CN110963877A - Preparation method of 1-chloro-1-chloroacetyl cyclopropane - Google Patents
Preparation method of 1-chloro-1-chloroacetyl cyclopropane Download PDFInfo
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- CN110963877A CN110963877A CN201911308799.XA CN201911308799A CN110963877A CN 110963877 A CN110963877 A CN 110963877A CN 201911308799 A CN201911308799 A CN 201911308799A CN 110963877 A CN110963877 A CN 110963877A
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- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/33—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties
- C07C45/34—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties in unsaturated compounds
- C07C45/35—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties in unsaturated compounds in propene or isobutene
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- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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Abstract
The application provides a preparation method of 1-chloro-1-chloroacetyl cyclopropane. The preparation method comprises the following steps: 1) reacting 1, 3-butadiene with diazomethane to produce vinylcyclopropane; 2) reacting a vinylcyclopropane with an oxidizing reagent to produce an acetylcyclopropane; and 3) reacting the acetylcyclopropane with a chlorinating agent to produce the target product 1-chloro-1-chloroacetylcyclopropane. The method can reduce the use of strong acid, strong base and chlorinating agent in the preparation of 1-chloro-1-chloroacetyl cyclopropane, thereby reducing the discharge of three wastes and the safety risk, and simultaneously can improve the synthesis yield so as to be suitable for industrial production.
Description
Technical Field
The invention relates to the field of fine organic synthesis, in particular to a preparation method of prothioconazole intermediate 1-chloro-1-chloroacetyl cyclopropane.
Background
Prothioconazole is a broad-spectrum triazolethione bactericide which is widely applied, can be used for diseases of crops such as cereals, wheat and beans, and has the advantages of high efficiency, low toxicity, no three causes (carcinogenesis, teratogenesis and mutagenesis), little influence on human and livestock and environmental safety. At present, a plurality of enterprises at home and abroad are producing or preparing the pesticide variety.
The 1-chloro-1-chloroacetylcyclopropane (CAS No: 120983-72-4) is a key intermediate in the prothioconazole production process, and the production technology mainly uses acetyl-gamma-butyrolactone as a starting material and obtains the product through four steps of chlorination, acidolysis, ring closure, secondary chlorination and the like. Such as US patent No. 4938791, chinese patent No. CN105384617, CN108586220, etc. As chlorine/sulfonyl chloride, caustic soda, concentrated hydrochloric acid and the like are required to be continuously used in the production process, a large amount of three wastes are generated, and the environmental damage is large. At present, various colleges and universities, enterprises and scientific research institutions have proposed related improvement schemes, such as the Chinese patent CN105384617 and the Chinese patent CN 107118090.
In view of the above problems faced in the preparation of prothioconazole intermediates, there is still a need to develop a new process that can synthesize prothioconazole intermediates in an environmentally friendly manner.
Disclosure of Invention
The invention aims to provide a novel preparation process of prothioconazole intermediate 1-chloro-1-chloroacetyl cyclopropane, which can reduce the use of strong acid, strong base and chlorinating agent, further reduce the discharge of three wastes and the safety risk, and simultaneously can improve the synthesis yield so as to adapt to industrial production.
The invention provides a preparation method of 1-chloro-1-chloroacetyl cyclopropane, which comprises the following steps:
(1) and (3) performing a naphthenic reaction: reacting 1, 3-butadiene with diazomethane to produce vinylcyclopropane;
(2) and (3) oxidation reaction: reacting a vinylcyclopropane with an oxidizing reagent to produce an acetylcyclopropane; and
(3) chlorination reaction: reacting the acetyl cyclopropane with a chlorinating agent to generate the target product 1-chloro-1-chloroacetyl cyclopropane.
In a specific embodiment, in the step (1), the catalyst used can be selected from palladium dichloride, palladium acetate or tris (dibenzylidene indene acetone) dipalladium, preferably palladium acetate, and the amount of the catalyst is 1-20% of the weight of the 1, 3-butadiene.
In a particular embodiment, in step (1), the solvent used may be selected from diethyl ether, dichloromethane, acetonitrile or chloroform, preferably diethyl ether or acetonitrile.
In a specific embodiment, in step (2), the oxidizing agent may be selected from oxygen, air or hydrogen peroxide, preferably oxygen.
In a specific embodiment, in the step (2), the catalyst used can be selected from palladium chloride and palladium acetate, the cocatalyst can be selected from cuprous chloride, cuprous acetate or silver nitrate, preferably, the palladium chloride and cuprous chloride are used as a catalytic system, and the amount of the catalytic system is 1-10% of the weight of the vinylcyclopropane.
In a specific embodiment, the solvent used in step (2) is a water-organic solvent mixed system in which the organic solvent may be selected from N, N-Dimethylformamide (DMF), N-dimethylacetamide, Dimethylsulfoxide (DMSO), acetonitrile, tetrahydrofuran, or 1, 4-dioxane, preferably, the organic solvent is DMF; in the water-organic solvent mixed system, the volume ratio of water to organic solvent is 1:10 to 10:1, preferably 1:1, for example, the water-organic solvent mixed system is a solvent system with the volume ratio of water to DMF being 1: 1.
In a specific embodiment, in step (3), the chlorinating agent may be selected from chlorine gas, sulfuryl chloride, thionyl chloride, alkyl sulfuryl chloride or N-chlorosuccinimide (NCS), preferably NCS.
In a specific embodiment, the solvent used in step (3) may be selected from dichloromethane, chloroform, carbon tetrachloride, acetonitrile or N, N-Dimethylformamide (DMF), preferably dichloromethane.
In a specific embodiment, the reaction temperature in the step (1) is 0-40 ℃, preferably 10-30 ℃;
the reaction temperature of the step (2) is 0-80 ℃, preferably 25-45 ℃, and more preferably 40 ℃; and
the reaction temperature in the step (3) is 0-80 ℃, preferably 20-30 ℃, and more preferably 25 ℃.
In a specific embodiment, in step (3), the addition manner and amount of the chlorinating agent are as follows: 1.0 to 1.1 moles of a chlorinating agent are added to 1 mole of acetylcyclopropane at 0 ℃, and after the temperature is raised to room temperature, 1.0 to 1.1 moles of the chlorinating agent is added to 1 mole of acetylcyclopropane again.
Advantageous effects
The preparation method of the prothioconazole intermediate disclosed by the invention has the following advantages:
1) 1, 3-butadiene which is a common product in the petrochemical industry is used as a raw material instead of acetyl-gamma-butyrolactone, so that the raw material source is wider and easily available, and the raw material cost is saved;
2) diazomethane is used as a naphthenic reagent, a byproduct is only nitrogen, the treatment of waste gas is simplified, and a catalyst and a solvent can be recycled;
3) the preparation of the acetyl cyclopropane uses air and the like as oxidation reagents, the atom utilization rate is high, the discharge of three wastes is less, and the catalyst can be recycled for multiple times;
4) in the chlorination step, NCS is preferably used as a chlorination reagent, so that the selectivity is high, the by-product is succinimide, and the succinimide can be regenerated and recycled in combination with chlor-alkali enterprises after simple distillation and purification;
5) compared with the traditional process, the method basically generates no wastewater, so that the whole process is green and environment-friendly.
Drawings
FIG. 1 is a gas chromatogram of the product 1-chloro-1-chloroacetylcyclopropane obtained in the present invention.
FIG. 2 is a nuclear magnetic resonance spectrum of the product 1-chloro-1-chloroacetylcyclopropane obtained in the present invention.
Detailed Description
The process disclosed herein is described below with reference to specific embodiments. These descriptions are not intended to limit the scope of the present invention.
Examples
Step 1: adding an ether solution of diazomethane and a catalytic amount of palladium acetate into a stainless steel reaction kettle with a tetrafluoro lining, then closing the reaction kettle, replacing the reaction kettle with nitrogen, starting stirring, slowly introducing 1, 3-butadiene at room temperature, and keeping the pressure at 0.4 MPa. As the reaction proceeded, the pressure began to decrease, and 1, 3-butadiene was continuously supplied until the pressure remained 0.4MPa and did not decrease, and the reaction was continued for 1 hour. After the reaction is finished, the reaction kettle is opened, the reaction solution is distilled, the ether and the product of the vinylcyclopropane are distilled out, and the catalyst palladium acetate is left at the bottom of the kettle and can be recycled along with the distilled ether. The boiling range of the product vinylcyclopropane is 40-42 ℃ under normal pressure. The reaction yield was > 90% calculated on diazomethane consumption.
1H-NMR(400MH，CDCl3)：δ＝5.44(1H,t),5.16(1H,m),4.94(1H,m),1.40(1H,m),0.72(2H,m),0.48(2H,m)。
Step 2: in an oil bath, a 500mL three-necked flask was placed, a gas inlet-receiving device was installed, and a tetrafluoro stirrer was added, and then 200mL of a mixed solvent of water and DMF (volume ratio 1:1) was placed in the flask, 20g (0.294mol) of vinylcyclopropane (product of step 1) was added, 0.5g of palladium chloride and 0.5g of cuprous chloride were added, the heating device was turned on, the system was warmed to 40 ℃ and oxygen gas introduction was started at an oxygen flow rate of 20 mL/min. The reaction time was 6 hours, during which the degree of reaction progress was checked by gas chromatography. After the reactant is completely converted, the device is changed into a fractionating device, samples at different stages are collected, and 19g of pale yellow oily liquid can be collected, wherein the yield is 80 percent, and the content is more than 98 percent.
1H-NMR(400MH，CDCl3)：δ＝2.20(3H,s),2.00(1H,m),0.92(2H,m),0.64(2H,m)。
And step 3: a250 ml three-necked round-bottomed flask was charged with 10g of acetylcyclopropane (0.12mol) and 30ml of methylene chloride, and the mixture was cooled in a 0 ℃ cooling bath, followed by addition of 33.5g of NCS (0.25mol), followed by stirring and slow warming to room temperature. Stirring for 2-3 hours. The reaction produced a large amount of precipitate. After the reaction was completed, the mixture was filtered in a fume hood. The filter cake was washed with a small amount of dichloromethane, the filtrates were combined, the solvent dichloromethane was distilled off from the filtrate, followed by distillation under reduced pressure to give the objective product as a pale yellow transparent oily liquid 16.8g, which was confirmed to be the product 1-chloro-1-chloroacetylcyclopropane with a purity of > 97% by GC-MS (FIG. 1) and H-NMR (FIG. 2). The yield thereof was found to be 92%. The recovered succinimide can be directly used for preparing NCS for recycling.
1H-NMR(400MH，CDCl3)：δ＝4.76(2H,s),1.76(2H,q),1.45(2H,q)。
The above examples show that the process flow of the invention is simple, the comprehensive yield is high, the invention can be used for preparing high-purity 1-chloro-1-chloroacetyl cyclopropane, and the invention is suitable for industrial scale production.
The above are only specific examples of the present invention, and any changes or modifications obvious to those skilled in the art using the method of the present invention are within the scope of the present patent.
Claims (10)
1. A method for preparing 1-chloro-1-chloroacetyl cyclopropane, which comprises the following steps:
(1) and (3) performing a naphthenic reaction: reacting 1, 3-butadiene with diazomethane to produce vinylcyclopropane;
(2) and (3) oxidation reaction: reacting a vinylcyclopropane with an oxidizing reagent to produce an acetylcyclopropane; and
(3) chlorination reaction: reacting the acetyl cyclopropane with a chlorinating agent to generate the target product 1-chloro-1-chloroacetyl cyclopropane.
2. The method according to claim 1, wherein in the step (1), the catalyst is selected from palladium dichloride, palladium acetate or tris (dibenzylideneacetone) dipalladium, preferably palladium acetate, and the amount of the catalyst is 1-20% of the weight of the 1, 3-butadiene.
3. The process according to claim 1, wherein in step (1), the solvent used is selected from diethyl ether, dichloromethane, acetonitrile or chloroform, preferably diethyl ether or acetonitrile.
4. The process according to claim 1, wherein in step (2), the oxidizing agent is selected from oxygen, air or hydrogen peroxide, preferably oxygen.
5. The method according to claim 1, wherein in the step (2), the catalyst is selected from palladium chloride and palladium acetate, the cocatalyst is selected from cuprous chloride, cuprous acetate or silver nitrate, preferably, the palladium chloride and cuprous chloride are used as a catalytic system, and the amount of the catalyst system is 1-10% of the weight of the vinylcyclopropane.
6. The method according to claim 1, wherein in step (2), the solvent used is a water-organic solvent mixed system in which the organic solvent is selected from N, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, acetonitrile, tetrahydrofuran or 1, 4-dioxane, preferably the organic solvent is N, N-dimethylformamide, and the volume ratio of water and organic solvent in the water-organic solvent mixed system is 1:10 to 10:1, preferably 1: 1.
7. The process according to claim 1, wherein in step (3) the chlorinating reagent is selected from chlorine gas, sulfuryl chloride, thionyl chloride, alkyl sulfuryl chloride or N-chlorosuccinimide, preferably N-chlorosuccinimide.
8. The process according to claim 1, wherein in step (3) the solvent used is selected from dichloromethane, chloroform, carbon tetrachloride, acetonitrile or N, N-dimethylformamide, preferably dichloromethane.
9. The method of claim 1, wherein,
the reaction temperature of the step (1) is 0-40 ℃, and preferably 10-30 ℃;
the reaction temperature of the step (2) is 0-80 ℃, preferably 25-45 ℃, and more preferably 40 ℃; and
the reaction temperature in the step (3) is 0-80 ℃, preferably 20-30 ℃, and more preferably 25 ℃.
10. The method according to claim 1, wherein in step (3), the chlorinating agent is added in the following manner and in the following amount: 1.0 to 1.1 moles of a chlorinating agent are added to 1 mole of acetylcyclopropane at 0 ℃, and after the temperature is raised to room temperature, 1.0 to 1.1 moles of the chlorinating agent is added to 1 mole of acetylcyclopropane again.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1054586A (en) * | 1990-03-08 | 1991-09-18 | 藤泽药品工业株式会社 | New substituted amine compound and preparation method thereof |
| CN105683146A (en) * | 2013-10-25 | 2016-06-15 | 奇华顿股份有限公司 | Preparation of homoallylic compounds by reaction of cyclopropylvinyl precursors with bronstedt acids |
| CN109748783A (en) * | 2019-01-31 | 2019-05-14 | 河北诚信集团有限公司 | A kind of preparation method of the chloro- 1- of 2- (1- chlorine cyclopropyl) ethyl ketone |
| CN110577484A (en) * | 2019-07-02 | 2019-12-17 | 凯莱英医药集团（天津）股份有限公司 | Method and device for continuously synthesizing cyclopropane compound |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1054586A (en) * | 1990-03-08 | 1991-09-18 | 藤泽药品工业株式会社 | New substituted amine compound and preparation method thereof |
| CN105683146A (en) * | 2013-10-25 | 2016-06-15 | 奇华顿股份有限公司 | Preparation of homoallylic compounds by reaction of cyclopropylvinyl precursors with bronstedt acids |
| CN109748783A (en) * | 2019-01-31 | 2019-05-14 | 河北诚信集团有限公司 | A kind of preparation method of the chloro- 1- of 2- (1- chlorine cyclopropyl) ethyl ketone |
| CN110577484A (en) * | 2019-07-02 | 2019-12-17 | 凯莱英医药集团（天津）股份有限公司 | Method and device for continuously synthesizing cyclopropane compound |
Non-Patent Citations (1)
| Title |
|---|
| DZHEMILEV, U. M. ET AL.: "Reaction of diazoalkanes with unsaturated compounds. 6. Catalytic cyclopropanation of various unsaturated hydrocarbons and their derivatives by diazomethane", 《IZVESTIYA AKADEMII NAUK SSSR, SERIYA KHIMICHESKAYA》 * |
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