drying ethiproles.
2. the preparation method of high-purity ethiprole as claimed in claim 1, it is characterised in that the micro-vacuum it is specific true
Reciprocal of duty cycle is -0.1 ~ -0.05Mpa.
3. the preparation method of high-purity ethiprole as claimed in claim 1, it is characterised in that the trifluoromethyl thionyl
Chlorine, 5- Amino 3 cyanos -1-（2,6- dichlor-4-trifluoromethyl phenyl）Pyrazoles, trimethyl benzyl ammonia chloride and dichloroethanes
Mass ratio is 2.2 ~ 2.5：4.3~4.7：0.1：15~20.
4. the preparation method of high-purity ethiprole as claimed in claim 1, it is characterised in that the filter cake A is molten with mixing
The mass ratio of agent is 1：4~6.
5. the preparation method of the high-purity worm nitrile as described in claim 1 or 4, it is characterised in that the mixed solvent is by body
Product is than being 1：4 ~ 5 butyl acetate and toluene composition.
6. the preparation method of the high-purity ethiprole as described in claim 1 or 4, it is characterised in that the mixed solvent by
Volume ratio is 1：2 ~ 4 n-hexane and toluene composition.
7. the preparation method of high-purity ethiprole as claimed in claim 1, it is characterised in that the drying temperature of the filter cake B
Spend for 110 ~ 130 DEG C, when drying time is 8 ~ 12 small.
8. the preparation method of high-purity ethiprole as claimed in claim 1, it is characterised in that the crystallisation by cooling it is specific
Method is：Be cooled to 0 ~ 5 DEG C, and keep the temperature standing 2 ~ 5 it is small when.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110256352A (en) * | 2019-06-28 | 2019-09-20 | 常州沃腾化工科技有限公司 | A kind of preparation method of high-purity Fipronil |
| CN110845340A (en) * | 2019-11-07 | 2020-02-28 | 苏州开元民生科技股份有限公司 | Preparation method of fipronil intermediate |
| CN113825743A (en) * | 2019-03-19 | 2021-12-21 | 格哈达化工有限公司 | Method for synthesizing fipronil |
| CN114213330A (en) * | 2021-12-29 | 2022-03-22 | 天和药业股份有限公司 | Method for treating fipronil refining mother liquor |
| CN115353490A (en) * | 2022-09-26 | 2022-11-18 | 安徽美诺华药物化学有限公司 | Purification process of fipronil |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113825743A (en) * | 2019-03-19 | 2021-12-21 | 格哈达化工有限公司 | Method for synthesizing fipronil |
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| CN114213330A (en) * | 2021-12-29 | 2022-03-22 | 天和药业股份有限公司 | Method for treating fipronil refining mother liquor |
| CN115353490A (en) * | 2022-09-26 | 2022-11-18 | 安徽美诺华药物化学有限公司 | Purification process of fipronil |
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Application publication date: 20180427 |