CN103102308B - Method of preparing pyraoxystrobin - Google Patents
Method of preparing pyraoxystrobin Download PDFInfo
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- CN103102308B CN103102308B CN201110356701.5A CN201110356701A CN103102308B CN 103102308 B CN103102308 B CN 103102308B CN 201110356701 A CN201110356701 A CN 201110356701A CN 103102308 B CN103102308 B CN 103102308B
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Abstract
The invention discloses a method of preparing pyraoxystrobin. The method comprises preparing pyraoxystrobin (III) from 3-(4-chlorophenyl)-1-methyl-1H-5-pyrazole-ol (I) and (E)-2-(2-chloromethylphenyl)-3-methoxyacrylate (II) under alkaline conditions in a polar aprotic solvent; adding a proper amount of water into the reaction solution after the reaction, adding alkane, haloalkane, aromatic hydrocarbon, substituted aromatic or ether solvents to extract the pyraoxystrobin, distilling and separating the solvents to obtain crude pyraoxystrobin, and re-crystallizing the crude pyraoxystrobin in alcohol solvents to obtain the pyraoxystrobin. The preparation method provided by the invention is safe, economic and efficient, suitable for industrial production, mild in reaction condition, simple in post-processing method, good in product appearance, and relatively high in yield; and a content of the pyraoxystrobin is 97 % or more.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of method preparing azoles bacterium ester.
Background technology
Azoles bacterium ester (English popular name: Pyraoxystrobin; Chemical name: (E)-2-(2-((3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-pyrazoles-5-base oxygen) methyl) phenyl)-3-methoxy-methyl acrylate) be a kind of high-efficiency low-toxicity, the disinfectant use in agriculture that has a extensive future.Chinese patent CN 1657524A makes public for the first time azoles bacterium ester structure, preparation and biological activity thereof.The preparation method reported in this patent for: the azoles bacterium ester of structure as shown in formula III can react preparation in the basic conditions by (E)-2-(2-the chloromethyl phenyl)-3-methoxy-methyl acrylate shown in 3-(4-the chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol shown in formula I and formula II, and reaction formula is as follows:
After having reacted, adopt the column chromatography method of laboratory routine to obtain product, product is thick thing, places after fixing.Above-mentioned preparation method only can meet use for laboratory in sampling needs, is not suitable for expanding large-scale industrial production needs.So far, the method that relevant industrial industrial scale prepares azoles bacterium ester has no report.
Summary of the invention
The object of the present invention is to provide a kind of method preparing azoles bacterium ester of applicable suitability for industrialized production.
Technical scheme of the present invention is as follows:
A kind of method preparing azoles bacterium ester:
3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol (I) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (II) react in the basic conditions, in polar aprotic solvent, prepare azoles bacterium ester (III); After reaction terminates, in reaction solution, add appropriate water, then add alkane, halogenated alkane, aromatic hydrocarbons, substituted arene or ether solvent extraction azoles bacterium ester, fractionation by distillation solvent obtains the thick product of azoles bacterium ester; Thick product recrystallization in alcoholic solvent obtains azoles bacterium ester.
Reaction conditions of the present invention is as follows: the charged molar ratio of Compound I and Compound II per is (0.9-1.5): 1, is preferably (1.0-1.1): 1; The mol ratio of alkali add-on and Compound II per is (0.5-5): 1, preferably (0.8-2.5): 1; Temperature of reaction 45 DEG C-90 DEG C, preferably 55 DEG C-75 DEG C; Reaction times 1-8 hour, preferred 3.5-5.5 hour.HPLC follows the tracks of and determines reaction end.
On the pyrazole ring that there is Compound I in above-mentioned reaction on the carbon of 4 and 5 connect the carbon o-alkylation competition of the oxygen of hydroxyl, and the competition of this carbon o-alkylation is confirmed in concrete experiment.According to " soda acid soft or hard is theoretical ", more easily there is C-alkylation in this reaction in theory, is namely easy to generate by product.Therefore, from the angle being beneficial to o-alkylation, namely the angle that azoles bacterium ester generates is beneficial to, suitable polar aprotic solvent is selected from acetone, butanone, pentanone, acetonitrile, DMF, DMSO or METHYLPYRROLIDONE etc., also the solvent that above-mentioned two or more solvents arbitrarily mix with arbitrary proportion can be adopted, the mixed solvent of preferred DMSO, METHYLPYRROLIDONE or its arbitrary proportion.The add-on of solvent be those skilled in the art be familiar with.In experimental condition optimization process, find that the too high C-alkylation by product that will increase of temperature of reaction generates simultaneously; The temperature of reaction too low then reaction times is oversize, and reaction not exclusively, therefore determines temperature of reaction choosing and preferred reaction that the present invention is suitable for.The suitable alkali that reaction adopts is selected from comparatively safe, economical sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus conventional in suitability for industrialized production, preferred sodium carbonate or salt of wormwood.
Reaction terminates to add water and extraction agent in backward reaction solution, and its add-on is well-known to those skilled in the art.Extraction agent is selected from sherwood oil, hexanaphthene, methylene dichloride, 1,2-ethylene dichloride, benzene,toluene,xylene, chlorobenzene, ether or Isosorbide-5-Nitrae-dioxane; Preferred methylene dichloride, 1,2-ethylene dichloride, benzene or toluene.
Recrystallization alcoholic solvent used is selected from methyl alcohol, ethanol, Virahol, butanols, and its two or more mixed solvent of arbitrary proportion any.Solvent adding amount and the thick product weight of azoles bacterium ester are than being (0.5-20): 1, preferably (1-10): 1.Conveniently operating method is, adds in recrystallization solvent by the thick product of azoles bacterium ester, and stir temperature rising reflux and all dissolve to azoles bacterium ester, slightly lower the temperature and leach indissoluble impurity while hot, suitable temperature is 25 DEG C-65 DEG C, preferably 30 DEG C-60 DEG C; Then cooling (-10 DEG C to 20 DEG C, preferably-5 DEG C to 5 DEG C) makes azoles bacterium ester separate out completely as far as possible, filters and obtains azoles bacterium ester product.
Solvent involved in preparation method of the present invention all can recovery.Such as, aqueous reaction solvent is used as reaction solvent again by reclaiming after rectifying tower rectifying; Extraction agent Distillation recovery is used for next batch extracting operation; Can recovery after the alcoholic solvent distillation that recrystallization is used.
Compared with prior art, advantage of the present invention is as follows: reaction conditions is gentle, and post-treating method is simple and easy to do, economical and effective, be easy to suitability for industrialized production, and product appearance is good, yield is higher and content is greater than 97%.Of the present invention complete for scale operation azoles bacterium ester commercial prod provide a kind of safe, economical, effective, be applicable to the preparation method of suitability for industrialized production.
Should it is clear that, in claim limited range of the present invention, can various condition transformation and change be carried out.
Embodiment
Following examples result is used for further illustrating the present invention, but does not mean that restriction the present invention.In each embodiment, the operation prepared in reference DE 4417837 of Compound I is carried out, and the operation prepared in reference US 4723034 of Compound II per is carried out.
Embodiment 1
1). in the reaction flask of 250 milliliters, add 3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol 11.0 grams (50.0 mmole), (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate 12.6 grams (50.0 mmole), 7.6 grams, saleratus powder (75.2 mmole) and DMSO 20.0 grams successively, slowly be warming up to 73 DEG C, insulation reaction 4.5 hours between 70 DEG C-75 DEG C, reaction terminates.
2). reaction solution is cooled to 40 DEG C, adds water 100.0 grams wherein, with the azoles bacterium ester in toluene 120.0 grams of extractive reaction liquid, leaves standstill, layering.Separate upper strata azoles bacterium ester toluene solution, distillation separates toluene for next batch extracting operation, residuum is the thick product of azoles bacterium ester 23.0 grams, outward appearance is reddish-brown dope, content 67.1%, yield 74.8% (in (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate, lower same).The DMSO of bottom aqueous reclaims DMSO by rectifying tower, operates for next batch building-up reactions.
3). in the thick product of azoles bacterium ester, add ethanol 50.0 grams, temperature rising reflux 2 hours, be cooled to 60 DEG C of filtered while hot, filtrate is cooled to-2 DEG C to 0 DEG C again, filter, filter cake dries to obtain white powder azoles bacterium ester 13.3 grams, content 97.4%, fusing point 130-132 DEG C, yield 62.8% (in (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate, lower same).Filtrate distillation separates ethanol for next batch recrystallization operation.
Embodiment 2
1). in the reaction flask of 500 milliliters, add DMF 70.0 grams, 3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol 34.0 grams (155.0 mmole), powdered sodium carbonate 24.6 grams (229.7 mmole) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate 37.8 grams (150.0 mmole) successively, slowly be warming up to 70 DEG C, insulation reaction 5.0 hours between 68 DEG C-75 DEG C, reaction terminates.
2). reaction solution is cooled to 40 DEG C, adds 350.0 grams, water wherein, with the azoles bacterium ester in methylene dichloride 350.0 grams of extractive reaction liquid, leaves standstill, layering.Separate lower floor's azoles bacterium ester dichloromethane solution, distillation separates methylene dichloride for next batch extracting operation, and residuum is the thick product of azoles bacterium ester 67.8 grams, and outward appearance is reddish-brown dope, content 67.6%, yield 74.1%.Separate after the moisture DMF in upper strata separates qualified DMF by rectifying tower rectifying and operate for next batch building-up reactions.
3). in the thick product of azoles bacterium ester, add ethanol 120.0 grams, temperature rising reflux 2 hours, be cooled to 55 DEG C of filtered while hot, then filtrate is cooled to 0 DEG C-5 DEG C, filter, filter cake dries to obtain pale yellow powder shape azoles bacterium ester 38.1 grams, content 97.1%, yield 59.8%.Filtrate distillation separates ethanol for next batch recrystallization operation.
Embodiment 3
1). in the reaction flask of 500 milliliters, add DMSO 70.0 grams, 3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol 34.0 grams (155.0 mmole), 32.0 grams, Anhydrous potassium carbonate powder (229.5 mmole) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate 37.8 grams (150.0 mmole) successively, slowly be warming up to 70 DEG C, insulation reaction 4.5 hours between 68 DEG C-72 DEG C, reaction terminates.
2). reaction solution is cooled to 40 DEG C, adds 350.0 grams, water wherein, with the azoles bacterium ester in methylene dichloride 350.0 grams of extractive reaction liquid, leaves standstill, layering.Separate lower floor's azoles bacterium ester dichloromethane solution, distillation separates methylene dichloride for next batch extracting operation, and residuum is the thick product of azoles bacterium ester 68.2 grams, and outward appearance is reddish-brown dope, content 68.0%, yield 75.0%.The DMSO rectifying separation recovery that upper strata is moisture.
3). in the thick product of azoles bacterium ester, add methyl alcohol 180.0 grams, temperature rising reflux 2 hours, be cooled to 55 DEG C of filtered while hot, then filtrate is cooled to 0 DEG C-3 DEG C, filter, filter cake dries to obtain pale yellow powder shape azoles bacterium ester 38.9 grams, content 97.0%, yield 61.0%.Filtrate distillation separates methyl alcohol for next batch recrystallization operation.
Embodiment 4
1). in the reactor of 500 liters, add DMSO 70.0 kilograms, 3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol 34.0 kilograms (155.0 moles), 31.5 kilograms, Anhydrous potassium carbonate powder (225.9 moles) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate 37.8 kilograms (150.0 moles) successively, slowly be warming up to 70 DEG C, insulation reaction 5.0 hours between 70 DEG C-72 DEG C, reaction terminates.
2). reaction solution is cooled to 40 DEG C, adds 350.0 kilograms, water wherein, with 1, azoles bacterium ester in 2-ethylene dichloride 375.0 kilograms of extractive reaction liquid, concrete operations are same as embodiment 2, obtain the thick product of azoles bacterium ester 67.9 kilograms, outward appearance is reddish-brown dope, content 65.5%, yield 71.9%.Reclaim DMSO concrete operations and be same as embodiment 2.
3). in the thick product of azoles bacterium ester, add ethanol 120.0 kilograms and Virahol 60.0 kilograms, temperature rising reflux 2 hours, be cooled to 55 DEG C, press filtration while hot, after the filtrate obtained is cooled to 0 DEG C-5 DEG C filter, centrifugal, dry, obtain pale yellow powder shape azoles bacterium ester solid 38.7 kilograms, content 97.0%, yield 59.0%.Filtrate distillation separates ethanol and isopropanol mixture for next batch recrystallization operation.
Claims (1)
1. prepare a method for azoles bacterium ester, reaction formula is as follows:
Reacted in the basic conditions, in polar aprotic solvent by 3-(4-chloro-phenyl-)-1-methyl isophthalic acid H-5-pyrazoles alcohol (I) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (II), prepare azoles bacterium ester (III); After reaction terminates, in reaction solution, add appropriate water, then add alkane, halogenated alkane, aromatic hydrocarbons, substituted arene or ether extration agent extraction azoles bacterium ester, fractionation by distillation solvent obtains the thick product of azoles bacterium ester; Thick product recrystallization in alcoholic solvent obtains azoles bacterium ester;
Described Compound I and the charged molar ratio of Compound II per are 1.0-1.1:1; The mol ratio of alkali add-on and Compound II per is 0.8-2.5:1; Temperature of reaction 55 DEG C-75 DEG C; Reaction times 3.5-5.5 hour;
Described polar aprotic solvent is selected from the mixed solvent of DMSO, METHYLPYRROLIDONE or its arbitrary proportion;
Described extraction agent is selected from methylene dichloride, 1,2-ethylene dichloride, benzene or toluene;
Recrystallization alcoholic solvent used is selected from methyl alcohol, ethanol, Virahol, butanols, or its two or more mixed solvent of arbitrary proportion any; Recrystallization alcoholic solvent add-on used and the thick product weight of azoles bacterium ester are than being 1-10:1.
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Effective date of registration: 20160128 Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No. Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD. Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28 Patentee before: Sinochem Corporation Patentee before: Shenyang Research Institute of Chemical Industry |