CN112301064A - Preparation method of dextro-cis-dichlorochrysanthemic acid - Google Patents
Preparation method of dextro-cis-dichlorochrysanthemic acid Download PDFInfo
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- CN112301064A CN112301064A CN201910686825.6A CN201910686825A CN112301064A CN 112301064 A CN112301064 A CN 112301064A CN 201910686825 A CN201910686825 A CN 201910686825A CN 112301064 A CN112301064 A CN 112301064A
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- cis
- esterase
- dichlorochrysanthemic
- dextro
- dichlorochrysanthemic acid
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
Abstract
The invention discloses a preparation method of dextro-cis-dichlorochrysanthemic acid, which comprises the step of selectively hydrolyzing racemic dichlorochrysanthemic acid ester in an aqueous solution in the presence of a biocatalyst esterase to obtain dextro-cis-dichlorochrysanthemic acid with ee value of more than 99%. The invention improves single hydrolysis selectivity of racemic dichlorochrysanthemate by selecting proper esterase, and the ee value of the finally obtained dextro-cis-dichlorochrysanthemic acid is more than 99 percent, so that the method can be directly used for producing various sanitary or agricultural pyrethroid products, avoids the steps of crystallization and purification of intermediates with low ee value and the like, and simplifies the production process.
Description
Technical Field
The invention relates to a preparation method of dextrorotatory cis-dichlorochrysanthemic acid, in particular to a method for preparing chiral dextrorotatory cis-dichlorochrysanthemic acid by using a biological resolution method.
Background
Dichlorochrysanthemic acid (also known as DV chrysanthemic acid, English name Permethrinic acid), 2-dimethyl-3- (2, 2-dichlorovinyl) cyclopropane carboxylic acid, is an important intermediate for synthesizing part of agricultural pyrethroid pesticide acid. The structure is as follows:
because two chiral carbon atoms exist on a cyclopropane ring, the levorotatory and dextrorotatory configurations exist, and the cis-trans isomers are added, so that the dichlorochrysanthemic acid has four isomers in total.
Uses the biological enzyme to catalyze the selective hydrolysis of dichlorochrysanthemic acid ester to prepare the dextro-cis-dichlorochrysanthemic acid, so far, no literature report is found,
in the traditional chemical resolution method, the ee value of the obtained dextro-cis-dichlorochrysanthemic acid is generally low, and the obtained dextro-cis-dichlorochrysanthemic acid cannot be directly used for synthesizing pyrethroid products, other chemical or physical crystallization and purification processes are required to improve the ee value, the manufacturing steps are increased, and the practical applicability of production is low. And the sources of chemical resolving agents are increasingly deficient, and the reasons of large pollution in the production process are gradually eliminated, so that research and development of an economic and simple biocatalytic resolution method for preparing the D-cis-dichlorochrysanthemic acid become a new important way.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a preparation method of dextro-cis-dichlorochrysanthemic acid aiming at the defects in the prior art, and the dextro-cis-dichlorochrysanthemic acid is prepared by a novel biological enzyme resolution method.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of dextro-cis-dichlorochrysanthemic acid comprises the following steps: in water solution, racemic dichlorochrysanthemic acid ester is hydrolyzed selectively in the presence of biological catalyst esterase to obtain dextro cis-dichlorochrysanthemic acid with ee value greater than 99%.
In the technical scheme, the racemized dichlorochrysanthemic acid ester is any one of methyl dichlorochrysanthemic acid, ethyl dichlorochrysanthemic acid, n-propyl dichlorochrysanthemic acid or isopropyl dichlorochrysanthemic acid with the self-made cis-trans ratio of 95/5-30/70.
In the technical scheme, the mass concentration of the racemic dichlorochrysanthemate in the aqueous solution is 1-20%.
In the technical scheme, the mass of the biocatalyst esterase is 0.1-1% of the mass of the racemic dichlorochrysanthemate.
In the technical scheme, the aqueous solution is any one of pure water, ammonia water, an aqueous solution of organic amine with the carbon atom number less than 4 and an aqueous solution of inorganic base.
In the technical scheme, the mass concentration of the solute in the aqueous solution of ammonia water, the aqueous solution of organic amine with the carbon atom number less than 4 and the aqueous solution of inorganic base is 0.1-10%.
In the technical scheme, the organic amine with the carbon atom number less than 4 is any one or a mixture of two or more of monomethylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine and diisopropylamine.
In the technical scheme, the inorganic base is any one or a mixture of two or more of sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate.
In the technical scheme, the biocatalyst esterase is an esterase commercialized by Sigma company in the United states: any one or a mixture of two or more of CEYR205 esterase, CEYR215 esterase, CEYR225 esterase and CEYR235 esterase.
In the technical scheme, the hydrolysis is carried out at the reaction temperature of 20-60 ℃ for 6-60 h.
The technical scheme of the invention has the advantages that: by selecting a specific buffer system, the biological environment of esterase is changed, the single hydrolysis selectivity of racemic dichlorochrysanthemic acid ester is improved, the ee value of the finally obtained dextrorotatory cis-dichlorochrysanthemic acid is more than 99 percent, the dextrorotatory cis-dichlorochrysanthemic acid can be directly used for the production and the manufacture of various sanitary or agricultural pyrethroid products, the steps of crystallization, purification and the like of an intermediate with low ee value are avoided, and the production process is simplified; the invention has the advantages that the chrysanthemic acid resolution enzyme is esterase obtained by carrying out gene mutagenesis and engineering modification on natural straw bacteria and solidifying, the use process is convenient, the recovery and the reutilization are facilitated, the production cost is lower, for example, EYR type enzyme commercialized by Sigma company in America is ensured, the source of the catalyst is further ensured, and the foundation is laid for the final industrial scale production.
In addition, according to the technical scheme of the invention, only the dichlorochrysanthemic acid ester with the cis-configuration is selectively split and hydrolyzed, when the raw material is cis-trans mixed dichlorochrysanthemic acid ester, the cis-dichlorochrysanthemic acid ester is split and hydrolyzed to obtain dextrorotatory cis-dichlorochrysanthemic acid with a high ee value, and the trans-dichlorochrysanthemic acid ester is not reacted or is in an ester state and can be separated and recovered through post-treatment. Therefore, the cis-inverse ratio of the dichlorochrysanthemate which is put into reaction can be unlimited, but in consideration of the practicability of industrial production, the dichlorochrysanthemate which is in the cis-inverse ratio of 95/5-30/70 is actually used as the raw material to be resolved, and the dichlorochrysanthemate with higher cis-trans isomer content is preferably used as the raw material by first carrying out fractional crystallization separation on cis-trans isomers.
Detailed Description
The following detailed description of the embodiments of the present invention is provided, but the present invention is not limited to the following descriptions:
example 1
A method for preparing dextro-cis-dichlorochrysanthemic acid comprises the following steps: 200g of methyl dichlorochrysanthemate (cis/trans-50/50), 1000g of water and 1g of CEYR205 esterase (Sigma in America) are put into a 1000ml four-mouth bottle, stirred and reacted for 48 hours at 40 ℃, 10% sodium hydroxide is used for regulating the pH of a system of 4-8 in the reaction process, an oil-water layer is separated after the reaction is finished (the enzyme is recovered by centrifugal separation or ultrafiltration membrane separation and raw materials are recycled), the pH of the system is regulated to 2 by splitting the water layer, solvent toluene is added for extracting an organic phase, the solvent is removed by exsolution of an extract liquid, about 44.7g of the needed product dextro-cis dichlorochrysanthemic acid is obtained, the analysis content of a gas chromatographic column is 99.52%, and the analysis content of dextro-cis capillary is 99.21% by the.
Example 2
A method for preparing dextro-cis-dichlorochrysanthemic acid comprises the following steps: 200g of ethyl dichlorochrysanthemate (cis/trans-70/30), 1000g of water and 1g of CEYR205 esterase (Sigma in America) are put into a 1000ml four-mouth bottle, stirred and reacted for 48 hours at 40 ℃, 10% sodium hydroxide is used for regulating the pH of a system of 4-8 in the reaction process, an oil-water layer is separated from the reaction product in the same example 1 after the reaction is finished, the water layer is acidified, extracted and desolventized to obtain about 58.8g of dextro-cis-dichlorochrysanthemic acid, the content of the dextro-cis-dichlorochrysanthemic acid is 99.42% by gas chromatography capillary column analysis, and the content of the dextro-cis-.
Example 3
A method for preparing dextro-cis-dichlorochrysanthemic acid comprises the following steps: 200g of methyl dichlorochrysanthemate (cis/trans-80/20), 1000g of 1% ammonia water and 1g of CEYR205 esterase (Sigma in America) are put into a 1000ml four-mouth bottle, stirred and reacted for 48 hours at 40 ℃, an oil-water layer is separated after the reaction is finished in the same way as in example 1, about 71.3g of dextro-cis-dichlorochrysanthemic acid is obtained by acidification, extraction and desolventization of the water layer, the content of the dextro-cis-dichlorochrysanthemic acid is 99.43% by gas chromatography capillary column analysis, and the content of the dextro-cis-isomer is 99.09% by.
Example 4
A method for preparing dextro-cis-dichlorochrysanthemic acid comprises the following steps: 200g of methyl dichlorochrysanthemate (cis/trans-50/50), 1000g of 3% sodium carbonate aqueous solution and 1g of CEYR205 esterase (Sigma in America) are put into a 1000ml four-mouth bottle, stirred and reacted at 40 ℃ for 48 hours, an oil-water layer is separated after the reaction is finished in the same example 1, about 44.6g of dextro-cis dichlorochrysanthemic acid is obtained by acidification, extraction and desolventization of the water layer, the content of the dextro-cis dichlorochrysanthemic acid is 99.53% by gas chromatography capillary column analysis, and the content of the dextro-cis isomer is 99.19% by gas chromatography chiral column.
Example 5
A method for preparing dextro-cis-dichlorochrysanthemic acid comprises the following steps: 200g of methyl dichlorochrysanthemate (cis/trans-40/60), 1000g of 3% potassium carbonate aqueous solution and 1g of CEYR205 esterase (Sigma in America) are put into a 1000ml four-mouth bottle, stirred and reacted at 40 ℃ for 48 hours, after the reaction is finished, an oil-water layer is separated from the mixture obtained in the same example 1, and after the water layer is acidified, extracted and desolventized, about 35.5g of dextro-cis dichlorochrysanthemic acid is obtained, the content of the dextro-cis-dichlorochrysanthemic acid is 99.39% by gas chromatography capillary column analysis and the content of the dextro-cis-isomer is 99.
The above examples are only for illustrating the technical concept and features of the present invention, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. A preparation method of dextro-cis-dichlorochrysanthemic acid is characterized by comprising the following steps: in water solution, racemic dichlorochrysanthemic acid ester is hydrolyzed selectively in the presence of biological catalyst esterase to obtain dextro cis-dichlorochrysanthemic acid with ee value greater than 99%.
2. The method of claim 1, wherein: the racemic dichlorochrysanthemic acid ester is any one of methyl dichlorochrysanthemic acid, ethyl dichlorochrysanthemic acid, n-propyl dichlorochrysanthemic acid or isopropyl dichlorochrysanthemic acid with the cis-trans ratio of 95/5-30/70.
3. The method of claim 1, wherein: the mass concentration of the racemic dichlorochrysanthemate in the water solution is 1-20%.
4. The method of claim 1, wherein: the mass of the biocatalyst esterase is 0.1-1% of the mass of the racemic dichlorochrysanthemate.
5. The method of claim 1, wherein: the water solution is any one of pure water, ammonia water, an organic amine water solution with the carbon atom number less than 4 and an inorganic base water solution.
6. The method of claim 1, wherein: the mass concentration of solute in the ammonia water, the water solution of organic amine with the carbon atom number less than 4 and the water solution of inorganic base is 0.1-10%.
7. The method of claim 1, wherein: the organic amine with the carbon atom number less than 4 is any one or a mixture of two or more of monomethylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine and diisopropylamine.
8. The method of claim 1, wherein: the inorganic base is any one or a mixture of two or more of sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate.
9. The method of claim 1, wherein: the biocatalyst esterase is an esterase commercialized by American Sigma company: any one or a mixture of two or more of CEYR205 esterase, CEYR215 esterase, CEYR225 esterase and CEYR235 esterase.
10. The method of claim 1, wherein: the hydrolysis is carried out at the reaction temperature of 20-60 ℃ for 6-60 h.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108486170A (en) * | 2018-03-12 | 2018-09-04 | 江苏扬农化工股份有限公司 | A kind of preparation method of d-trans dichlor chrysanthemic acid |
| CN108486171A (en) * | 2018-03-12 | 2018-09-04 | 江苏扬农化工股份有限公司 | A kind of preparation method of the first chrysanthemumic acid of d-trans |
| CN112301065A (en) * | 2019-07-29 | 2021-02-02 | 江苏扬农化工股份有限公司 | Preparation method of dextro-cis-first chrysanthemic acid |
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2019
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108486170A (en) * | 2018-03-12 | 2018-09-04 | 江苏扬农化工股份有限公司 | A kind of preparation method of d-trans dichlor chrysanthemic acid |
| CN108486171A (en) * | 2018-03-12 | 2018-09-04 | 江苏扬农化工股份有限公司 | A kind of preparation method of the first chrysanthemumic acid of d-trans |
| CN112301065A (en) * | 2019-07-29 | 2021-02-02 | 江苏扬农化工股份有限公司 | Preparation method of dextro-cis-first chrysanthemic acid |
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Application publication date: 20210202 |