CN101591284B - Method for preparing chlorfenapyr and analog thereof - Google Patents
Method for preparing chlorfenapyr and analog thereof Download PDFInfo
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- CN101591284B CN101591284B CN 200910043790 CN200910043790A CN101591284B CN 101591284 B CN101591284 B CN 101591284B CN 200910043790 CN200910043790 CN 200910043790 CN 200910043790 A CN200910043790 A CN 200910043790A CN 101591284 B CN101591284 B CN 101591284B
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- alkali
- bromothalonil
- analogue
- bromo
- chloro
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- 0 *OC[n](c(C(F)(F)F)c1Br)c(-c(cc2)ccc2Cl)c1C#N Chemical compound *OC[n](c(C(F)(F)F)c1Br)c(-c(cc2)ccc2Cl)c1C#N 0.000 description 1
- MUULRWGTEBNRSH-UHFFFAOYSA-N CCOCOC[n](c(C(F)(F)F)c1Br)c(-c(cc2)ccc2Cl)c1C#N Chemical compound CCOCOC[n](c(C(F)(F)F)c1Br)c(-c(cc2)ccc2Cl)c1C#N MUULRWGTEBNRSH-UHFFFAOYSA-N 0.000 description 1
- XNFIRYXKTXAHAC-UHFFFAOYSA-N N#Cc1c(-c(cc2)ccc2Cl)[nH]c(C(F)(F)F)c1Br Chemical compound N#Cc1c(-c(cc2)ccc2Cl)[nH]c(C(F)(F)F)c1Br XNFIRYXKTXAHAC-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing chlorfenapyr and analog thereof by using 4-bromo-2-(4-chlorphenyl)-5-trifluoromethylpyrrole-3-nitrile and chloromethyl ether as raw materials in the presence of ketones solvent and inorganic alkali acid-binding agent. The chemical reaction formula is as picture. The method for synthesizing the chlorfenapyr and the analog thereof by adopting the ketonessolvent and the inorganic alkali acid-binding agent has the advantages of simple process, mild reaction condition, low production cost and the like, and has good industrial application prospect.
Description
Technical field
The present invention relates to the preparation method of a kind of bromothalonil and analogue thereof, especially, in the presence of ketones solvent and mineral alkali acid binding agent, prepare the method for bromothalonil and analogue thereof by being raw material with 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile.
Background technology
Bromothalonil, have another name called eliminate, Chlorfenapyr, chemical name 4-bromo-2-(4-chloro-phenyl-)-1-(ethoxyl methyl)-5-trifluoromethyl pyrpole-3-nitrile, chemical structural formula is:
Bromothalonil is a kind of new type heterocycle class desinsection of being succeeded in developing by American Cyanamid Company, kills mite, nematocides.Bromothalonil has advantages such as desinsection speed is fast, insecticidal spectrum is wide, and control is thorough, and the period is long.Test for many years through the land for growing field crops and practical application shows, 70 various pests in the orders such as lepidopteran, Homoptera, Coleoptera all there is fabulous preventive effect, especially to special efficacys such as the small cabbage moth in the vegetables resistant insect, beet armyworm, prodenia litura, Americal rice leaf miner, the wild snout moth's larva of beans, thrips, red spiders.
The new compound HNPC-A3061 chemical name with insecticidal activity of Hunan Chemical Research Institute's initiative is: 4-bromo-2-(4-chloro-phenyl-)-1-[2-(chloroethoxy) methyl]-5-trifluoromethyl pyrpole-3-nitrile, chemical structural formula is:
The new compound HNPC-A3108 chemical name with insecticidal activity of Hunan Chemical Research Institute's initiative is: methyl 4-bromo-2-(4-chloro-phenyl-)-1-[(oxyethyl group methoxy base)]-5-trifluoromethyl pyrpole-3-nitrile, chemical structural formula is:
HNPC-A3061 and HNPC-A3108 are the analogues of bromothalonil, have similar chemical structure and use advantage.
The method of synthetic bromothalonil is more, is raw material with 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile mostly, is prepared under the acid binding agent effect.As Journal of Organic Chemistry, 49 (1) p.203 (1984), US 5151536 to introduce with hydrogen sodium be acid binding agent; US5010098 then is acid binding agent with the sodium tert-butoxide; But these acid binding agents are comparatively expensive, and certain danger is arranged, and the solvent for use tetrahydrofuran (THF) is also somewhat expensive, and the rate of recovery is not high yet.US5359090 is that acid binding agent, toluene etc. are solvent with the triethylamine, has solved foregoing problems preferably, is production method commonly used at present, and its deficiency is that the triethylamine that adds the alkali recovery can not directly be applied mechanically, and still needs through dehydration or rectifying.
The inventor is surprised to find that adopting ketones solvent, mineral alkali is that acid binding agent can carry out the preparation of bromothalonil and analogue thereof economical, convenient, with high yield in the industrialized processes of series compound such as research bromothalonil analogue HNPC-A3061.
Summary of the invention
The purpose of this invention is to provide with 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile and monochloromethyl-ether is raw material, is acid binding agent with the mineral alkali, is the method that reaction solvent prepares bromothalonil and analogue thereof with the ketones solvent.Reaction formula of the present invention is:
In the above-claimed cpd 1 and 2, R is C
1-C
4Alkyl and haloalkane alkyl, especially ethyl, 2-chloroethyl, chloromethyl.
Concrete preparation method of the present invention comprises the steps: 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile and mineral alkali acid binding agent are joined in the ketones solvent, after the dissolving, add monochloromethyl-ether, temperature reaction after monitoring reaction is intact, is reduced under the room temperature and is added entry, transfer PH＜7 with dilute hydrochloric acid or dilute sulphuric acid, layering, precipitation gets former medicine.Former medicine can further be purified.
In the above-mentioned steps, monochloromethyl-ether can be chloromethyl ethyl ether or chloromethyl chloroethyl ether, chloromethyl monochloromethyl-ether etc.;
In the above-mentioned steps, mineral alkali is alkali-metal oxyhydroxide, oxide compound, carbonate, supercarbonate, phosphoric acid hydrogen disalt, phosphoric acid salt, preferably sodium hydroxide, potassium hydroxide, salt of wormwood, Sodium phosphate dibasic.The mineral alkali consumption is 1～3 times of raw material 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile weight;
In the above-mentioned steps, ketones solvent is C
3--C
6Alkane ketone and naphthenone, preferably butanone, hexone and pimelinketone, the ketones solvent consumption is 1～10 times of raw material 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile weight;
In the above-mentioned steps, 40～120 ℃ of temperature of reaction, 1～8 hour reaction times;
In the above-mentioned steps, the solvent of former medicine purification usefulness is to be used for recrystallization after any one and the water in methyl alcohol, ethanol, Virahol, the trimethyl carbinol is mixed.
Advantage of the present invention: adopt synthetic bromothalonil of ketones solvent and mineral alkali acid binding agent and analogue thereof, have advantages such as technology is simple, reaction conditions is gentle, reaction yield is high, production cost is low, have better industrial application prospect.
Below the invention will be further described with embodiment, but the present invention is not limited to following examples, under the scope of described aim, changes and implement to be included in the technical scope of the present invention before and after not breaking away from.
Embodiment
Embodiment 1
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 8 gram sodium hydroxide, 200ml methyl-isobutyl methyl ketone in the there-necked flask, stirred 20 minutes, drip 20 gram chloromethyl ethyl ethers, be warming up to 60 ℃, and under this temperature, reacted 2 hours sampling monitoring, react completely, reduce under the room temperature, add 200ml water, transfer PH＜7 with 10% dilute hydrochloric acid, layering, precipitation, drying gets the former medicine of 45.0 gram bromothalonils.Content 90%, yield 99%.In the material behind precipitation, the trimethyl carbinol that adds 150ml80% carries out recrystallization, gets the former medicine of bromothalonil of 38 grams 98%.
Embodiment 2
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 12 gram potassium hydroxide, 200ml methyl-isobutyl methyl ketone in the there-necked flask, stirred 20 minutes, drip 20 gram chloromethyl chloroethyl ethers, be warming up to 55 ℃, and under this temperature, reacted 1 hour sampling monitoring, react completely, reduce under the room temperature, add 200ml water, transfer PH to 5 with 10% dilute hydrochloric acid, layering, precipitation adds the ethyl alcohol recrystallization of 150ml 80%, the former medicine of HNPC-A3061 of 42.0 gram content 98%.
Embodiment 3
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 9 gram sodium hydroxide, 200ml pimelinketone in the there-necked flask, stirred 20 minutes, drip 20 gram chloromethyl chloroethyl ethers, be warming up to 40 ℃, and under this temperature, reacted 3 hours, sampling monitoring reacts completely, reduce under the room temperature, add 200ml water, transfer PH to 5, layering with 10% dilute hydrochloric acid, precipitation, the recrystallizing methanol that adds 150ml 80% gets the former medicine of HNPC-A3061.
Embodiment 4
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 20 gram Sodium phosphate dibasics, 200ml methyl-isobutyl methyl ketone in the there-necked flask, stirred 20 minutes, be warming up to 100 ℃, drip 20 gram chloromethyl chloroethyl ethers, and under this temperature, reacted 3 hours, reduce under the room temperature, add 200ml water, transfer PH to 5, layering with 10% dilute sulphuric acid, precipitation gets the former medicine of HNPC-A3061.
Embodiment 5
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 20 gram salt of wormwood, 200ml butanone in the there-necked flask, stirred 20 minutes, be warming up to backflow, drip 20 gram chloromethyl chloroethyl ethers, and under this temperature, reacted sampling monitoring, transformation efficiency 99% 8 hours.
Embodiment 6
Add 35 gram 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitriles, 20 gram salt of wormwood, 400ml methyl-isobutyl methyl ketone in the there-necked flask, be decompressed to the 20mmHg dehydration under stirring, slough 200ml methyl-isobutyl methyl ketone again, be cooled to room temperature, drip 18 gram chloromethyl monochloromethyl-ethers, be warming up to 55 ℃, and under this temperature, reacted 1 hour, sampling monitoring is after having reacted, add 20 gram sodium ethylates, back flow reaction 1 hour.Reduce under the room temperature, add 200ml water, transfer PH to 5 with 10% dilute hydrochloric acid, layering, precipitation adds the Virahol recrystallization of 150ml 80%, the 40.0 former medicines of HN PC-A3108 that restrain content 90%.
Claims (3)
1. the preparation method of bromothalonil and analogue thereof, it is characterized in that with 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile and monochloromethyl-ether be raw material, with the mineral alkali is acid binding agent, is that reaction solvent prepares bromothalonil and analogue thereof with the ketones solvent, and its chemical equation is:
R in formula 1 compound and formula 2 compounds is meant C
1-C
4Alkyl or C
1-C
4The haloalkane alkyl;
The concrete operations step is that 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile and mineral alkali acid binding agent are joined in the ketones solvent, after the dissolving, add monochloromethyl-ether, temperature reaction after monitoring reaction is intact, is reduced under the room temperature and is added entry, transfer PH＜7 with dilute hydrochloric acid or dilute sulphuric acid, layering, precipitation gets bromothalonil and the former medicine of analogue; Described mineral alkali acid binding agent is alkali-metal oxyhydroxide or alkali-metal oxide compound, alkali-metal carbonate, phosphoric acid hydrogen disalt, and mineral alkali acid binding agent consumption is 1～3 times of 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile weight; Described ketones solvent is C
3--C
6Alkane ketone or C
3--C
6Naphthenone, C
3--C
6Alkane ketone or C
3--C
6Naphthenone is meant butanone or hexone, pimelinketone, and the ketones solvent consumption is 1～10 times of 4-bromo-2-(4-chloro-phenyl-)-5-trifluoromethyl pyrpole-3-nitrile weight; Any one and the water back that is mixed is carried out recrystallization to it and is purified in former medicinal solvent methyl alcohol of bromothalonil that makes and analogue or ethanol, Virahol, the trimethyl carbinol.
2. according to the preparation method of described a kind of bromothalonil of claim 1 and analogue thereof, it is characterized in that C
1-C
4Alkyl or C
1-C
4The haloalkane alkyl is ethyl or 2-chloroethyl, chloromethyl.
3. according to the preparation method of described a kind of bromothalonil of claim 1 and analogue thereof, it is characterized in that alkali-metal oxyhydroxide or alkali-metal oxide compound, alkali-metal carbonate, phosphoric acid hydrogen disalt are meant sodium hydroxide or potassium hydroxide, salt of wormwood, Sodium phosphate dibasic.
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| CN 200910043790 CN101591284B (en) | 2009-06-29 | 2009-06-29 | Method for preparing chlorfenapyr and analog thereof |
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Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432517A (en) * | 2011-11-30 | 2012-05-02 | 山东亿嘉农化有限公司 | Method for producing chlorfenapyr raw material pesticide |
| CN102731363B (en) * | 2011-12-15 | 2013-09-25 | 青岛农业大学 | Pyrrole pesticide compounds |
| CN102617439A (en) * | 2012-02-27 | 2012-08-01 | 山东潍坊双星农药有限公司 | Preparation method of chlorfenapyr |
| CN104016899A (en) * | 2014-05-16 | 2014-09-03 | 浙江师范大学 | Synthetic method for chlorfenapyr |
| CN105949126B (en) * | 2016-05-24 | 2018-10-23 | 湖南化工研究院有限公司 | The preparation method of fipronil derivative |
| AU2016259360B1 (en) * | 2016-11-16 | 2017-09-07 | Rotam Agrochem International Company Limited | A novel crystalline form of chlorfenapyr, a process for its preparation and use of the same |
| CN108976157A (en) * | 2018-09-13 | 2018-12-11 | 天津市天地创智科技发展有限公司 | chlorfenapyr crystal form II and preparation method thereof |
| CN109438315A (en) * | 2018-11-14 | 2019-03-08 | 江苏宝众宝达药业有限公司 | A kind of preparation method of capillary |
| CN110041312B (en) * | 2019-05-28 | 2021-12-31 | 贵州省茶叶研究所 | Bromopyrrole nitrile dimer and preparation method and application thereof |
| CN110218170A (en) * | 2019-07-03 | 2019-09-10 | 山东潍坊双星农药有限公司 | A kind of mixed catalyst catalyzes and synthesizes the production technology of capillary |
| CN115536568B (en) * | 2021-06-30 | 2024-05-17 | 湖南化工研究院有限公司 | Method for continuously synthesizing chlorfenapyr |
| CN114436932A (en) * | 2022-01-12 | 2022-05-06 | 山东潍坊双星农药有限公司 | Synthetic process of chlorfenapyr homolog |
| CN115286551A (en) * | 2022-04-15 | 2022-11-04 | 陕西美邦药业集团股份有限公司 | Preparation method of chlorfenapyr and analogue thereof |
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