Preparation method of high-purity 2-fluoroethanol

Abstract

The invention discloses a preparation method of high-purity 2-fluoroethanol, and particularly relates to the technical field of preparation of 2-fluoroethanol, which comprises the following steps: S1, in a dual-catalyst system consisting of a phase transfer catalyst and a Lewis acid catalyst and an organic solvent, carrying out fluoridation reaction on 2-chloroethanol and anhydrous potassium fluoride at 60-120 DEG C for 2-10 hours to obtain 2-chloroethanol; and S2, sequentially carrying out integrated purification of filtration, reduced pressure distillation, adsorption treatment and rectification on the reaction mixture. According to the invention, through synergistic activation and mass transfer of double catalysts, the reaction rate and selectivity are significantly improved, the water segregator is utilized to remove reaction water to push equilibrium movement, the conversion rate is improved, and water and impurities are systematically removed by virtue of composite adsorption and precise rectification of molecular sieves and activated carbon, so that high-quality 2-fluoroethanol with high purity and low moisture is finally obtained. The whole preparation process is mild in condition, high in yield, good in safety and suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of 2-fluoroethanol preparation, more particularly, the present application relates to a preparation method of high-purity 2-fluoroethanol. BACKGROUND

[0002] 2-fluoroethanol is an important fluorine-containing organic synthesis intermediate, and its high-purity product has wide application value in the fields of medicine, pesticide and high-end electronic chemicals, etc. For example, it is a key chiral building block for synthesizing some anticancer drugs, antibiotics and high-efficiency insecticides.

[0003] At present, the synthesis methods of 2-fluoroethanol mainly include the following categories: Epoxide fluorination method: this method directly reacts ethylene oxide with anhydrous hydrogen fluoride as raw materials, although this route is short, but has obvious defects: first, anhydrous hydrogen fluoride has strong corrosive and toxic, the production equipment material quality is extremely high, and there is serious safety hazard, second, the reaction is a violent exothermic process, which is easy to cause the ring-opening polymerization of ethylene oxide and other side reactions, generating water, difluorodiethyl ether and other by-products, resulting in the purity of the final product is generally low, it is difficult to meet the needs of high-end applications; 2-chloroethanol fluorination substitution method: this method uses 2-chloroethanol and fluorinating reagent to carry out nucleophilic substitution reaction, although this route avoids the use of high-risk hydrogen fluoride, the safety is improved, but due to the low solubility and reactivity of potassium fluoride in organic medium, the traditional process needs to use extremely high reaction temperature, long reaction time and excessive potassium fluoride, these harsh reaction conditions not only lead to high energy consumption, but also aggravate the dehydration, oxidation and decomposition of raw materials and other side reactions, resulting in the color of the final product is deepened, the residual amount of chlorine is high, the purity is not ideal and other problems.

[0004] In summary, the existing technology generally faces the problems of low product purity, many by-products, use of dangerous reagents, harsh reaction conditions, high energy consumption and difficult control of key impurities, etc. Therefore, the present application provides a preparation method of high-purity 2-fluoroethanol. SUMMARY

[0005] In order to overcome the above-mentioned defects of the prior art, the present application provides a preparation method of high-purity 2-fluoroethanol to solve the problems in the above background art.

[0006] To achieve the above purpose, the present application provides the following technical scheme: a preparation method of high-purity 2-fluoroethanol, comprising the following steps: S1, fluorination of 2-chloroethanol with potassium fluoride in the presence of a double catalyst system consisting of a phase transfer catalyst and a Lewis acid catalyst, and an organic solvent, at 60-120℃ for 2-10h, the molar ratio of potassium fluoride to 2-chloroethanol being (1-1.5):1, to form a reaction mixture containing 2-fluoroethanol; S2, purification treatment of the reaction mixture of step S1 to obtain 2-fluoroethanol with a purity of not less than 99.9%.

[0007] Preferably, the mass ratio of the phase transfer catalyst to the Lewis acid catalyst is 1:1 to 10:1.

[0008] Preferably, the phase transfer catalyst is at least one of tetrabutylammonium bromide, tetrabutylammonium chloride or tetrabutylammonium hydrogen sulfate, and the Lewis acid catalyst is at least one of boron trifluoride diethyl ether complex, zinc chloride or aluminum trichloride.

[0009] Preferably, the organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide or N-methyl pyrrolidone.

[0010] Preferably, the potassium fluoride is anhydrous powder with an average particle size of 100-400 mesh.

[0011] Preferably, the purification treatment in step S2 includes the following steps performed in sequence: a) filtering the reaction mixture, and collecting 2-fluoroethanol crude product by distillation of the obtained filtrate under reduced pressure; b) adsorbing treatment of 2-fluoroethanol crude product by contacting with an adsorbent; c) collecting the high-purity 2-fluoroethanol by rectifying the liquid after adsorbing treatment at 62-64℃ / 30mmHg.

[0012] Preferably, the adsorbent includes molecular sieves and activated carbon, and the molecular sieves are at least one of 3A molecular sieves or 4A molecular sieves.

[0013] Preferably, the mass ratio of the molecular sieves to the activated carbon is 1:1 to 3:1.

[0014] Preferably, in step b), the adsorbing treatment is performed at a temperature of 20-40℃ for 2-6h, and stirring is continuously performed during the adsorbing process.

[0015] Preferably, the fluorination reaction is performed in a reaction device equipped with a water trap for real-time separation and removal of water generated during the reaction.

[0016] Technical effects and advantages of the present application: 1. By using a double-catalyst system composed of a phase transfer catalyst and a Lewis acid catalyst, the two catalysts work together, the phase transfer catalyst greatly improves the concentration and reactivity of fluoride ions in the organic phase, and the Lewis acid effectively activates the C-Cl bond in the 2-chloroethanol molecule, which greatly reduces the energy barrier of the fluorination reaction, making the reaction faster and more complete, reducing the generation of by-products from the source, thereby achieving high product purity and high yield under mild reaction conditions; 2. By carrying out the fluorination reaction in a reaction device equipped with a water separator, the generated water is separated and removed in real time by physical methods, which meets the principle of chemical equilibrium movement, continuously promotes the reaction equilibrium to the direction of generating 2-fluoroethanol, significantly improves the conversion rate and atom economy, at the same time, allows the reaction to reach a high conversion level in a lower temperature and shorter time, effectively reduces the overall energy consumption and production cost, and is more suitable for industrial scale production; 3. By using a combination of vacuum distillation, adsorption treatment and precision rectification purification process, a multi-stage and targeted purification method is formed, in which a specific proportion of molecular sieve and activated carbon composite adsorbent can effectively remove trace amounts of water molecules and organic impurities such as dyes, and the subsequent precision rectification ensures that the final product has an extremely narrow distillation range, ensuring the stability of product quality, so that the water content is stably controlled below 0.01%, and the product appearance is colorless and transparent, meeting the stringent requirements of key impurities in high-end electronic chemicals and pharmaceutical intermediates and other fields. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 It is the overall step flowchart of the present application; Figure 2 It is the specific flowchart in step S2 of the present application. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0019] Embodiment 1, The embodiments of the present application provide a preparation method of high-purity 2-fluoroethanol, comprising the following steps: S1, in a 500 mL three-necked flask equipped with a water separator, condenser and mechanical stirrer, 100 g (1.24 mol) of 2-chloroethanol, 80 g (1.38 mol, molar ratio 1.11:1) of anhydrous potassium fluoride (average particle size 200 mesh), 5 g of tetrabutylammonium bromide (phase transfer catalyst), 2 g of boron trifluoride etherate (Lewis acid catalyst, mass ratio to phase transfer catalyst 2.5:1) and 300 mL of N,N-dimethylformamide were added; The reaction was stirred and heated to 80°C under nitrogen protection for 6 h, and the generated water was removed by the water separator; S2, after the reaction was completed, it was cooled to room temperature, and the solid was removed by filtration. The filtrate was distilled under reduced pressure at a pressure of 50 mmHg, and the fraction collected at 60-65°C was 2-fluoroethanol crude product. The crude product was mixed with 20 g of 3A molecular sieves and 10 g of activated carbon (mass ratio 2:1), stirred at 30°C for 4 h, filtered, and the filtrate was subjected to rectification under reduced pressure at a pressure of 30 mmHg, and the fraction collected at 62-64°C was colorless transparent 2-fluoroethanol product.

[0020] Example 2, The basic conditions of this example were the same as those of Example 1, but the following parameters were changed: The phase transfer catalyst was changed to 7 g of tetrabutylammonium hydrogen sulfate; The Lewis acid catalyst was changed to 3 g of zinc chloride, and the mass ratio to the phase transfer catalyst was about 2.33:1; The adsorbent used was 15 g of 4A molecular sieves and 15 g of activated carbon, and the mass ratio was 1:1; During the purification treatment, the adsorption treatment conditions were changed to stirring at 25°C for 6 h. The remaining steps were the same as those of Example 1.

[0021] Example 3, The basic conditions of this example were the same as those of Example 1, but the following parameters were changed: The solvent was changed to dimethyl sulfoxide; The reaction temperature was 90°C, and the reaction time was 4 h; The amount of potassium fluoride was adjusted to 72 g (1.24 mol, molar ratio 1.0:1), and the average particle size was 300 mesh; During the purification treatment, the adsorption treatment conditions were changed to stirring at 40°C for 2 h, and the remaining steps were the same as those of Example 1.

[0022] Comparative Example 1, without Lewis acid catalyst The basic conditions of this example were the same as those of Example 1, but no boron trifluoride etherate (Lewis acid catalyst) was added, and only 5 g of tetrabutylammonium bromide was used as a catalyst.

[0023] Comparative Example 2, without water separator The basic conditions of this example are the same as those of Example 1, but the reaction device is not equipped with a water trap, and the water generated in the reaction remains in the system.

[0024] Comparative Example 3, traditional single-step purification The reaction steps of this example are the same as those of Example 1, but during purification, only the post-reaction mixture is filtered and subjected to one atmospheric distillation, and the 130-135°C fraction is collected, without adsorption treatment and rectification steps.

[0025] Comparative Example 4, single adsorbent The reaction steps of this example are the same as those of Example 1, but during purification, only 30g of 3A molecular sieves are used for adsorption treatment, and no activated carbon is used, and the remaining purification steps are the same as those of Example 1.

[0026] The following tests were conducted on Examples 1-3 and Comparative Examples 1-4 described above, respectively, using the following test methods: Purity analysis: determined using a gas chromatograph equipped with an FID detector, and the area normalization method was used for calculation; Moisture content: determined using a Karl Fischer moisture meter; Yield calculation: yield = (actual mass of 2-fluoroethanol obtained / theoretical yield) x 100%. The theoretical yield is calculated based on the complete conversion of 2-chloroethanol; 2-Chloroethanol residue: qualitative and quantitative analysis was performed using a gas chromatograph-mass spectrometer.

[0027] The final test results are shown in the following table: According to the test data described above, it can be seen that: 1. Comparison of Example 1 and Comparative Example 1: after the absence of a Lewis acid catalyst, the product purity dropped to 95.3%, the 2-chloroethanol residue was as high as 2.8%, and the yield was also significantly reduced, which proves that the combination of a phase transfer catalyst and a Lewis acid catalyst greatly improves the reaction rate, selectivity, and conversion rate; 2. Comparison of Example 1 and Comparative Example 2: without using a water trap, although the purity is acceptable, the moisture content is significantly higher than that of Example 1, and the yield is reduced by more than 10 percentage points, which indicates that the water trap effectively promotes the reaction equilibrium to move in the direction of generating products by removing reaction water in a timely manner, significantly improving the yield and reducing the moisture of the final product; 3. Comparison of Example 1 and Comparative Example 3: the product of Comparative Example 3, which only undergoes simple distillation, has low purity, high moisture, many impurities, and poor appearance, while the combined purification process of vacuum distillation, molecular sieve / activated carbon adsorption, and rectification of the present application solves the problems of moisture, color, and chlorine residue; Example 1 vs. Comparative Example 4: only molecular sieve is used without activated carbon, although the water content is still acceptable, but the residual 2-chloroethanol is much higher than that of Example 1, which proves that the combination of molecular sieve and activated carbon has complementary and synergistic effect on the removal of different kinds of impurities.

[0028] In summary: The present application solves the problems of low purity, low yield, many by-products and high water content in the prior art by the organic combination of the dual catalyst system, the water separator and the combined purification process, and finally realizes the efficient and stable preparation of high-purity 2-fluoroethanol.

[0029] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing high-purity 2-fluoroethanol, characterized in that: Includes the following steps: S1. In the presence of a dual catalyst system consisting of a phase transfer catalyst and a Lewis acid catalyst, and an organic solvent, 2-chloroethanol and potassium fluoride are subjected to a fluorination reaction at 60-120°C for 2-10 h, wherein the molar ratio of potassium fluoride to 2-chloroethanol is (1-1.5):1, to generate a reaction mixture containing 2-fluoroethanol. S2. The reaction mixture from step S1 is purified to obtain 2-fluoroethanol with a purity of not less than 99.9%.

2. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The mass ratio of the phase transfer catalyst to the Lewis acid catalyst is from 1:1 to 10:

1.

3. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The phase transfer catalyst is at least one of tetrabutylammonium bromide, tetrabutylammonium chloride, or tetrabutylammonium bisulfate, and the Lewis acid catalyst is at least one of boron trifluoride diethyl ether complex, zinc chloride, or aluminum trichloride.

4. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, or N-methylpyrrolidone.

5. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The potassium fluoride is an anhydrous powder with an average particle size of 100-400 mesh.

6. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The purification process in step S2 includes the following steps performed sequentially: a) Filter the reaction mixture, and distill the filtrate under reduced pressure to collect crude 2-fluoroethanol; b) The crude 2-fluoroethanol was contacted with an adsorbent for adsorption treatment; c) The liquid after adsorption treatment is distilled to collect the fraction at 62-64℃ / 30mmHg to obtain the high-purity 2-fluoroethanol.

7. The method for preparing high-purity 2-fluoroethanol according to claim 6, characterized in that: The adsorbent includes molecular sieves and activated carbon, wherein the molecular sieve is at least one of 3A molecular sieve or 4A molecular sieve.

8. The method for preparing high-purity 2-fluoroethanol according to claim 7, characterized in that: The mass ratio of the molecular sieve to activated carbon is 1:1 to 3:

1.

9. The method for preparing high-purity 2-fluoroethanol according to claim 6, characterized in that: In step b), the adsorption treatment temperature is 20-40℃, the adsorption time is 2-6h, and the mixture is continuously stirred during the adsorption process.

10. The method for preparing high-purity 2-fluoroethanol according to claim 1, characterized in that: The fluorination reaction is carried out in a reaction apparatus equipped with a water separator to separate and remove the water generated during the reaction in real time.

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