CN107602365B - Preparation method of 2-chloro-1- (1-chlorocyclopropyl) ethanone - Google Patents
Preparation method of 2-chloro-1- (1-chlorocyclopropyl) ethanone Download PDFInfo
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- CN107602365B CN107602365B CN201710886901.9A CN201710886901A CN107602365B CN 107602365 B CN107602365 B CN 107602365B CN 201710886901 A CN201710886901 A CN 201710886901A CN 107602365 B CN107602365 B CN 107602365B
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Abstract
The invention discloses a preparation method of 2-chloro-1- (1-chlorocyclopropyl) ethanone, which comprises the steps of introducing chlorine into a solvent system dissolved with 1-acetyl-1-chlorocyclopropane or directly introducing chlorine into the 1-acetyl-1-chlorocyclopropane in the presence of a Lewis acid salt catalyst and a quaternary ammonium salt phase transfer catalyst, controlling the reaction temperature to be 5-25 ℃ for chlorination reaction, and preparing the 2-chloro-1- (1-chlorocyclopropyl) ethanone. The content and molar yield of the 2-chloro-1- (1-chlorocyclopropyl) ethanone prepared by the method can reach more than 90 percent.
Description
Technical Field
The invention belongs to the technical field of pesticide chemical synthesis, relates to synthesis of a pesticide intermediate, and particularly relates to a preparation method of an intermediate 2-chloro-1- (1-chlorocyclopropyl) ethanone of prothioconazole which is a high-efficiency bactericide.
Background
Prothioconazole (Prothioconazole) is a novel broad-spectrum triazolethione fungicide, and acts as a sterol demethylation (ergosterol biosynthesis) inhibitor (DMIs) by inhibiting the demethylation at the 14-position of lanosterol or 2, 4-methylenedihydrolanosterol, the sterol precursor in fungi.
The prothioconazole has good systemic action, excellent protection, treatment and eradication activity and long lasting period. Prothioconazole has a broader bactericidal spectrum than other triazole bactericides and is mainly used for disease control of crops such as wheat, barley, rape, peanut, rice, beans, beet, field vegetables and the like.
The prothioconazole can be quickly and widely absorbed in the animal body and is quickly discharged out of the body mainly through excrement without potential accumulation; metabolizing in the plant body through peroxidation and cracking reactions; can be rapidly degraded in soil/environment, and the leaching and accumulation effects of parent compounds and metabolites are small. A large number of field efficacy test results show that prothioconazole has no environmental risk concern, good crop safety, good disease prevention and treatment effects, obvious yield increase, low toxicity, no teratogenicity or mutagenicity, no toxicity to embryos, safety to people and the environment and the like, and is one of the triazole bactericides with the most promising prospect.
But the structure of the prothioconazole and the intermediate thereof is complex, the synthesis is difficult, the synthesis cost is high, the yield is low, and the production and application are limited.
2-chloro-1- (1-chlorocyclopropyl) ethanone, molecular formula C5H6OCl2The molecular weight of 153.01, the structural formula is as follows, is light yellow transparent liquid, is an important fine chemical intermediate, and is one of the key intermediates of the bactericide prothioconazole in particular.
The existing production process basically takes sulfonyl chloride or sulfonyl chloride-alcohol mixed solution as a reaction chlorinating agent to perform chlorination reaction on 1-acetyl-1-chlorocyclopropane in a chloroform solvent to generate a target product.
The disadvantages of the above synthetic method are mainly reflected in the following aspects.
1) When the sulfuryl chloride is adopted for chlorination, a large amount of sulfur dioxide gas is generated, and mixed acid is formed with a chlorination reaction byproduct, namely hydrogen chloride, and is difficult to treat.
2) When the sulfuryl chloride is used alone for chlorination, the reaction rate is slow, the reaction period is long, and the method cannot meet the requirement of industrial mass production. The reaction rate is improved by adding the catalyst alcohol, but the difficulty of the post-reaction treatment is also increased.
3) And the consumption of sulfonyl chloride in the chlorination reaction is large, and the molar consumption of the sulfonyl chloride is 1.5-2.0 times of that of 1-acetyl-1-chlorocyclopropane, so that a large amount of waste of raw materials is caused.
4) Sulfuryl chloride is easily decomposed and requires low-temperature storage. The increase of the environmental temperature can cause the decomposition of partial sulfuryl chloride into hydrogen chloride and sulfur dioxide, which pollutes the environment and has larger safety risk.
Disclosure of Invention
The invention aims to overcome the defects of the existing synthesis method and provide a preparation method of 2-chloro-1- (1-chlorocyclopropyl) ethanone, so as to simplify the post-reaction treatment, reduce the production cost and better protect the environment.
The preparation method of the 2-chloro-1- (1-chlorocyclopropyl) ethanone provided by the invention comprises the following steps: in the presence of a catalyst and a phase transfer catalyst, introducing chlorine gas into a solvent system in which 1-acetyl-1-chlorocyclopropane is dissolved or directly into 1-acetyl-1-chlorocyclopropane, and controlling the reaction temperature to be 5-25 ℃ to carry out chlorination reaction so as to prepare the target product 2-chloro-1- (1-chlorocyclopropyl) ethanone.
Wherein the catalyst is Lewis acid salt catalyst, and the phase transfer catalyst is quaternary ammonium salt catalyst.
Specifically, the Lewis acid salt catalyst may be CuCl2、ZnCl2、AlCl3And the like. CuCl is preferably used in the present invention2。
The quaternary ammonium salt catalyst can be any one of triethylamine, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate (TBAB), methyltributylammonium chloride, benzyltriethylammonium chloride (TEBA), dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride and the like. Tetrabutylammonium bromide is preferably used in the present invention.
More specifically, the molar amount of the Lewis acid salt catalyst is 0.3-2% of the molar amount of the raw material 1-acetyl-1-chlorocyclopropane.
The molar amount of the quaternary ammonium salt catalyst is 0.3-3% of the molar amount of the raw material 1-acetyl-1-chlorocyclopropane.
In the present invention, the solvent system for dissolving 1-acetyl-1-chlorocyclopropane includes various common halogenated hydrocarbon solvents. Specifically, the halogenated hydrocarbon solvent is selected from dichloromethane, 1, 2-dichloroethane, chloroform, chlorobenzene, and the like.
Further, the amount of the halogenated hydrocarbon solvent used in the present invention is 0 to 5 times the weight of 1-acetyl-1-chlorocyclopropane.
Preferably, the chlorine gas introducing time of the chlorination reaction is controlled to be 4-10 hr.
More preferably, the time for introducing the chlorine gas is 5-7 hr, and the speed for introducing the chlorine gas is fast and slow.
The post-treatment method of the target product 2-chloro-1- (1-chlorocyclopropyl) ethanone after the reaction is finished is very simple, and the target product 2-chloro-1- (1-chlorocyclopropyl) ethanone can be obtained only by introducing inert gas into the reaction system or exhausting the reaction system to remove residual chlorine and hydrogen chloride gas generated in the reaction, adding water into the reaction liquid, neutralizing the reaction liquid to be neutral by using dilute alkali liquor, layering, collecting an organic phase and removing a solvent.
The content and the molar yield of the 2-chloro-1- (1-chlorocyclopropyl) ethanone in the target product prepared by the method are detected by adopting a gas chromatography, and both reach more than 90 percent in terms of 1-acetyl-1-chlorocyclopropane.
In the preparation method of the 2-chloro-1- (1-chloro-cyclopropyl) ethanone, in a solvent or solvent-free system, the 1-acetyl-1-chlorocyclopropane serving as a raw material increases a gas-liquid interphase reaction interface under the action of a phase transfer catalyst, so that the reaction speed with chlorine is accelerated; the catalyst not only reduces the reaction activation energy, but also improves the directional chlorination performance to a certain extent; the reaction speed is accelerated under the combined action of the chlorine gas and the chlorine gas, the accumulation of the chlorine gas in a reaction system is avoided, and the reaction yield and the product content are improved.
The invention uses cheap chlorine to replace traditional chlorinating agents such as sulfuryl chloride and the like, thereby avoiding the generation of waste gases such as sulfur dioxide and the like; meanwhile, the method avoids the use of alcohol catalysts, simplifies the post-treatment of the reaction, reduces the energy consumption and the production cost, better protects the environment and is very suitable for industrial mass production.
Detailed Description
The present invention is further described in detail with reference to specific embodiments below in order to make the above advantages more comprehensible to those skilled in the art.
Example 1.
300g of 96.0% 1-acetyl-1-chlorocyclopropane and CuCl are sequentially added into a dry 500mL reaction bottle provided with a mechanical stirring pipe, a reflux condenser pipe, a chlorine insertion pipe, a thermometer and a tail gas absorber (secondary bubbling absorption)21.32g and 5.0g of tetrabutylammonium bromide, starting stirring, cooling the system to 5-10 ℃ by freezing, and introducing chlorine gas to carry out chlorination reaction. And in the reaction process, the reaction temperature of the system is controlled to be 10-15 ℃.
After reacting for 4 hours, reducing the content of the 1-acetyl-1-chlorocyclopropane in the system to be below 3.0 percent, stopping introducing chlorine, continuing to perform heat preservation reaction for 30-60 min to ensure that the content of the 1-acetyl-1-chlorocyclopropane in the system is less than 1.0 percent, and stopping the reaction.
And introducing nitrogen into the reaction bottle, completely removing redundant chlorine and hydrogen chloride gas generated by the reaction in the system, and collecting light yellow transparent liquid in the reaction bottle.
50g of water is firstly dropwise added into the collected reaction liquid, then saturated sodium carbonate solution is slowly dropwise added, the reaction liquid is neutralized to be neutral, and the mixture is kept stand and layered to obtain 372.96g of light yellow transparent liquid 2-chloro-1- (1-chloro-cyclopropyl) ethanone. The product molar yield is 90.60%, and the content is 90.33% by gas chromatography analysis.
The characterization data of the target product are as follows: GC-MS (M/z) 152 (M)+,33), 117(23), 103(100), 75(71), 51(16)。1H NMR(400MHz,CDCl3): 2.44 (s,2H, CH2), 1.63 (t,2H, CH2), 1.36 (t,2H, CH2)。
Example 2.
200g of 96.0% 1-acetyl-1-chlorocyclopropane and CuCl are sequentially added into a dry 500mL reaction bottle provided with a mechanical stirring pipe, a reflux condenser pipe, a chlorine insertion pipe, a thermometer and a tail gas absorber (secondary bubbling absorption)22.20g and 5.28g of tetrabutylammonium bromide, starting stirring, cooling the system to 10-15 ℃ by freezing, and introducing chlorine gas to carry out chlorination reaction. Controlling the reaction temperature of the system in the reaction processAt 10-20 ℃.
And after reacting for 5 hours, reducing the content of the 1-acetyl-1-chlorocyclopropane in the system to be below 3.0 percent, stopping introducing chlorine, continuing to perform heat preservation reaction for 30-60 min to ensure that the content of the 1-acetyl-1-chlorocyclopropane in the system is less than 1.0 percent, and stopping the reaction.
Controlling the temperature in the reaction bottle to be less than or equal to 20 ℃, decompressing and exhausting the reaction bottle for 2-3 hours, removing redundant chlorine gas in the bottle and hydrogen chloride gas generated by reaction, and collecting light yellow transparent liquid in the reaction bottle.
50g of water is firstly dropwise added into the collected reaction liquid, then saturated sodium carbonate solution is slowly dropwise added, the reaction liquid is neutralized to be neutral, and the mixture is kept stand and layered to obtain 251.93g of light yellow transparent liquid 2-chloro-1- (1-chloro-cyclopropyl) ethanone. The molar yield of the product was 92.30%, and the content was 90.82% by gas chromatography.
Example 3.
To a dry, anhydrous 500mL reaction flask equipped with a mechanical stirrer, reflux condenser, chlorine insertion tube, thermometer, and tail gas absorber (two-stage bubble absorption) were sequentially added 200mL of dichloromethane, 150g of 97.0% 1-acetyl-1-chlorocyclopropane, FeCl32.05g of tetrabutylammonium bromide and 4.10g of tetrabutylammonium bromide, starting stirring, cooling the system to 15-20 ℃ by freezing, and introducing chlorine gas to carry out chlorination reaction. And controlling the reaction temperature of the system to be 15-25 ℃ in the reaction process.
And after reacting for 5 hours, reducing the content of the 1-acetyl-1-chlorocyclopropane in the system to be below 3.0 percent, stopping introducing chlorine, continuing to perform heat preservation reaction for 30-60 min to ensure that the content of the 1-acetyl-1-chlorocyclopropane in the system is less than 1.0 percent, and stopping the reaction.
Adding 50g water dropwise into the reaction flask, slowly adding saturated sodium carbonate solution dropwise, neutralizing the reaction solution to neutrality, standing for 0.5hr for layering, removing the upper water layer, and collecting the lower organic layer.
The organic layer was freed from the solvent dichloromethane at normal pressure to give 191.08g of 2-chloro-1- (1-chlorocyclopropyl) ethanone as a pale yellow transparent liquid. The molar yield of the product was 93.10%, and the GC content was 91.53%.
The above examples are merely illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements of the present invention may be made by those skilled in the art without departing from the spirit of the present invention, and are intended to be included within the scope of the present invention as defined in the appended claims.
Claims (10)
1. A preparation method of 2-chloro-1- (1-chlorocyclopropyl) ethanone comprises the steps of introducing chlorine into a solvent system in which 1-acetyl-1-chlorocyclopropane is dissolved or directly introducing chlorine into the 1-acetyl-1-chlorocyclopropane in the presence of a catalyst and a phase transfer catalyst, and controlling the reaction temperature to be 5-25 ℃ to carry out chlorination reaction, wherein the catalyst is a Lewis acid salt catalyst, and the phase transfer catalyst is a quaternary ammonium salt catalyst.
2. The process for the preparation of 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 1, characterized in that said Lewis acid salt type catalyst is CuCl2、ZnCl2Or AlCl3。
3. The process for the preparation of 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 2, characterized in that said Lewis acid salt type catalyst is CuCl2。
4. The process for producing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 2 or 3, wherein the molar amount of the Lewis acid salt-based catalyst is 0.3 to 2% of the molar amount of the starting material 1-acetyl-1-chlorocyclopropane.
5. The method for preparing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 1, wherein the quaternary ammonium salt catalyst is any one of tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, methyltributylammonium chloride, benzyltriethylammonium chloride, dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride.
6. The process for preparing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 5, characterized in that said catalyst of quaternary ammonium salt type is tetrabutylammonium bromide.
7. The process for producing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 5 or 6, wherein the molar amount of the quaternary ammonium salt catalyst is 0.3 to 3% of the molar amount of the raw material 1-acetyl-1-chlorocyclopropane.
8. The process for preparing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 1, characterized in that said solvent system is a halogenated hydrocarbon solvent.
9. The process for the preparation of 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 8, characterized in that said halogenated hydrocarbon solvent is dichloromethane, 1, 2-dichloroethane, chloroform or chlorobenzene.
10. The method for producing 2-chloro-1- (1-chlorocyclopropyl) ethanone according to claim 8 or 9, wherein the amount of the halogenated hydrocarbon solvent is 0 to 5 times the weight of 1-acetyl-1-chlorocyclopropane.
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| CN110256223A (en) * | 2019-05-20 | 2019-09-20 | 江苏蓝丰生物化工股份有限公司 | A method of 1- (1- chlorine cyclopropyl) ethyl ketone is prepared using micro passage reaction |
| CN114292178B (en) * | 2021-12-24 | 2023-05-19 | 河北威远生物化工有限公司 | Synthesis method of 2-chloro-1- (1-chlorocyclopropyl) ethanone |
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