Process for the preparation of 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane

Abstract

The application discloses a preparation method of 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, which comprises the following steps: step one, sodium methoxide methanol solution is put in, and a trichloromethyl reagent is added to react; an intermediate tetramethyl orthocarbonate is prepared; step two, sodium borohydride is added into a reaction organic reagent, and the reaction is stirred under the condition of-30 o C~ -20 o C, methyl trifluoroacetate is added dropwise, after dropwise addition is completed, stirring reaction is kept, after the reaction is completed, an acid is added to quench to be acidic, then the reaction liquid is post-treated to obtain an intermediate 3,3,3-trifluoro-1,2-propanediol; step three, the 3,3,3-trifluoro-1,2-propanediol is put into a reaction container together with a catalyst; 80 o C~100 o C, tetramethyl orthocarbonate is added dropwise under the condition of refluxing and stirring, after dropwise addition is completed, the reaction is stirred; after the reaction is completed, deionized water is added to quench, a third organic solvent is extracted, then filtration, spin-drying and rectification are sequentially performed to obtain a final product. The application has the advantages of high yield, simple process route, easy operation and easy acquisition of raw materials.

Description

Technical Field

[0001] This invention relates to the field of organofluorine synthesis technology, specifically to a method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane. Background Technology

[0002] Organofluorine compounds are highly valued in the field of organic synthesis due to their unique physicochemical properties and are widely used in various disciplines and fields such as medicine, pesticides, surfactants, and battery additives. Very few natural organofluorine compounds exist in nature; most are synthesized artificially. Currently, the synthesis of organofluorine compounds still faces many technical limitations, which significantly restricts their applications. Summary of the Invention

[0003] The purpose of this invention is to provide a method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, which uses readily available raw materials, has a simple preparation process, and achieves a high yield.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is: a method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, comprising the following steps.

[0005] 1. Add sodium methoxide to a methanol solution, add trichloromethyl reagent, and react to prepare the intermediate tetramethyl carbonate.

[0006] II. Sodium borohydride is added to the reacting organic reagent, -30 o C~-20 o Stirring under C conditions, methyl trifluoropyruvate was added dropwise. After the addition was complete, stirring was maintained to continue the reaction. After the reaction was completed, acid was added to quench the reaction until it became acidic. The reaction solution was then post-treated to obtain the intermediate 3,3,3-trifluoro-1,2-propanediol.

[0007] 3. 3,3,3-Trifluoro-1,2-propanediol and a catalyst are added to a reaction vessel, wherein the catalyst is selected from sulfuric acid and pyridine 4-methylbenzenesulfonic acid (PPTS); 80 o C~100 o Tetramethyl carbonate was added dropwise under C conditions. After the addition was complete, the mixture was kept under reflux and stirred. After the reaction was completed, the mixture was quenched with deionized water, extracted with a third organic solvent, and then filtered, evaporated, and distilled to obtain the final product.

[0008] The reaction principle described above is as follows: .

[0009] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, the concentration of sodium methoxide in the sodium methoxide methanol solution is 30 wt%.

[0010] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, the trichloromethyl reagent has the following general formula: The R group in the formula is a cyano, nitro, or thiochloro group; the molar ratio of trichloromethyl reagent to sodium methoxide is 1:(4-4.2).

[0011] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, the R group is a thiochloro group.

[0012] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, if the trichloromethyl reagent is perchloromethanethiol, then at 0... o C-5 o Add the solution dropwise under C conditions, and maintain the temperature at 0°C after the addition is complete. o C-5 o C. Stir the reaction for 8-16 hours; if trichloromethyl reagent is trichloroacetonitrile or trichloronitromethane, then at 30°C... o C-40 o The reaction solution was added dropwise under C conditions. A large amount of heat was released during the dropwise addition until reflux was achieved. After the dropwise addition was completed, the reaction was kept under reflux for 2-4 hours. After the reaction was completed, the reaction solution was post-treated to obtain the intermediate tetramethyl carbonate.

[0013] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, the first step of the reaction solution post-treatment step includes filtration, distillation of the filtrate under normal pressure to obtain a distillate, addition of a first organic solvent for fractional distillation, and collection of the residue to obtain the intermediate tetramethyl carbonate; the first organic solvent is selected from one of diethyl ether, dichloromethane, and methyl tert-butyl ether; the mass ratio of the distillate to the first organic solvent is 1:(8-15).

[0014] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the second step, the organic reagent used in the reaction is selected from one of tetrahydrofuran, methanol, and ethanol.

[0015] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, the second step of the reaction solution post-treatment step includes: extraction and rotary evaporation with a second organic solvent to obtain the intermediate 3,3,3-trifluoro-1,2-propanediol; the second organic solvent is selected from dichloromethane, ethyl acetate, and diethyl ether; the mass ratio of methyl trifluoropyruvate to the second organic solvent is 1:(5-10).

[0016] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the second step, the molar ratio of methyl trifluoropyruvate to sodium borohydride is 1:(1.0-1.5).

[0017] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the second step, the acid used for quenching is selected from one of 10 wt% hydrochloric acid, 10 wt% sulfuric acid, and 30 wt% citric acid aqueous solution.

[0018] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the second step, after the methyl trifluoropyruvate is added, the mixture is stirred at room temperature for 0.5-1.5 hours.

[0019] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the third step, the molar ratio of 3,3,3-trifluoro-1,2-propanediol to the catalyst is 1:(0.02~0.035).

[0020] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the third step, the molar ratio of 3,3,3-trifluoro-1,2-propanediol to tetramethyl carbonate is 1:(1.1~1.5).

[0021] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the third step, the third organic solvent is selected from one of dichloromethane (DCM), ethyl acetate, and diethyl ether.

[0022] Furthermore, in the aforementioned method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, in the third step, after the original tetramethyl carbonate is added dropwise, the mixture is kept under reflux and stirred for 2-5 hours.

[0023] The advantages of this invention are: 1. It provides a preparation process for 2,2-dialkoxy-4-(trifluoromethyl)-1,3-dioxolane, which has a high yield. 2. The process route is simple and the reaction is easy to control. 3. The raw materials are readily available. 4. The two intermediate products and the final product have high purity and good yield; one production line can prepare three products, thus making it suitable for industrial production. Attached Figure Description

[0024] Figure 1 This is the carbon NMR spectrum of the product prepared in Example 1.

[0025] Figure 2 The image shows the NMR fluorine spectrum of the product prepared in Example 1.

[0026] Figure 3 This is the 1H NMR spectrum of the product prepared in Example 1. Implementation

[0027] The preparation method of 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to the present invention will be described in detail below through specific embodiments.

[0028] Example 1: 1. Add 775g of sodium methoxide methanol solution, the concentration of sodium methoxide is 30 wt%, 0 o 200g of perchloromethanethiol was added dropwise under ice-water bath conditions. A large amount of heat was released during the addition, which was completed over 2 hours. After the addition was complete, the mixture was stirred in the ice-water bath for 10 hours. The solution was filtered, and the filtrate was distilled at atmospheric pressure to obtain 623g of distillate. This distillate was then purified by adding 6kg of dichloromethane and distilling again. The residue was collected to obtain 132g of the intermediate tetramethyl carbonate. The yield of tetramethyl carbonate was 90%, and the purity was 93%.

[0029] 2. 73g of sodium borohydride was added to 1.3kg of tetrahydrofuran, at -30°C. o Stirring at C, slowly add 250 g of methyl trifluoropyruvate dropwise over 2 hours, maintaining the mixture at room temperature (25°C) and stirring for 0.5 hours. Quench with 10% hydrochloric acid to acidity (pH < 7), extract with ethyl acetate, and rotary evaporate to obtain 178 g of intermediate 3,3,3-trifluoro-1,2-propanediol, with a yield of 85% and a purity of 98%.

[0030] 3. Add 112g of 3,3,3-trifluoro-1,2-propanediol and 4.8g of PPTS to a three-necked flask, 100 o Add 130g of tetramethyl orthocarbonate dropwise. After the addition is complete, maintain reflux and stir for 3 hours. Quench with deionized water, extract with DCM, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 152g of the final product. Yield: 87%, purity: 99.3%. The carbon NMR spectrum of the product is shown below. Figure 1 As shown, the NMR fluorine spectrum of the product is shown in the figure. Figure 2As shown, the product's 1H NMR spectrum is shown below. Figure 3 As shown.

[0031] Example 2: 1. Add 1000g of sodium methoxide methanol solution (sodium methoxide concentration 30 wt%) and 200g of trichloroacetonitrile dropwise at 40℃. A large amount of heat is released during the dropwise addition until reflux is achieved. The addition is completed in 1 hour, and the mixture is stirred under reflux for 2 hours. Filter the solution, collect the filtrate, and distill it at atmospheric pressure to obtain 850g of distillate. Add 8kg of dichloromethane for further distillation, and collect the residue from the still to obtain 170g of the intermediate tetramethyl carbonate, with a yield of 90% and a purity of 92%.

[0032] 2. 73g of sodium borohydride was added to 1.3kg of tetrahydrofuran, at -30°C. o Stirring at C, 250 g of methyl trifluoropyruvate was added dropwise over 2 hours, and the mixture was stirred at room temperature (25°C) for 0.5 hours. The mixture was then quenched with 10% hydrochloric acid to acidity (pH < 7), extracted with ethyl acetate, and rotary evaporated to obtain 177 g of the intermediate 3,3,3-trifluoro-1,2-propanediol, with a yield of 85% and a purity of 97%.

[0033] 3. Add 150g of 3,3,3-trifluoro-1,2-propanediol and 5.7g of PPTS to a three-necked flask, 100 o Add 170g of tetramethyl carbonate dropwise. After the addition is complete, maintain reflux and stir for 3 hours. Quench with deionized water, extract with DCM, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 195g of the final product, yield: 85%, purity: 99.2%.

[0034] Example 3: 1. Add 880g of sodium methoxide methanol solution, the concentration of sodium methoxide is 30 wt%, 30 o 200g of trichloronitromethane was added dropwise under C conditions. A large amount of heat was released during the addition until reflux was achieved, and the addition was completed in 1 hour. After the addition was complete, the mixture was kept under reflux with stirring for 2 hours. The mixture was filtered, and the filtrate was collected and distilled at atmospheric pressure to obtain 723g of distillate. 7kg of dichloromethane was added for further distillation, and the residue was collected to obtain 137g of the intermediate tetramethyl carbonate, with a yield of 83% and a purity of 93%.

[0035] 2. 73g of sodium borohydride was added to 1.3kg of tetrahydrofuran, at -30°C. o Stirring at C, slowly add 250g of methyl trifluoropyruvate dropwise over 2 hours, maintaining the mixture at room temperature and stirring for 0.5 hours. Quench with 10% hydrochloric acid to acidity (pH < 7), extract with ethyl acetate and rotary evaporate to give 181g of intermediate 3,3,3-trifluoro-1,2-propanediol; yield: 87%, purity: 98%.

[0036] 3. Add 117g of 3,3,3-trifluoro-1,2-propanediol and 5g of PPTS to a three-necked flask, 90 oAdd 135g of tetramethyl carbonate dropwise. After the addition is complete, maintain reflux and stir for 3 hours. Quench with deionized water, extract with DCM, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 160g of the final product. Yield: 88%, purity: 99.2%.

[0037] Example 4: 1. Add 815g of sodium methoxide methanol solution (sodium methoxide concentration 30 wt%) and add 200g of perchloromethane mercaptan dropwise under an ice-water bath at 5°C. A large amount of heat is released during the dropwise addition, which is completed in 2 hours. After the addition is complete, maintain stirring in the ice-water bath for 10 hours. Filter, collect the filtrate, and distill at atmospheric pressure to obtain 631g of distillate. Add 6kg of dichloromethane for rectification, collect the residue, and obtain 121g of the intermediate tetramethyl orthocarbonate, with a yield of 83% and a purity of 92%.

[0038] 2. 91g of sodium borohydride was added to 1.3kg of methanol, at -20°C. o Stirring at C, 250 g of methyl trifluoropyruvate was added dropwise over 3 hours, and the mixture was stirred at room temperature for 0.5 hours. The solution was then quenched to acidity (pH < 7) by adding a 30% citric acid aqueous solution. Extraction with dichloromethane and rotary evaporation yielded 183 g of the intermediate 3,3,3-trifluoro-1,2-propanediol. Yield: 88%, purity: 98%.

[0039] 3. Add 104g of 3,3,3-trifluoro-1,2-propanediol and 6g of PPTS to a three-necked flask, then add 100g of PPTS. o C. Add 120g of tetramethyl carbonate dropwise. After the addition is complete, maintain reflux and stir for 2 hours. Quench with deionized water, extract with ethyl acetate, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 152g of the final product, yield: 87%, purity: 99.3%.

[0040] Example 5: 1. Add 795g of sodium methoxide methanol solution, the concentration of sodium methoxide is 30 wt%, 0 o 200g of perchloromethanethiol was added dropwise under ice-water bath conditions. A large amount of heat was released during the addition, which was completed in 2 hours. After the addition was complete, the mixture was stirred in the ice-water bath for 16 hours. The mixture was filtered, and the filtrate was distilled at atmospheric pressure to obtain 629g of distillate. This distillate was then purified by adding 6kg of dichloromethane and distilling again. The residue was collected to obtain 126g of the intermediate tetramethyl orthocarbonate, with a yield of 86% and a purity of 92%.

[0041] 2. Add 60g of sodium borohydride to 1.3kg of ethanol, -25 o Stirring at C, 250g of methyl trifluoropyruvate was added dropwise over 2.5h. The mixture was stirred at room temperature for 0.5h. The mixture was then quenched to acidity with 10% sulfuric acid by mass, extracted with dichloromethane, and rotary evaporated to obtain 181g of the intermediate 3,3,3-trifluoro-1,2-propanediol, with a yield of 87% and a purity of 98%.

[0042] 3. Add 80g of 3,3,3-trifluoro-1,2-propanediol and 3.7g of PPTS to a three-necked flask, then add 100ml of water. o Add 125g of tetramethyl carbonate dropwise. Once the addition is complete, maintain reflux and stir for 5 hours. Quench with deionized water, extract with ethyl acetate, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 110g of the final product, yield 89%, purity 99.2%.

[0043] Example 6: 1. Add 795g of sodium methoxide methanol solution, the concentration of sodium methoxide is 30 wt%, 0 o 200g of perchloromethanethiol was slowly added under ice-water bath conditions. A large amount of heat was released during the dropwise addition, which was completed over 2 hours. After the addition was complete, the mixture was stirred in the ice-water bath for 10 hours. The mixture was filtered, and the filtrate was distilled at atmospheric pressure to obtain 637g of distillate. This distillate was then purified by adding 9kg of dichloromethane and distilling again. The residue was collected to yield 127g of the intermediate tetramethyl orthocarbonate, with a yield of 87% and a purity of 92%.

[0044] 2. 67g of sodium borohydride was added to 2.5kg of tetrahydrofuran, at -25°C. o Stirring at C, slowly add 250g of methyl trifluoropyruvate dropwise over 2.5h until the addition is complete. Maintain stirring at room temperature for 0.5h. Quench with 10% hydrochloric acid to acidity, extract with diethyl ether and rotary evaporate to obtain 185g of intermediate 3,3,3-trifluoro-1,2-propanediol, yield 89% and purity 98%.

[0045] 3. Add 100g of 3,3,3-trifluoro-1,2-propanediol and 1.9g of sulfuric acid (98% by mass) to a three-necked flask, 80 o Add 125g of tetramethyl carbonate dropwise. Once the addition is complete, maintain reflux and stir for 5 hours. Quench with deionized water, extract with ethyl acetate, dry, filter, and evaporate to dryness to obtain the crude product. Distill to obtain 136g of the final product. Yield 88%, purity 99.3%.

[0046] The advantages of this invention are: 1. It provides a novel preparation process for 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane, which yields a high amount of oxidized ...

Claims

A method for preparing 1,2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane includes the following steps:

1. Add sodium methoxide to a methanol solution and add trichloromethyl reagent to react; after the reaction is complete, the reaction solution is post-treated to obtain the intermediate tetramethyl carbonate; in the first step, the reaction solution post-treatment step includes filtration, distillation of the filtrate at atmospheric pressure to obtain a distillate, adding a first organic solvent for rectification, and taking the residue to obtain the intermediate tetramethyl carbonate; the first organic solvent is selected from one of diethyl ether, dichloromethane, and methyl tert-butyl ether; the mass ratio of the distillate to the first organic solvent is 1:(8-15). The trichloromethyl reagent is perchloromethanethiol, which is added dropwise at 0℃~5℃. After the addition is complete, the mixture is stirred at 0℃~5℃ for 8~16 hours. Alternatively, the trichloromethyl reagent is trichloroacetonitrile or trichloronitromethane, which is added dropwise at 30℃~40℃. During the addition, a large amount of heat is released until reflux is reached. After the addition is complete, the mixture is refluxed for 2~4 hours.

2. Sodium borohydride was added to the organic reagents for the reaction, and the mixture was stirred at -30℃ to -20℃. Methyl trifluoropyruvate was added dropwise, and the reaction was continued with stirring until the mixture was finished. After the reaction was completed, acid was added to quench the reaction until it became acidic. The reaction solution was then post-treated to obtain the intermediate 3,3,3-trifluoro-1,2-propanediol.

3. 3,3,3-trifluoro-1,2-propanediol and catalyst are added to a reaction vessel, wherein the catalyst is selected from sulfuric acid and pyridine 4-methylbenzenesulfonic acid; in the third step, the molar ratio of 3,3,3-trifluoro-1,2-propanediol to catalyst is 1:(0.02~0.035). Tetramethyl carbonate was added dropwise at 80℃~100℃. After the addition was complete, the mixture was stirred under reflux. After the reaction was completed, the mixture was quenched with deionized water, extracted with a third organic solvent, and then filtered, evaporated, and distilled to obtain the final product.

2. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: The concentration of sodium methoxide in the sodium methoxide methanol solution is 30 wt%.

3. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: The molar ratio of trichloromethyl reagent to sodium methoxide is 1:(4-4.2).

4. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 3, characterized in that: Trichloromethyl reagent is perchloromethanethiol.

5. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the second step, the organic reagent used in the reaction is selected from one of tetrahydrofuran, methanol, and ethanol.

6. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the second step, the post-treatment step of the reaction solution includes: extraction and rotary evaporation with a second organic solvent to obtain the intermediate 3,3,3-trifluoro-1,2-propanediol; the second organic solvent is selected from one of dichloromethane, ethyl acetate, and diethyl ether; the mass ratio of methyl trifluoropyruvate to the second organic solvent is 1:(5-10).

7. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the second step, the molar ratio of methyl trifluoropyruvate to sodium borohydride is 1:(1.0 to 1.5).

8. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the second step, the acid used for quenching is selected from one of the following: 10wt% hydrochloric acid, 10wt% sulfuric acid, and 30wt% citric acid aqueous solution.

9. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the second step, after the methyl trifluoropyruvate is added, the mixture is stirred at room temperature for 0.5 to 1.5 hours.

10. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the third step, the molar ratio of 3,3,3-trifluoro-1,2-propanediol to tetramethyl carbonate is 1:(1.1~1.5).

11. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the third step, the third organic solvent is selected from dichloromethane, ethyl acetate, and diethyl ether.

12. The method for preparing 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane according to claim 1, characterized in that: In the third step, after the original tetramethyl carbonate is added dropwise, the mixture is kept under reflux and stirred for 2 to 5 hours.

Images