A catalyst for ethyl difluoroacetate synthesis and preparation method thereof

Abstract

The invention relates to the technical field of catalysis, and in particular to a catalyst for ethyl difluoroacetate synthesis and a preparation method thereof. The catalyst comprises a carrier and a catalyst shell layer, wherein the catalyst shell layer is loaded on the carrier; the catalyst shell layer is obtained by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-transition metal complex; the catalyst of the invention can catalyze the synthesis of ethyl difluoroacetate at a relatively low temperature, and has high yield, few side reactions, high product purity, and no problems such as equipment corrosion.

Description

Technical Field

[0001] The invention relates to the technical field of catalysis, in particular to a catalyst for synthesizing ethyl difluoroacetate and a preparation method thereof. Background Art

[0002] Ethyl difluoroacetate (CAS No. 454-31-9) is an important intermediate of fluorine-containing fine chemicals and is often used as a CF 2 The reagents introducing HCO- groups can be used to synthesize pesticides and pharmaceutical raw materials through reduction, condensation, amidation and other reactions. According to their different uses, they can be divided into: 1. Difluoroethyl acetate is reduced to synthesize difluoroethanol, and difluoroethanol is used as a raw material to synthesize the sulfonamide herbicide penoxsulam; 2. Synthesis of ethyl difluoroacetoacetate by condensation reaction, mainly used to synthesize fluorine-containing pyrazole rings, and then synthesize pesticides containing difluoroamide structures, or directly use ethyl difluoroacetoacetate as an intermediate to synthesize pyrimidine rings to prepare drugs for the prevention and treatment of neurodegenerative diseases; 3. Amidation reaction to synthesize difluoroethylamine and difluoroacetamide, and synthesize butenoic acid lactone insecticide; 4. Ethyl difluoroacetate is directly used as an intermediate for amidation to obtain a chloramphenicol derivative.

[0003] At present, the synthesis methods of ethyl difluoroacetate include: using tetrafluoroethylene as a raw material through addition, cracking, and esterification to obtain it; using difluoroethylene as a raw material through chlorination, acyl chloride, esterification, and dehalogenation to obtain it; using dichloroacetyl chloride as a raw material through amidation, fluorination, hydrolysis, and esterification to obtain it, among which the esterification reaction is a necessary step. At present, the esterification reaction mostly uses concentrated sulfuric acid as a catalyst, which has many disadvantages, such as many by-products in the esterification process, low product purity and yield, and serious equipment corrosion. Summary of the invention

[0004] Purpose of the invention: In view of the above technical problems, the present invention provides a catalyst for the synthesis of ethyl difluoroacetate and a preparation method thereof.

[0005] The technical solutions adopted are as follows: A catalyst for ethyl difluoroacetate synthesis, comprising a carrier and a catalyst shell layer, wherein the catalyst shell layer is supported on the carrier; The catalyst shell layer is obtained by free radical polymerization of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate and 4-vinylpyridine-transition metal complex; The carrier is ZrO 2 -SiO 2 Composite aerogel, the ZrO 2 -SiO 2 The preparation method of composite aerogel is as follows: Zirconium oxynitrate, anhydrous ethanol and deionized water are mixed to obtain a mixed solution, formamide and polyethylene glycol 400 are added to the mixed solution, and after stirring evenly, tetraethyl orthosilicate and 1,2-propylene oxide are added dropwise, and stirring is continued to make it fully mixed, and then placed in a 40-60°C oven for gelation, the obtained wet gel is solvent replaced with n-hexane, and then the wet gel after solvent replacement is aged, and finally vacuum freeze-dried.

[0006] Furthermore, the molar ratio of zirconyl nitrate to tetraethyl orthosilicate is 1:1-10.

[0007] Furthermore, during the aging treatment, the wet gel after solvent replacement is immersed in an anhydrous ethanol solution of ethyl orthosilicate having a temperature of 40-60° C. and a mass concentration of 1-10% for 12-48 hours.

[0008] Further, the preparation method of the 1-allyl-3-(4-sulfonic acid butyl) imidazole hydrogen sulfate is as follows: Mix imidazole, sodium ethoxide and acetonitrile, heat to reflux reaction for 5-10 hours, then add 3-bromo-1-propylene, continue to reflux reaction for 5-10 hours, then add 1,4-butane sultone, keep warm for reaction for 10-20 hours, then add concentrated sulfuric acid, continue to keep warm for reaction for 10-20 hours, distill under reduced pressure after the reaction is completed, wash the product with ethyl acetate and dry it in vacuum.

[0009] Furthermore, the 4-vinylpyridine-transition metal complex is a 4-vinylpyridine-nickel complex.

[0010] Furthermore, the preparation method of the 4-vinylpyridine-nickel complex is as follows: Nickel salt and 4-vinylpyridine in a molar ratio of 1:4 are added to anhydrous ethanol to obtain solution A and solution B, respectively. Solution A and solution B are mixed under stirring, and allowed to stand to allow complete complexation. The precipitate is collected, washed, and vacuum dried.

[0011] The present invention also provides a method for preparing a catalyst for ethyl difluoroacetate synthesis, which is as follows: Under nitrogen protection, the carrier is added to a dipolar solvent, and then 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 4-vinylpyridine-transition metal complex and free radical initiator are added, and the reaction is stirred at 60-80°C for 12-48h. After the reaction is completed, the precipitate is collected, washed and vacuum dried.

[0012] Furthermore, the mass ratio of the 1-allyl-3-(4-sulfonatebutyl)imidazole hydrogen sulfate and the 4-vinylpyridine-transition metal complex is 1:0.05-0.1.

[0013] Furthermore, the dipolar solvent is dimethyl sulfoxide and / or dimethylformamide.

[0014] Beneficial effects of the present invention: The present invention provides a catalyst for synthesizing ethyl difluoroacetate, ZrO 2 -SiO 2 Composite aerogel as a carrier, the porous characteristics of aerogel provides a huge specific surface area, which is conducive to the adsorption and mass transfer of reactant molecules, thereby improving the catalytic efficiency, and Zr 4+ It replaces some Si atoms in the silicon-oxygen tetrahedron to form Zr-O-Si, breaking the charge balance and generating Brønsted acid sites. The Brønsted acid sites can protonate the carbonyl oxygen of difluoroacetic acid, enhancing its electrophilicity and promoting the nucleophilic attack of ethanol, thereby improving the catalytic efficiency. 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate can provide a strong Bronsted acid site, which can protonate the carbonyl oxygen of difluoroacetic acid, enhance its electrophilicity, and promote the nucleophilic attack of ethanol. The complex formed by the 4-vinylpyridine ligand and the transition metal may activate the hydroxyl group of the carboxylic acid or alcohol through the Lewis acid action, reduce the reaction activation energy, accelerate the esterification process, and jointly increase the esterification reaction rate through the synergistic effect. The two are fixed in the shell through free radical polymerization to form a stable three-dimensional network structure, which can avoid the loss of catalytic active components and maintain the high efficiency of heterogeneous catalysis. The catalyst of the invention can catalyze the synthesis of ethyl difluoroacetate at a relatively low temperature, and has high product yield, few side reactions, high product purity, and no problems such as equipment corrosion. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The synthetic route of 1-allyl-3-(4-sulfonylbutyl)imidazole hydrogen sulfate in Example 1 is shown in FIG. DETAILED DESCRIPTION

[0016] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or the conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially. The techniques not mentioned in the present invention are all referenced to the prior art. Unless otherwise specified, the following examples and comparative examples are parallel experiments, using the same processing steps and parameters.

[0017] Embodiment 1: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: 40mmol zirconium oxynitrate, 150ml anhydrous ethanol and 50ml deionized water were mixed to obtain a mixed solution, 160mmol formamide and 8ml polyethylene glycol 400 were added to the mixed solution, and 120mmol tetraethyl orthosilicate and 960mmol 1,2-propylene oxide were added dropwise and stirred, and the mixture was stirred and mixed thoroughly, and then placed in a 40℃ oven for gelation for 30min, and the obtained wet gel was solvent replaced with n-hexane, and then the wet gel after solvent replacement was aged. During the aging treatment, the wet gel after solvent replacement was placed in a tetraethyl orthosilicate anhydrous ethanol solution with a temperature of 60℃ and a mass concentration of 10% and immersed for 24h, and finally taken out and vacuum freeze-dried to obtain ZrO 2 -SiO 2 Composite aerogel carrier; Mix 40mmol imidazole, 40mmol sodium ethoxide and 100ml acetonitrile, heat to reflux reaction for 8h, add 40mmol 3-bromo-1-propylene and continue reflux reaction for 5h, then add 40mmol 1,4-butane sultone and continue reflux reaction for 15h, then add 2.5g concentrated sulfuric acid and continue reflux reaction for 10h. After the reaction is completed, remove small molecules by vacuum distillation, wash the product with ethyl acetate and vacuum dry to obtain 1-allyl-3-(4-sulfonic acid butyl) imidazole hydrogen sulfate. For details, see Figure 1 ; Nickel chloride hexahydrate and 4-vinylpyridine in a molar ratio of 1:4 are added to an appropriate amount of anhydrous ethanol to obtain solution A and solution B, respectively. Solution A and solution B are mixed under stirring, and allowed to stand at room temperature for 5 hours to allow the complexation to be complete. The precipitate is collected, washed with anhydrous ethanol, and then vacuum dried to obtain a 4-vinylpyridine-nickel complex. Under nitrogen protection, 1g ZrO 2 -SiO 2 The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.05 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0018] Embodiment 2: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2 The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: ZrO 2 -SiO 2 The preparation method of the composite aerogel carrier, 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is the same as that of Example 1; Under nitrogen protection, 1g ZrO 2 -SiO 2 The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.06 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0019] Embodiment 3: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2 The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: ZrO 2 -SiO 2 The preparation method of the composite aerogel carrier, 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is the same as that of Example 1; Under nitrogen protection, 1g ZrO 2 -SiO 2The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.07 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0020] Embodiment 4: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2 The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: ZrO 2 -SiO 2 The preparation method of the composite aerogel carrier, 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is the same as that of Example 1; Under nitrogen protection, 1g ZrO 2 -SiO 2 The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.08 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0021] Embodiment 5: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2 The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: ZrO 2 -SiO 2The preparation method of the composite aerogel carrier, 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is the same as that of Example 1; Under nitrogen protection, 1g ZrO 2 -SiO 2 The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.09 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0022] Embodiment 6: This embodiment provides a catalyst for synthesizing ethyl difluoroacetate, comprising ZrO 2 -SiO 2 The composite aerogel carrier and catalyst shell layer are prepared by free radical polymerization of 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex. The catalyst shell layer is supported on ZrO 2 -SiO 2 On a composite aerogel carrier; The preparation method of the above-mentioned ethyl difluoroacetate synthesis catalyst is as follows: ZrO 2 -SiO 2 The preparation method of the composite aerogel carrier, 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is the same as that of Example 1; Under nitrogen protection, 1g ZrO 2 -SiO 2 The composite aerogel carrier was added into 100 ml of dimethylformamide, and then 1 g of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 0.1 g of 4-vinylpyridine-nickel complex and a catalytic amount of azobisisobutyronitrile were added. The mixture was stirred at 80 °C for 24 h. After the reaction was completed, the room temperature was restored, the precipitate was collected, washed with anhydrous ethanol and then dried in vacuum.

[0023] Comparative Example 1: It is basically the same as Example 1, except that SiO2 aerogel (Cabot ENOVA IC3100) is used instead of ZrO2-SiO2 composite aerogel as the carrier.

[0024] Comparative Example 2: is basically the same as Example 1, except that the catalyst shell does not contain 4-vinylpyridine-nickel complex.

[0025] Performance test: difluoroacetic acid and ethanol in a molar ratio of 1:50 were mixed evenly, and then the catalysts prepared in Examples 1-6 and Comparative Example 1-2 were added respectively, and the amount of catalyst added was 1% of the mass of difluoroacetic acid. The reaction system was heated to 50°C, and the reaction was stirred at a speed of 350rpm for 1h. During the reaction, the water produced by the reaction was separated by a water separator. After the reaction, the catalyst was collected, and the unreacted ethanol was removed by vacuum distillation to obtain a crude difluoroacetic acid ethyl ester. The yield was calculated and the purity of the product was tested. In addition, the same mass of concentrated sulfuric acid was added as a catalyst to catalyze the esterification reaction. The reaction parameters were the same. After the reaction, 50 times the volume of the reaction solution was added with ethyl acetate and a saturated sodium bicarbonate solution. After sufficient stirring, the ethyl acetate phase was collected, dried with anhydrous sodium sulfate, and then vacuum distilled to obtain a crude difluoroacetic acid ethyl ester. The yield was calculated and the purity of the product was tested; The results are shown in Table 1 below:

[0026] From the comparison of Examples 1-6 in Table 1 above, it can be seen that the catalyst prepared by the present invention can catalyze the synthesis of ethyl difluoroacetate at a relatively low temperature, and has a high yield, few side reactions, and high product purity. When the mass ratio of 1-allyl-3-(4-sulfonic acid butyl) imidazole hydrogen sulfate and 4-vinylpyridine-nickel complex is 1:0.08 during free radical polymerization, the reaction has the highest yield; From the comparison between Example 1 and Comparative Example 1 in Table 1 above, it can be seen that the use of ZrO 2 -SiO 2 The composite aerogel as a carrier played a positive role in improving the yield of ethyl difluoroacetate; From the comparison between Example 1 and Comparative Example 2 in Table 1 above, it can be seen that the catalyst shell layer obtained by copolymerization of 4-vinylpyridine-nickel complex plays a positive role in improving the yield of ethyl difluoroacetate.

[0027] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A catalyst for the synthesis of ethyl difluoroacetate, characterized in that: It comprises a carrier and a catalyst shell layer, wherein the catalyst shell layer is supported on the carrier; The catalyst shell layer is obtained by free radical polymerization of 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate and 4-vinylpyridine-transition metal complex; The carrier is a ZrO2-SiO2 composite aerogel; The preparation method of the ZrO2-SiO2 composite aerogel is as follows: Zirconium oxynitrate, anhydrous ethanol and deionized water are mixed to obtain a mixed solution, formamide and polyethylene glycol 400 are added to the mixed solution, and after stirring evenly, tetraethyl orthosilicate and 1,2-propylene oxide are added dropwise, and stirring is continued to make it fully mixed, and then placed in a 40-60°C oven for gelation, the obtained wet gel is solvent replaced with n-hexane, and then the wet gel after solvent replacement is aged, and finally vacuum freeze-dried.

2. The catalyst for ethyl difluoroacetate synthesis according to claim 1, wherein The molar ratio of the zirconyl nitrate to tetraethyl orthosilicate is 1:1-10.

3. The catalyst for ethyl difluoroacetate synthesis according to claim 1, wherein During the aging treatment, the wet gel after solvent replacement is immersed in an anhydrous ethanol solution of ethyl orthosilicate with a mass concentration of 1-10% and a temperature of 40-60° C. for 12-48 hours.

4. The catalyst for ethyl difluoroacetate synthesis according to claim 1, wherein The preparation method of the 1-allyl-3-(4-sulfonic acid butyl) imidazole hydrogen sulfate is as follows: Mix imidazole, sodium ethoxide and acetonitrile, heat to reflux reaction for 5-10 hours, then add 3-bromo-1-propylene, continue to reflux reaction for 5-10 hours, then add 1,4-butane sultone, keep warm for reaction for 10-20 hours, then add concentrated sulfuric acid, continue to keep warm for reaction for 10-20 hours, distill under reduced pressure after the reaction is completed, wash the product with ethyl acetate and dry it in vacuum.

5. The catalyst for ethyl difluoroacetate synthesis according to claim 1, wherein The 4-vinylpyridine-transition metal complex is a 4-vinylpyridine-nickel complex.

6. The catalyst for ethyl difluoroacetate synthesis according to claim 5, characterized in that The preparation method of the 4-vinylpyridine-nickel complex is as follows: Nickel salt and 4-vinylpyridine in a molar ratio of 1:4 are added to anhydrous ethanol to obtain solution A and solution B, respectively. Solution A and solution B are mixed under stirring, and allowed to stand to allow complete complexation. The precipitate is collected, washed, and vacuum dried.

7. A method for preparing a catalyst for ethyl difluoroacetate synthesis as claimed in any one of claims 1 to 6, characterized in that: The details are as follows: Under nitrogen protection, the carrier is added to a dipolar solvent, and then 1-allyl-3-(4-sulfonylbutyl) imidazole hydrogen sulfate, 4-vinylpyridine-transition metal complex and free radical initiator are added, and the reaction is stirred at 60-80°C for 12-48h. After the reaction is completed, the precipitate is collected, washed and vacuum dried.

8. The method for preparing a catalyst for ethyl difluoroacetate synthesis as claimed in claim 7, wherein: The mass ratio of the 1-allyl-3-(4-sulfonate butyl) imidazole hydrogen sulfate and the 4-vinylpyridine-transition metal complex is 1:0.05-0.1.

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