CN115160116B - Preparation method of cyclopropyl methyl ketone - Google Patents

Preparation method of cyclopropyl methyl ketone Download PDF

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CN115160116B
CN115160116B CN202210670173.9A CN202210670173A CN115160116B CN 115160116 B CN115160116 B CN 115160116B CN 202210670173 A CN202210670173 A CN 202210670173A CN 115160116 B CN115160116 B CN 115160116B
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acid
ketone according
reaction
producing
acetoacetate
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CN115160116A (en
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张汉杰
张星
王镜淇
蒋榕培
孙海云
项锴
马军强
方涛
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Beijing Institute of Aerospace Testing Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • 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
    • C07C45/67—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 isomerisation; by change of size of the carbon skeleton
    • C07C45/673—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 isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C07C45/676—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 isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
    • C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a preparation method of cyclopropyl methyl ketone, which comprises the following steps: 1) Adding solid alkali into a mixture of acetoacetate, 1, 2-dihaloethane and a phase transfer catalyst, heating and stirring to react; 2) Cooling after the reaction is finished, filtering, washing the filtrate by pure water, and separating an aqueous phase from an organic phase; 3) Heating the organic phase obtained in the step 2), and distilling under reduced pressure to remove unreacted 1, 2-dihaloethane to obtain an intermediate product 1-acetyl cyclopropane-1-formate; 4) Mixing the intermediate product obtained in the step 3) with a solvent, water and an acid catalyst, heating and preserving heat for reaction; 5) And continuously heating, distilling, and collecting condensate, wherein the obtained condensate is the target product cyclopropyl methyl ketone. In the preparation method, the raw materials are green and low in toxicity, the yield of the target product is high, and the catalyst and the solvent can be recycled, so that the preparation method is suitable for further industrial amplification.

Description

Preparation method of cyclopropyl methyl ketone
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of cyclopropyl methyl ketone.
Background
Cyclopropyl methyl ketone is colorless volatile liquid with pungent smell, and is partially dissolved in water to form azeotrope with water, and can be mutually dissolved with alcohols, ethers, amides and alkanes organic solvents. In the prior art, cyclopropyl methyl ketone is mainly used as an important organic synthesis raw material. For example, the preparation method is mainly used for synthesizing antifungal agents cyproconazole and cyprodinil in the aspect of pesticides, and is used for preparing an anti-HIV drug efavirenz in the aspect of medicines. In addition, cyclopropyl methyl ketone has a tension ring structure, can be used for preparing a series of high-energy compounds, and is also valued in the field of energetic materials.
At present, the domestic cyclopropyl methyl ketone industrial product is prepared by mainly taking furfural as a raw material and carrying out 4 steps of catalytic hydrogenation, acid hydrolysis, chlorination and cyclization. The price of furfural, which is limited by biomass raw material, often fluctuates greatly, so that the selling price of cyclopropyl methyl ketone is not lower than 8 ten thousand yuan/ton all the time. On the other hand, hydrochloric acid is used for acidification in the process, a large amount of tarry byproducts are generated, the direct discharge can pollute the environment, the post-treatment is more complicated, and the overall yield is low.
Another existing preparation process is to use 2-acetyl-gamma-butyrolactone to crack under the catalysis of sodium iodide to obtain cyclopropyl methyl ketone. The process can realize one-step production of cyclopropyl methyl ketone, but has high requirement on process safety because the upstream raw material of 2-acetyl-gamma-butyrolactone uses high-toxic ethylene oxide, and does not accord with the green chemical concept. Meanwhile, the price of the catalyst sodium iodide is high, about 22 ten thousand yuan/ton, and the loss of the catalyst in the reaction process is large, so that the cost is high. In addition, the reaction is carried out at 170-200 ℃, which has high requirements on high temperature resistance and corrosion resistance of equipment and is not beneficial to the industrial production of cyclopropyl methyl ketone.
The existing industrial preparation method of cyclopropyl methyl ketone has limitations on cost or environmental friendliness, or uses high-toxicity and strong-corrosiveness reaction conditions, or can generate three wastes which are difficult to treat. In addition, the overall yield of the existing preparation method is not high, and a considerable amount of byproducts are generated, so that improvement is needed.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to solve the technical problems of overcoming the defects of the prior art and providing the preparation method of the cyclopropyl methyl ketone, which has the advantages of green and low toxicity of the used raw materials, high product yield and suitability for industrial amplification.
In order to solve the technical problems, the invention adopts the basic conception of the technical scheme that:
a method for preparing cyclopropyl methyl ketone, comprising the following steps:
1) Adding solid alkali into a mixture of acetoacetate, 1, 2-dihaloethane and a phase transfer catalyst, heating and stirring to react;
2) Cooling after the reaction is finished, filtering, washing filtrate with deionized water, and separating an aqueous phase and an organic phase;
3) Distilling the organic phase obtained in the step 2) under reduced pressure to remove unreacted 1, 2-dihaloethane to obtain an intermediate product 1-acetyl cyclopropane-1-formate;
4) Mixing the intermediate product obtained in the step 3) with a solvent, water and an acid catalyst, heating and preserving heat for reaction;
5) And continuously heating, distilling, and collecting condensate, wherein the obtained condensate is the target product cyclopropyl methyl ketone.
In the scheme, acetoacetate and 1, 2-dihaloethane are adopted as raw materials, and the target product cyclopropyl methyl ketone can be prepared through two-stage reactions of cyclopropanation reaction and decarboxylation reaction. The raw materials for the reaction are simple, low in cost and easy to obtain, and the method has the characteristics of green and low toxicity, and solves the problems of high cost and easy environmental pollution of the existing process for preparing the cyclopropyl methyl ketone. By utilizing the high activity of methylene in the acetoacetate as a raw material and the good leaving property of halogen ions in the 1, 2-dihaloethane, the yield of cyclopropanation reaction can reach a higher level. Meanwhile, the ester group in the intermediate product is subjected to beta-carbonyl electron-withdrawing effect, the decarboxylation reaction is more likely to occur, the reaction is irreversible, the intermediate product is further subjected to the decarboxylation reaction to obtain the target product cyclopropyl methyl ketone, the selectivity of the reaction is improved, and further, compared with the cyclopropyl methyl ketone preparation process in the prior art, the yield is improved. The preparation method accords with the green chemical concept, has high product yield, can obviously reduce the production cost, and is suitable for further industrialized amplification.
The reaction conditions of each step are simple, complex environments such as high temperature, high pressure and the like are not needed, and strict requirements on reaction equipment are not needed. After the cyclopropanation reaction stage is finished, only the unreacted complete raw material 1, 2-dihaloethane is distilled off after water washing, no further purification operation is needed, the obtained intermediate product can be directly used for the decarboxylation reaction of the later stage, and continuous feeding can be realized when the intermediate product is applied to industrial production.
Further, in the step 4), the reaction mixture is heated to 90-100 ℃ for reaction;
in the step 5), the temperature is continuously increased to 114-117 ℃ and the heat is preserved, and the target product cyclopropyl methyl ketone is distilled out.
In the above scheme, the temperature of the step 4) is relatively low, the reaction can be carried out in the temperature range to generate the target product cyclopropyl methyl ketone, and meanwhile, the step 4) is kept for a period of time, and meanwhile, the acid catalyst with volatility in the reaction mixture can be distilled off. If the acid catalyst used is not volatile, water in the reaction mixture can also be distilled off. And step 5) is further heated, so that the target product is extracted from the reaction mixture in a distillation mode, and the rest solvent and the acid catalyst without volatility can be recycled, thereby saving the cost.
Further, in the step 4), the mass ratio of the solvent to the intermediate product is (0.4-2): 1, preferably (0.4 to 1.5): 1, more preferably (0.5 to 0.6): 1.
preferably, the solvent comprises one or a combination of several of acetic acid, propionic acid, N-butyric acid, N-dimethylformamide, N-dimethylacetamide and dimethyl sulfoxide.
Further, in step 4), the molar ratio of water to intermediate is (2-6): 1.
further, in step 4), the molar ratio of the acid catalyst to the intermediate product is (1 to 10): 1.
preferably, the acid catalyst comprises one or a combination of several of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, p-toluenesulfonic acid, o-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid and trichloroacetic acid.
Further, in step 1), the mass of the phase transfer catalyst is 0.1 to 2.0% of the mass of the acetoacetate ester, preferably 0.5 to 1.0%.
In the present invention, the phase transfer catalyst may be any one of the compounds listed below:
(1) Quaternary ammonium salt: tetramethyl ammonium halide, ethyl ammonium halide, n-butyl ammonium halide, benzyl triethyl ammonium halide, dodecyl trimethyl ammonium halide, tetradecyl trimethyl ammonium halide, hexadecyl trimethyl ammonium halide, octadecyl trimethyl ammonium halide;
(2) Quaternary phosphonium salts: tetramethyl phosphonium halide, ethyl phosphonium halide, n-butyl phosphonium halide, phenyl phosphonium halide, dodecyl trimethyl phosphonium halide, tetradecyl trimethyl phosphonium halide, hexadecyl trimethyl phosphonium halide, octadecyl trimethyl phosphonium halide;
(3) Nonionic: beta-cyclodextrin, polyethylene glycol (average molecular weight 400-80000), polyethylene glycol dimethyl ether;
(4) Zwitterionic: betaines.
In the cyclopropanation reaction of the first stage of the preparation method, the carbanion from the acetoacetate is combined with the cation in the solid alkali to generate solid-phase salt, and the carbanion can be transferred from the solid phase to the solution phase for substitution reaction by adding a phase transfer catalyst, so that the purpose of generating the intermediate product 1-acetyl cyclopropane-1-formate by the reaction of the acetoacetate and the 1, 2-dihaloethane is realized.
In the above embodiments, the phase transfer catalyst is preferably a quaternary ammonium salt type phase transfer catalyst. Compared with a nonionic phase transfer catalyst, the quaternary ammonium salt type phase transfer catalyst has stronger transfer capability to anions, so that carbanions can be more fully transferred from a solid phase to a solution phase for substitution reaction, the yield of intermediate products in the cyclopropanation reaction stage is improved, and the overall yield of cyclopropane methyl ketone as a target product is further improved. The invention can control the overall yield of the target product to be not less than 89% by using a small amount of phase transfer catalyst, and can effectively control the production cost of the cyclopropyl methyl ketone.
Further, in the step 2), after washing the filtrate with deionized water 2 to 3 times, the aqueous phase and the organic phase are separated.
Further, in the step 2), the separated water phase is heated and evaporated to dryness, and the phase transfer catalyst in the water phase is obtained and is used for recycling.
In the scheme, the water phase obtained in the step 2) is heated and evaporated to dryness, so that the phase transfer catalyst in the water phase can be recovered, and the cost is further reduced.
Further, in step 1), the molar ratio of the solid base to acetoacetate is (2-4): 1, a step of;
preferably, the solid base comprises lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, potassium phosphate, sodium methoxide, lithium methoxide, sodium ethoxide, lithium ethoxide, sodium tert-butoxide or potassium tert-butoxide;
more preferably, the solid base is lithium hydroxide, sodium hydroxide or potassium hydroxide.
Further, in step 1), solid alkali is added to the mixture in batches;
preferably, the solid alkali is put into 3-6 batches, or 1/3-1/6 of the total mass of the solid alkali is put into each batch;
preferably, the mixture is stirred, and the solid alkali is added in batches during the stirring process;
more preferably, stirring is continued after the solid alkali is fully put into the reactor, and heating is started after the solid alkali is fully crushed.
In the scheme, the solid alkali is added in batches, so that the solid alkali is quickly crushed in the mixed liquid. After the solid alkali is completely crushed, the temperature is raised to perform the reaction, so that the reaction is started in an alkaline environment, and the problem that the solid alkali is insufficiently dissolved and cannot fully play a role is avoided.
Further, in step 1), the molar ratio of the 1, 2-dihaloethane to acetoacetate is (1 to 12): 1, preferably (6 to 10): 1, more preferably (7 to 9): 1, a step of;
preferably, the halogen in the 1, 2-dihaloethane is chlorine, bromine or iodine.
Further, in step 3), the temperature of the reduced pressure distillation is 80 to 90 ℃, preferably the boiling point of 1, 2-dihaloethane;
preferably, the pressure of the reduced pressure distillation is 0.1 to 0.6atm.
Further, condensate generated by reduced pressure distillation is collected to obtain the 1, 2-dihalogenated ethane for recycling.
In the scheme, the temperature of reduced pressure distillation is controlled to be near the boiling point of the 1, 2-dihaloethane, so that excessive reaction raw material 1, 2-dihaloethane is removed from a reaction system, the obtained intermediate product is ensured to have higher purity, and the purity of the finally obtained target product can be ensured. The reduced pressure distillation process is continued until no condensate is generated, and the collected condensate is the excessive reaction raw material 1, 2-dihaloethane, so that the recycle can be realized, and the cost is further reduced.
Further, in step 1), the acetoacetate is a C1-C4 alkyl acetoacetate.
Further, in the step 1), the temperature is raised to 40-75 ℃ to react, and the temperature is kept for 1-12 hours, and then the step 2) is carried out;
preferably, the reaction is carried out in step 1) by heating to 55 to 75 ℃, more preferably to 60 to 70 ℃.
In the scheme, the reaction temperature in the step 1) is controlled at 40-75 ℃, so that the raw material loss caused by the evaporation of the reaction raw material 1, 2-dihaloethane is avoided, the temperature is kept for 1-12 h to ensure that the cyclopropanation reaction in the first stage is fully carried out, and the temperature is kept for 3-6 h preferably.
Specifically, in the preparation method of cyclopropyl methyl ketone, the reaction route is shown as follows:
wherein R is C1-C4 alkyl, X is Cl, br or I. Base denotes the solid Base used, PTC denotes the phase transfer catalyst used, cat.
The preparation method specifically comprises the following steps of:
1) At room temperature, adding acetoacetate, 1, 2-dihaloethane and a phase transfer catalyst into a reaction bottle, stirring and mixing, adding solid alkali into the mixture in batches in the reaction bottle under the state of mechanical stirring, heating to 40-75 ℃ after the solid alkali is completely crushed, and carrying out heat preservation and stirring reaction for 1-12 h;
2) Cooling the reaction mixture to room temperature, filtering to remove insoluble solids, washing the filtrate with deionized water for 2-3 times, separating an aqueous phase from an organic phase, evaporating the aqueous phase to dryness to obtain a phase transfer catalyst for recycling;
3) Distilling the organic phase obtained in the step 2) under reduced pressure at 80-90 ℃, collecting condensate to obtain unreacted 1, 2-dihaloethane for cyclic application, distilling under reduced pressure until condensate is not generated any more, and obtaining an intermediate product 1-acetyl cyclopropane-1-formate in a reaction bottle;
4) Adding solvent, water and acid catalyst into the intermediate product obtained in the step 3), heating to 90-100 ℃ and preserving heat for 1-2 hours for reaction, and then distilling under reduced pressure to remove low-boiling impurities;
5) Continuously heating to 114-117 ℃ and preserving heat, continuously decompressing and distilling, and collecting the generated condensate, wherein the obtained condensate is the target product cyclopropyl methyl ketone.
By adopting the technical scheme, compared with the prior art, the invention has the following beneficial effects.
1. The invention adopts acetoacetate and 1, 2-dihaloethane as raw materials to prepare the target product cyclopropyl methyl ketone, the raw materials used are simple, cheap and easy to obtain, and are green and nontoxic, and the atomic utilization rate in the reaction process is higher, so that the high yield of the product can be realized, and the invention is suitable for further industrialized amplification.
2. In the preparation method, the reaction conditions of each step are simple, the difficulty of application to industrial production is low, after the cyclopropanation reaction of the first stage is finished, only water is needed to be washed, low-boiling-point substances are distilled off, and an intermediate product which can be directly used for the decarboxylation reaction of the second stage can be obtained, and further purification operations such as rectification are not needed to obtain the intermediate product, so that the preparation method is suitable for being applied to continuous feeding in industrial production.
3. In the preparation method, the phase transfer catalyst used in the cyclopropanation reaction stage, the solvent and the acid catalyst used in the decarboxylation reaction stage and the possible excessive 1, 2-dihaloethane serving as reaction raw materials can be recovered in the preparation process or after the preparation is completed, so that the cyclic utilization is realized, and the preparation method is favorable for reducing the production cost when being applied to industrial production.
The following describes the embodiments of the present invention in further detail with reference to the accompanying drawings.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention. In the drawings:
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the intermediate ethyl 1-acetylcyclopropane-1-carboxylate prepared in example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of cyclopropylmethyl ketone prepared in example 1 of the present invention.
It should be noted that these drawings and the written description are not intended to limit the scope of the inventive concept in any way, but to illustrate the inventive concept to those skilled in the art by referring to the specific embodiments.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the following examples will be clearly and completely described, and the following examples are provided for illustrating the present invention but are not intended to limit the scope of the present invention.
Example 1
This example prepared cyclopropylmethyl ketone using the following procedure:
1) 130g (1 mol) of ethyl acetoacetate, 792g (8 mol) of 1, 2-dichloroethane and 1.30g of benzyl triethyl ammonium chloride are put into a 2.5L round bottom flask at room temperature, stirred and mixed, 448g of potassium hydroxide is put into the flask in batches under the condition of mechanical stirring, and after the potassium hydroxide is completely crushed, the temperature is raised to 65 ℃, and the temperature is kept for stirring and reacting for 12 hours;
2) The reaction mixture is cooled to room temperature, insoluble solids are removed by filtration, the filtrate is washed with 60ml of deionized water for 2 times, an aqueous phase and an organic phase are separated, and the aqueous phase is evaporated to dryness to obtain benzyl triethyl ammonium chloride for recycling;
3) Distilling the organic phase obtained in the step 2) under reduced pressure at 80 ℃, collecting condensate to obtain unreacted 1, 2-dichloroethane for cyclic application, distilling under reduced pressure until condensate is not generated any more, and obtaining 146g of intermediate 1-acetyl cyclopropane-1-ethyl formate in a flask, wherein the yield is 94%, and the purity is 95% as measured by a gas chromatography internal standard method;
4) 67g of acetic acid, 36g of water and 104g of concentrated hydrochloric acid are added into the intermediate product obtained in the step 3), the mixture is heated to 100 ℃ and kept for 2 hours for reaction, and then the hydrochloric acid aqueous solution is distilled off under reduced pressure;
5) Continuously heating to 114 ℃ and preserving heat, continuously distilling under reduced pressure, and collecting the generated condensate to obtain 75g of the target product cyclopropyl methyl ketone, wherein the yield is 95%, and the purity is 97% as measured by a gas chromatography internal standard method. The rest hydrochloric acid solution can be recycled.
In this example, the nuclear magnetic resonance hydrogen spectrum of the intermediate product ethyl 1-acetyl cyclopropane-1-carboxylate obtained in step 3) is shown in fig. 1, and the nuclear magnetic resonance hydrogen spectrum of the target product cyclopropyl methyl ketone is shown in fig. 2. The overall yield of the target product cyclopropylmethyl ketone was 89% calculated on ethyl acetoacetate.
Example 2
This example prepared cyclopropylmethyl ketone using the following procedure:
1) 130g (1 mol) of ethyl acetoacetate, 188g (1 mol) of 1, 2-dibromoethane and 1.30g of tetra-n-butyl ammonium bromide are put into a 2.5L round-bottom flask at room temperature, stirred and mixed, 336g of potassium hydroxide is put into the flask in batches under the condition of mechanical stirring, and after the potassium hydroxide is completely crushed, the temperature is raised to 50 ℃, and the temperature is kept for stirring and reacting for 12 hours;
2) Cooling the reaction mixture to room temperature, filtering to remove insoluble solids, washing the filtrate with 60ml of deionized water for 2 times, separating an aqueous phase from an organic phase, and evaporating the aqueous phase to dryness to obtain tetra-n-butyl ammonium bromide for recycling;
3) Distilling the organic phase obtained in the step 2) under reduced pressure at 80 ℃ to remove low-boiling impurities, distilling under reduced pressure until condensate is not generated any more, and obtaining 154g of intermediate 1-acetyl cyclopropane-1-ethyl formate in a flask, wherein the yield is 99%, and the purity is 99% as measured by a gas chromatography internal standard method;
4) 73g of acetic acid, 36g of water and 104g of concentrated hydrochloric acid are added into the intermediate product obtained in the step 3), the mixture is heated to 100 ℃ and kept for 2 hours for reaction, and then the hydrochloric acid aqueous solution is distilled off under reduced pressure;
5) Continuously heating to 114 ℃ and preserving heat, continuously distilling under reduced pressure, and collecting the generated condensate to obtain 82g of the target product cyclopropyl methyl ketone, wherein the yield is 95%, and the purity is 97% as measured by a gas chromatography internal standard method. The rest hydrochloric acid solution can be recycled.
In this example, the overall yield of the target product cyclopropylmethyl ketone, calculated as ethyl acetoacetate, reached 96%.
Example 3
This example prepared cyclopropylmethyl ketone using the following procedure:
1) 116g (1 mol) of methyl acetoacetate, 792g (8 mol) of 1, 2-dichloroethane and 1.16g of benzyl triethyl ammonium chloride are put into a 2.5L round bottom flask at room temperature, stirred and mixed, 448g of potassium hydroxide is put into the flask in batches under the condition of mechanical stirring, and after the potassium hydroxide is completely broken, the temperature is raised to 65 ℃, and the temperature is kept for stirring and reacting for 12 hours;
2) The reaction mixture is cooled to room temperature, insoluble solids are removed by filtration, the filtrate is washed with 60ml of deionized water for 2 times, an aqueous phase and an organic phase are separated, and the aqueous phase is evaporated to dryness to obtain benzyl triethyl ammonium chloride for recycling;
3) Distilling the organic phase obtained in the step 2) under reduced pressure at 80 ℃, collecting condensate to obtain unreacted 1, 2-dichloroethane for cyclic application, distilling under reduced pressure until condensate is not generated any more, and obtaining 129g of intermediate product 1-acetyl cyclopropane-1-methyl formate in a flask, wherein the yield is 91%, and the purity is 95% as measured by a gas chromatography internal standard method;
4) 66g of acetic acid, 36g of water and 104g of concentrated hydrochloric acid are added into the intermediate product obtained in the step 3), the mixture is heated to 100 ℃ and kept for 2 hours for reaction, and then the hydrochloric acid aqueous solution is distilled off under reduced pressure;
5) Continuously heating to 114 ℃ and preserving heat, continuously distilling under reduced pressure, and collecting the generated condensate to obtain 71g of the target product cyclopropyl methyl ketone, wherein the yield is 93%, and the purity is 97% as measured by a gas chromatography internal standard method. The rest hydrochloric acid solution can be recycled.
In this example, the overall yield of the desired product, cyclopropylmethyl ketone, was 84% based on methyl acetoacetate.
Example 4
This example prepared cyclopropylmethyl ketone using the following procedure:
1) 158g (1 mol) of tert-butyl acetoacetate, 792g (8 mol) of 1, 2-dichloroethane and 1.16g of benzyl triethyl ammonium chloride are put into a 2.5L round bottom flask at room temperature, stirred and mixed, and 448g of potassium hydroxide is put into the flask in batches under the condition of mechanical stirring, and after the potassium hydroxide is completely broken, the temperature is raised to 65 ℃, and the temperature is kept for stirring and reacting for 12 hours;
2) The reaction mixture is cooled to room temperature, insoluble solids are removed by filtration, the filtrate is washed with 60ml of deionized water for 2 times, an aqueous phase and an organic phase are separated, and the aqueous phase is evaporated to dryness to obtain benzyl triethyl ammonium chloride for recycling;
3) Distilling the organic phase obtained in the step 2) under reduced pressure at 80 ℃, collecting condensate to obtain unreacted 1, 2-dichloroethane for cyclic application, distilling under reduced pressure until condensate is not generated any more, and obtaining 158g of intermediate 1-acetyl cyclopropane-1-tert-butyl formate in a flask, wherein the yield is 86%, and the purity is 95% as determined by a gas chromatography internal standard method;
4) Adding 82g of acetic acid, 36g of water and 104g of concentrated hydrochloric acid into the intermediate product obtained in the step 3), heating to 100 ℃ and preserving heat for 2 hours for reaction, and then distilling under reduced pressure to remove hydrochloric acid aqueous solution;
5) Continuously heating to 114 ℃ and preserving heat, continuously distilling under reduced pressure, and collecting the generated condensate to obtain 69g of the target product cyclopropyl methyl ketone, wherein the yield is 95%, and the purity is 97% as measured by a gas chromatography internal standard method. The rest hydrochloric acid solution can be recycled.
In this example, the overall yield of the desired product, cyclopropylmethyl ketone, was 82% based on methyl acetoacetate.
Comparative example 1
This example prepared cyclopropylmethyl ketone using the following procedure:
1) 200g of 2-methylfuran, 150g of 10% hydrochloric acid and 25g of 5% palladium-carbon catalyst are added into a 1L stainless steel reaction kettle at room temperature, uniformly stirred, continuously introduced with 0.3MPa hydrogen and continuously stirred for 24 hours;
2) Transferring the reaction mixture into a neutralization kettle, adding 8% sodium carbonate aqueous solution to neutralize residual hydrochloric acid, standing for liquid separation, discarding lower aqueous phase liquid, and performing reduced pressure distillation on an organic phase to obtain 236g of 5-hydroxy-2-pentanone, wherein the yield is 95% and the purity is 92%;
3) Adding 200g of 5-hydroxy-2-pentanone obtained in the step 2) and 560g of 20% hydrochloric acid into a 1L reaction bottle, heating to 60 ℃, preserving heat and stirring for about 1h, continuously heating to 90 ℃, preserving heat, collecting distilled products to obtain 145g of 5-chloro-2-pentanone, wherein the yield is 61%, the purity is 94%, and the hydrochloric acid is recovered and reused;
4) 110g of 5-chloro 2-pentanone obtained in the step 3), 43g of sodium hydroxide and 66g of deionized water are added into a 1L reaction bottle, stirred, heated and refluxed for 2h, cooled to room temperature, 60ml of tert-butyl methyl ether is added for extraction, the lower water phase is discarded after separation, and the solvent is removed by evaporation under reduced pressure from the organic phase, thus obtaining 74g of the target product cyclopropyl methyl ketone, the yield is 97%, and the purity is 95%.
In this comparative example, the overall yield of the final target product cyclopropylmethyl ketone was 56% based on the initial starting material 2-methylfuran.
As can be seen from the above examples 1 to 4 and comparative example 1, the overall yield of cyclopropylmethyl ketone prepared by the preparation method of the present invention can be not lower than 89%, whereas the overall yield of cyclopropylmethyl ketone prepared by the preparation method of comparative example 1 of the prior art is only 56%. Therefore, the preparation method of the cyclopropyl methyl ketone has high atom utilization rate, and can realize higher overall yield of the target product.
Test example 1
This test example was conducted in the same manner as in example 1 except that the amount of 1, 2-dichloroethane fed in step 1) was changed to examine the effect of the ratio of acetoacetate to 1, 2-dihaloethane in the reaction raw material on the objective product, and the results are shown in Table 1.
TABLE 1 Table of test data for the influence of the ratio of acetoacetate to 1, 2-dihaloethane on the objective product
In the cyclopropanation stage of the preparation process of the present invention, the molar ratio of the reacted 1, 2-dihaloethane to acetoacetate should be 1:1 theoretically. From the above test results, it can be seen that when the 1, 2-dihaloethane is fed in excess compared to the theoretical amount, for example, the molar ratio of 1, 2-dihaloethane to acetoacetate is greater than 3:1, the purity of the target product can reach more than 70 percent. And the molar ratio of the two is controlled to be (6-10): 1, the yield of the intermediate product, namely the cyclopropanation reaction reaches 85 percent and above, and the purity of the target product is not lower than 86 percent and the yield is not lower than 80 percent. Further controlling the molar ratio of the two to (7-9): 1, the yield of the intermediate product is increased to not less than 90%, the purity of the target product is further increased to not less than 95%, and the yield is increased to not less than 85%.
Therefore, in the present invention, in step 1), an excess of 1, 2-dihaloethane is fed, and the molar ratio of 1, 2-dihaloethane to acetoacetate is preferably (6 to 10): 1, more preferably (7 to 9): 1.
test example 2
This test example was conducted by examining the effect of the amount of the phase transfer catalyst on the objective product, and the results are shown in Table 2, except that the amount of benzyltriethylammonium chloride added in step 1) was changed as described in example 1.
TABLE 2 data sheet for test of the effect of the amount of phase transfer catalyst on the target product
Benzyl triethyl ammonium chloride (g) X(％) Intermediate yield (%) Purity of target product (%) Overall yield (%)
0.13 0.1 53 95 50
0.39 0.3 69 95 66
0.65 0.5 82 97 78
1.30 1.0 94 97 89
1.95 1.5 94 97 89
2.60 2.0 94 97 89
3.25 2.5 94 97 89
3.90 3.0 94 97 89
From the above test results, it can be seen that as the input quality of the phase transfer catalyst (i.e., benzyltriethylammonium chloride) increases, the yield of the intermediate product increases, and thus the purity and yield of the target product also correspondingly increase. When the mass of the phase transfer catalyst exceeds 1% of the mass of the ethyl acetoacetate, the yield of the intermediate product, and the purity and yield of the corresponding target product are not increased significantly.
Under the condition of considering production cost, the mass of the phase transfer catalyst is preferably controlled to be 0.5% -1.0% of the mass of the acetoacetate, the purity of a target product can reach 97%, and the yield can reach not lower than 78%.
Test example 3
This test example was conducted in the same manner as in example 1 except that the temperature of the heat-retaining layer in step 1) was changed to examine the effect of the reaction temperature on the target product in the cyclopropanation reaction in the first stage, and the results are shown in Table 3.
TABLE 3 data sheet for test of the effect of cyclopropanation reaction temperature on target product
Step 1) incubation temperature (. Degree. C.) Intermediate yield (%) Purity of target product (%) Overall yield (%)
40 73 97 69
45 80 95 76
50 84 96 80
55 87 94 83
60 89 95 86
65 91 97 89
70 95 92 90
75 98 84 93
As can be seen from Table 3 above, the yield of the intermediate product can be controlled to be not lower than 80% by controlling the holding temperature in step 1) to 45 to 75℃and further the purity of the objective product to be not lower than 84% and the yield to be not lower than 76%. When the temperature is controlled between 55 and 75 ℃, the yield of the intermediate product is increased to 87 percent or more, and the yield of the target product is increased to not less than 83 percent. When the temperature is between 60 and 70 ℃, the purity of the target product can reach 92 to 95 percent, and the yield reaches 86 to 90 percent.
Thus, the reaction is carried out in step 1) by heating the reaction mixture to 45 to 75 ℃, preferably to 55 to 75 ℃, more preferably to 60 to 70 ℃.
Test example 4
The experimental example was used to examine the effect of the solvent amount on the target product in the decarboxylation reaction of the second stage, and the implementation method was the same as that of example 1, and only the addition amount of acetic acid in step 4) was changed, and the mass ratio of acetic acid to the intermediate product was Y:1 and the results are shown in table 4.
TABLE 4 data table of the effect of decarboxylation solvent dosage on target product
The test results in table 4 above show that as the mass of the solvent (i.e., acetic acid) increases in the decarboxylation reaction stage, the purity of the target product gradually increases and eventually stabilizes around 97%, while the overall yield of the target product tends to decrease. The mass ratio of the solvent to the intermediate product in the decarboxylation reaction stage is controlled to be (0.4-1.5): 1, the purity of the target product can reach 90-97%, and the total yield is controlled at 72-89%. And the mass ratio of the solvent to the intermediate product is controlled to be (0.5-0.6): in the process 1, the purity of the target product can be increased to 96% -97%, and the overall yield is increased to 86% -89%.
Test example 5
This test example was conducted in the same manner as in example 1 except that the type of phase transfer catalyst in step 1) was changed to examine the effect of a different type of phase transfer catalyst on the objective product in the cyclopropanation reaction in the first stage, and the results are shown in Table 5.
TABLE 5 data sheet for test of the effect of phase transfer catalyst type on target product
Phase transfer catalyst Intermediate yield (%) Purity of target product (%) Overall yield (%)
Benzyl triethyl ammonium chloride 94 97 89
Tetra-n-butyl ammonium bromide 93 97 88
Tetraphenyl phosphonium chloride 74 98 70
Tetra-n-butylphosphonium chloride 91 99 86
Beta-cyclodextrin 82 94 77
Polyethylene glycol dimethyl ether 70 92 67
Betaine (betaine) 85 95 81
From the above test results, it can be seen that, in the same amount, the quaternary ammonium salt type phase transfer catalyst represented by benzyltriethylammonium chloride and tetra-n-butylammonium bromide gave an intermediate product having a higher yield of 93% to 94% in the cyclopropanation reaction of the first stage, as compared with other types of phase transfer catalysts. While other types of phase transfer catalysts, the corresponding intermediate yields are lower, especially nonionic phase transfer catalysts such as beta-cyclodextrin and polyethylene glycol dimethyl ether, which give yields of only 82% and 70%, respectively.
For the cyclopropane methyl ketone as a target product, the quaternary ammonium salt type phase transfer catalyst achieves 97% of purity of the target product, and achieves a higher level compared with other types of phase transfer catalysts, and meanwhile, the quaternary ammonium salt type phase transfer catalyst has 88% -89% of overall yield, which is higher than that of other types of phase transfer catalysts.
Therefore, the quaternary ammonium salt type phase transfer catalyst is preferable in the invention, and the high purity and the high overall yield of the target product cyclopropane methyl ketone can be simultaneously realized under the condition of low dosage of the phase transfer catalyst.
The foregoing description is only illustrative of the preferred embodiment of the present invention, and is not to be construed as limiting the invention, but is to be construed as limiting the invention to any and all simple modifications, equivalent variations and adaptations of the embodiments described above, which are within the scope of the invention, may be made by those skilled in the art without departing from the scope of the invention.

Claims (18)

1. The preparation method of the cyclopropyl methyl ketone is characterized by comprising the following steps:
1) Adding solid alkali into a mixture of acetoacetate, 1, 2-dihaloethane and a phase transfer catalyst, heating and stirring to react;
2) Cooling after the reaction is finished, filtering, washing filtrate with deionized water, and separating an aqueous phase and an organic phase;
3) Distilling the organic phase obtained in the step 2) under reduced pressure to remove unreacted 1, 2-dihaloethane to obtain an intermediate product 1-acetyl cyclopropane-1-formate;
4) Mixing the intermediate product obtained in the step 3) with a solvent, water and an acid catalyst, heating and preserving heat for reaction;
5) Continuously heating, distilling, and collecting condensate, wherein the condensate is the target product cyclopropyl methyl ketone;
in the step 1), the temperature is raised to 60-70 ℃ to react, the temperature is kept for 1-12 h, and then the step 2) is carried out;
in the step 1), the molar ratio of the 1, 2-dihaloethane to the acetoacetate is (6-10): 1, wherein the mass of the phase transfer catalyst is 0.5-1.0% of that of acetoacetate;
in the step 4), the reaction mixture is heated to 90-100 ℃ for reaction;
in the step 5), the temperature is continuously increased to 114-117 ℃ and the heat is preserved, and the target product cyclopropyl methyl ketone is distilled out.
2. The method for producing cyclopropylmethyl ketone according to claim 1, wherein in step 4), the mass ratio of the solvent to the intermediate product is (0.4 to 2): 1.
3. the method for preparing cyclopropylmethyl ketone according to claim 2, wherein the mass ratio of the solvent to the intermediate product is (0.4 to 1.5): 1.
4. the method for producing cyclopropylmethyl ketone according to claim 3, wherein the mass ratio of the solvent to the intermediate product is (0.5 to 0.6): 1.
5. the method for producing cyclopropylmethyl ketone according to claim 2, wherein the solvent comprises one or a combination of several of acetic acid, propionic acid, N-butyric acid, N-dimethylformamide, N-dimethylacetamide and dimethylsulfoxide.
6. The method for producing cyclopropylmethyl ketone according to claim 1, wherein in step 4), the molar ratio of the acid catalyst to the intermediate product is (1 to 10): 1.
7. the method for producing cyclopropylmethyl ketone according to claim 6, wherein the acid catalyst comprises one or a combination of several of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, p-toluenesulfonic acid, o-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid and trichloroacetic acid.
8. The method for producing cyclopropylmethyl ketone according to any one of claims 1 to 7, wherein in step 1), the phase transfer catalyst comprises tetramethyl ammonium halide, ethyl ammonium halide, n-butyl ammonium halide, benzyl triethyl ammonium halide, dodecyl trimethyl ammonium halide, tetradecyl trimethyl ammonium halide, hexadecyl trimethyl ammonium halide, octadecyl trimethyl ammonium halide, tetramethyl phosphonium halide, ethyl phosphonium halide, n-butyl phosphonium halide, phenyl phosphonium halide, dodecyl trimethyl phosphonium halide, tetradecyl trimethyl phosphonium halide, hexadecyl trimethyl phosphonium halide, octadecyl trimethyl phosphonium halide, β -cyclodextrin, polyethylene glycol dimethyl ether, or betaine.
9. The process for the preparation of cyclopropylmethyl ketone according to any one of claims 1 to 7, characterized in that in step 1) the molar ratio of solid base to acetoacetate is (2-4): 1.
10. the method for producing cyclopropylmethyl ketone according to claim 9, wherein the solid base comprises lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, potassium phosphate, sodium methoxide, lithium methoxide, sodium ethoxide, lithium ethoxide, sodium tert-butoxide, or potassium tert-butoxide.
11. The method for producing cyclopropylmethyl ketone according to claim 10, wherein the solid base is lithium hydroxide, sodium hydroxide or potassium hydroxide.
12. The process for preparing cyclopropylmethyl ketone according to any one of claims 1 to 7, wherein in step 1), solid base is added to the mixture in batches.
13. The process for producing cyclopropylmethyl ketone according to claim 12, wherein the solid alkali is introduced in 3 to 6 batches.
14. The method for producing cyclopropylmethyl ketone according to claim 12, wherein the mixture is stirred, and the solid base is added in portions during the stirring.
15. The method for producing cyclopropylmethyl ketone according to claim 14, wherein stirring is continued after the solid alkali is completely added, and the temperature is raised after the solid alkali is completely broken.
16. The process for the preparation of cyclopropylmethyl ketone according to any one of claims 1 to 7, characterized in that in step 1) the molar ratio of 1, 2-dihaloethane to acetoacetate is (7 to 9): 1.
17. the method for producing cyclopropylmethyl ketone according to claim 16, wherein the halogen in the 1, 2-dihaloethane is chlorine, bromine or iodine.
18. The process for the preparation of cyclopropylmethyl ketone according to any one of claims 1 to 7, wherein in step 1) the acetoacetate is a C1-C4 alkyl acetoacetate.
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