CN114105876A - Method for preparing pyrazoxyfen-ethyl intermediate - Google Patents
Method for preparing pyrazoxyfen-ethyl intermediate Download PDFInfo
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- CN114105876A CN114105876A CN202111489875.9A CN202111489875A CN114105876A CN 114105876 A CN114105876 A CN 114105876A CN 202111489875 A CN202111489875 A CN 202111489875A CN 114105876 A CN114105876 A CN 114105876A
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- ethyl
- ethiazole
- pyrazole ester
- nitrile intermediate
- acaricidal
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to chemical synthesis, in particular to a method for preparing an ethiprole intermediate (3-methyl-1-ethyl-1H-pyrazole-5-ethyl formate). Adding an acid-binding agent and a catalyst into pyrazole ester under the condition of a solvent, introducing halogenated ethane gas into the system, and reacting until the system is qualified to obtain an ethyl substance. The invention uses the halogenated ethane to replace diethyl sulfate for ethylation reaction, the reaction raw materials are cheap and easy to obtain, the process of post-treatment by water is cancelled, the discharge of COD is directly reduced from the process source, and the reaction period is greatly reduced.
Description
Technical Field
The invention relates to chemical synthesis, in particular to a method for preparing an ethiprole intermediate (3-methyl-1-ethyl-1H-pyrazole-5-ethyl formate).
Background
Chlorfenapyr (Experimental code SYP-9625) belongs to a novel acrylonitrile acaricide, and mainly kills mites through contact poisoning and stomach poisoning. The chemical name of the compound is (Z) -2- (p-tert-butylphenyl) -2-cyano-1- (1-ethyl-3-methylpyrazole-5-yl) pivaloyloxyethylene, the original drug is a white solid, the melting point is 92-93 ℃, the compound is easily soluble in dimethylformamide, acetonitrile, acetone, methanol, ethyl acetate, dichloromethane and the like, and the compound is soluble in petroleum ether and heptane and is hardly soluble in water. The preparation is 30% suspending agent, is a white flowable viscous liquid in appearance, has the density of 1.0739g/cm3(20 ℃), the pH value of 5.0-8.0, the flash point of more than 93 ℃, and is non-explosive and non-corrosive.
The conventional method for preparing the ethaboxam nitrile is to obtain a target product by taking diethyl oxalate as a starting material and carrying out 6-step reaction, wherein in step 4, the pyrazole ester and diethyl sulfate are subjected to ethylation reaction, hydrogen on the ortho-position nitrogen of the carboxylic acid ethyl ester on a pyrazole ring is replaced by ethyl of the diethyl sulfate to obtain a crude ethyl product, and the ethyl product is washed by sodium carbonate and distilled and rectified to obtain the ethyl product.
According to related patent CN1626520A, (examples C-D), this patent describes the use of dimethyl sulfate as a methylation reaction, pyrazole ester and dimethyl sulfate in a dichloromethane system, reaction for 4 hours at 40 ℃ for 4 hours, cooling, washing with water, sodium bicarbonate, and sodium chloride to obtain crude ethyl product. The yield of the product obtained by the reaction is 55-60%.
The above patent protects both methylation reaction and ethylation reaction, and uses diethyl sulfate, one of which is ethyl of diethyl sulfate to replace hydrogen on pyrazole ring in pyrazole ester, to carry out ethylation reaction to obtain ethyl product, but has some defects, one of which is excessive, the separation operation from the system is complex, and the other is reaction to generate by-product ethyl hydrogen sulfate, which will be present in waste water in large amount in the subsequent separation process, resulting in high COD in waste water and poor biodegradability. Further, in the process of synthesizing ethyl compound, the problems of simplifying operation, reducing waste water discharge and the like need to be solved.
Disclosure of Invention
The invention aims to provide a method for preparing an ethiprole intermediate (3-methyl-1-ethyl-1H-pyrazole-5-ethyl formate) which is simple to operate and environment-friendly.
In order to achieve the purpose, the invention adopts the technical scheme that:
a method for preparing an ethiazole acarid nitrile intermediate has a reaction formula
Adding an acid-binding agent and a catalyst into pyrazole ester under the condition of a solvent, introducing halogenated ethane gas into the system, and reacting until the system is qualified to obtain an ethyl substance.
The halogenated ethane is chloroethane, bromoethane or iodoethane; wherein the molar ratio of the pyrazole ester to the halogenated ethane is 1:1-1: 10.
Preferably, the halogenated ethane is ethyl chloride or ethyl bromide; wherein the molar ratio of the pyrazole ester to the halogenated ethane is 1:1-1: 3.
and heating the pyrazole ester to 95-98 ℃ in an ethanol solution of pyrazole ester, and removing ethanol under reduced pressure for later use.
The solvent is one or more of DMF, DMSO, toluene, ethanol, n-hexane and cyclohexane; wherein the mass ratio of the pyrazole ester to the solvent is 1:1-1: 5.
Preferably, the solvent is DMF, DMSO or toluene.
The catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium sulfate, tetrabutylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride; wherein the mass ratio of the pyrazole ester to the catalyst is 1: 0.5-1: 1%.
The acid-binding agent is one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, solid sodium hydroxide, solid potassium hydroxide, sodium amide, sodium methoxide and sodium ethoxide; wherein the mass ratio of the pyrazole ester to the acid-binding agent is 1:1-1: 2.
Preferably, the acid-binding agent is sodium carbonate, potassium carbonate or sodium bicarbonate.
And filtering and removing the collected supernatant (removing the residual acid-binding agent and the byproduct halide) after the ethylation reaction, heating, evaporating the solvent under reduced pressure (reducing the pressure to-83 kPa, heating for desolventizing, and evaporating the solvent to 130 ℃) to obtain the ethyl extract crude extract.
Slightly cooling the ethyl extract crude extract, changing distillation into rectification, adjusting the vacuum degree of the system to-97.5 kPa, rectifying to 147.5 ℃, and rectifying to obtain the ethyl extract.
The reaction principle of the invention is as follows: the invention uses halogenated ethane, especially chloroethane to replace diethyl sulfate, to carry out ethylation reaction with pyrazole ester, the boiling point of chloroethane is 12.7 ℃, the reaction is gas-liquid reaction at normal temperature, and chloroethane gas is slowly inserted into the liquid phase until the ethylation reaction is finished.
The invention has the advantages that:
the invention uses halogenated ethane (especially chloroethane gas) to replace diethyl sulfate for ethylation reaction, the reaction raw materials are cheap and easy to obtain, the process of water post-treatment is cancelled, the discharge of COD is directly reduced from the process source, and the reaction period is greatly reduced. Meanwhile, the method can realize industrialized application, because the operations such as hydrolysis, delamination and the like are reduced, only filtration and distillation are carried out, the production period is reduced by 14 hours/batch, and COD reduces the emission of 2 tons/ton of ethyl substances.
Detailed Description
The following examples are presented to further illustrate embodiments of the present invention, and it should be understood that the embodiments described herein are for purposes of illustration and explanation only and are not intended to limit the invention.
The method uses halogenated ethane, particularly chloroethane to replace diethyl sulfate, uses ethyl of chloroethane to replace hydrogen on a pyrazole ring in pyrazole ester, and performs ethylation reaction to obtain an ethyl substance.
Example 1
Taking 268.9g of pyrazole ester ethanol solution (the quantitative content of pyrazole ester in the pyrazole ester ethanol solution is 13.39%), heating to 98 ℃, distilling the ethanol under reduced pressure to 98 ℃/-98kPa, stopping distillation, slightly cooling, dropwise adding 50g of DMF and 0.3 g of catalyst (TBAB (tetrabutylammonium bromide)) into the system while the solution is hot, cooling to 40 ℃, adding 50g of sodium carbonate solid, heating to 70 ℃, starting bottom plugging and introducing chloroethane gas, wherein the aeration flow is 25g/h, and analyzing that the content of the pyrazole ester is less than or equal to 3.5% as a raw material to be qualified after introducing for 5 hours. After the analysis is qualified, cooling and filtering to obtain mother liquor, namely DMF solution of the ethyl substance;
heating the mother liquor, carrying out vacuum desolventizing to 130 ℃/-83kPa, slightly cooling to 100 ℃, improving the vacuum degree, continuing vacuum rectification, stopping rectification until 147.5 ℃/-97.5kPa, distilling to obtain 37.2 g of ethyl (the isomers of the ethyl are not distilled out, but are left in a bottle). The reaction yield of the step is 86.0 percent, and the content of ethyl substances is 98.5 percent.
Example 2
Taking 268.9g of pyrazole ester ethanol solution (the quantitative content is 13.39%), heating to 98 ℃, distilling the ethanol under reduced pressure until 98 ℃/-98kPa, stopping distillation, dropwise adding 50g of DMF and 0.3 g of catalyst into the system while the solution is hot, cooling to 40 ℃, adding 50g of sodium carbonate solid, heating to 70 ℃, dropwise adding 50g of bromoethane, completing dropwise adding within 2 hours, and analyzing that the content of the pyrazole ester is less than or equal to 3.5 as a raw material to be qualified. After the analysis is qualified, the temperature is reduced and the filtration is carried out, the mother liquor is the DMF solution of the ethyl substance,
heating the mother liquor, carrying out vacuum desolventizing to 130 ℃/-83kPa, cooling to 110 ℃, improving the vacuum degree, continuing vacuum rectification, stopping rectification until the temperature is 147.5 ℃/-97.5kPa, and distilling to obtain 36.0 g of ethyl. The reaction yield of the step is 83.0 percent, and the content of ethyl substances is 98.1 percent.
Example 3
The method comprises the steps of industrially producing a batch of pyrazole ester ethanol solution, wherein the weight is 4100kg, the quantitative content is 15.75%, vacuumizing a system to-98 kPa, heating, carrying out decompression desolventizing to 98 ℃/-98kPa, stopping distillation, dropwise adding 1000kg into the system, cooling to room temperature, adding 1000kg of sodium carbonate and 10kg of TBAB into a kettle, heating a reaction kettle to 70 ℃, slowly introducing chloroethane gas into the kettle at the introducing rate of 50 kg/hour for 5-6 hours, and sampling to analyze that the content of pyrazole ester is less than or equal to 3.5% to be qualified. And after the analysis is qualified, cooling the reaction kettle to room temperature, putting the feed liquid into a pressure filter to filter out solids, and filtering out the liquid-level ethyl substance DMF solution.
And introducing the filtrate into a reaction kettle, vacuumizing the system to minus 83kPa, heating, carrying out vacuum desolventizing to 130 ℃/-83kPa, stopping heating, naturally cooling to 115 ℃, adjusting the vacuum of the system to minus 97.5kPa, switching to a rectification mode, continuously heating, receiving the distilled fraction, carrying out vacuum rectification to 147.5 ℃/-97.5kPa, stopping the rectification operation, and obtaining 670kg of ethyl product with the content of 99.2%.
Claims (8)
1. A method for preparing an ethiazole mite nitrile intermediate is characterized by comprising the following steps: reaction formula is
Adding an acid-binding agent and a catalyst into pyrazole ester under the condition of a solvent, introducing halogenated ethane gas into the system, and reacting until the system is qualified to obtain an ethyl substance.
2. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: the halogenated ethane is chloroethane, bromoethane or iodoethane; wherein the molar ratio of the pyrazole ester to the halogenated ethane is 1:1-1: 10.
3. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: and heating the pyrazole ester to 95-98 ℃ in an ethanol solution of pyrazole ester, and removing ethanol under reduced pressure for later use.
4. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: the solvent is one or more of DMF, DMSO, toluene, ethanol, n-hexane and cyclohexane; wherein the mass ratio of the pyrazole ester to the solvent is 1:1-1: 5.
5. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: the catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium sulfate, tetrabutylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride; wherein the mass ratio of the pyrazole ester to the catalyst is 1: 0.5-1: 1%.
6. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: the acid-binding agent is one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, solid sodium hydroxide, solid potassium hydroxide, sodium amide, sodium methoxide and sodium ethoxide; wherein the mass ratio of the pyrazole ester to the acid-binding agent is 1:1-1: 2.
7. The process for the preparation of an ethiazole acaricidal nitrile intermediate as set forth in claim 1, wherein: and filtering to remove and collect supernatant after the ethylation reaction, heating, and evaporating the solvent under reduced pressure to obtain an ethyl extract crude extract.
8. The process for preparing an ethiazole acarid nitrile intermediate as claimed in claim 7, wherein: and rectifying the ethyl extract crude extract to obtain an ethyl extract.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1104636A (en) * | 1992-06-11 | 1995-07-05 | 罗纳-普朗克农业有限公司 | New compositions of matter |
| US20100298320A1 (en) * | 2007-12-19 | 2010-11-25 | Cancer Research Technology Limited | Pyrido[2,3-b]pyrazin-8-substituted Compounds and Their Use |
| CN108863936A (en) * | 2018-06-28 | 2018-11-23 | 长沙麓兴生物科技有限公司 | A kind of pyrazoles N- alkylation |
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2021
- 2021-12-08 CN CN202111489875.9A patent/CN114105876A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1104636A (en) * | 1992-06-11 | 1995-07-05 | 罗纳-普朗克农业有限公司 | New compositions of matter |
| US20100298320A1 (en) * | 2007-12-19 | 2010-11-25 | Cancer Research Technology Limited | Pyrido[2,3-b]pyrazin-8-substituted Compounds and Their Use |
| CN108863936A (en) * | 2018-06-28 | 2018-11-23 | 长沙麓兴生物科技有限公司 | A kind of pyrazoles N- alkylation |
Non-Patent Citations (1)
| Title |
|---|
| 陈小阳: "具生物活性吡唑丙烯腈类化合物的合成与性质研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》, no. 3, pages 19 * |
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