CN114702455A - Environment-friendly production process of prothioconazole - Google Patents
Environment-friendly production process of prothioconazole Download PDFInfo
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- CN114702455A CN114702455A CN202210318310.2A CN202210318310A CN114702455A CN 114702455 A CN114702455 A CN 114702455A CN 202210318310 A CN202210318310 A CN 202210318310A CN 114702455 A CN114702455 A CN 114702455A
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- prothioconazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
Abstract
The invention relates to a prothioconazole green production process, which specifically comprises the following steps: adding butyrolactone, and dropping sulfonyl chloride while reducing the temperature to obtain chlorobutyrolactone; adding hydrochloric acid into a reaction kettle to obtain dichloropentanone; adding sodium hydroxide into a reaction kettle, dropwise adding dichloropentanone, and stirring to obtain chlorocyclopropane; adding chlorocyclopropane into a reaction kettle, dropwise adding sulfonyl chloride, and stirring to obtain chlorocyclopropyl ketone; adding magnesium, tetrahydrofuran and toluene into a reaction kettle, heating, dropwise adding o-chlorobenzyl chloride, stirring, hydrolyzing to obtain a Grignard compound, drying by using a solid drying agent, and performing rotary evaporation to obtain the intermediate compound; and dissolving the intermediate compound in an organic solvent, adding a reducing agent, precipitating crystals, and filtering to obtain the target compound prothioconazole. The invention has the advantages that: the process has high conversion rate and selectivity, cheap and easily obtained synthetic raw materials, mild and easily controlled reaction conditions, simple and convenient operation, easy product purification, reduced production cost and low three wastes, and conforms to the concept of green chemical industry.
Description
Technical Field
The invention relates to a process for green production of prothioconazole.
Background
Prothioconazole is a novel broad-spectrum triazolethione bactericide, is mainly used for preventing and treating a plurality of diseases of cereals, wheat and bean crops and the like, has low toxicity, no teratogenesis, mutation type, no toxicity to embryos and safety to people and environment. The mechanism of action is to inhibit the demethylation of lanosterol or 2, 4-methylenedihydrolanostane 14, which are precursors of sterols in fungi. However, the existing prothioconazole preparation process is not green enough, and how to provide a prothioconazole green production process becomes a research direction.
Disclosure of Invention
The invention aims to provide a prothioconazole green production process to solve the problems in the background technology.
In order to solve the technical problems, the technical scheme provided by the invention is as follows: a green production process of prothioconazole specifically comprises the following steps:
1) adding butyrolactone into a reaction kettle, cooling, dropwise adding sulfonyl chloride, and reacting for 4.5 hours to obtain chlorobutyrolactone;
2) adding hydrochloric acid into a reaction kettle, heating and dropwise adding the chlorobutyrolactone obtained in the step 1), and stirring for reaction for 2-5 hours to obtain dichloropentanone;
3) adding sodium hydroxide into a reaction kettle, dropwise adding the dichloropentanone obtained in the step 2), and stirring for reacting for 2 hours to obtain chlorocyclopropane;
4) adding the chlorocyclopropane obtained in the step 3) into a reaction kettle, dropwise adding sulfonyl chloride, and stirring for reacting for 1-2 hours to obtain chlorocyclopropyl ketone;
5) magnesium, tetrahydrofuran and toluene were mixed in a molar ratio of 1: 1: 1.2 adding the mixture into a reaction kettle, heating and dropwise adding o-chlorobenzyl chloride, dropwise adding the chloro-cyclopropyl ketone obtained in the step 4) after dropwise adding, stirring for reacting for 2 hours, and hydrolyzing to obtain a Grignard compound;
6) adding the Grignard compound obtained in the step 5) into a reaction kettle, heating to 20-100 ℃, adding 2- (1-chlorocyclopropyl) -3-chloro-1- (2-chlorophenyl) -2-propanol, cooling to room temperature after reaction, performing suction filtration, washing filtrate with saturated saline solution, extracting with ethyl acetate, washing organic phase with saturated saline solution, separating out organic phase, drying with a solid drying agent, and performing rotary evaporation to obtain the intermediate compound;
7) dissolving the intermediate compound in an organic solvent, adding a reducing agent, stirring and reacting at the reaction temperature of 20-60 ℃, recrystallizing, separating out crystals, and filtering to obtain the target compound prothioconazole.
As a preferable scheme, the molar ratio of butyrolactone to sulfonyl chloride in the step 1) is 1: 1.
as a preferable scheme, the molar ratio of the hydrochloric acid to the chlorobutyrolactone in the step 2) is 1: 1.
as a preferable scheme, the molar ratio of the sodium hydroxide to the dichloropentanone in the step 3) is 1.1: 1.
as a preferable scheme, the mole ratio of the chlorocyclopropane to the sulfonyl chloride in the step 4) is 1: 1
Preferably, the drying in step 6) is performed by using at least one of anhydrous sodium sulfate, anhydrous calcium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride and activated alumina as a solid drying agent.
Preferably, the organic solvent in step 7) is at least one of isopropanol, acetonitrile, methanol, ethanol and acetone.
As a preferable scheme, in the step 7), the reducing agent is at least one of sodium borohydride and lithium aluminum hydride.
The invention has the advantages that: the environment-friendly prothioconazole production process is high in process conversion rate and selectivity, cheap and easily-obtained in synthesis raw materials, mild and easily-controlled in reaction conditions, simple and convenient to operate, easy in product purification, low in production cost, low in three wastes and in line with the environment-friendly chemical concept.
Detailed Description
The invention is illustrated below by means of specific examples, without being restricted thereto.
Examples
A green production process of prothioconazole specifically comprises the following steps:
1) adding butyrolactone into a reaction kettle, cooling, dropwise adding sulfonyl chloride, and reacting for 4.5h to obtain chlorobutyrolactone;
2) adding hydrochloric acid into a reaction kettle, heating and dropwise adding the chlorobutyrolactone obtained in the step 1), and stirring to react for 2-5 hours to obtain dichloropentanone;
3) adding sodium hydroxide into a reaction kettle, dropwise adding the dichloropentanone obtained in the step 2), and stirring for reacting for 2 hours to obtain chlorocyclopropane;
4) adding the chlorocyclopropane obtained in the step 3) into a reaction kettle, dropwise adding sulfonyl chloride, and stirring for reacting for 1-2 hours to obtain chlorocyclopropyl ketone;
5) magnesium, tetrahydrofuran and toluene were mixed in a molar ratio of 1: 1: 1.2 adding the mixture into a reaction kettle, heating and dropwise adding o-chlorobenzyl chloride, dropwise adding the chloro-cyclopropyl ketone obtained in the step 4) after dropwise adding, stirring for reacting for 2 hours, and hydrolyzing to obtain a Grignard compound;
6) adding the Grignard compound obtained in the step 5) into a reaction kettle, heating to 20-100 ℃, adding 2- (1-chlorocyclopropyl) -3-chloro-1- (2-chlorophenyl) -2-propanol, cooling to room temperature after reaction, performing suction filtration, washing filtrate with saturated saline solution, extracting with ethyl acetate, washing organic phase with saturated saline solution, separating out organic phase, drying with a solid drying agent, and performing rotary evaporation to obtain the intermediate compound;
7) dissolving the intermediate compound in an organic solvent, adding a reducing agent, stirring and reacting at the reaction temperature of 20-60 ℃, recrystallizing, separating out crystals, and filtering to obtain the target compound prothioconazole.
As a preferred embodiment of this example, the molar ratio of butyrolactone to sulfonyl chloride in step 1) is 1: 1.
as a preferred embodiment of this embodiment, the molar ratio of hydrochloric acid to chlorobutyrolactone in step 2) is 1: 1.
as a preferred embodiment of this embodiment, the molar ratio of sodium hydroxide to dichloropentanone in step 3) is 1.1: 1.
as a preferred embodiment of this embodiment, the mole ratio of chlorocyclopropane and sulfonyl chloride in the step 4) is 1: 1
In a preferred embodiment of this embodiment, the drying in step 6) is performed by using at least one solid drying agent selected from anhydrous sodium sulfate, anhydrous calcium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride, and activated alumina.
As a preferred embodiment of this embodiment, the organic solvent in step 7) is at least one of isopropanol, acetonitrile, methanol, ethanol, and acetone.
As a preferred implementation manner of this embodiment, in the step 7), the reducing agent is at least one of sodium borohydride and lithium aluminum hydride.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (8)
1. The green production process of prothioconazole is characterized by comprising the following steps:
1) adding butyrolactone into a reaction kettle, cooling, dropwise adding sulfonyl chloride, and reacting for 4.5h to obtain chlorobutyrolactone;
2) adding hydrochloric acid into a reaction kettle, heating and dropwise adding the chlorobutyrolactone obtained in the step 1), and stirring to react for 2-5 hours to obtain dichloropentanone;
3) adding sodium hydroxide into a reaction kettle, dropwise adding the dichloropentanone obtained in the step 2), and stirring for reacting for 2 hours to obtain chlorine
Substituted cyclopropane;
4) adding the chlorocyclopropane obtained in the step 3) into a reaction kettle, dropwise adding sulfonyl chloride, and stirring for reacting for 1-2 hours to obtain chlorocyclopropyl ketone;
5) magnesium, tetrahydrofuran and toluene were mixed in a molar ratio of 1: 1: 1.2 adding into a reaction kettle, heating and dropwise adding o-chlorobenzyl chloride, dropwise adding
After the reaction is finished, dropwise adding the chloro-cyclopropyl-ketone obtained in the step 4), stirring for reacting for 2 hours, and hydrolyzing to obtain a Grignard compound;
6) adding the Grignard compound obtained in the step 5) into a reaction kettle, heating to 20-100 ℃, adding 2- (1-chlorocyclopropyl) -3-chloro-1- (2-chlorphenyl) -2-propanol, cooling to room temperature after reaction, performing suction filtration, washing filtrate with saturated saline solution, extracting with ethyl acetate,
washing the organic phase with saturated saline solution, separating the organic phase, drying with a solid drying agent, and performing rotary evaporation to obtain the intermediate compound;
7) dissolving the intermediate compound in an organic solvent, adding a reducing agent, stirring and reacting at the reaction temperature of 20-60 ℃, recrystallizing, separating out crystals, and filtering to obtain the target compound prothioconazole.
2. The process for the green production of prothioconazole according to claim 1, wherein the production process comprises the following steps: the molar ratio of butyrolactone to sulfonyl chloride in step 1) is 1: 1.
3. the process for the green production of prothioconazole according to claim 1, characterized in that: the molar ratio of the hydrochloric acid to the chlorobutyrolactone in the step 2) is 1: 1.
4. the process for the green production of prothioconazole according to claim 1, wherein the production process comprises the following steps: the molar ratio of sodium hydroxide to dichloropentanone in the step 3) is 1.1: 1.
5. the process for the green production of prothioconazole according to claim 1, characterized in that: the mol ratio of the chlorocyclopropane to the sulfonyl chloride in the step 4) is 1: 1.
6. the process for the green production of prothioconazole according to claim 1, wherein the production process comprises the following steps: and in the step 6), the solid drying agent is at least one of anhydrous sodium sulfate, anhydrous calcium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride and activated alumina.
7. The process for the green production of prothioconazole according to claim 1, wherein the production process comprises the following steps: the organic solvent in the step 7) is at least one of isopropanol, acetonitrile, methanol, ethanol and acetone.
8. The process for the green production of prothioconazole according to claim 1, wherein the production process comprises the following steps: the reducing agent in the step 7) is at least one of sodium borohydride and lithium aluminum hydride.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104292089A (en) * | 2014-09-30 | 2015-01-21 | 大连九信生物化工科技有限公司 | Synthetic process of 1-chloro-cyclopropanecarbonyl chloride |
| CN107043359A (en) * | 2017-05-31 | 2017-08-15 | 江苏七洲绿色化工股份有限公司 | A kind of preparation method of prothioconazoles intermediate |
| CN107473949A (en) * | 2017-09-26 | 2017-12-15 | 安徽国星生物化学有限公司 | A kind of synthesis technique of the pentanone of 3,5 dichloro 2 |
| CN107628928A (en) * | 2017-09-27 | 2018-01-26 | 长治市晋宁化工有限公司 | The preparation method of 2 (base of 1 chlorcyclopropane 1) 3 chlorine 1 (2 chlorphenyl) 2 propyl alcohol |
| CN108752283A (en) * | 2018-06-11 | 2018-11-06 | 江苏澄扬作物科技有限公司 | A kind of prothioconazoles new technique for synthesizing |
| CN110483243A (en) * | 2019-09-17 | 2019-11-22 | 西安近代化学研究所 | A kind of 1-(2- chlorphenyl) -2-(1- chlorine cyclopropyl) the chloro- 2- propyl alcohol of -3- preparation method |
-
2022
- 2022-03-29 CN CN202210318310.2A patent/CN114702455A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104292089A (en) * | 2014-09-30 | 2015-01-21 | 大连九信生物化工科技有限公司 | Synthetic process of 1-chloro-cyclopropanecarbonyl chloride |
| CN107043359A (en) * | 2017-05-31 | 2017-08-15 | 江苏七洲绿色化工股份有限公司 | A kind of preparation method of prothioconazoles intermediate |
| CN107473949A (en) * | 2017-09-26 | 2017-12-15 | 安徽国星生物化学有限公司 | A kind of synthesis technique of the pentanone of 3,5 dichloro 2 |
| CN107628928A (en) * | 2017-09-27 | 2018-01-26 | 长治市晋宁化工有限公司 | The preparation method of 2 (base of 1 chlorcyclopropane 1) 3 chlorine 1 (2 chlorphenyl) 2 propyl alcohol |
| CN108752283A (en) * | 2018-06-11 | 2018-11-06 | 江苏澄扬作物科技有限公司 | A kind of prothioconazoles new technique for synthesizing |
| CN110483243A (en) * | 2019-09-17 | 2019-11-22 | 西安近代化学研究所 | A kind of 1-(2- chlorphenyl) -2-(1- chlorine cyclopropyl) the chloro- 2- propyl alcohol of -3- preparation method |
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