CN114956969B

CN114956969B - Preparation method of 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone

Info

Publication number: CN114956969B
Application number: CN202210815464.2A
Authority: CN
Inventors: 任川; 吴承骏; 魏兴辉; 胡海峰; 毛春晖
Original assignee: Ningxia Yongnong Biological Science Co ltd; YONGNONG BIOSCIENCES CO Ltd
Current assignee: Ningxia Yongnong Biological Science Co ltd; YONGNONG BIOSCIENCES CO Ltd
Priority date: 2022-07-12
Filing date: 2022-07-12
Publication date: 2024-04-16
Anticipated expiration: 2042-07-12
Also published as: CN114956969A

Abstract

The invention provides a preparation method of 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone, which comprises the following steps of: the preparation method comprises the steps of reacting trifluoroacetyl chloride with vinyl diethyl ether as a raw material, and performing aftertreatment to obtain 4-ethoxy-1, 1-trifluoro-3-butene-2-one, wherein the organic base is selected from N-methylmorpholine and/or N-methylimidazole. According to the invention, the pyridine is replaced by the N-methylmorpholine or N-methylimidazole, so that the quality of the product is improved, the environmental pollution is reduced, the alkali residue can be effectively removed after washing in the post-treatment process, and the problem of degradation of the final product in the solvent evaporating process is solved.

Description

Preparation method of 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone

Technical Field

The invention relates to the field of chemical synthesis, in particular to a preparation method of 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone.

Background

The 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone has active performance, and can be used as a raw material to synthesize a series of compounds containing trifluoromethyl, which are widely applied to the fields of medicines, pesticides, materials and the like. In the field of medicine, 4-ethoxy-1, 1-trifluoro-3-buten-2-one can be used for synthesizing antiviral drugs, anticancer drugs, anti-inflammatory drugs and the like; in the field of pesticides, 4-ethoxy-1, 1-trifluoro-3-buten-2-one has been successfully used for the industrialized preparation of commercial pesticides flonicamid and sulfoxaflor; in the field of materials, 4-ethoxy-1, 1-trifluoro-3-buten-2-one can be used for preparing metal ligands, ionic liquids and parting agents. The synthesis method is reported at home and abroad.

The synthesis methods of 4-ethoxy-1, 1-trifluoro-3-buten-2-one in the literature mainly comprise the following steps:

(1) The method has the advantages that the trifluoroacetic anhydride and vinyl ether are used as raw materials to react in a solvent in the presence of alkali, one molecule of trifluoroacetic acid generated after the trifluoroacetic anhydride reacts is not involved in the reaction, and the raw material utilization rate is low.

(2) Many researchers have also performed addition reaction of trifluoroacetyl chloride and vinyl ether in a solvent in the presence of a base, including pyridine, quinoline, triethylamine, dimethylaniline, diethylaniline, 4-dimethylaminopyridine, etc.; or the hydrogen chloride can be eliminated after addition, and the reaction product can be neutralized by heating or adding alkali. However, only pyridine is suitable for industrial production, but pyridine has malodor and strong irritation; can anesthetize central nervous system. Has stimulating effect on eyes and upper respiratory tract. After high concentration inhalation, the lighter people have euphoria or choking sensation, and then depression, muscle weakness and vomiting appear; loss of consciousness, incontinence of urine and faeces, spasticity, and blood pressure decrease in the serious patients. Misadministration can be fatal. Long-term inhalation is manifested by dizziness, headache, insomnia, gait instability and digestive tract dysfunction. Liver and kidney damage can occur. Dermatitis can be caused. Therefore, the requirements on workshop production conditions are high.

(3) Researchers have also performed addition reactions of trifluoroacetyl chloride with vinyl ether in the absence of solvents, removing hydrogen chloride by heating or low pressure. The trifluoroacetic acid is needed to prepare the trifluoroacetyl chloride, the impurities of the product are more when the solvent is not used in heating, the post-reaction treatment is complex, the environmental pollution is serious, and the method is not suitable for industrial production.

(4) Patent CN1330622C reacts vinyl ethyl ether with trifluoroacetyl chloride or trifluoroacetic anhydride in the presence of an onium salt of trifluoroacetic acid at room temperature. The solvent includes dichloromethane, hexane, etc., and the onium salt is preferably methyl pyridinium trifluoroacetate. The trifluoroacetic acid and pyridine are required to be firstly used as onium salts, so that the production cost is high, the environmental pollution is serious, and the method is not suitable for industrial production.

In conclusion, the existing preparation method of 4-ethoxy-1, 1-trifluoro-3-buten-2-one has the defects of harsh reaction conditions, serious environmental pollution, complicated post-treatment steps, low reaction yield, high production cost, unfavorable industrial production and the like.

Disclosure of Invention

Object of the Invention

In order to overcome the defects, the invention aims to provide the preparation method of the 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone, which has the advantages of few reaction steps, mild reaction conditions, environment friendliness, simple post-treatment steps, high reaction yield, high product purity and low production cost, and is suitable for industrial production.

Solution scheme

In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:

in a first aspect, the present invention provides a method for preparing 4-ethoxy-1, 1-trifluoro-3-buten-2-one, comprising the steps of: the preparation method comprises the steps of reacting trifluoroacetyl chloride with vinyl diethyl ether as a raw material, and performing aftertreatment to obtain 4-ethoxy-1, 1-trifluoro-3-butene-2-one, wherein the organic base is selected from N-methylmorpholine and/or N-methylimidazole.

Further, the post-treatment method includes washing with water, drying, and recovering the organic solvent.

Further, the water washing method comprises the following steps: water was added until the solids dissolved, the layers were separated by standing and the organic layer was dried.

Further, the aqueous layer is used for recovering the organic base.

Further, the organic layer was dried over anhydrous magnesium sulfate.

Further, the method for evaporating and recovering the organic solvent is to control the temperature to be lower than 50 ℃, and the vacuum distillation is carried out, and optionally, the vacuum degree is-0.09 to-0.1 Mpa. The evaporation to dryness to recover the solvent means that the dried organic layer is distilled under reduced pressure to recover the organic solvent.

Further, the molar ratio of the vinyl ethyl ether to the organic base is 1:1-1:5, preferably 1:1-1:2.

Further, the molar ratio of trifluoroacetyl chloride to vinyl ether is 1:1-2:1, preferably 1:1-1.1:1.

Further, the organic base is N-methylmorpholine.

Further, the feeding sequence is as follows: firstly adding vinyl diethyl ether, an organic solvent and an organic base, and then introducing trifluoroacetyl chloride gas for reaction.

Further, the organic solvent adopts alkane substituted by chlorine; alternatively, the organic solvent is dichloroethane or dichloromethane.

Further, the reaction temperature is 0-10 ℃.

Further, the reaction time after the trifluoroacetyl chloride is introduced is 0.5 to 3 hours.

Advantageous effects

(1) According to the invention, the pyridine is replaced by the N-methylmorpholine or N-methylimidazole, so that the quality of the product is improved, the environmental pollution is reduced, the alkali residue can be effectively removed after washing in the post-treatment process, and the problem of degradation of the final product in the solvent evaporating process is solved. Mainly because the inventors of the present invention found that pyridine could not be completely removed by washing with water, and residual pyridine could cause degradation of the final product. The inventor of the invention discovers that the adoption of N-methylmorpholine or N-methylimidazole can not only improve the reaction yield and quality, but also remove the residue through simple water washing, thereby not only effectively recycling the organic solvent, but also reducing the possibility of degradation of the final product.

(2) The method has the advantages of mild reaction conditions, simple post-treatment steps, high reaction yield, high product purity and low production cost, and is suitable for industrial production.

Drawings

One or more embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings. The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration. Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

Fig. 1: GC spectra of example 1 of the present invention for sample detection of dried organic layers; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Fig. 2: GC spectrogram of the product sampling detection of example 1 of the present invention; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Fig. 3: GC spectra of example 2 of the present invention for sample detection of dried organic layers; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Fig. 4: GC spectra of comparative example 1 of the invention for sampling detection of dried organic layers; wherein 3.9min is residual pyridine, and about 5min is the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one).

Fig. 5: the GC spectrogram of the distilled residue liquid sampling detection of the comparative example 1; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Fig. 6: GC spectra of comparative example 3 of the present invention for sample detection of dried organic layer; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Fig. 7: GC spectra of comparative example 4 of the present invention for sample detection of dried organic layer; wherein, the product (4-ethoxy-1, 1-trifluoro-3-buten-2-one) is about 5 min.

Wherein, the peaks about 3min in figures 1, 3, 4, 6 and 7 are mainly organic solvents, and can be evaporated to dryness in the distillation process in the later stage.

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 embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

In addition, numerous specific details are set forth in the following description in order to provide a better illustration of the invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, elements, methods, means, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present invention.

Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising", etc. will be understood to include the stated element or component without excluding other elements or components.

In the following examples, the spectrum refers to GC spectrum, i.e. gas chromatography detection. The temperature is lower than 50 ℃ when the solvent is recovered, the vacuum distillation is carried out, and the vacuum degree is between-0.09 and-0.1 Mpa.

Example 1

25g of vinyl ether, 100ml of dichloromethane and 38.1. 38.1g N-methylmorpholine are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, recovering N-methylmorpholine from a water layer, drying an organic layer by using anhydrous sodium sulfate, sampling and detecting the dried organic layer, and obtaining a spectrogram result shown in figure 1. After recovering the solvent by distillation under reduced pressure, a product with a GC purity of 99% was obtained, and a sample of the product was shown in FIG. 2. The yield was 99.5%,100% was cis structure.

Example 2

25g of vinyl ether, 150ml of dichloroethane and 30.8-g N-methylimidazole are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, and trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, recovering N-methylimidazole from the water layer, drying the organic layer by using anhydrous magnesium sulfate, sampling and detecting the dried organic layer, and obtaining a spectrogram result shown in figure 3. The solvent was recovered by distillation under reduced pressure to give a product with a GC purity of 99% and a yield of 99% with a cis structure of 100%.

Example 3

25g of vinyl diethyl ether, 100ml of dichloroethane and 38.1. 38.1g N-methylmorpholine are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, and trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, recovering N-methylmorpholine from the water layer, and drying the organic layer by using anhydrous sodium sulfate. The solvent was recovered by distillation under reduced pressure to give a product having a GC purity of 99% (almost no impurity peak as a result of the GC spectrum) and a yield of 99% and a cis structure of 100%.

Example 4

25g of vinyl ether, 150ml of dichloromethane and 30.8. 30.8g N-methylimidazole are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, recovering N-methylimidazole from the water layer, and drying the organic layer by using anhydrous magnesium sulfate. The solvent was recovered by distillation under reduced pressure to give a product with a GC purity of 99.4% in a yield of 99.2% and 100% in cis.

The above examples 1 to 4 illustrate that the organic base (N-methylmorpholine or N-methylimidazole) is effectively removed by simple washing with water and drying, and the product has no impurity peak (i.e., no impurity) after the solvent is recovered by evaporation to dryness, which means that the specific organic base (N-methylmorpholine or N-methylimidazole) selected in the invention is not only easily removed by washing with water, but also can improve the yield and the productivity of the product, and the post-treatment steps are simple and easy to operate, thereby being suitable for industrial production.

Comparative example 1

25g of vinyl ether, 150ml of dichloromethane and 30.0g of pyridine are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, drying the organic layer by using anhydrous magnesium sulfate, sampling and detecting the dried organic layer, and the spectrogram result is shown in figure 4. The solvent was recovered by distillation under reduced pressure to give a product with a GC purity of 97% in 92% yield and 100% in cis structure. The sample spectrum of the distilled residue (the residue containing the product and trace solvent at the later stage of reduced pressure distillation) is shown in FIG. 5, and the distilled residue is further purified to obtain the satisfactory product.

The results of comparative example 1 show that the spectrum peak in fig. 5 is relatively simple compared with fig. 4, but the amount of the organic solvent in fig. 5 is obviously reduced, but more miscellaneous peaks appear, the yield is also reduced, the organic solvent is recovered by a solvent evaporation method when pyridine is adopted, the production is not easy to carry out, and the inventor finds that the pyridine cannot be effectively removed in the water washing process through continuous analysis, and trace pyridine residues degrade the product in the evaporation process. The inventor has found through continuous attempts and experiments that N-methylmorpholine or N-methylimidazole can be effectively removed by water washing, so that the product degradation is reduced while the reaction yield is improved.

Comparative example 2

25g of vinyl diethyl ether, 150ml of dichloroethane and 30.0g of pyridine are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, preserving heat for reaction for 1h, adding 80g of water after sampling and analysis are qualified, stirring until the solid is completely dissolved for 10min, standing for layering, drying an organic layer by using anhydrous magnesium sulfate, and distilling under reduced pressure to recover the solvent to obtain a product with GC purity of 96% (the GC spectrogram shows that the product has a miscellaneous peak and possibly is degraded), wherein the yield is 90% and 100% is in a cis structure.

Comparative example 3

25g of vinyl ether, 150ml of dichloromethane and 30.8g of triethylamine are put into a 250ml four-mouth bottle, the system is closed, the temperature is reduced to 0-10 ℃, and trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, drying the organic layer by using anhydrous magnesium sulfate, sampling and detecting the dried organic layer, and the spectrogram result is shown in figure 6. The solvent was recovered by distillation under reduced pressure to give the product with GC purity 95% and yield 70% and 100% in cis structure.

This comparative example 3 illustrates that the use of triethylamine as the base may be detrimental to the reaction due to too strong basicity and the reaction may be more contaminated.

Comparative example 4

25g of vinyl ether, 150ml of dichloroethane and 35.0g of diisopropylethylamine are put into a 250ml four-necked flask, the system is closed, the temperature is reduced to 0-10 ℃, and trifluoroacetyl chloride gas is introduced into the system through a steel bottle, and the reaction temperature is maintained at 0-10 ℃. Stopping ventilation after the ventilation amount reaches 45.5g, carrying out heat preservation reaction for 1h, adding 80g of water after sampling analysis is qualified, stirring until the solid is completely dissolved for 10min, standing for layering, drying the organic layer by using anhydrous magnesium sulfate, sampling and detecting the dried organic layer, and the spectrogram result is shown in figure 7. The solvent was recovered by distillation under reduced pressure to give the product with GC purity 96% and yield 40% and 100% in cis structure.

This comparative example 4 illustrates that diisopropylethylamine as a base may be too basic to facilitate the reaction, and impurities are more abundant in the reaction.

Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A preparation method of 4-ethoxy-1, 1-trifluoro-3-buten-2-one is characterized in that in an organic solvent, under the condition of existence of organic alkali: reacting trifluoroacetyl chloride with vinyl diethyl ether as raw material, post-treating to obtain 4-ethoxy-1, 1-trifluoro-3-butene-2-ketone,

the organic base is selected from N-methylmorpholine and/or N-methylimidazole;

the mol ratio of the vinyl diethyl ether to the organic base is 1:1-1:5;

the molar ratio of the trifluoroacetyl chloride to the vinyl diethyl ether is 1:1-2:1.

2. The method of claim 1, wherein the post-treatment process comprises washing with water, drying, and recovering the organic solvent.

3. The method according to claim 2, wherein the water washing method comprises: adding water until the solid is dissolved, standing and layering; the organic layer was dried.

4. A process according to claim 3, wherein the aqueous layer is used for recovery of organic bases.

5. The method according to claim 3, wherein the organic layer is dried over anhydrous magnesium sulfate.

6. The method according to claim 2, wherein the method for recovering the organic solvent is: controlling the temperature below 50deg.C, and distilling under reduced pressure.

7. The process according to claim 6, wherein the vacuum degree of reduced pressure distillation is-0.09 to-0.1 MPa.

8. The method according to claim 1, wherein the molar ratio of vinyl ethyl ether to organic base is 1:1 to 1:2.

9. The process according to claim 1, wherein the molar ratio of trifluoroacetyl chloride to vinyl ether is 1:1 to 1.1:1.

10. The process according to claim 1, wherein the organic base is N-methylmorpholine.

11. The method according to any one of claims 1 to 10, wherein the order of addition is: firstly adding vinyl diethyl ether, an organic solvent and an organic base, and then introducing trifluoroacetyl chloride gas for reaction.

12. The method according to any one of claims 1 to 10, wherein the organic solvent is a chlorine-substituted alkane.

13. The preparation method according to any one of claims 1 to 10, wherein the organic solvent is dichloroethane or dichloromethane.

14. The preparation method according to any one of claims 1 to 10, wherein the reaction temperature is 0 to 10 ℃;

and/or the reaction time after the trifluoroacetyl chloride is introduced is 0.5 to 3 hours.