CN111072463A - Continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one - Google Patents
Continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one Download PDFInfo
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Abstract
The invention provides a continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone. The continuous synthesis method comprises the following steps: continuously feeding raw materials containing vinyl ethyl ether, triethylamine and trifluoroacetic anhydride into a continuous reactor for reaction to obtain a product system containing 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one; and (3) continuously extracting the product system to obtain the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one. By using a continuous process, the raw materials can be conveniently and accurately injected into a continuous reactor, and after the reaction is finished, the continuous extraction is also utilized for post-treatment, so that the whole process is quick, simple and efficient, the efficiency of the whole synthesis process is greatly improved, and the loss of product damage is reduced; the potential safety hazard of batch production is avoided. The amplification effect does not exist after amplification, and the safety and higher synthesis efficiency can still be maintained.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone.
Background
4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone is an important chemical synthesis intermediate, is widely applied to the organic synthesis industry, but has unstable chemical property, and the traditional synthesis idea is complex to operate, so that the application of the intermediate in the scale-up production process has various inconveniences. The existing synthesis process of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone comprises the following steps:
trifluoroacetic acid and vinyl ethyl ether as raw materials: mixing 10V of dichloromethane and 2.0eq of pyridine at normal temperature, controlling the temperature of the system to-5 ℃, slowly dripping trifluoroacetic acid into the system, mixing and stirring for 10 minutes, adding 1.0eq of vinyl ethyl ether into the system, keeping the low temperature, slowly dripping 1.0eq of methylsulfonyl chloride, naturally raising the temperature of the system to 20 ℃ after dripping is finished, and then stirring overnight. After the reaction was completed, the following post-treatments were carried out: firstly, a large amount of solids are separated out after the reaction is finished, a filter cake is washed by dichloromethane, products possibly taken away by the filter cake are washed away, then a filtrate is concentrated at 58 ℃ and normal pressure, a solvent is taken away, finally, a system is distilled under reduced pressure, the product is distilled out at 48 ℃/10mmHg, and the yield of the process is as high as 99.5%. The advantages of this process are evident: the yield is very high, but the defect of the method is clear at a glance, the raw materials are slowly dripped at low temperature in the whole process by controlling twice, the method is time-consuming and inconvenient to operate, more raw materials are used, the cost is relatively high, and the amplification effect which is usually possible to occur in batch reaction in the subsequent amplification production process can be generated.
Trifluoroacetyl chloride and vinyl ethyl ether as raw materials: 1.0eq of vinyl ethyl ether and 1.5eq of pyridine were dissolved in 10V of dichloromethane, and 1.5eq of trifluoroacetyl chloride was added dropwise to the system under nitrogen protection at 30 ℃ and the system was stirred at room temperature for 1.5 hours after the addition. And (3) post-treatment: dropwise adding 6.7V ice water into the reaction system, stirring, extracting, washing an organic phase with water and a saturated sodium chloride aqueous solution, drying the organic phase with anhydrous sodium sulfate, concentrating the collected organic phase at 60 ℃ to remove the solvent, and finally carrying out reduced pressure distillation to obtain a product at 10mbar and 85 ℃, wherein the yield is 81%. Although the method is simplified by a lot compared with the previous process operation and has shorter reaction time, the yield is not very high, and trifluoroacetyl chloride is active and unstable, and needs an inert gas protection system in the operation process, otherwise, the method is easy to lose efficacy.
Meanwhile, other methods exist in the prior art, such as a synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone, a system of trifluoroacetic acid and phosphorus pentachloride by taking vinyl ether as a reference material; trifluoroacetic anhydride and DMAP system; trifluoroacetic acid, triethylamine systems, and the like. However, none of these synthetic routes meets the requirements for an economical, efficient and safe synthesis of 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one.
The synthesis method mostly adopts batch reaction as a main reaction mode, the operation is complex, the efficiency is low, the method is not very economical and convenient, and the batches have common defects, namely, amplification effect may exist, the problem that the product is easy to deteriorate when meeting water is not solved, the yield is low, and the method is not suitable for practical application of commercial production and the like.
Disclosure of Invention
The invention mainly aims to provide a continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone, so as to solve the problem that the synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone in the prior art is difficult to adapt to industrial scale-up production.
In order to achieve the above objects, according to one aspect of the present invention, there is provided a continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one, comprising: continuously feeding raw materials containing vinyl ethyl ether, triethylamine and trifluoroacetic anhydride into a continuous reactor for reaction to obtain a product system containing 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one; and (3) continuously extracting the product system to obtain the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one.
Further, the molar ratio of the vinyl ethyl ether to the trifluoroacetic anhydride is 1:1 to 1.5:1, preferably 1.1: 1-1.3: 1, the molar ratio of triethylamine to trifluoroacetic anhydride is 1: 1-1.5: 1, preferably 1.2: 1-1.3: 1.
further, the vinyl ethyl ether, triethylamine and trifluoroacetic anhydride are continuously fed into the continuous reactor in the form of solution, and the solvent in the solution is preferably a polar solvent.
Further, the reaction temperature of the reaction is-40 to 100 ℃, the reaction preferably comprises a first stage reaction and a second stage reaction which are sequentially and continuously carried out, the reaction temperature T1 of the first stage reaction is-40 to 40 ℃, the retention time of the first stage reaction is preferably 40 to 80min, the reaction temperature T2 of the second stage reaction is 0 to 100 ℃, the retention time of the second stage reaction is preferably 40 to 80min, and the reaction temperature T1 is more preferably less than or equal to the reaction temperature T2.
Further, the continuous reactor comprises a first continuous reactor and a second continuous reactor which are arranged in series, and the process of continuously feeding the raw materials into the continuous reactors for reaction comprises the following steps: dissolving vinyl ethyl ether and triethylamine in a first polar solvent to obtain a mixed solution; dissolving trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution; respectively and continuously feeding the mixed solution and the anhydride solution into a first continuous reactor to carry out a first-stage reaction to obtain a primary reaction system; and continuously feeding the initial reaction system into a second continuous reactor to carry out second-stage reaction to obtain a product system.
Further, the continuous reactor is provided with a first reaction section and a second reaction section which are communicated, the first reaction section and the second reaction section are respectively provided with a temperature control structure, and the process of continuously feeding the raw materials into the continuous reactor for reaction comprises the following steps: dissolving vinyl ethyl ether and triethylamine in a first polar solvent to obtain a mixed solution; dissolving trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution; and respectively and continuously feeding the mixed solution and the anhydride solution into a first reaction section, and carrying out a first-stage reaction in the first reaction section and a second-stage reaction in a second reaction section to obtain a product system.
Further, the volume of the first polar solvent used per gram of the vinyl ethyl ether is 0.95 to 1.1mL, the volume of the second polar solvent used per gram of the trifluoroacetic anhydride is 0.95 to 1.1mL, the first polar solvent and the second polar solvent are preferably selected from any one of the group consisting of chloroform, dichloromethane and carbon tetrachloride, and the first polar solvent and the second polar solvent are more preferably the same.
Further, the process of continuously extracting the product system comprises the following steps: continuously feeding the product system and the acidic solution into a first extraction column to continuously perform acid extraction, so as to obtain a separated first organic phase and an acid water phase; continuously feeding the first organic phase and the alkaline solution into a second extraction column to continuously perform alkaline extraction to obtain a second separated organic phase and an alkaline aqueous phase; the solvent in the second organic phase is removed to give 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one.
The acidic solution is hydrochloric acid, citric acid, or trifluoroacetic acid, and the basic solution is preferably any one of an aqueous sodium bicarbonate solution, an aqueous potassium bicarbonate solution, an aqueous sodium carbonate solution, and an aqueous potassium carbonate solution.
Further, the retention time of the acid extraction is 10-80 min, and the retention time of the alkali extraction is 10-80 min.
By applying the technical scheme of the invention and using the continuous process, the raw materials can be conveniently and accurately injected into the continuous reactor, the continuous extraction is also utilized for post-treatment after the reaction is finished, the whole process is quick, simple and efficient, the efficiency of the whole synthesis process is greatly improved, and the product is timely and continuously extracted and separated along with continuous output, so that the loss of product damage is reduced; and the reactor can be recycled, thereby reducing the use cost. Meanwhile, a large amount of heat generated in the reaction process can be discharged through the continuous reactor in time and efficiently, so that the potential safety hazard of batch production is avoided. Moreover, the continuous synthesis method has no amplification effect after amplification, and still can keep the safety and higher synthesis efficiency.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:
FIG. 1 shows an intermediate product at a certain point in the course of the reaction according to example 1 of the present invention1HNMR spectrogram; and
FIG. 2 shows the end product of example 1 according to the invention1HNMR spectrogram.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.
As analyzed in the background of the present application, the synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one of the prior art is difficult to adapt to industrial scale-up production, and in order to solve this problem, the applicant tried to perform each synthesis method of the prior art in a continuous manner, but is limited to special control of reaction conditions, and cannot synthesize 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one inexpensively by continuously and precisely controlling the reaction. Through the intensive chemical mechanism research and experimental verification, the applicant proposes that the triethylamine is used for catalyzing the reaction of vinyl ethyl ether and trifluoroacetic anhydride, and realizes the continuous operation of the reaction.
Based on the above research, the present application provides a continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one, which comprises the following steps: continuously feeding raw materials containing vinyl ethyl ether, triethylamine and trifluoroacetic anhydride into a continuous reactor for reaction to obtain a product system containing 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one; and (3) continuously extracting the product system to obtain the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one.
The reaction route of the above reaction is as follows:
the continuous process is used, the raw materials can be conveniently and accurately injected into the continuous reactor, the continuous extraction is also used for post-treatment after the reaction is finished, the whole process is quick, simple and efficient, the efficiency of the whole synthesis process is greatly improved, and the product is timely and continuously extracted and separated along with continuous output, so that the loss of product damage is reduced; and the reactor can be recycled, thereby reducing the use cost. Meanwhile, a large amount of heat generated in the reaction process can be discharged through the continuous reactor in time and efficiently, so that the potential safety hazard of batch production is avoided. Moreover, the continuous synthesis method has no amplification effect after amplification, and still can keep the safety and higher synthesis efficiency.
In order to increase the conversion rate of the reactants, the molar ratio of the vinyl ethyl ether to the trifluoroacetic anhydride is preferably 1.0: 1-1.5: 1, preferably 1.1: 1-1.3: 1, and in order to ensure the catalytic efficiency of triethylamine and control the heat output, the molar ratio of the triethylamine to the trifluoroacetic anhydride is preferably 1.0: 1-1.5: 1, preferably 1.2: 1-1.3: 1.
in order to improve the conveying efficiency of each material and control the reaction rate, the vinyl ethyl ether, the triethylamine and the trifluoroacetic anhydride are preferably continuously fed into the continuous reactor in a solution mode, the materials are conveyed in the solution mode, the solvent is used for dilution, the materials participating in the reaction in unit time are effectively controlled, and further the output of reaction heat is effectively controlled. In order to improve the solubility of each substance, the solvent in the solution is preferably a polar solvent.
Because the reaction is exothermic and the reaction efficiency between materials is high, the reaction temperature of the reaction is preferably-40 to 100 ℃ to avoid the sudden increase of instantaneous heat production so as to ensure the safety, and the reaction rate is controlled by utilizing the reaction temperature. On the premise of ensuring safety, in order to improve production efficiency as much as possible, the preferable reaction comprises a first-stage reaction and a second-stage reaction which are sequentially and continuously carried out, wherein the reaction temperature T1 of the first-stage reaction is-40 ℃, the preferable retention time of the first-stage reaction is 40-80 min, the reaction temperature T1 of the second-stage reaction is 0-100 ℃, the preferable retention time of the second-stage reaction is 40-80 min, and the more preferable reaction temperature T1 is less than or equal to the reaction temperature T2. The first stage reaction is carried out at a relatively low temperature to allow the substrate to react gradually, and the concentration of the substrate in the system is reduced as the reaction proceeds, and then the reaction temperature is raised to enter the second stage reaction to secure the reaction rate.
In one embodiment of the present application, the continuous reactor includes a first continuous reactor and a second continuous reactor arranged in series, and the process of continuously feeding the raw materials into the continuous reactors for reaction includes: dissolving vinyl ethyl ether and triethylamine in a first polar solvent to obtain a mixed solution; dissolving trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution; respectively and continuously feeding the mixed solution and the anhydride solution into a first continuous reactor to carry out a first-stage reaction to obtain a primary reaction system; and continuously feeding the initial reaction system into a second continuous reactor to carry out second-stage reaction to obtain a product system.
Vinyl ethyl ether and triethylamine are mixed to form a mixed solution, and then the mixed solution and an anhydride solution are sent into a first continuous reactor, so that the triethylamine and trifluoroacetic anhydride are prevented from contacting and generating heat in advance. And two continuous reactors connected in series are used for carrying out continuous reaction, so that the temperature of the first-stage reaction and the second-stage reaction is effectively controlled, and the high-efficiency production efficiency is ensured.
In another embodiment of the present application, the continuous reactor has a first reaction section and a second reaction section that are arranged in communication, and the first reaction section and the second reaction section each have a temperature control structure, so that the process of continuously feeding the raw materials into the continuous reactor to perform a reaction includes: dissolving vinyl ethyl ether and triethylamine in a first polar solvent to obtain a mixed solution; dissolving trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution; and respectively and continuously feeding the mixed solution and the anhydride solution into a first reaction section, and carrying out a first-stage reaction in the first reaction section and a second-stage reaction in a second reaction section to obtain a product system. The first-stage reaction and the second-stage reaction are integrated in the same continuous reactor, so that the structure of the device is simplified, and the cost of the device is reduced.
The above-mentioned continuous reactor may employ a continuous reactor commonly used in the art, preferably a continuous coil reactor or a continuous column reactor. And the first continuous reactor and the second continuous reactor are both provided with a temperature control structure, such as a temperature control jacket, and the temperature control structures of the first reaction section and the second reaction section can also be temperature control jackets.
For precise control of the reaction progress, it is preferable that the volume of the first polar solvent used per gram of vinyl ether is 0.95 to 1.1mL, and the volume of the second polar solvent used per gram of trifluoroacetic anhydride is 0.95 to 1.1 mL. The first polar solvent and the second polar solvent used in the present application may be selected from polar solvents commonly used in the art, and preferably, the first polar solvent and the second polar solvent are each independently selected from any one of the group consisting of chloroform, dichloromethane, and carbon tetrachloride. In order to further increase the convenience of the post-treatment, it is preferable that the first polar solvent and the second polar solvent are the same.
In another embodiment of the present application, the above-mentioned continuous extraction process of the product system comprises: continuously feeding the product system and the acidic solution into a first extraction column to continuously perform acid extraction, so as to obtain a separated first organic phase and an acid water phase; continuously feeding the first organic phase and the alkaline solution into a second extraction column to continuously perform alkaline extraction to obtain a second separated organic phase and an alkaline aqueous phase; the solvent in the second organic phase is removed to give 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one. The acid solution is used for removing the alkaline catalyst in the reaction, and then the alkaline solution is used for washing off acidic impurities in the system, so that the high-efficiency extraction of the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one in the product system is realized. Because the contact time of the acid solution and the alkaline solution with the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone is short in the continuous extraction, the problem that the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone is easy to deteriorate when contacting with water is effectively controlled.
In order to save cost, the acidic solution is preferably hydrochloric acid, citric acid, or trifluoroacetic acid, and the basic solution is preferably any one of an aqueous sodium bicarbonate solution, an aqueous potassium bicarbonate solution, an aqueous sodium carbonate solution, and an aqueous potassium carbonate solution.
On the basis of ensuring higher extraction separation efficiency, in order to control the deterioration of the 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one as much as possible, the retention time of the acid extraction is preferably 10-80 min, preferably 40-80 min, and the retention time of the alkali extraction is preferably 10-80 min, preferably 40-80 min.
The advantageous effects of the present application will be further described below with reference to examples and comparative examples.
Example 1
Preparing equipment: four plunger pumps; a coil reactor which is divided into two sections which are communicated with each other, wherein the outside of each section is provided with a temperature control jacket, and the temperature is controlled by circulating water; a diaphragm pump: two extraction columns, 500ml liquid holdup, 2% hydrochloric acid extraction column RT 0.85hr, T0 deg.C, extraction column 2 8% NaHCO3The extraction column RT 1.06hr, T0 ℃.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 2.4g/min, and the feeding speed of the plunger pump B is set to be 2.4 g/min. The first reaction section is kept at the temperature of minus 10 ℃ for 60 min; the second reaction section is subjected to heat preservation at 40 ℃, the retention time is 60min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 3.0g/min, and the feeding speed of the plunger pump B is set to be 3.0 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 5.75g/min, and the retention time of the extraction column 1 is 51 min; the lower organic phase of the extraction column 1 was discharged and connected to a plunger pump D, the feed rate of the plunger pump D was set to 2.8g/min, and a 4V 8% sodium bicarbonate solution (matching the plunger pump D) was pumped into the extraction column 2 by a diaphragm pump E, the feed rate of the diaphragm pump E was set to 3.83g/min, and the retention time of the extraction column 2 was 64 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. Concentrating the organic phase to 327g under the conditions of 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 141g of the product when the temperature of the tower bottom is 50-55 ℃ and the temperature of the tower top is 40-48 ℃, wherein the yield is 83.2%.
Tracking the reaction by nuclear magnetic resonance at a certain moment during the reaction1The HNMR spectrum is shown in FIG. 1, of the final product1The HNMR spectrum is shown in FIG. 2.
Example 2
The difference from example 1 is that the first reaction stage is incubated at-10 ℃ and the second reaction stage is incubated at-10 ℃. 88.7g of the product was distilled off, resulting in a yield of 52.3%.
Example 3
The difference from example 1 is that the first reaction stage is maintained at 0 ℃ and the second reaction stage at 0 ℃. 94.6g of the product was distilled off, the yield being 55.8%.
Example 4
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 1.8g/min, and the feeding speed of the plunger pump B is set to be 1.8 g/min. The first reaction section is kept at the temperature of minus 40 ℃ for 80 min; the second reaction section is subjected to heat preservation at 0 ℃, the retention time is 80min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 2.25g/min, and the feeding speed of the plunger pump B is set to be 2.25 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 5.75g/min, and the retention time of the extraction column 1 is 51 min; the lower organic phase of the extraction column 1 was discharged and connected to a plunger pump D, the feed rate of the plunger pump D was set to 2.8g/min, and a 4V 8% sodium bicarbonate solution (matching the plunger pump D) was pumped into the extraction column 2 by a diaphragm pump E, the feed rate of the diaphragm pump E was set to 3.83g/min, and the retention time of the extraction column 2 was 64 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. And (3) concentrating 308g of the organic phase at 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 86g of the product at the tower bottom temperature of 50-55 ℃ and the tower top temperature of 40-48 ℃ with the yield of 65.1%.
Example 5
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 2.88g/min, and the feeding speed of the plunger pump B is set to be 2.88 g/min. The first reaction section is kept at 0 ℃ for 50 min; the second reaction section is subjected to heat preservation at 40 ℃, the retention time is 50min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 3.6g/min, and the feeding speed of the plunger pump B is set to be 3.6 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 5.75g/min, and the retention time of the extraction column 1 is 51 min; the lower organic phase of the extraction column 1 was discharged and connected to a plunger pump D, the feed rate of the plunger pump D was set to 2.8g/min, and a 4V 8% sodium bicarbonate solution (matching the plunger pump D) was pumped into the extraction column 2 by a diaphragm pump E, the feed rate of the diaphragm pump E was set to 3.83g/min, and the retention time of the extraction column 2 was 64 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. Concentrating the organic phase to 321.7g under the conditions of 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 130.1g of product at the tower bottom temperature of 50-55 ℃ and the tower top temperature of 40-48 ℃, wherein the yield is 78.2%.
Example 6
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 3.6g/min, and the feeding speed of the plunger pump B is set to be 3.6 g/min. The first reaction section is kept at 40 ℃ for 40 min; the second reaction section is subjected to heat preservation at 100 ℃, the retention time is 40min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 4.5g/min, and the feeding speed of the plunger pump B is set to be 4.5 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 5.75g/min, and the retention time of the extraction column 1 is 51 min; the lower organic phase of the extraction column 1 was discharged and connected to a plunger pump D, the feed rate of the plunger pump D was set to 2.8g/min, and a 4V 8% sodium bicarbonate solution (matching the plunger pump D) was pumped into the extraction column 2 by a diaphragm pump E, the feed rate of the diaphragm pump E was set to 3.83g/min, and the retention time of the extraction column 2 was 64 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. And concentrating 330g of the organic phase at 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 123. 5g of the product at the tower bottom temperature of 50-55 ℃ and the tower top temperature of 40-48 ℃, wherein the yield is 75%.
Example 7
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 2.4g/min, and the feeding speed of the plunger pump B is set to be 2.4 g/min. The first reaction section is kept at the temperature of minus 10 ℃ for 60 min; the second reaction section is subjected to heat preservation at 40 ℃, the retention time is 60min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 3.0g/min, and the feeding speed of the plunger pump B is set to be 3.0 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 7.34g/min, and the retention time of the extraction column 1 is 40 min; the lower organic phase of the extraction column 1 is discharged and then connected with a plunger pump D, the feeding speed of the plunger pump D is set to be 2.8g/min, meanwhile, a 4V 8% sodium bicarbonate solution (matched with the plunger pump D) is pumped into the extraction column 2 by a diaphragm pump E, the feeding speed of the diaphragm pump E is set to be 6.12g/min, and the retention time of the extraction column 2 is 40 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. Concentrating the organic phase to 292.8g under the conditions of 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 121.7g of the product when the temperature of the tower bottom is 50-55 ℃ and the temperature of the tower top is 40-48 ℃, wherein the yield is 80.2%.
Example 8
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 2.4g/min, and the feeding speed of the plunger pump B is set to be 2.4 g/min. The first reaction section is kept at the temperature of minus 10 ℃ for 60 min; the second reaction section is subjected to heat preservation at 40 ℃, the retention time is 60min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by chloroform, the feeding speed of the plunger pump A is set to be 3.0g/min, and the feeding speed of the plunger pump B is set to be 3.0 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 3.67g/min, and the retention time of the extraction column 1 is 80 min; the lower organic phase of the extraction column 1 is discharged and then connected with a plunger pump D, the feeding speed of the plunger pump D is set to be 2.8g/min, meanwhile, a 4V 8% sodium bicarbonate solution (matched with the plunger pump D) is pumped into the extraction column 2 by a diaphragm pump E, the feeding speed of the diaphragm pump E is set to be 3.06g/min, and the retention time of the extraction column 2 is 80 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. Concentrating 280g of organic phase at 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling to obtain 118.5g of distillate at the tower bottom temperature of 50-55 ℃ and the tower top temperature of 40-48 ℃, wherein the yield is 73.5%.
Example 9
The apparatus was prepared as in example 1.
Preparing a mixed solution from 95.19g of vinyl ethyl ether, 139.66g of triethylamine and 230ml of dichloromethane, and placing the mixed solution in a material stirring bottle A; 230g of trifluoroacetic anhydride and 230ml of dichloromethane were taken to prepare an anhydride solution, which was placed in a topping bottle B. And (3) starting to pump materials into the coil reactor through the plunger pump A and the plunger pump B, wherein the feeding speed of the plunger pump A is set to be 2.4g/min, and the feeding speed of the plunger pump B is set to be 2.4 g/min. The first reaction section is kept at the temperature of minus 10 ℃ for 60 min; the second reaction section is subjected to heat preservation at 40 ℃, the retention time is 60min, and the internal pressure is controlled to be 0.02-0.60 MPa; after the raw materials are beaten, the materials are ejected by dichloromethane, the feeding speed of a plunger pump A is set to be 3.0g/min, and the feeding speed of a plunger pump B is set to be 3.0 g/min. The discharge port of the coil reactor is directly connected with the extraction column 1, a plunger pump C pumps 6V 2% hydrochloric acid solution into the extraction column 1, and the feeding speed of the plunger pump C is set as: 3.67g/min, and the retention time of the extraction column 1 is 80 min; the lower organic phase of the extraction column 1 is discharged and then connected with a plunger pump D, the feeding speed of the plunger pump D is set to be 2.8g/min, meanwhile, a 4V 8% sodium bicarbonate solution (matched with the plunger pump D) is pumped into the extraction column 2 by a diaphragm pump E, the feeding speed of the diaphragm pump E is set to be 3.06g/min, and the retention time of the extraction column 2 is 80 min. After the material is filled, a 3L four-mouth bottle is used for receiving the organic phase discharged from the lower layer of the extraction column 2, and two 3L conical bottles are used for respectively receiving the acid water phase and the alkali water phase overflowing from the upper layers of the extraction column 1 and the extraction column 2 in the whole process. And concentrating 277.6g of the organic phase at 35 ℃ and 0.1MPa, performing reduced pressure distillation, and distilling 102g of the organic phase at the tower bottom temperature of 50-55 ℃ and the tower top temperature of 40-48 ℃ to obtain 68.3% of yield.
Example 10
The apparatus was prepared as in example 1. Except that the raw materials of example 10 were as follows: preparing a mixed solution from 79.0g of vinyl ethyl ether, 110.8g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.3g/min and the feed rate to plunger pump B was set to 2.5g/min, giving a calculated yield of 67.3% of the final product of 114 g.
Example 11
The apparatus was prepared as in example 1. Except that the raw materials of example 11 were as follows: 1180.4g of vinyl ethyl ether, 166.2g of triethylamine and 230ml of chloroform are taken to prepare a mixed solution which is put into a material mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.5g/min and the feed rate to plunger pump B was set to 2.3g/min, giving a calculated yield of 72.6% of 123g of final product.
Example 12
The apparatus was prepared as in example 1. Except that the raw materials of example 12 were as follows: preparing a mixed solution from 86.9g of vinyl ethyl ether, 133.0g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.4g/min and the feed rate to plunger pump B was set to 2.4g/min, giving a calculated yield of 81.4% of the final product, 138 g.
Example 13
The apparatus was prepared as in example 1. Except that the starting materials for example 13 were as follows: preparing a mixed solution from 102.7g of vinyl ethyl ether, 144.0g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.4g/min and the feed rate to plunger pump B was set to 2.4g/min, giving a calculated yield of 82.0% of the final product of 139 g.
Example 14
The apparatus was prepared as in example 1. Except that the starting materials for example 14 were as follows: preparing a mixed solution from 103g of vinyl ethyl ether, 144g of triethylamine and 219ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 219ml of dichloromethane were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.4g/min and the feed rate to plunger pump B was set to 2.4g/min, giving a calculated yield of 76.7% of the final product of 130 g.
Example 15
The apparatus was prepared as in example 1. Except that the raw materials of example 15 were as follows: preparing a mixed solution from 71.1g of vinyl ethyl ether, 105.3g of triethylamine and 230ml of chloroform, and placing the mixed solution in a material-mixing bottle A; 230g of trifluoroacetic anhydride and 230ml of chloroform were taken to prepare an anhydride solution, which was placed in a topping bottle B. The feed rate to plunger pump A was set to 2.3g/min and the feed rate to plunger pump B was set to 2.5g/min, giving a final product of 71.9g, a calculated yield of 42.4%.
From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects:
the continuous process is used, the raw materials can be conveniently and accurately injected into the continuous reactor, the continuous extraction is also used for post-treatment after the reaction is finished, the whole process is quick, simple and efficient, the efficiency of the whole synthesis process is greatly improved, and the product is timely and continuously extracted and separated along with continuous output, so that the loss of product damage is reduced; and the reactor can be recycled, thereby reducing the use cost. Meanwhile, a large amount of heat generated in the reaction process can be discharged through the continuous reactor in time and efficiently, so that the potential safety hazard of batch production is avoided. Moreover, the continuous synthesis method has no amplification effect after amplification, and still can keep the safety and higher synthesis efficiency.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-ketone is characterized by comprising the following steps:
continuously feeding raw materials containing vinyl ethyl ether, triethylamine and trifluoroacetic anhydride into a continuous reactor for reaction to obtain a product system containing 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one;
and continuously extracting the product system to obtain the 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one.
2. The continuous synthesis method according to claim 1, wherein the molar ratio of the vinyl ethyl ether to the trifluoroacetic anhydride is 1: 1-1.5: 1, preferably 1.1: 1-1.3: 1, the molar ratio of the triethylamine to the trifluoroacetic anhydride is 1: 1-1.5: 1, preferably 1.2: 1-1.3: 1.
3. the continuous synthesis method according to claim 1, wherein the vinyl ethyl ether, the triethylamine and the trifluoroacetic anhydride are continuously fed into the continuous reactor in a solution manner, and preferably, a solvent in the solution is a polar solvent.
4. The continuous synthesis method according to claim 1, wherein the reaction temperature of the reaction is-40 to 100 ℃, preferably the reaction comprises a first stage reaction and a second stage reaction which are sequentially and continuously performed, the reaction temperature T1 of the first stage reaction is-40 to 40 ℃, preferably the retention time of the first stage reaction is 40 to 80min, the reaction temperature T2 of the second stage reaction is 0 to 100 ℃, preferably the retention time of the second stage reaction is 40 to 80min, and more preferably the reaction temperature T1 is less than or equal to the reaction temperature T2.
5. The continuous synthesis method according to claim 4, wherein the continuous reactor comprises a first continuous reactor and a second continuous reactor which are arranged in series, and the process of continuously feeding the raw materials into the continuous reactors for reaction comprises the following steps:
dissolving the vinyl ethyl ether and the triethylamine in a first polar solvent to obtain a mixed solution;
dissolving the trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution;
continuously feeding the mixed solution and the anhydride solution into the first continuous reactor respectively to perform the first-stage reaction to obtain a primary reaction system;
and continuously feeding the initial reaction system into the second continuous reactor to carry out the second-stage reaction to obtain the product system.
6. The continuous synthesis method according to claim 4, wherein the continuous reactor has a first reaction section and a second reaction section which are arranged in communication, each of the first reaction section and the second reaction section has a temperature control structure, and the process of continuously feeding the raw materials into the continuous reactor for reaction comprises:
dissolving the vinyl ethyl ether and the triethylamine in a first polar solvent to obtain a mixed solution;
dissolving the trifluoroacetic anhydride in a second polar solvent to obtain an anhydride solution;
and continuously feeding the mixed solution and the anhydride solution into the first reaction section respectively, and carrying out the first-stage reaction in the first reaction section and the second-stage reaction in the second reaction section to obtain the product system.
7. The continuous synthesis method according to claim 5 or 6, wherein the volume of the first polar solvent used per gram of the vinyl ethyl ether is 0.95-1.1 mL, the volume of the second polar solvent used per gram of the trifluoroacetic anhydride is 0.95-1.1 mL, preferably the first polar solvent and the second polar solvent are each independently selected from any one of the group consisting of chloroform, dichloromethane and carbon tetrachloride, more preferably the first polar solvent and the second polar solvent are the same.
8. The continuous synthesis method according to claim 1, wherein the continuous extraction of the product system comprises:
continuously feeding the product system and the acidic solution into a first extraction column to continuously perform acid extraction, so as to obtain a separated first organic phase and an acid water phase;
continuously feeding the first organic phase and the alkaline solution into a second extraction column to continuously perform alkaline extraction to obtain a second separated organic phase and an alkaline aqueous phase;
removing the solvent from the second organic phase to obtain the 4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one.
9. The continuous synthesis method according to claim 8, wherein the acidic solution is hydrochloric acid, citric acid, or trifluoroacetic acid, and preferably the alkaline solution is any one of aqueous sodium bicarbonate solution, aqueous potassium bicarbonate solution, aqueous sodium carbonate solution, and aqueous potassium carbonate solution.
10. The continuous synthesis method according to claim 8, wherein the retention time of the acid extraction is 10-80 min, and the retention time of the alkali extraction is 10-80 min.
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|---|---|---|---|---|
| CN113121374A (en) * | 2021-04-06 | 2021-07-16 | 安徽丰本生物科技有限公司 | Preparation method of N- (2-methoxycarbonylvinyl) -4,4, 4-trifluoro-3-ketone-1-butenamine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1628087A (en) * | 2002-02-08 | 2005-06-15 | 索尔微氟及衍生物有限公司 | Production of alkenones |
| WO2011017389A1 (en) * | 2009-08-05 | 2011-02-10 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors useful against viral infections, particularly hcv |
| WO2014089378A1 (en) * | 2012-12-07 | 2014-06-12 | Siga Technologies, Inc. | Thienopyridine derivatives for the treatment and prevention of dengue virus infections |
| CN103965183A (en) * | 2014-03-17 | 2014-08-06 | 上海应用技术学院 | Fluorine-containingoxazolidinonecompound as well as preparation method and application thereof |
| CN104326891A (en) * | 2014-11-05 | 2015-02-04 | 联化科技(上海)有限公司 | Preparation method of 3-trifluoromethylpyrazole intermediate |
| CN104478911A (en) * | 2014-12-19 | 2015-04-01 | 成都安斯利生物医药有限公司 | Method for preparing 3-trifluoromethyl pyrrole boric acid |
-
2019
- 2019-12-03 CN CN201911222583.1A patent/CN111072463A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1628087A (en) * | 2002-02-08 | 2005-06-15 | 索尔微氟及衍生物有限公司 | Production of alkenones |
| WO2011017389A1 (en) * | 2009-08-05 | 2011-02-10 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors useful against viral infections, particularly hcv |
| WO2014089378A1 (en) * | 2012-12-07 | 2014-06-12 | Siga Technologies, Inc. | Thienopyridine derivatives for the treatment and prevention of dengue virus infections |
| CN103965183A (en) * | 2014-03-17 | 2014-08-06 | 上海应用技术学院 | Fluorine-containingoxazolidinonecompound as well as preparation method and application thereof |
| CN104326891A (en) * | 2014-11-05 | 2015-02-04 | 联化科技(上海)有限公司 | Preparation method of 3-trifluoromethylpyrazole intermediate |
| CN104478911A (en) * | 2014-12-19 | 2015-04-01 | 成都安斯利生物医药有限公司 | Method for preparing 3-trifluoromethyl pyrrole boric acid |
Non-Patent Citations (4)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121374A (en) * | 2021-04-06 | 2021-07-16 | 安徽丰本生物科技有限公司 | Preparation method of N- (2-methoxycarbonylvinyl) -4,4, 4-trifluoro-3-ketone-1-butenamine |
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