CN109678652B - Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane - Google Patents
Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane Download PDFInfo
- Publication number
- CN109678652B CN109678652B CN201811623994.7A CN201811623994A CN109678652B CN 109678652 B CN109678652 B CN 109678652B CN 201811623994 A CN201811623994 A CN 201811623994A CN 109678652 B CN109678652 B CN 109678652B
- Authority
- CN
- China
- Prior art keywords
- alpha
- ionic liquid
- reaction
- methyl ketone
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/18—Preparation of halogenated hydrocarbons by replacement by halogens of oxygen atoms of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane, which comprises the steps of adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) as a catalyst and a solvent into a reaction kettle, adding cyclopropyl methyl ketone, starting stirring and mixing, after water and oxygen are removed from a reaction system, slowly adding a chlorinating reagent raw material at the reaction temperature of 0-60 ℃, feeding and reacting for 1-2 hours, continuing to react for 2-4 hours after the feeding is finished, and the like. The production of three wastes containing phosphorus is completely avoided in the reaction process, and the environment is protected. Meanwhile, the adopted ionic liquid can be reused, so that the cost is greatly reduced.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane.
Background
Alpha, alpha-dichloroethyl cyclopropane is an important intermediate, and the structural formula of the intermediate is as follows:
the compound is a key intermediate for synthesizing cyclopropyl acetylene, and the cyclopropyl acetylene is used as an important drug intermediate, particularly a key intermediate of certain anti-AIDS drugs such as efavirenz, and the synthesis of the compound is particularly important.
The cyclopropynyl is an important synthon of cyclopropyl skeleton of drug molecule, and becomes the research focus of many research groups and research units, such as Merck, Kuraray, DuPont, Wiley, etc., and the market demand is still on the rise.
Before the present invention is provided, in the prior art, the chemical synthesis method of alpha, alpha-dichloroethyl cyclopropane mainly uses cyclopropyl methyl ketone as a raw material, pyridine as a catalyst, PCl5 as a chlorinated reagent and CCl4 as a solvent to generate alpha, alpha-dichloroethyl cyclopropane and alpha-vinylchloride cyclopropane, and the yield of the step is 76% (CN 1226548A). The method has the advantages of easily obtained raw materials, low conversion rate and yield, and harsh reaction conditions, and causes difficulty in industrial production. In particular, during the destruction of the residual PCl5 with water after the reaction with PCl5, the temperature of the reaction system must be kept low, otherwise the HCl formed would cause the ring opening of the three-membered ring to form 2, 5-dichloro-2-pentyne as a by-product, possibly even the only product.
The method also produces a large amount of phosphorus-containing wastewater which is difficult to treat, has high corrosivity to equipment, serious pollution problem and prominent environmental problem; phosgene in the phosgene method is a highly toxic gas, and transport and use are forbidden in United nations. The industrial production of phosgene (COCl2) has high requirements on the sealing property of reaction equipment, the investment is large, and phosgene in tail gas brings great troubles from the environmental protection perspective.
The existing preparation method of the alpha, alpha-dichloroethylcyclopropane product has more or less defects, or the product yield is too low, or the product purity is too low. The existing technical routes need to be improved both in terms of environmental friendliness and cost.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a method for preparing alpha, alpha-dichloroethyl cyclopropane promoted by ionic liquid.
In order to solve the technical problems, the technical scheme provided by the invention is as follows:
the invention discloses a preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane, which comprises the following steps:
1) adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) serving as a catalyst and a solvent into a reaction kettle, adding cyclopropyl methyl ketone, and stirring and mixing;
2) after the reaction system is subjected to water removal and oxygen removal, slowly adding a chlorinating reagent raw material at the reaction temperature of 0-60 ℃, adding materials and reacting for 1-2 hours, and continuing to react for 2-4 hours after the addition is finished;
3) after the reaction is finished, adding a normal hexane extraction product, stirring for 10 minutes, stopping stirring, standing for layering, removing the solvent in vacuum after collecting an upper extraction liquid layer and a lower ionic liquid layer to obtain the high-purity alpha, alpha-dichloroethyl cyclopropane product
As a further improvement, the chlorinating reagent provided by the invention is one of thionyl chloride and oxalyl chloride.
As a further improvement, the mass ratio of the cyclopropyl methyl ketone to the ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) to the chlorination reagent is 1:1: 1.2-2.0.
As a further improvement, the dosage of the cyclopropyl methyl ketone and the normal hexane is 1:5-10 by mass ratio.
As a further improvement, the high-purity alpha, alpha-dichloroethyl cyclopropane prepared by the method has the content of more than 99 percent and the reaction yield of more than 97 percent.
The invention has the beneficial effects that:
in the invention, the ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) is used as a catalyst and a solvent, so that the catalyst has a special catalytic effect on the system, the chlorination reaction activity of the chlorinated reagent can be greatly enhanced, and the reaction rate and the reaction selectivity are improved. The probable reason is that protons on imidazole ring C2 of the imidazole type ionic liquid easily form hydrogen bonds with atoms with strong electronegativity, so that the reaction energy barrier is reduced, the reaction intermediate has relative stability, and the reaction rate and selectivity are greatly improved.
The invention overcomes the high risk of phosphorus pentachloride in the traditional method, and does not need to treat a large amount of phosphorus-containing wastewater. The method adopts cheap and easily available thionyl chloride and oxalyl chloride, not only has low price, but also has simple post-treatment, and ensures the purity of the product. And the product can be stored stably because the system is anhydrous, acid-free and oxygen-free. The application of the novel reaction method is the core and key technology for realizing the preparation of high-purity products.
In addition, the content of the product obtained by the method is more than 99%, and the total reaction yield is more than 97%, which are far higher than those of the traditional method and the literature reports. The production of three wastes containing phosphorus is completely avoided in the reaction process, and the environment is protected. Meanwhile, the adopted ionic liquid can be reused, so that the cost is greatly reduced.
Detailed Description
The technical scheme of the invention is further explained by the following specific embodiments:
example 1
(1) In a reaction kettle, adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) as a catalyst and a solvent (275.3g, 1mol), adding cyclopropyl methyl ketone (84.1 g, 1mol), and stirring and mixing.
(2) After the reaction system is dehydrated and deoxidized, a chlorination reagent thionyl chloride raw material (238g) is slowly added at the reaction temperature of 0 ℃, and the materials are added for reaction for 2 hours. The reaction was continued for 4 hours after the end of the addition.
(3) And after the reaction is finished, adding n-hexane to extract the product, stirring for 10 minutes, stopping stirring, and standing for layering. An upper extraction liquid layer and a lower ionic liquid layer. 841g of n-hexane was removed. And after the extraction liquid layer is collected, removing the solvent in vacuum to obtain the high-purity alpha, alpha-dichloroethyl cyclopropane. The product content is 99.5%, and the total reaction yield is 97.2%.
Example 2
(1) In a reaction kettle, adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) as a catalyst and a solvent (275.3g, 1mol), adding cyclopropyl methyl ketone (84.1 g, 1mol), and stirring and mixing.
(2) After removing water and oxygen from the reaction system, a chlorinating agent oxalyl chloride starting material (152.4g) was slowly added at a reaction temperature of 60 ℃ and reacted for 1 hour. The reaction was continued for 2 hours after the end of the addition.
(3) And after the reaction is finished, adding n-hexane to extract the product, stirring for 10 minutes, stopping stirring, and standing for layering. An upper extraction liquid layer and a lower ionic liquid layer. 421g of n-hexane was removed. And after the extraction liquid layer is collected, removing the solvent in vacuum to obtain the high-purity alpha, alpha-dichloroethyl cyclopropane. The product content is 99.0 percent, and the total reaction yield is 98.0 percent.
Example 3
(1) In a reaction kettle, adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) as a catalyst and a solvent (275.3g, 1mol), adding cyclopropyl methyl ketone (84.1 g, 1mol), and stirring and mixing.
(2) After the reaction system is dehydrated and deoxidized, a chlorination reagent thionyl chloride raw material (166.6g) is slowly added at the reaction temperature of 30 ℃, and the materials are added for reaction for 1 hour. The reaction was continued for 3 hours after the end of the addition.
(3) And after the reaction is finished, adding n-hexane to extract the product, stirring for 10 minutes, stopping stirring, and standing for layering. An upper extraction liquid layer and a lower ionic liquid layer. 600g of n-hexane was removed. And after the extraction liquid layer is collected, removing the solvent in vacuum to obtain the high-purity alpha, alpha-dichloroethyl cyclopropane. The product content is 99.3%, and the total reaction yield is 98.9%.
Finally, it should also be noted that the above list is only a specific implementation example of the present invention. It is obvious that the invention is not limited to the above embodiment examples, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
Claims (1)
1. A method for preparing alpha, alpha-dichloroethylcyclopropane promoted by ionic liquid is characterized by comprising the following steps:
1) adding ionic liquid 1-octyl-3-methylimidazolium bromide ([ OMIM ] Br) serving as a catalyst and a solvent into a reaction kettle, adding cyclopropyl methyl ketone, and stirring and mixing;
2) after the reaction system is subjected to water removal and oxygen removal, slowly adding a chlorinating reagent raw material at the reaction temperature of 0-60 ℃, adding materials and reacting for 1-2 hours, and continuing to react for 2-4 hours after the addition is finished;
3) after the reaction is finished, adding a normal hexane extraction product, stirring for 10 minutes, stopping stirring, standing for layering, removing the solvent in vacuum after collecting an upper extraction liquid layer and a lower ionic liquid layer to obtain the high-purity alpha, alpha-dichloroethyl cyclopropane product
The chlorination reagent is one of thionyl chloride and oxalyl chloride;
the mass ratio of the cyclopropyl methyl ketone to the ionic liquid 1-octyl-3-methylimidazole bromine salt ([ OMIM ] Br) to the chlorination reagent is 1:1: 1.2-2.0;
the dosage of the cyclopropyl methyl ketone and the normal hexane is 1:5-10 according to the mass ratio;
the content of the high-purity alpha, alpha-dichloroethyl cyclopropane prepared by the method is more than 99 percent, and the reaction yield is more than 97 percent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811623994.7A CN109678652B (en) | 2018-12-28 | 2018-12-28 | Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811623994.7A CN109678652B (en) | 2018-12-28 | 2018-12-28 | Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109678652A CN109678652A (en) | 2019-04-26 |
| CN109678652B true CN109678652B (en) | 2021-10-26 |
Family
ID=66190863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811623994.7A Active CN109678652B (en) | 2018-12-28 | 2018-12-28 | Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109678652B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999007658A1 (en) * | 1997-08-12 | 1999-02-18 | Great Lakes Chemical Corporation | Preparation of gem-dihaloalkanes |
| CN103664465A (en) * | 2012-09-12 | 2014-03-26 | 九江中天药业有限公司 | Synthetic method of intermediate cyclopropyl acetylene of anti-aids drug efavirenz |
| CN105152846A (en) * | 2015-09-25 | 2015-12-16 | 九江中天药业有限公司 | Method for efficiently preparing cylopropyl ethylnen |
| CN108440229A (en) * | 2018-04-20 | 2018-08-24 | 瑞孚信江苏药业股份有限公司 | A kind of preparation method of anti-AIDS drug big human relations intermediate cyclopropyl acetylene in accordance with the law |
-
2018
- 2018-12-28 CN CN201811623994.7A patent/CN109678652B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999007658A1 (en) * | 1997-08-12 | 1999-02-18 | Great Lakes Chemical Corporation | Preparation of gem-dihaloalkanes |
| CN103664465A (en) * | 2012-09-12 | 2014-03-26 | 九江中天药业有限公司 | Synthetic method of intermediate cyclopropyl acetylene of anti-aids drug efavirenz |
| CN105152846A (en) * | 2015-09-25 | 2015-12-16 | 九江中天药业有限公司 | Method for efficiently preparing cylopropyl ethylnen |
| CN108440229A (en) * | 2018-04-20 | 2018-08-24 | 瑞孚信江苏药业股份有限公司 | A kind of preparation method of anti-AIDS drug big human relations intermediate cyclopropyl acetylene in accordance with the law |
Non-Patent Citations (1)
| Title |
|---|
| 离子液体制备及其化工应用进展;蒋平平等;《化工进展》;20141231;第33卷(第11期);第2815-2828页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109678652A (en) | 2019-04-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100478338C (en) | Process for preparing annular carbonate | |
| CN107827730B (en) | Method for synthesizing p-hydroxymethyl benzoic acid by taking p-xylene (PX) as raw material | |
| CN1962602B (en) | Process for preparing dimethyl carbonate by reacting methanol, carbon monoxide and oxygen | |
| CN101830821A (en) | Chemical synthesis method of N-alcoxyloxalyl alanine ester | |
| CN101172253B (en) | Esterification catalysts and esterification process of organic acid | |
| CN104844411A (en) | Method for synthesizing hexafluoro-1,3-butadiene | |
| CN109678652B (en) | Preparation method of ionic liquid promoted alpha, alpha-dichloroethyl cyclopropane | |
| CN102060837B (en) | Preparation method of cyclic carbonic ester | |
| CN110590497B (en) | Method for synthesizing m-dichlorobenzene | |
| CN104275210A (en) | Catalytic system for preparing 2, 5-furan dicarboxaldehyde by using 5-hydroxymethyl furfural and application thereof | |
| CN108164393B (en) | Preparation method of deuterated tert-butyl alcohol | |
| CN107337576B (en) | Normal temperature catalytic synthesis of 2-bromo-5-fluorobenzotrifluoride | |
| CN109678651B (en) | Preparation method of high-purity alpha, alpha-dichloroethyl cyclopropane | |
| CN103319335B (en) | Preparation method of D-(-)-O-methyl mandelic acid chloride | |
| CN112794787B (en) | Method for continuously preparing 3,3, 3-trifluoro-2- (trifluoromethyl) -1-propylene in gas phase | |
| CN108976122A (en) | The method for preparing 1,3- dicarbonyl compound based on metal hydride/palladium compound system | |
| CN104211590A (en) | Preparation method of 2, 4-dichloro-fluorobenzoyl chloride | |
| CN114644587A (en) | Synthesis process of intermediate bicyclic imine of anti-novel coronavirus pneumonia medicine Paxlovid | |
| CN108047032A (en) | By α-ketoglutaric acid to glutaric acid synthetic method | |
| CN116239496A (en) | Method for continuously preparing heptafluoroisobutyronitrile | |
| CN112680497A (en) | Method for separating prostanoid drug key intermediate (1S,5R) -Corey lactone by using biological enzyme | |
| CN105418358A (en) | Method for preparing o-chlorotoluene | |
| CN108069832B (en) | Preparation method of 2,3,5, 6-tetrafluorophenol | |
| CN109734564B (en) | Method for synthesizing trifluoroethyl aromatic compound | |
| CN109970501B (en) | New preparation method of 1, 2-diphenylethane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |