CN109336848B - Tebuconazole intermediate and preparation method of tebuconazole - Google Patents
Tebuconazole intermediate and preparation method of tebuconazole Download PDFInfo
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- CN109336848B CN109336848B CN201811257664.0A CN201811257664A CN109336848B CN 109336848 B CN109336848 B CN 109336848B CN 201811257664 A CN201811257664 A CN 201811257664A CN 109336848 B CN109336848 B CN 109336848B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/08—Compounds containing oxirane rings with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals
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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
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Abstract
The invention relates to a tebuconazole intermediate and a preparation method thereof, which comprises the steps of adding 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, trimethyl thionyl chloride or trimethyl thionyl bromide, alkali and a solvent into a reactor, stirring and reacting to obtain the tebuconazole intermediate, wherein the structural formula of the tebuconazole intermediate is shown in the specification
Description
Technical Field
The invention particularly relates to a tebuconazole intermediate and a preparation method of tebuconazole.
Background
The 2- [ 2- (4-chlorphenyl) ethyl ] -2- (1, 1-dimethylethyl) oxirane is a key intermediate for synthesizing the pesticide tebuconazole, the tebuconazole is a triazole bactericidal pesticide with high efficiency, broad spectrum and systemic property, and has three functions of protection, treatment and eradication, wide bactericidal spectrum and long lasting period. The research finds that: tebuconazole, like all triazole fungicides, is able to inhibit the biosynthesis of fungal ergosterol. Tebuconazole is used as a seed treatment agent and foliar spray all over the world, has a wide bactericidal spectrum, and not only has high activity but also has a long lasting period. Tebuconazole is mainly used for preventing and treating various fungal diseases of crops such as wheat, rice, peanuts, vegetables, bananas, apples, pears, corn sorghum and the like, and is registered and widely applied to more than 60 crops in more than 50 countries all over the world. The product can be used for preventing and treating sclerotinia rot of colza, and has the effects of resisting lodging, increasing yield, inhibiting demethylation of ergosterol on cell membrane, and killing bacteria.
Many researches on synthesis of tebuconazole are carried out, the routes are basically the same, p-chloroformaldehyde is mostly used as an initial raw material, and the tebuconazole is prepared through steps of aldehyde-ketone condensation, catalytic hydrogenation, epoxidation reaction, addition reaction and the like, so that the preparation process still has many problems, the process period is long, three wastes are many, and the like, and great difficulty is brought to industrial production.
The structural formula of the 2- [ 2- (4-chlorphenyl) ethyl ] -2- (1, 1-dimethylethyl) oxirane is as follows
The intermediate is mature in generation process, and the traditional synthesis method is mainly characterized in that 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is used as a raw material and is prepared through epoxidation reaction, but dimethyl sulfide used in the reaction has low boiling point and large smell, and the generation loss is serious. Therefore, a more efficient and environment-friendly method for synthesizing 2- [ 2- (4-chlorophenyl) ethyl ] -2- (1, 1-dimethylethyl) oxirane is needed to be found, so that the generated smell is reduced, and meanwhile, the synthesis cost of tebuconazole is greatly reduced, so that great economic benefits are brought.
Disclosure of Invention
The invention aims to provide a tebuconazole intermediate with simple process and a preparation method of tebuconazole.
In order to solve the technical problems, the invention adopts the following technical scheme:
an object of the present invention is to provide a method for preparing tebuconazole intermediate, 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone (formula 1), trimethyl chloridized sulfinolAdding sulfone or trimethyl sulfoxide bromide, alkali and solvent into a reactor, stirring and reacting to obtain the tebuconazole intermediate, wherein the structural formula of the tebuconazole intermediate is shown in the specification
Preferably, the feeding molar ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the trimethyl thionyl chloride or thionyl bromide is 1: 1-3, and more preferably 1: 1-2.
Preferably, the charging molar ratio of the 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone to the base is 1: 0.5-3, and more preferably 1: 1-2.
Preferably, the feeding mass ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the solvent is 1: 0.5-10, and more preferably 1: 1-5.
Preferably, the reaction is carried out at 25-120 ℃, and more preferably at 30-50 ℃.
Preferably, the alkali is one or more of potassium hydroxide, sodium tert-butoxide, sodium amide and sodium hydride.
Preferably, the solvent is one or more of dimethyl sulfoxide (DMSO), N-Dimethylformamide (DMF), N-methylpyrrolidone (NMP) and Tetrahydrofuran (THF).
The invention also aims to provide a preparation method of tebuconazole, which is characterized in that triazole salt is added into a reaction system prepared by the preparation method of the tebuconazole intermediate, and the tebuconazole (formula 3) is prepared by reaction at 110-130 ℃.
The tebuconazole is prepared by a two-step one-pot method, the tebuconazole intermediate does not need to be subjected to separate post-treatment, and the operation is simple and convenient.
Preferably, the feeding molar ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the triazole salt is 1: 0.9-2.
Preferably, the triazole salt is added in the form of triazole sodium or triazole potassium, or in the form of triazole, potassium hydroxide or sodium hydroxide.
Preferably, after the reaction is finished, desolventizing, adding methylcyclohexane, then washing with water, layering, recrystallizing, filtering with suction, and drying to obtain the tebuconazole.
The reaction equation of the invention is as follows:
due to the implementation of the technical scheme, compared with the prior art, the invention has the following advantages:
the preparation method is a new route for synthesizing tebuconazole, has the advantages of relatively simple process, easily obtained raw materials, relatively low toxicity of reagents and medicines used in the operation process, mild reaction conditions, short time, simpler operation compared with the conventional method and higher total yield, so the preparation method has the advantages of greatly low synthesis cost, less three wastes and high content of target products, and is very suitable for industrial production.
Detailed Description
The present invention will be described in further detail with reference to specific examples. It is to be understood that these embodiments are provided to illustrate the basic principles, essential features and advantages of the present invention, and the present invention is not limited by the following embodiments. The implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not indicated are generally the conditions in routine experiments.
Example 1
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 100g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 45g of triazole sodium, reacting at 120 ℃, completing the reaction, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 127g of tebuconazole, wherein the yield is 90% and the purity is 97%.
Example 2
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 300g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 45g of triazole sodium, reacting at 120 ℃, after the reaction is finished, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 128.5g of tebuconazole, wherein the yield is 91%, and the purity is 97%.
Example 3
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 100g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 40g of triazole sodium, reacting at 120 ℃, completing the reaction, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 126g of tebuconazole, wherein the yield is 90%, and the purity is 98%.
Example 4
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 86g of trimethyl sulfoxide chloride, 38g of potassium hydroxide and 100g of dimethyl sulfoxide (DMSO) into a reaction bottle provided with a stirrer, a thermometer and a condenser after nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 45g of triazole sodium, reacting at 120 ℃, after the reaction is finished, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 130g of tebuconazole, wherein the yield is 90% and the purity is 95%.
Example 5
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 100g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 60g of triazole sodium, reacting at 120 ℃, after the reaction is finished, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 130g of tebuconazole, wherein the yield is 91%, and the purity is 96%.
Example 6
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 500g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 45g of triazole sodium, reacting at 120 ℃, after the reaction is finished, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 125g of tebuconazole, wherein the yield is 89%, and the purity is 98%.
Comparative example 1
Adding 100g of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, 63g of trimethyl sulfoxide chloride, 28g of potassium hydroxide and 30g of dimethyl sulfoxide (DMSO) into a reaction bottle which is provided with a stirrer, a thermometer and a condenser and subjected to nitrogen replacement, stirring, reacting at 40 ℃ until the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is completely reacted, adding 45g of triazole sodium, reacting at 120 ℃, after the reaction is finished, desolventizing, adding 100g of methylcyclohexane, washing with 30g of water, layering at 70 ℃, separating water, recrystallizing at 25 ℃, performing suction filtration, and drying to obtain 121g of tebuconazole, wherein the yield is 85%, and the purity is 96%.
The above embodiments are merely illustrative of the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the invention, and not to limit the scope of the invention, and all equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of the present invention.
Claims (4)
1. A preparation method of tebuconazole is characterized by comprising the following steps: adding 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, trimethyl thionyl chloride or trimethyl sulphoxide bromide, alkali and solvent into a reactor, stirring for reaction to obtain a tebuconazole intermediate, and adding the tebuconazole intermediate into the reactorAdding triazole salt into the reaction system, and reacting at 110-130 ℃ to obtain tebuconazole; the structural formula of the tebuconazole intermediate is shown in the specification
The feeding molar ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the trimethyl thionyl chloride or thionyl bromide is 1: 1-3; the feeding molar ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the alkali is 1: 0.5-3; the solvent is dimethyl sulfoxide, the feeding mass ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the solvent is 1: 1-5, and the reaction of the tebuconazole intermediate is carried out at 25-40 ℃; the alkali is potassium hydroxide.
2. The process for the preparation of tebuconazole according to claim 1, characterized in that: the feeding molar ratio of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone to the triazole salt is 1: 0.9-2.
3. The process for the preparation of tebuconazole according to claim 1, characterized in that: the triazole salt is fed in the form of sodium triazole or potassium triazole.
4. The process for the preparation of tebuconazole according to claim 1, characterized in that: and after the reaction is finished, desolventizing, adding methylcyclohexane, and then washing, layering, recrystallizing, filtering and drying to obtain the tebuconazole.
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| CN117143934A (en) * | 2023-07-18 | 2023-12-01 | 常州大学 | Method for preparing (R) -tebuconazole by enzyme chemical method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4632999A (en) * | 1983-04-29 | 1986-12-30 | Bayer Aktiengesellschaft | Process for the preparation of oxiranes |
| CN102491959A (en) * | 2011-12-19 | 2012-06-13 | 江苏澄扬作物科技有限公司 | Preparation method of oxirane derivative |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4632999A (en) * | 1983-04-29 | 1986-12-30 | Bayer Aktiengesellschaft | Process for the preparation of oxiranes |
| CN102491959A (en) * | 2011-12-19 | 2012-06-13 | 江苏澄扬作物科技有限公司 | Preparation method of oxirane derivative |
Non-Patent Citations (1)
| Title |
|---|
| 环氧化反应在医药、农药合成中的应用;王宇;《中国优秀博硕士学位论文全文数据库 工程科技I辑》;20030915(第03期);第B014-18页 * |
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