CN107353255A - A kind of synthetic method of azoxystrobin intermediate - Google Patents
A kind of synthetic method of azoxystrobin intermediate Download PDFInfo
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- CN107353255A CN107353255A CN201710515427.9A CN201710515427A CN107353255A CN 107353255 A CN107353255 A CN 107353255A CN 201710515427 A CN201710515427 A CN 201710515427A CN 107353255 A CN107353255 A CN 107353255A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/10—Process efficiency
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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Abstract
The invention discloses a kind of synthetic method of azoxystrobin intermediate.The present invention is operated, one kettle way obtains condensation product in high yield first using benzofuranone, trimethyl orthoformate and aceticanhydride as raw material by reactive distillation；Again by condensation product in the methanol solution of sodium methoxide, and 2,6 dichloro pyrimidine one pot reactions；Reaction terminates rear acid adjustment, reclaim methanol, the reaction of catalyst p-methyl benzenesulfonic acid is added after alkali cleaning, in crude product after concentration, obtains intermediate (E) 2 [2 (the base epoxide of 6 chlorine pyrimidine 4) phenyl] 3 methoxy-methyl acrylates of kresoxim-methyl.The inventive method is simple to operate, and high income, accessory substance is few, is adapted to industrialized production.
Description
Technical field
The invention belongs to chemical products production technical field, is related to a kind of synthetic method of pesticide intermediate, specifically relates to
A kind of and synthetic method of azoxystrobin intermediate.
Background technology
Fluoxastrobin has a very wide range of fungicidal spectrum, can be to almost all of fungal disease such as powdery mildew, rust, black star
Disease, downy mildew, rice blast etc. have fabulous activity, and early application typically occurs in protectiveness processing or disease, and to crop
Plantation influences little；Efficient bactericidal effect is that its central factor Fluoxastrobin won has well with excellent economic benefit
Physicochemical property, various preparations can be prepared into, including：Wettable powder, water dispersible granules, suspending agent etc..(E)-2-[2-(6-
Chlorine pyrimidine-4-yl epoxide) phenyl] -3- methoxy-methyl acrylates be its most critical intermediate, structure is such as shown in (I):
The compound mainly has two kinds of synthetic routes：
The first synthetic route (ep0242081), it is the first esterification using o-hydroxy phenylacetic acid as reactant, recycles benzyl
Base protection phenolic hydroxyl group is converted into 2- benzyloxies methyl phenylacetate, carries out formylation reaction, methylation reaction again, most afterwards through deprotection
Reaction synthesis (E) -3- methoxyl groups -2- (2- hydroxy phenyls)-methyl acrylate, is then closed with 4,6- dichloro pyrimidines, condensation reaction
Into as shown in formula (2).
Not only step is more for the route, and cumbersome total recovery is very low, and cost is also relative to higher, so this route discomfort
Share in industrialized production.
Second of synthetic route is using o-hydroxy phenylacetic acid as raw material, benzofuran -2 (3H) -one is obtained after dehydration condensation, so
React to obtain condensation product 3- (methoxyl groups of α mono-) methene benzofuran -2 (3H) -one with trimethyl orthoformate and aceticanhydride afterwards, be condensed
Thing obtains intermediate (I) (E) -2- [2- (6- chlorine pyrimidine-4-yls epoxide) phenyl] -3- first with the reaction synthesis of 4,6- dichloro pyrimidines again
Epoxide methyl acrylate, specifically as shown in formula (3).
The route synthetic method is more, as United States Patent (USP) us5847138 reports benzofuranone and trimethyl orthoformate
Reaction, by oil water separator, receives the methyl phenylacetate of low boiling, is dissolved by substantial amounts of dichloromethane, washes, and concentrates methanol
Crystallization obtains condensation product, then is reacted in the presence of sodium methoxide with methanol esterification, is reacted afterwards with 4,6- dichloro pyrimidines, in catalyst sulphur
Under potassium hydrogen phthalate, high-temperature vacuum is reset to obtain intermediate (I).Dong Jie, (fine-chemical intermediate, 2007,37 (2), 25-27) is waited,
By one pot process, low boiling substance is separated by oil water separator, obtains condensation product, without processing directly with 4 after molten contracting,
6- dichloro pyrimidines react, and under catalyst sulfuric acid hydrogen potassium, high-temperature vacuum is reset to obtain intermediate (I).This method water-oil separating
Device, many trimethyl orthoformates and aceticanhydride are entrained with, cause the reaction of raw material benzofuranone endless, influence yield and cost, under
The single step reaction time is oversize, and adding potassium acid sulfate needs high vacuum and high-temperature, and this causes to have the impurity of height boiling to produce, and influences to produce
The problems such as purity and yield of product.
The content of the invention
For above-mentioned technical problem of the prior art, it is an object of the invention to provide a kind of new azoxystrobin intermediate
Synthetic method；The azoxystrobin intermediate synthetic method of the present invention will solve cumbersome miscellaneous in the prior art, and byproduct is more, receive
The low technical problem of rate.
Technical scheme is specifically described as follows.
A kind of synthetic method of azoxystrobin intermediate, is comprised the following steps that：
1) benzofuranone, trimethyl orthoformate and aceticanhydride are mixed, band rectifier unit carries out distillation reaction, and reaction terminates
Afterwards, it is evaporated under reduced pressure and obtains condensation product 3- (α-methoxyl group)-methylenebenzofuran -2 (3 hydrogen) -one；
2) condensation product for obtaining step 1) is in methyl alcohol, anti-with 2,6- dichloro pyrimidine one kettle ways under sodium methoxide effect
Should, after reaction terminates, alkali lye is washed again for acid adjustment, recycling design, and catalyst is added in the crude product after concentration, in 80-90 DEG C of temperature
Under reacted, obtain intermediate (E) -2- [2- (6- chlorine pyrimidine-4-yls epoxide) phenyl] -3- methoxy acrylic acids of kresoxim-methyl
Methyl esters；Wherein：The catalyst is p-methyl benzenesulfonic acid.
In the present invention, in step 1), band rectifier unit carries out distillation reaction and referred on reaction bulb, plus 20-40 centimetres
Long rectifying column, rectifying column packing glass spring or ceramic material.
In the present invention, in step 2), the reaction temperature of one kettle way is 20-25 DEG C.
The reaction equation of present invention synthesis azoxystrobin intermediate (I) is as follows：
Compared to the prior art, the beneficial effects of the present invention are：
The present invention by the method for rectification process, reduces the loss of raw material, promotes reaction to carry completely using device is changed
In high yield, cost reduces；Step 2) uses one pot reaction, and operation simplifies；Catalyst is made using p-methyl benzenesulfonic acid, reduces reaction
Temperature, yield is improved, the yield of step 2) of the present invention is more than 80%.
Embodiment
In order that those skilled in the art more fully understand the present invention, the present invention is done furtherly by the following examples
It is bright, but these embodiments are not limit the scope of the invention.
Embodiment 1
Benzofuranone 400g (2.98mol) trimethyl orthoformate 600g (5.66mol) and vinegar are added in four-hole boiling flask
Acid anhydride 670ml, and plus the rectifying column of a root long 20cm on bottleneck, filler is glass spring, progress distillation reaction, in reaction bulb
Temperature is slowly raised to 95-100 DEG C, and heat up about 2-3h, is incubated about 10h.During the course of the reaction, reaction is distilled out by rectifying column
The low boiling methyl acetate of generation, and the raw materials such as trimethyl orthoformate and the aceticanhydride of entrainment are reduced, slightly cooling is evaporated under reduced pressure to 100
DEG C, 1h is extracted again after not going out liquid, adds toluene stirring and dissolving, without processing directly using (quantitative yield in next step
96.5%).
488g 2,6- dichloro pyrimidines are added in four-hole boiling flask, add 900ml toluene, add the condensation product of previous step
Toluene solution, the 650g of 30% sodium methoxide is added dropwise, slowly titration, controls 20-25 DEG C of the temperature of reaction, react follow-up continuation of insurance temperature and stir
Mix, HPLC reaction monitorings.After reaction terminates, acid adjustment, methanol is recovered under reduced pressure, adds dilute sulfuric acid aqueous solution washing layering, add 4%
Sodium hydrate aqueous solution 1000g, heating washing layering, oil reservoir concentration add 5g Catalyzed by p-Toluenesulfonic Acid agent, 80-90 DEG C, protected
Warm 3h, toluene is added, add 4% sodium hydrate aqueous solution 500g washings, oil reservoir is concentrated to give intermediate (I).HPLC contents
95.6%, yield 82.3%.
Embodiment 2
Benzofuranone 400g (2.98mol) trimethyl orthoformate 505g (4.76mol) and vinegar are added in four-hole boiling flask
Acid anhydride 600ml, and plus the rectifying column of a root long 40cm on bottleneck, filler is ceramic packing, progress distillation reaction, in reaction bulb
Temperature is slowly raised to 95-100 DEG C, and heat up about 2-3h, is incubated about 10h.During the course of the reaction, reaction is distilled out by rectifying column
The low boiling methyl acetate of generation, and the raw materials such as trimethyl orthoformate and the aceticanhydride of entrainment are reduced, slightly cooling is evaporated under reduced pressure to 100
DEG C, 1h is extracted again after not going out liquid, adds toluene stirring and dissolving, without processing directly using (quantitative yield in next step
93.3%).
488g 2,6- dichloro pyrimidines are added in four-hole boiling flask, add 900ml toluene, add the condensation product of previous step
Toluene solution, the 650g of 30% sodium methoxide is added dropwise, slowly titration, controls 20-25 DEG C of the temperature of reaction, react follow-up continuation of insurance temperature and stir
Mix, HPLC reaction monitorings.After reaction terminates, acid adjustment, methanol is recovered under reduced pressure, adds dilute sulfuric acid aqueous solution washing layering, add 4%
Sodium hydrate aqueous solution 1000g, heating washing layering, oil reservoir concentration add 5g Catalyzed by p-Toluenesulfonic Acid agent, 80-90 DEG C, protected
Warm 3h, toluene is added, add 4% sodium hydrate aqueous solution 500g washings, oil reservoir is concentrated to give intermediate (I).HPLC contents
95.1%, yield 80.4%.
Claims (3)
1. a kind of synthetic method of azoxystrobin intermediate, it is characterised in that comprise the following steps that：
1) benzofuranone, trimethyl orthoformate and aceticanhydride being mixed, band rectifier unit carries out distillation reaction, after reaction terminates,
Vacuum distillation obtains condensation product 3- (α-methoxyl group)-methylenebenzofuran -2 (3 hydrogen) -one；
2) condensation product for obtaining step 1) in methyl alcohol, sodium methoxide effect under with 2,6- dichloro pyrimidine one pot reactions, instead
After should terminating, alkali lye is washed again for acid adjustment, recycling design, and catalyst is added in the crude product after concentration, is carried out at a temperature of 80-90 DEG C
Reaction, obtains intermediate (E) -2- [2- (6- chlorine pyrimidine-4-yls epoxide) phenyl] -3- methoxy-methyl acrylates of kresoxim-methyl；
Wherein：The catalyst is p-methyl benzenesulfonic acid.
2. synthetic method according to claim 1, it is characterised in that in step 1), band rectifier unit carries out distillation reaction
Refer on reaction bulb, plus the rectifying column of 20-40 centimeter lengths, rectifying column packing glass spring or ceramic material.
3. synthetic method according to claim 1, it is characterised in that in step 2), the reaction temperature of one kettle way is 20-25
℃。
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| CN201710515427.9A CN107353255A (en) | 2017-06-29 | 2017-06-29 | A kind of synthetic method of azoxystrobin intermediate |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776326A (en) * | 2019-01-24 | 2019-05-21 | 安徽广信农化股份有限公司 | A kind of synthesis technology of azoxystrobin intermediate |
| CN115557901A (en) * | 2022-10-21 | 2023-01-03 | 湖北有宜新材料科技有限公司 | Efficient production method of pyrimidofuranone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1062139A (en) * | 1990-11-16 | 1992-06-24 | 帝国化学工业公司 | The method for preparing phenoxyprimidine compounds |
| CN102417498A (en) * | 2011-08-24 | 2012-04-18 | 重庆紫光化工股份有限公司 | Synthetic method of 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone |
| CN102942543A (en) * | 2012-11-08 | 2013-02-27 | 重庆紫光化工股份有限公司 | Preparation method for 3-(Alpha-methoxy)methylenebenzofuran-2(3h)-one |
-
2017
- 2017-06-29 CN CN201710515427.9A patent/CN107353255A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1062139A (en) * | 1990-11-16 | 1992-06-24 | 帝国化学工业公司 | The method for preparing phenoxyprimidine compounds |
| CN102417498A (en) * | 2011-08-24 | 2012-04-18 | 重庆紫光化工股份有限公司 | Synthetic method of 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone |
| CN102942543A (en) * | 2012-11-08 | 2013-02-27 | 重庆紫光化工股份有限公司 | Preparation method for 3-(Alpha-methoxy)methylenebenzofuran-2(3h)-one |
Non-Patent Citations (2)
| Title |
|---|
| 杨朋: "杀菌剂嘧菌酯的合成和工艺优化", 《中国优秀硕士学位论文全文数据库，工程科技I辑》 * |
| 董捷等: "嘧菌酯的合成", 《精细化工中间体》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776326A (en) * | 2019-01-24 | 2019-05-21 | 安徽广信农化股份有限公司 | A kind of synthesis technology of azoxystrobin intermediate |
| CN115557901A (en) * | 2022-10-21 | 2023-01-03 | 湖北有宜新材料科技有限公司 | Efficient production method of pyrimidofuranone |
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