Synthetic method of 3-fluoro-1-propanol

Abstract

The invention belongs to the technical field of synthesis of organic chemicals, and particularly relates to a synthesis method of 3-fluoro-1-propanol. The synthesis method of the 3-fluoro-1-propanol comprises the following steps: mixing 3-chloro-1-propanol with fluoride, a catalyst and an organic solvent, carrying out a heating reaction under a stirring condition, monitoring the consumption of raw materials and the generation condition of a product, ending the reaction until the selectivity of the product is not improved any more, continuously stirring the obtained reaction liquid, and cooling to room temperature to obtain the 3-fluoro-1-propanol. And adding water which is 1-2 times of the volume of the reaction liquid, extracting by adopting an extracting agent, removing water from an organic phase, carrying out reduced pressure distillation, and collecting fractions to obtain the 3-fluoro-1-propanol. The molar ratio of the 3-chloro-1-propanol to the fluoride is 1: (1.2-1.5). The fluoride is one of potassium fluoride, sodium fluoride, cesium fluoride or tetrabutylammonium fluoride. The synthesis method of 3-fluoro-1-propanol provided by the invention has the advantages of mild reaction conditions, high selectivity, low cost and environmental friendliness.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of organic chemicals, and particularly relates to a method for synthesizing 3-fluoro-1-propanol. Background Art

[0002] In the field of organic synthesis, fluorinated compounds are widely used in medicine, pesticides, materials and other fields due to their unique chemical properties and biological activities. 3-Fluoro-1-propanol, as an important organic synthesis intermediate, has important application value in various fields. However, the current synthesis method of 3-fluoro-1-propanol has many problems, which limits its application in industrial production.

[0003] At present, the synthesis methods of 3-fluoro-1-propanol mainly include the following: 3-Chloro-1-propanol is used as a raw material to synthesize 3-fluoro-1-propanol through multiple reaction steps such as acetylation, fluorination, and hydrolysis. This method has many operating steps, complex reactions, and a low overall yield.

[0004] Using propylene oxide as the starting material, the Grignard reagent is first prepared, and then reacted with a fluorinated reagent, and 3-fluoro-1-propanol is obtained through hydrolysis. This method has a complex route and extremely high requirements for experimental operation. In addition, improper control of the reagent dosage and reaction conditions during the reaction process can easily lead to a decrease in yield.

[0005] 3-Fluoro-1-propanol is synthesized from 1,3-dichloropropane via base catalysis, addition reaction and other steps. This method has relatively many steps, but the raw material 1,3-dichloropropane is relatively common and has low cost. However, the anhydrous hydrogen fluoride used in the reaction process is toxic and highly corrosive, and has strict requirements on equipment and personnel operation.

[0006] Therefore, there are still many problems in the synthesis of 3-fluoro-1-propanol: many reaction steps and complicated operations lead to reduced product selectivity and increased difficulty in subsequent product separation and purification; some synthetic methods use toxic or expensive reagents, which are not conducive to large-scale industrial production; the reaction conditions are harsh and the equipment requirements are extremely high, which increases the equipment investment cost and poses a safety hazard; the production cost is high, which limits the wide application of 3-fluoro-1-propanol in various fields. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the above-mentioned defects of the prior art and provide a method for synthesizing 3-fluoro-1-propanol, which has mild reaction conditions, high selectivity, low cost and is environmentally friendly.

[0008] The method for synthesizing 3-fluoro-1-propanol of the present invention comprises the following steps: mixing 3-chloro-1-propanol with a fluoride, a catalyst and an organic solvent, and performing a heating reaction under stirring conditions; monitoring the consumption of the raw materials and the generation of the product; and terminating the reaction until the product selectivity is no longer improved; and separating and purifying the obtained reaction solution to obtain 3-fluoro-1-propanol.

[0009] The fluoride is one of potassium fluoride, sodium fluoride, cesium fluoride or tetrabutylammonium fluoride. Potassium fluoride and sodium fluoride are cheap and widely available, and have low cost; cesium fluoride has high reactivity, can significantly accelerate the reaction rate, and has low requirements for reaction time; tetrabutylammonium fluoride, as an organic fluorine source, can be better dissolved and dispersed in the reaction system of the present invention, which is conducive to improving the uniformity of the reaction.

[0010] The molar ratio of the 3-chloro-1-propanol to the fluoride is 1:1.2-1.5.

[0011] The catalyst is a quaternary ammonium salt compound, such as tetrabutylammonium bromide, tetrabutylammonium chloride, etc. Quaternary ammonium salt compounds enhance the nucleophilicity of fluoride ions by forming ion pairs, thereby effectively reducing the activation energy of the reaction and promoting the substitution reaction of fluorine atoms for chlorine atoms.

[0012] The amount of the catalyst used is 3%-8% of the mass of 3-chloro-1-propanol.

[0013] The organic solvent is one of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and N-methylpyrrolidone (NMP), which has good solubility and suitable polarity, can provide a homogeneous environment for the reaction, and promote sufficient contact between the reactants and the reaction. The amount of the organic solvent used is 5-10 mL per gram of 3-chloro-1-propanol.

[0014] The stirring speed is 200-500 rpm.

[0015] The heating temperature is 100-150°C.

[0016] The specific steps of separation and purification are: stirring the reaction solution continuously and cooling it to room temperature, adding water 1-2 times the volume of the reaction solution, extracting with an extractant, removing water from the organic phase, performing vacuum distillation, and collecting fractions.

[0017] The extractant is one of dichloromethane, ethyl acetate and ether.

[0018] During the dehydration process of the organic phase, anhydrous sodium sulfate is added to remove water.

[0019] The vacuum degree of the reduced pressure distillation is controlled at -0.08 MPa to -0.1 MPa, and the temperature is controlled at 40-60°C.

[0020] The present invention adopts 3-chloro-1-propanol, a byproduct of epichlorohydrin, as a starting raw material, ensures the high quality of the raw material to reduce the interference of impurities on the reaction, and can pre-treat the byproduct raw material by distillation to further improve its purity to 98%. Since the hydroxyl group in 3-chloro-1-propanol is affected by the space and electronic effects of the chlorine atom on the beta-carbon in the molecule and the special interaction between molecules, the steric hindrance is relatively large, and then a suitable fluoride is selected under neutral and alkaline conditions, and the hydroxyl group in 3-chloro-1-propanol does not participate in the reaction and does not affect the synthesis of 3-fluoro-1-propanol.

[0021] Specifically, the synthesis method of 3-fluoro-1-propanol comprises the following steps: (1) Add weighed 3-chloro-1-propanol (purity 98%), fluoride, catalyst and organic solvent into a reaction vessel, stir at 200-500 rpm (to ensure that the reactants are fully mixed so that the reaction can proceed evenly), turn on the oil bath heating device, control the temperature of the reaction system at 100-150° C. (precise control of this temperature is crucial. Too high a temperature may lead to an increase in side reactions, such as the generation of olefins by elimination reactions; too low a temperature may slow down the reaction rate and prolong the reaction time), and carry out the reaction. Use gas chromatography to sample and analyze the reaction liquid every hour to monitor the consumption of the raw materials and the generation of the products. After reacting for 3-5 hours, the reaction is terminated when the conversion rate of the raw material 3-chloro-1-propanol reaches the expected level and the selectivity of the product is no longer significantly improved.

[0022] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue to stir to prevent the product from crystallizing or precipitating due to temperature changes, which will cause agglomeration and affect subsequent separation. Add water to the cooled reaction liquid for dilution. Add water to dissolve impurities such as inorganic salts in the reaction system in water, which is convenient for subsequent separation from the organic phase. At the same time, the addition of water can also reduce the solubility of organic products in the organic phase, which is beneficial to the extraction process. Then use the extractant for 3-5 extractions. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation or stirring, and then let it stand for stratification to separate the organic phase. During the extraction process, pay attention to whether the stratification interface is clear. If emulsification occurs, break the emulsion by adding a small amount of sodium chloride or using centrifugation. Combine the organic phases obtained from multiple extractions, then add anhydrous sodium sulfate for drying (anhydrous sodium sulfate has strong water absorption and can remove trace moisture in the organic phase). After adding anhydrous sodium sulfate, stir for 0.5-1h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Remove the organic solvent by vacuum distillation, and use a rotary evaporator for vacuum distillation. During the distillation process, control the vacuum degree and temperature, maintain the vacuum degree at -0.08MPa to -0.1MPa, and control the temperature at 40-60°C until no more fractions are distilled out, and continue distillation to obtain high-purity 3-fluoro-1-propanol.

[0023] Compared with the prior art, the present invention has the following beneficial effects: (1) The method for synthesizing 3-fluoro-1-propanol of the present invention ensures that the reactants can be fully mixed and the reaction proceeds evenly by precisely controlling the reaction temperature and stirring speed, thereby improving the conversion rate of 3-chloro-1-propanol and the product selectivity of 3-fluoro-1-propanol. Compared with the prior art, the present invention can achieve the expected conversion rate and selectivity in a shorter reaction time, reduce the occurrence of side reactions, and improve the overall synthesis efficiency.

[0024] (2) The method for synthesizing 3-fluoro-1-propanol of the present invention effectively prevents crystallization or precipitation of the product by natural cooling and dilution with water after the reaction is completed, thereby reducing the difficulty of subsequent separation. In addition, through multiple extraction and drying treatments, the present invention can more effectively remove impurities and improve the purity of 3-fluoro-1-propanol. Compared with the prior art, the complexity of product separation and purification is reduced, and the quality of the product is improved.

[0025] (3) The synthesis method of 3-fluoro-1-propanol of the present invention has mild conditions, which reduces energy consumption and equipment investment costs. At the same time, by using relatively environmentally friendly extractants and desiccants, the risk of environmental pollution is reduced. In addition, the present invention reduces the consumption of raw materials and reagents and reduces production costs by optimizing process parameters, making the large-scale industrial production of 3-fluoro-1-propanol more economical and feasible. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the gas chromatogram of 3-fluoro-1-propanol prepared in Example 4. DETAILED DESCRIPTION

[0027] The present invention will be further described below in conjunction with specific embodiments.

[0028] The following 3-chloro-1-propanol is a by-product of epichlorohydrin, which is distilled to increase its purity to 98%.

[0029] Other raw materials and additives used in the following examples are all commercially available products.

[0030] Example 1 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 70 g of potassium fluoride, 5 g of tetrabutylammonium bromide catalyst and 500 mL of N,N-dimethylformamide organic solvent were added to a reaction vessel. Under stirring at 300 rpm, an oil bath heating device was turned on to control the temperature of the reaction system at 150°C for reaction. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of raw materials and the formation of products. After 5 hours of reaction, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 99%, and the selectivity of the product 3-fluoro-1-propanol no longer increased, and the reaction was terminated.

[0031] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue stirring, add 600 mL of water to the cooled reaction liquid for dilution, and then use the organic solvent dichloromethane for 4 extractions. During each extraction, the extractant and the reaction liquid are fully mixed, and the mass transfer is promoted by oscillation. Then, the mixture is allowed to stand for stratification to separate the organic phase. During the extraction process, emulsification occurs. A small amount of sodium chloride is added for demulsification. The organic phases obtained from multiple extractions are combined, and then anhydrous sodium sulfate is added and stirred for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase. Then, the anhydrous sodium sulfate solid is removed by suction filtration, and the organic solvent is removed by reduced pressure distillation using a rotary evaporator. The vacuum degree is controlled at -0.08 MPa and the temperature is controlled at 50°C until no more fractions are distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 68.7 g of 3-fluoro-1-propanol is obtained. The purity is detected to be 98.5%, and the yield is calculated to be 88%.

[0032] Example 2 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 63 g of sodium fluoride, 8 g of tetrabutylammonium bromide catalyst and 600 mL of dimethyl sulfoxide (DMSO) were weighed and added into a reaction vessel. Under stirring at 200 rpm, the oil bath heating device was turned on and the temperature of the reaction system was controlled at 100°C for reaction. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of raw materials and the formation of products. After 4 h of reaction, the conversion rate of the raw material 3-chloro-1-propanol reached 98.5%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0033] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue stirring, add 700 mL of water to the cooled reaction liquid for dilution, and then extract it 5 times with the organic solvent ethyl acetate. During each extraction, the extractant and the reaction liquid are fully mixed, and the mass transfer is promoted by stirring. Then, the mixture is allowed to stand for stratification to separate the organic phase. The organic phases obtained from multiple extractions are combined, and then anhydrous sodium sulfate is added for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. The organic solvent is removed by reduced pressure distillation using a rotary evaporator, and the vacuum degree is controlled at -0.09 MPa and the temperature is controlled at 40°C until no more fractions are distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 68 g of 3-fluoro-1-propanol is obtained, and its purity is detected to be 98.1%. The calculated yield is 87%.

[0034] Example 3 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 182.3 g of cesium fluoride, 3 g of tetrabutylammonium chloride catalyst and 600 mL of dimethyl sulfoxide (DMSO) were added to a reaction vessel. The oil bath heating device was turned on and the temperature of the reaction system was controlled at 100° C. under stirring at 500 rpm to carry out the reaction. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After 4 h of reaction, the conversion rate of the raw material 3-chloro-1-propanol reached 99.2%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0035] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue stirring, add 700 mL of water to the cooled reaction liquid for dilution, and then use the organic solvent ethyl acetate for 5 extractions. During each extraction, the extractant and the reaction liquid are fully mixed, and the mass transfer is promoted by oscillation. Then, the mixture is allowed to stand for stratification to separate the organic phase. The organic phases obtained from multiple extractions are combined, and then anhydrous sodium sulfate is added for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. The organic solvent is removed by reduced pressure distillation using a rotary evaporator, and the vacuum degree is controlled at -0.1 MPa and the temperature is controlled at 60°C until no more fractions are distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 70.3 g of 3-fluoro-1-propanol is obtained, and its purity is detected to be 98.7%. The calculated yield is 90%.

[0036] Example 4 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of tetrabutylammonium chloride as catalyst and 970 mL of N-methylpyrrolidone as an organic solvent were added to a reaction vessel. Under stirring at 400 rpm, an oil bath heating device was turned on to control the temperature of the reaction system at 100° C. The reaction was carried out. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 99.6%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0037] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue stirring. Add 1000 mL of water to the cooled reaction liquid for dilution, and then extract it with organic solvent ether 5 times. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation, and then let it stand to separate the organic phase. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate to dry. After adding anhydrous sodium sulfate, stir for 0.5h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to remove the organic solvent by reduced pressure distillation. The vacuum degree is controlled at -0.1MPa and the temperature is controlled at 50°C until no more fractions are evaporated. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 71.1g of 3-fluoro-1-propanol is obtained, such as Figure 1 As shown, the purity was detected to be 99.2% and the yield was calculated to be 91%.

[0038] Comparative Example 1 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 68.4 g of ammonium bifluoride, 3 g of tetrabutylammonium chloride as a catalyst and 970 mL of N-methylpyrrolidone as an organic solvent were added to a reaction vessel. Under stirring at 400 rpm, an oil bath heating device was turned on and the temperature of the reaction system was controlled at 100° C. The reaction was carried out. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 33%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0039] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue to stir, add 600 mL of water to the cooled reaction liquid for dilution, and then extract with organic solvent ether for 5 times. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation, and then stand for stratification to separate the organic phase. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to remove the organic solvent by reduced pressure distillation, control the vacuum degree at -0.1 MPa, and control the temperature at 50°C until no more fractions are distilled out. Continue distillation to obtain 3-fluoro-1-propanol, and a total of 18.0 g of 3-fluoro-1-propanol is obtained. The purity is 31.5% and the yield is calculated to be 23%.

[0040] Comparative Example 2 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 313.8 g (1.2 mol) of tetrabutylammonium fluoride and 970 mL of an organic solvent, N-methylpyrrolidone, were added to a reaction vessel. The oil bath heating device was turned on and the temperature of the reaction system was controlled at 100° C. under stirring at 400 rpm to carry out the reaction. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, the conversion rate of the raw material 3-chloro-1-propanol reached 83%, and the selectivity was no longer improved, so the reaction was terminated.

[0041] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue to stir, add 600 mL of water to the cooled reaction liquid for dilution, and then extract with organic solvent ether for 5 times. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation, and then stand for stratification to separate the organic phase. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to remove the organic solvent by reduced pressure distillation, control the vacuum degree at -0.1 MPa, and control the temperature at 50°C until no more fractions are distilled out. Continue distillation to obtain 3-fluoro-1-propanol, and a total of 56.2 g of 3-fluoro-1-propanol is obtained. The purity is detected to be 81.5%, and the yield is calculated to be 72%.

[0042] Comparative Example 3 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of tetrabutylammonium chloride as catalyst and 970 mL of cyclohexane as an organic solvent were added to a reaction vessel. Under stirring at 400 rpm, an oil bath heating device was turned on to control the temperature of the reaction system at 100° C. The reaction was carried out. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 75%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0043] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue to stir, add 600 mL of water to the cooled reaction liquid for dilution, and then extract with organic solvent ether for 5 times. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation, and then stand for stratification to separate the organic phase. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to remove the organic solvent by reduced pressure distillation, control the vacuum degree at -0.1 MPa, and control the temperature at 50°C until no more fractions are distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 53 g of 3-fluoro-1-propanol is obtained, and its purity is 72% and its yield is calculated to be 65%.

[0044] Comparative Example 4 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of tetrabutylammonium chloride as catalyst and 970 mL of N-methylpyrrolidone as an organic solvent were added to a reaction vessel. Under stirring at 400 rpm, an oil bath heating device was turned on to control the temperature of the reaction system at 180° C. The reaction was carried out. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 99.5%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0045] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction liquid cool naturally to room temperature. During the cooling process, continue to stir. Add 600 mL of water to the cooled reaction liquid for dilution, and then extract with organic solvent ether for 5 times. During each extraction, fully mix the extractant and the reaction liquid, promote mass transfer by oscillation, and then stand for stratification to separate the organic phase. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate for drying. After adding anhydrous sodium sulfate, stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to remove the organic solvent by reduced pressure distillation. The vacuum degree is controlled at -0.1 MPa and the temperature is controlled at 50°C until no more fractions are distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 62.4 g of 3-fluoro-1-propanol is obtained. The purity is detected to be 96.2%, and the yield is calculated to be 80%.

[0046] Comparative Example 5 The synthetic method of 3-fluoro-1-propanol comprises the following steps: (1) 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of tetrabutylammonium chloride as catalyst and 970 mL of N-methylpyrrolidone as an organic solvent were added to a reaction vessel. Under stirring at 400 rpm, an oil bath heating device was turned on to control the temperature of the reaction system at 100° C. The reaction was carried out. The reaction liquid was sampled and analyzed every hour by gas chromatography to monitor the consumption of the raw materials and the formation of the products. After reacting for 3 h, it was detected that the conversion rate of the raw material 3-chloro-1-propanol reached 99.6%, and the selectivity of the product 3-fluoro-1-propanol was no longer improved, and the reaction was terminated.

[0047] (2) Separation and purification: After the reaction is completed, the heating device is turned off and the reaction solution is allowed to cool naturally to room temperature. During the cooling process, stirring is continued and then the reaction solution is allowed to stand for stratification. The organic phase is separated and vacuum distilled using a rotary evaporator to obtain 3-fluoro-1-propanol. A total of 64 g of 3-fluoro-1-propanol is obtained with a purity of 96% and a calculated yield of 82%.

Claims

1. A method for synthesizing 3-fluoro-1-propanol, characterized in that: Mixing 3-chloro-1-propanol with a fluoride, a catalyst and an organic solvent, and performing a heating reaction under stirring conditions, monitoring the consumption of the raw materials and the generation of the product, and terminating the reaction until the product selectivity is no longer improved, and separating and purifying the obtained reaction solution to obtain 3-fluoro-1-propanol; The fluoride is one of potassium fluoride, sodium fluoride, cesium fluoride or tetrabutylammonium fluoride; The catalyst is a quaternary ammonium salt compound; The organic solvent is one of N,N-dimethylformamide, dimethyl sulfoxide and N-methylpyrrolidone.

2. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The catalyst is tetrabutylammonium bromide or tetrabutylammonium chloride.

3. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The stirring speed is 200-500 rpm.

4. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The heating temperature is 100-150°C.

5. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The molar ratio of the 3-chloro-1-propanol to the fluoride is 1:1.2-1.

5.

6. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The amount of the catalyst used is 3%-8% of the mass of 3-chloro-1-propanol.

7. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The specific steps of separation and purification are: stirring the reaction solution continuously and cooling it to room temperature, adding water 1-2 times the volume of the reaction solution, extracting with an extractant, removing water from the organic phase, performing vacuum distillation, and collecting fractions.

8. The method for synthesizing 3-fluoro-1-propanol according to claim 7, characterized in that: The extractant is one of dichloromethane, ethyl acetate and ether.

9. The method for synthesizing 3-fluoro-1-propanol according to claim 8, characterized in that: During the dehydration process of the organic phase, anhydrous sodium sulfate is added to remove water.

10. The method for synthesizing 3-fluoro-1-propanol according to claim 9, characterized in that: The vacuum degree of the reduced pressure distillation is controlled at -0.08 MPa to -0.1 MPa, and the temperature is controlled at 40-60°C.

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