Synthesis method of 3-fluoro-1-propanol
By controlling the reaction conditions and stirring and heating in the reaction of 3-chloro-1-propanol with fluoride, catalyst and organic solvent, the existing 3-fluoro-1-propanol synthesis methods are solved, and a high selectivity and low cost synthesis process is achieved.
Patent Information
- Application Number
- CN202510339840.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-21
- Publication Date
- 2025-06-03
- Estimated Expiration
- 2045-03-21
AI Technical Summary
The existing synthesis method of 3-fluoro-1-propanol has problems such as many reaction steps, complex operation, low product selectivity, high reagent toxicity or expensive, high equipment requirements and high production costs, which limits its application in industrial production.
The reaction was carried out by mixing 3-chloro-1-propanol with fluoride, catalyst and organic solvent, and the reaction was carried out by stirring and heating, and the raw material consumption and product generation were monitored until the reaction was completed when the selectivity was no longer increased. Then separation and purification were carried out to obtain high-purity 3-fluoro-1-propanol.
The synthesis of 3-fluoro-1-propanol is achieved with mild reaction conditions, high selectivity, low cost and environmentally friendly synthesis, which reduces production costs, improves product quality, and simplifies the separation and purification process.
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Figure CN119841710B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of the 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, fluorine-containing compounds are widely used in many fields such as medicine, pesticides, and materials due to their unique chemical properties and biological activities. As an important organic synthesis intermediate, 3-fluoro-1-propanol has important application values in various fields. However, there are many problems in the current synthesis methods of 3-fluoro-1-propanol, which limit its application in industrial production.
[0003] Currently, the main synthesis methods of 3-fluoro-1-propanol are as follows:
[0004] Using 3-chloro-1-propanol as a raw material, 3-fluoro-1-propanol is synthesized through multiple reaction steps such as acetylation, fluorination, and hydrolysis. This method has many operation steps, complex reactions, and a relatively low overall yield.
[0005] Using propylene oxide as a starting material, first preparing a Grignard reagent, then reacting with a fluorinating reagent, and obtaining 3-fluoro-1-propanol after hydrolysis. This method has a complex route, extremely high requirements for experimental operations, and improper control of the reagent dosage and reaction conditions during the reaction easily leads to a decrease in the yield.
[0006] Using 1,3-dichloropropane as a raw material, 3-fluoro-1-propanol is synthesized through steps such as base catalysis and addition reaction. This method has relatively more steps, but the raw material 1,3-dichloropropane is relatively common and has a low cost. However, the anhydrous hydrogen fluoride used in the reaction process is toxic and highly corrosive, and has strict requirements for equipment and personnel operations.
[0007] Therefore, there are still many problems in the current synthesis of 3-fluoro-1-propanol: many reaction steps and complex operations lead to a decrease in product selectivity and an increase in the difficulty of subsequent product separation and purification; some of the reagents used in the synthesis methods are toxic or expensive, which is not conducive to large-scale industrial production; the reaction conditions are harsh, with extremely high requirements for equipment, increasing the equipment investment cost and posing safety hazards; the production cost is relatively high, restricting the wide application of 3-fluoro-1-propanol in various fields. Summary of the Invention
[0008] The technical problem to be solved by the present invention is to overcome the above-mentioned defects existing in 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.
[0009] Synthesis method of 3-fluoro-1-propanol according to the present invention: Mix 3-chloro-1-propanol with a fluoride, a catalyst and an organic solvent, and carry out a heating reaction under stirring conditions. Monitor the consumption of raw materials and the formation of products until the product selectivity no longer increases, then end the reaction. The obtained reaction solution is separated and purified to obtain 3-fluoro-1-propanol.
[0010] The fluoride is one of potassium fluoride, sodium fluoride, cesium fluoride or tetrabutylammonium fluoride. Potassium fluoride and sodium fluoride are inexpensive and widely sourced, with low costs; cesium fluoride has high reaction activity, can significantly accelerate the reaction rate, and has low requirements for reaction time; tetrabutylammonium fluoride, as an organic fluorine source, can better dissolve and disperse in the reaction system of the present invention, which is beneficial to improving the homogeneity of the reaction.
[0011] The molar ratio of 3-chloro-1-propanol to the fluoride is 1:1.2 - 1.5.
[0012] The catalyst is a quaternary ammonium salt compound, such as tetrabutylammonium bromide, tetrabutylammonium chloride, etc. The quaternary ammonium salt compound enhances 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.
[0013] The dosage of the catalyst is 3% - 8% of the mass of 3-chloro-1-propanol.
[0014] The organic solvent is one of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), which has good solubility and appropriate polarity, can provide a homogeneous environment for the reaction, and promote the full contact and reaction between reactants. The dosage of the organic solvent is 5 - 10 mL per gram of 3-chloro-1-propanol.
[0015] The stirring speed is 200 - 500 revolutions per minute.
[0016] The heating temperature is 100 - 150 °C.
[0017] The specific steps of the separation and purification are as follows: Continuously stir the reaction solution to cool it to room temperature, add 1 - 2 times the volume of water of the reaction solution, extract with an extractant, dehydrate the organic phase, and carry out vacuum distillation to collect the distillate.
[0018] The extractant is one of dichloromethane, ethyl acetate, and ether.
[0019] During the dehydration of the organic phase, anhydrous sodium sulfate is added for dehydration.
[0020] The vacuum degree of the vacuum distillation is controlled at -0.08 MPa to -0.1 MPa, and the temperature is controlled at 40 - 60 °C.
[0021] The present invention uses 3-chloro-1-propanol, a by-product of epichlorohydrin, as the starting material to ensure high-quality raw materials and reduce the interference of impurities on the reaction. The by-product raw materials can be pretreated by distillation to further increase their purity to 98%. Due to the influence of the spatial and electronic effects of the chlorine atom on the β-carbon in the molecule and the special intermolecular interaction on the hydroxyl group in 3-chloro-1-propanol, its steric hindrance is relatively large. By selecting a suitable fluoride, under neutral and alkaline conditions, 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.
[0022] Specifically, the synthesis method of 3-fluoro-1-propanol includes the following steps:
[0023] (1) Weigh 3-chloro-1-propanol (purity 98%), fluoride, catalyst, and organic solvent and add them to the reaction vessel. Stir at 200 - 500 revolutions per minute (to ensure sufficient mixing of the reactants and uniform progress of the reaction). Turn on the oil bath heating device and control the temperature of the reaction system at 100 - 150 °C (accurate control of this temperature is crucial. Too high a temperature may lead to an increase in side reactions, such as the elimination reaction to form alkenes, etc.; too low a temperature will slow down the reaction rate and prolong the reaction time). Conduct the reaction and use gas chromatography analysis to sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the formation of products. End the reaction when the conversion rate of the raw material 3-chloro-1-propanol reaches the expectation and the selectivity of the product no longer increases significantly after reacting for 3 - 5 h.
[0024] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir to prevent the product from crystallizing or precipitating due to temperature changes, which may cause agglomeration and affect subsequent separation. Add water to the cooled reaction solution for dilution, so that impurities such as inorganic salts in the reaction system dissolve in the water, facilitating subsequent separation from the organic phase. At the same time, the addition of water can also reduce the solubility of the organic product in the organic phase, which is beneficial to the extraction process. Then, use an extractant for extraction 3 - 5 times. Each time during extraction, fully mix the extractant with the reaction solution, and promote mass transfer by shaking or stirring, and then let it stand for layering to separate the organic phase. During the extraction process, it is necessary to pay attention to observing whether the layering interface is clear. If emulsification occurs, perform demulsification treatment by adding a small amount of sodium chloride or using methods such as centrifugation. Combine the organic phases obtained from multiple extractions, and then add anhydrous sodium sulfate for drying (anhydrous sodium sulfate has strong water absorption and can remove trace amounts of water in the organic phase). After adding anhydrous sodium sulfate, stir for 0.5 - 1 h to allow anhydrous sodium sulfate to fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Remove the organic solvent by vacuum distillation, and perform vacuum distillation operation using a rotary evaporator. During the distillation process, control the vacuum degree and temperature. The vacuum degree is maintained at -0.08 MPa to -0.1 MPa, and the temperature is controlled at 40 - 60 °C until no more distillate is distilled out, and continue distillation to obtain high-purity 3-fluoro-1-propanol.
[0025] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0026] (1) In the synthesis method of 3-fluoro-1-propanol of the present invention, by precisely controlling the reaction temperature and stirring speed, it is ensured that the reactants can be fully mixed, enabling the reaction to proceed uniformly, thereby increasing 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.
[0027] (2) In the synthesis method of 3-fluoro-1-propanol of the present invention, after the reaction is completed, through natural cooling and water dilution, the crystallization or precipitation of the product is effectively prevented, reducing the difficulty of subsequent separation. In addition, through multiple extractions 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 product quality is improved.
[0028] (3)The synthesis method of 3-fluoro-1-propanol of the present invention has mild conditions, reducing energy consumption and equipment investment costs. At the same time, by using relatively environmentally friendly extractants and desiccants, the environmental pollution risk is reduced. In addition, the present invention optimizes process parameters, reduces the consumption of raw materials and reagents, and lowers production costs, making the large-scale industrial production of 3-fluoro-1-propanol more economically feasible. Description of the Drawings
[0029] Figure 1 It is the gas chromatogram of 3-fluoro-1-propanol prepared in Example 4. Detailed Embodiments
[0030] The present invention will be further described below with specific embodiments.
[0031] The following 3-chloro-1-propanol is a by-product of epichlorohydrin, and its purity is increased to 98% by rectification.
[0032] Other raw materials and auxiliaries used in the following examples are all commercially available products.
[0033] Example 1
[0034] The synthesis method of the said 3-fluoro-1-propanol comprises the following steps:
[0035] (1) Weigh 97 g of 3-chloro-1-propanol, 70 g of potassium fluoride, 5 g of catalyst tetrabutylammonium bromide and 500 mL of organic solvent N,N-dimethylformamide and add them into a reaction vessel. Under the stirring condition of 300 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 150 °C, and carry out the reaction. By means of gas chromatographic analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. After reacting for 5 h, the conversion rate of raw material 3-chloro-1-propanol reaches 99%, and the reaction ends when the selectivity of the product 3-fluoro-1-propanol no longer increases.
[0036] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir. Add 600 mL of water to the cooled reaction solution for dilution, and then extract it 4 times with the organic solvent dichloromethane. Each time during extraction, fully mix the extractant with the reaction solution, promote mass transfer through shaking, and then let it stand for layer separation to separate the organic phase. During the extraction process, an emulsification phenomenon occurs, and it is demulsified by adding a small amount of sodium chloride. Combine the organic phases obtained from multiple extractions, then add anhydrous sodium sulfate and stir for 0.5 h to allow the anhydrous sodium sulfate to fully contact the organic phase. Then remove the anhydrous sodium sulfate solid by suction filtration, and perform vacuum distillation using a rotary evaporator to remove the organic solvent. The vacuum degree is controlled at -0.08 MPa, and the temperature is controlled at 50 °C until no more distillate is 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, its purity is detected to be 98.5%, and its yield is calculated to be 88%.
[0037] Example 2
[0038] The synthesis method of the described 3-fluoro-1-propanol includes the following steps:
[0039] (1) Add 97 g of 3-chloro-1-propanol, 63 g of sodium fluoride, 8 g of the catalyst tetrabutylammonium bromide, and 600 mL of the organic solvent dimethyl sulfoxide to the reaction vessel. Under the stirring condition of 200 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. Use gas chromatography analysis means to sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. After reacting for 4 h, the conversion rate of the raw material 3-chloro-1-propanol is detected to reach 98.5%, and the reaction ends when the selectivity of the product 3-fluoro-1-propanol no longer increases.
[0040] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir. Add 700 mL of water to the cooled reaction solution for dilution, and then extract it 5 times with the organic solvent ethyl acetate. Each time during extraction, fully mix the extractant with the reaction solution, promote mass transfer through stirring, and then let it stand for layer separation 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. Then remove the anhydrous sodium sulfate solid by suction filtration, and perform vacuum distillation using a rotary evaporator to remove the organic solvent. The vacuum degree is controlled at -0.09 MPa, and the temperature is controlled at 40 °C until no more distillate is distilled out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 68 g of 3-fluoro-1-propanol is obtained, its purity is detected to be 98.1%, and its yield is calculated to be 87%.
[0041] Example 3
[0042] The described synthesis method of 3-fluoro-1-propanol comprises the following steps:
[0043] (1) Add 97 g of 3-chloro-1-propanol, 182.3 g of cesium fluoride, 3 g of the catalyst tetrabutylammonium chloride, and 600 mL of the organic solvent dimethyl sulfoxide into a reaction vessel. Under the stirring condition of 500 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. After reacting for 4 h, the conversion rate of the raw material 3-chloro-1-propanol reaches 99.2%, and when the selectivity of the product 3-fluoro-1-propanol no longer increases, the reaction ends.
[0044] (2) Separation and purification: After the reaction ends, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, keep stirring, add 700 mL of water to the cooled reaction solution for dilution, and then extract 5 times with the organic solvent ethyl acetate. Each time during extraction, fully mix the extractant with the reaction solution, promote mass transfer through oscillation, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to carry out vacuum distillation to remove the organic solvent, control the vacuum degree at -0.1 MPa, and control the temperature at 60 °C until no more distillate distills out, and 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%, and its yield is calculated to be 90%.
[0045] Example 4
[0046] The described synthesis method of 3-fluoro-1-propanol comprises the following steps:
[0047] (1) Add 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of the catalyst tetrabutylammonium chloride, and 970 mL of the organic solvent N-methylpyrrolidone into a reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. After reacting for 3 h, the conversion rate of the raw material 3-chloro-1-propanol reaches 99.6%, and when the selectivity of the product 3-fluoro-1-propanol no longer increases, the reaction ends.
[0048] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, keep stirring. Add 1000 mL of water to the cooled reaction solution for dilution, and then extract with the organic solvent ether 5 times. Each time of extraction, fully mix the extractant with the reaction solution, promote mass transfer through oscillation, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator for vacuum distillation to remove the organic solvent. The vacuum degree is controlled at -0.1 MPa, and the temperature is controlled at 50 °C until no more distillate distills out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 71.1 g of 3-fluoro-1-propanol is obtained. As Figure 1 shown, its purity is detected to be 99.2%, and its yield is calculated to be 91%.
[0049] Comparative Example 1
[0050] The synthesis method of 3-fluoro-1-propanol described above includes the following steps:
[0051] (1) Add 97 g of 3-chloro-1-propanol, 68.4 g of ammonium bifluoride, 3 g of the catalyst tetrabutylammonium chloride, and 970 mL of the organic solvent N-methylpyrrolidone to the reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device and control the temperature of the reaction system at 100 °C for reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. After reacting for 3 h, the conversion rate of the raw material 3-chloro-1-propanol is detected to reach 33%, and the reaction ends when the selectivity of the product 3-fluoro-1-propanol no longer increases.
[0052] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, keep stirring. Add 600 mL of water to the cooled reaction solution for dilution, and then extract with the organic solvent ether 5 times. Each time of extraction, fully mix the extractant with the reaction solution, promote mass transfer through oscillation, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator for vacuum distillation to remove the organic solvent. The vacuum degree is controlled at -0.1 MPa, and the temperature is controlled at 50 °C until no more distillate distills out. Continue distillation to obtain 3-fluoro-1-propanol. A total of 18.0 g of 3-fluoro-1-propanol is obtained. Its purity is detected to be 31.5%, and its yield is calculated to be 23%.
[0053] Comparative Example 2
[0054] The described synthesis method of 3-fluoro-1-propanol comprises the following steps:
[0055] (1) Add 97 g of 3-chloro-1-propanol, 313.8 g (1.2 mol) of tetrabutylammonium fluoride, and 970 mL of the organic solvent N-methylpyrrolidone into a reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the formation of products. After reacting for 3 h, when the conversion rate of the raw material 3-chloro-1-propanol reaches 83% and the selectivity no longer increases, end the reaction.
[0056] (2) Separation and purification: After the reaction ends, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, keep stirring. Add 600 mL of water to the cooled reaction solution for dilution, and then extract with the organic solvent ether 5 times. Each time during extraction, fully mix the extractant with the reaction solution, promote mass transfer through oscillation, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to carry out vacuum distillation to remove the organic solvent, control the vacuum degree at -0.1 MPa, and control the temperature at 50 °C until no more distillate distills out. Continue distillation to obtain 3-fluoro-1-propanol. A total of 56.2 g of 3-fluoro-1-propanol is obtained, its purity is detected to be 81.5%, and its yield is calculated to be 72%.
[0057] Comparative Example 3
[0058] The described synthesis method of 3-fluoro-1-propanol comprises the following steps:
[0059] (1) Add 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of the catalyst tetrabutylammonium chloride, and 970 mL of the organic solvent cyclohexane into a reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the formation of products. After reacting for 3 h, when the conversion rate of the raw material 3-chloro-1-propanol reaches 75% and the selectivity of the product 3-fluoro-1-propanol no longer increases, end the reaction.
[0060] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir. Add 600 mL of water to the cooled reaction solution for dilution, and then extract it 5 times with the organic solvent ether. Each time of extraction, fully mix the extractant with the reaction solution, promote mass transfer by shaking, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to carry out vacuum distillation to remove the organic solvent. The vacuum degree is controlled at -0.1 MPa, and the temperature is controlled at 50 °C until no more distillate distills out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 53 g of 3-fluoro-1-propanol is obtained, its purity is detected to be 72%, and its yield is calculated to be 65%.
[0061] Comparative Example 4
[0062] The synthesis method of the 3-fluoro-1-propanol described above comprises the following steps:
[0063] (1) Add 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of the catalyst tetrabutylammonium chloride, and 970 mL of the organic solvent N-methylpyrrolidone to the reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 180 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the generation of products. When the conversion rate of the raw material 3-chloro-1-propanol reaches 99.5% after reacting for 3 h and the selectivity of the product 3-fluoro-1-propanol no longer increases, end the reaction.
[0064] (2) Separation and purification: After the reaction is completed, turn off the heating device and let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir. Add 600 mL of water to the cooled reaction solution for dilution, and then extract it 5 times with the organic solvent ether. Each time of extraction, fully mix the extractant with the reaction solution, promote mass transfer by shaking, and then let it stand for layering 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 make anhydrous sodium sulfate fully contact with the organic phase, and then remove the anhydrous sodium sulfate solid by suction filtration. Use a rotary evaporator to carry out vacuum distillation to remove the organic solvent. The vacuum degree is controlled at -0.1 MPa, and the temperature is controlled at 50 °C until no more distillate distills out. Continue distillation to obtain high-purity 3-fluoro-1-propanol. A total of 62.4 g of 3-fluoro-1-propanol is obtained, its purity is detected to be 96.2%, and its yield is calculated to be 80%.
[0065] Comparative Example 5
[0066] The described synthesis method of 3-fluoro-1-propanol comprises the following steps:
[0067] (1) Add 97 g of 3-chloro-1-propanol, 313.8 g of tetrabutylammonium fluoride, 3 g of the catalyst tetrabutylammonium chloride, and 970 mL of the organic solvent N-methylpyrrolidone into a reaction vessel. Under the stirring condition of 400 revolutions per minute, turn on the oil bath heating device, control the temperature of the reaction system at 100 °C, and carry out the reaction. By means of gas chromatography analysis, sample and analyze the reaction solution every hour to monitor the consumption of raw materials and the formation of products. When the conversion rate of the raw material 3-chloro-1-propanol reaches 99.6% after 3 h of reaction and the selectivity of the product 3-fluoro-1-propanol no longer increases, end the reaction.
[0068] (2) Separation and purification: After the reaction ends, turn off the heating device, let the reaction solution cool naturally to room temperature. During the cooling process, continuously stir, then let it stand for liquid separation, separate the organic phase, and carry out vacuum distillation using a rotary evaporator to obtain 3-fluoro-1-propanol. A total of 64 g of 3-fluoro-1-propanol is obtained. Detect its purity to be 96%, and calculate its yield to be 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 organic solvent is one of N,N-dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone; The catalyst is tetrabutylammonium bromide or tetrabutylammonium chloride.
2. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The stirring speed is 200-500 rpm.
3. The method for synthesizing 3-fluoro-1-propanol according to claim 1, characterized in that: The heating temperature is 100-150°C.
4. 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.
5. 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.
6. 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.
7. The method for synthesizing 3-fluoro-1-propanol according to claim 6, characterized in that: The extractant is one of dichloromethane, ethyl acetate and ether.
8. The method for synthesizing 3-fluoro-1-propanol according to claim 7, characterized in that: During the dehydration process of the organic phase, anhydrous sodium sulfate is added to remove water.
9. The method for synthesizing 3-fluoro-1-propanol according to claim 8, 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.
Citation Information
Patent Citations
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