Preparation method of asymmetric hydrofluoroether

Abstract

The invention discloses a preparation method of asymmetric hydrofluoroether, and belongs to the technical field of organic fluorine chemical synthesis. The asymmetric hydrofluoroether is 1-methoxy heptafluoropropane, and the method comprises two continuous reaction steps: step S1, in an inert atmosphere, mixing fluorophosgene and a fluorination catalyst in an anhydrous stable solvent until the mixture is saturated, and slowly introducing tetrafluoroethylene to generate perfluoropropionyl fluoride; and S2, directly introducing the reaction mixture obtained in the step S1 into a reactor, and reacting with a methylation reagent and an optional alcohol auxiliary agent to generate 1-methoxyheptafluoropropane without separation and purification of an intermediate product. According to the present invention, the cheap raw material tetrafluoroethylene is adopted, and the catalyst combination, the solvent system and the process control are optimized, such that the high total yield, the high selectivity and the safe and continuous process are achieved under the mild condition, and the method is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organofluorine chemical synthesis technology, specifically relating to a method for preparing asymmetric hydrofluoroethers. Background Technology

[0002] 1-Methoxyheptafluoropropane (CF3CF2CF2OCH3), a typical asymmetric hydrofluoroether, has received widespread attention in recent years due to its environmentally friendly properties. In the pharmaceutical field, 1-methoxyheptafluoropropane can be used as an adjunct to local anesthesia or as a low-temperature cleaning agent for precision medical instruments. In the field of electronic chemistry, its excellent solubility and insulation properties make it a highly efficient cleaning agent for residual photoresist and fluoride impurities during semiconductor chip manufacturing. In the fields of fire protection and refrigeration, this compound, due to its non-flammability and thermal stability, can serve as an ideal substitute for halon-based fire extinguishing agents and traditional Freon refrigerants, meeting current global environmental regulations' requirements for the greening of fluorinated compounds. Traditional methods for synthesizing perfluoroethers or hydrofluoroethers mainly include the oxidation of perfluoroolefins, the alkylation of perfluoroacyl fluorides, and the ring-opening of epoxide perfluoroalkanes. However, these methods generally suffer from problems such as expensive raw materials, cumbersome procedures, low yields, or the generation of large amounts of byproducts, making it difficult to meet the needs of green chemistry and industrial production.

[0003] Chinese invention patent application CN119390542A discloses a method for preparing perfluoropropionyl fluoride via isomerization of hexafluoropropylene oxide, followed by reaction with dimethyl sulfate to synthesize 1-methoxyheptafluoropropane. While this method yields the target product, it has significant drawbacks: First, the starting material, hexafluoropropylene oxide, is expensive and difficult to obtain; second, the isomerization step requires a carbon-based supported metal catalyst such as Ni, Fe, Co, or Cu, and the preparation of this catalyst is extremely complex—it requires pore-forming treatment at 800°C, followed by water washing and hydrogen reduction, which is not only energy-intensive and dangerous (involving high temperatures and flammable and explosive hydrogen), but also results in high catalyst costs and poor reusability; furthermore, the process requires filtration and purification of the intermediate product, perfluoropropionyl fluoride, increasing process complexity and production costs.

[0004] On the other hand, while the route for synthesizing perfluoropropionyl fluoride from tetrafluoroethylene is theoretically more economical, it faces multiple challenges in practical applications: the reaction between fluorinated phosgene and tetrafluoroethylene requires a specific catalytic system, and conventional fluoride catalysts (such as NaF) are insufficiently active, easily leading to low conversion rates; if the solvent is not chosen appropriately (such as toluene, dimethyl sulfoxide, or acetonitrile), it may fail to effectively dissolve fluorinated phosgene or cause side reactions with the reactants, resulting in COF3... -The inhibition of active species formation leads to the self-polymerization of tetrafluoroethylene or the generation of byproducts such as CF4, significantly reducing the selectivity and yield of the target product. In addition, there are few reports in the existing technology of continuously integrating the synthesis of perfluoropropionyl fluoride with its subsequent methylation step. The separation of intermediate products is not only time-consuming and energy-intensive, but may also decompose due to exposure to moisture or high temperature environments.

[0005] Therefore, there is an urgent need to develop a method for preparing 1-methoxyheptafluoropropane that uses inexpensive and readily available raw materials, has simple process steps, mild reaction conditions, high selectivity, excellent yield, and is suitable for continuous industrial production, in order to overcome the shortcomings of existing technologies in terms of cost, safety, efficiency, and environmental protection. Summary of the Invention

[0006] The purpose of this application is to provide a method for preparing 1-methoxyheptafluoropropane that is inexpensive to produce, has a continuous process, mild conditions, high yield, and is suitable for industrial continuous production, in order to overcome the shortcomings of existing technologies such as high cost, complicated steps, poor safety, and low yield.

[0007] To achieve the above-mentioned objectives, this application adopts the following technical solution: A method for preparing an asymmetric hydrofluoroether, wherein the asymmetric hydrofluoroether is 1-methoxyheptafluoropropane, comprises the following two consecutive reaction steps, and the intermediate product proceeds directly to the next reaction step without separation and purification: Step S1: Under an inert atmosphere, fluorinated phosgene is mixed with one or more fluorinated catalysts in an anhydrous stable solvent until saturation; then tetrafluoroethylene is slowly introduced at a rate of 0.01–0.1 L / min, and the mixture is reacted at 10–100 °C and 0–0.5 MPa to produce perfluoropropionyl fluoride. Step S2: The reaction mixture containing perfluoropropionyl fluoride obtained in step S1 is directly fed into the reactor and reacted with the methylating agent and optional alcohol auxiliaries in the same or similar solvent system at 10–100 °C and 0–0.5 MPa to generate 1-methoxyheptafluoropropane.

[0008] Furthermore, the fluorination catalyst is selected from one or more of potassium fluoride (KF), cesium fluoride (CsF), aluminum fluoride (AlF3), and cobalt fluoride (CoF2).

[0009] Furthermore, when using two catalysts, a mixture of CsF and KF is used, with a molar ratio of 1:1 to 1:4.

[0010] Furthermore, the anhydrous stable solvent is a mixture of perfluoroalkane and ether, wherein the perfluoroalkane accounts for 60–90% by volume, and the water content of the mixture is less than 50 ppm.

[0011] Furthermore, the perfluoroalkane is selected from one or more of perfluorohexane, perfluorononane, and perfluorodecane; the ether is selected from one or more of diethyl ether, tetrahydrofuran, and methyl tert-butyl ether.

[0012] Furthermore, in step S1, 0.5–2 mol% of a phase transfer catalyst is added, wherein the phase transfer catalyst is selected from tetrabutylammonium bromide or polyethylene glycol dimethyl ether.

[0013] Furthermore, the methylating agent in step S2 is dimethyl sulfate or iodomethane, the alcohol auxiliary is methanol or ethanol, and the water content of the reaction system in step S2 is less than 50 ppm.

[0014] Furthermore, in step S2, the intensity change of the C=O characteristic peak of perfluoropropionyl fluoride is monitored by online infrared. The reaction is terminated when the peak intensity decreases by ≥90% relative to the initial intensity of the C=O characteristic peak of perfluoropropionyl fluoride in step S2.

[0015] This application achieves efficient in-situ generation of perfluoropropionyl fluoride using tetrafluoroethylene and fluorinated phosgene as starting materials, combined with a specific fluorination catalyst and an inert anhydrous solvent system. Furthermore, 1-methoxyheptafluoropropane is directly produced via a continuous methylation reaction, eliminating the need for intermediate product separation and purification. This method achieves superior technical effects—high overall conversion, high yield, and high selectivity—under mild reaction conditions, significantly outperforming existing technologies. Simultaneously, by optimizing the catalyst combination, solvent ratio, phase transfer catalysis, and process control, side reactions and self-polymerization of the starting materials are effectively suppressed, improving process safety and stability, and demonstrating good scalability and industrial application prospects. Detailed Implementation

[0016] The present application will be further illustrated by the following embodiments, but the scope of protection of the present application is not limited to the embodiments.

[0017] All raw materials used in the following examples are commercially available analytical grade reagents, and the equipment used is conventional chemical reaction equipment; "water content" was detected by Karl Fischer moisture analyzer, "product yield" was calculated by gas chromatography (GC-2014, Shimadzu) external standard method, and "product purity" was determined by gas chromatography-mass spectrometry (GC-MSQP2010Ultra, Shimadzu).

[0018] All solvents used in the examples were dried using 4Å molecular sieves, and the water content was confirmed to be less than 50 ppm by a Karl Fischer moisture analyzer.

[0019] Example 1: In this embodiment, the specific steps are as follows: Step S1: Preparation of perfluoropropionyl fluoride 1. Reaction system setup: Add 200 mL of anhydrous stable solvent, which is a mixture of perfluorohexane and tetrahydrofuran in a volume ratio of 7:3 and dried through a 4Å molecular sieve with a water content of <30 ppm, to a 500 mL reaction vessel. Then add 15.2 g (0.1 mol) of cesium fluoride (CsF) fluorination catalyst and stir until the catalyst is completely dissolved to form a homogeneous and transparent solution.

[0020] 2. Inert atmosphere protection: Nitrogen gas is introduced into the reaction vessel for 30 minutes to replace the air in the vessel and maintain a slight positive pressure of nitrogen (0.02 MPa) as a protective atmosphere.

[0021] 3. Formation of active species: Slowly introduce 10.8 g (0.11 mol) of fluorinated phosgene (COF2) at a rate of 0.03 L / min, while stirring at 300 rpm. React at room temperature (25℃) for 30 min until a stable nucleophilic active species, COF3, is formed in the solution. - (by nuclear magnetic resonance fluorine spectroscopy) 19 FNMR monitoring showed the presence of COF3 at δ = -89.5 ppm. - Characteristic peaks).

[0022] 4. Tetrafluoroethylene reaction: The reaction temperature was raised to 50℃, the reaction pressure was adjusted to 0.2 MPa, and 11.6 g (0.116 mol) of tetrafluoroethylene (C2F4) was introduced at a rate of 0.05 L / min. The reaction was stirred continuously for 4 h. During the reaction, samples were taken periodically through the sampling port. GC analysis showed that the amount of perfluoropropionyl fluoride generated increased with reaction time, and the selectivity of perfluoropropionyl fluoride reached 98.2% after 4 h.

[0023] Step S2: Preparation of 1-methoxyheptafluoropropane 1. Continuous reaction feed: The reaction mixture containing perfluoropropionyl fluoride obtained in step S1 (without separation and purification) is directly pumped into another 500 mL reaction vessel. The vessel is pre-filled with 50 mL of the same anhydrous stable solvent as in step S1 to maintain the water content of the reaction system <30 ppm.

[0024] 2. Methylation reaction: Add 15.4 g (0.122 mol) of dimethyl sulfate, a methylating agent, and 5.8 g (0.181 mol) of methanol (anhydrous, water content <20 ppm), an alcohol auxiliary agent, to the reaction vessel and stir until homogeneous; lower the reaction temperature to 40℃, adjust the reaction pressure to 0.1 MPa, and bubble nitrogen gas at a rate of 0.03 L / min (to assist mass transfer) and continue the reaction for 3 h.

[0025] 3. Product separation and detection: After the reaction was completed, the product mixture was passed sequentially through an anhydrous sodium sulfate drying column (to remove trace amounts of moisture) and a silica gel chromatography column (to remove unreacted dimethyl sulfate), and then by distillation (collecting the fraction at 33.8-34.2℃) to obtain 32.6g of 1-methoxyheptafluoropropane product.

[0026] Test results: Product yield 95.3% (based on tetrafluoroethylene), purity 98.1%. 19 FNMR verification confirmed the absence of obvious byproducts (such as CF4 and polymethylation impurities). Example 2:

[0027] This embodiment combines a mixed fluorination catalyst and a phase transfer catalyst, and the specific steps are as follows: Step S1: Preparation of perfluoropropionyl fluoride 1. Catalyst and solvent preparation: 200 mL of anhydrous stable solvent is a mixture of perfluorohexane and tetrahydrofuran at a volume ratio of 8:2 (water content <25 ppm). Add the mixed fluorination catalyst (CsF and KF mixed at a molar ratio of 1:2, with a total amount of 0.1 mol, including 5.1 g of CsF and 11.7 g of KF), and then add 0.16 g of the phase transfer catalyst tetrabutylammonium bromide (TBAB) (0.5 mol%, relative to the molar amount of fluorinated phosgene). Stir until completely dissolved.

[0028] 2. Subsequent operations: Fluorophosgene injection rate 10.8g (0.11mol), tetrafluoroethylene injection rate 0.06L / min (dosage 12.0g, 0.12mol), reaction temperature 60℃, pressure 0.25MPa, reaction time 3.5h; the remaining operations are the same as step S1 in Example 1.

[0029] Intermediate testing: The selectivity of perfluoropropionyl fluoride was improved to 99.1%, and the content of tetrafluoroethylene self-polymerization byproducts (oligomers) was <0.5%.

[0030] Step S2: Preparation of 1-methoxyheptafluoropropane 1. Methylation system preparation: The methylation reagent is 16.0 g (0.127 mol) of dimethyl sulfate and 6.0 g (0.1875 mol) of methanol as an alcohol auxiliary agent. The reaction temperature is 45℃, the pressure is 0.15 MPa, and the reaction time is 2.5 h. The remaining operations are the same as step S2 in Example 1.

[0031] 2. Product detection: 33.5 g of 1-methoxyheptafluoropropane was obtained, with a yield of 97.8% (based on tetrafluoroethylene) and a purity of 98.7%.

[0032] Optimization effect: The mixed catalyst improved COF3 - The generation efficiency was improved, and the phase transfer catalyst promoted the mass transfer between phosgene and tetrafluoroethylene, further reducing byproducts. Example 3:

[0033] In this embodiment, the specific steps are as follows: Step S1: Preparation of perfluoropropionyl fluoride 1. Solvent and catalyst preparation: The anhydrous stable solvent is a mixture of perfluorononane and methyl tert-butyl ether at a volume ratio of 8:2 in 200 mL. 8.4 g (0.1 mol) of aluminum fluoride catalyst is added and stirred to form a suspension (AlF3 is a solid catalyst, suspended and dispersed).

[0034] 2. Reaction parameter control: Fluorophosgene injection rate 11.0 g (0.112 mol), tetrafluoroethylene injection rate 0.04 L / min (dosage 11.2 g, 0.112 mol), reaction temperature 45℃, pressure 0.18 MPa, reaction time 4.5 h; the remaining operations are the same as step S1 in Example 1.

[0035] Step S2: Preparation of 1-methoxyheptafluoropropane 1. Online Infrared Monitoring Setup: Connect an online infrared spectrometer (Nicoleti S50, Thermo) to the sampling port of the reaction vessel to monitor the C=O characteristic peak (wavenumber 1882 cm⁻¹) of perfluoropropionyl fluoride. -1 The reaction will automatically terminate when the peak intensity decreases by ≥90% due to intensity changes.

[0036] 2. Methylation system preparation: The methylating agent is 17.5g (0.123mol) of iodomethane, and the alcohol auxiliary agent is 8.2g (0.178mol) of ethanol (anhydrous, water content <20ppm). The reaction temperature is 35℃, the pressure is 0.08MPa, and the stirring speed is 350rpm.

[0037] 3. Reaction termination and product processing: After 2.8 hours of reaction, online infrared monitoring showed that the intensity of the C=O characteristic peak decreased by 92.3% compared with the initial value. Stirring was stopped immediately and the reaction was terminated. After drying and distillation, 31.8g of 1-methoxyheptafluoropropane was obtained.

[0038] Test results: Product yield 93.6% (based on tetrafluoroethylene), purity 99.0%; online infrared monitoring accurately controlled the reaction endpoint, avoiding polymethylation byproducts (content <0.3%) caused by over-reaction. Example 4:

[0039] In this embodiment, the anhydrous stable solvent is prepared by mixing perfluorohexane and tetrahydrofuran at a volume ratio of 7:3, with a water content of <30ppm. The specific steps are as follows (basic operations such as inert atmosphere replacement and product separation, which are the same as in Example 1, are omitted): Step S1: Preparation of perfluoropropionyl fluoride Preparation of catalyst, solvent and phase transfer catalyst: Add 200 mL of anhydrous stable solvent (made by mixing perfluorohexane and tetrahydrofuran in a volume ratio of 7:3, with a water content of <30 ppm after drying by molecular sieve) to a 500 mL reaction vessel, add 5.8 g (0.1 mol) of potassium fluoride (KF) fluorination catalyst, and stir until completely dissolved; then add 0.32 g (1 mol%, relative to the molar amount of fluorinated phosgene) of tetrabutylammonium bromide (TBAB) phase transfer catalyst, and continue stirring for 10 min until the system is homogeneous.

[0040] Reaction parameters were controlled as follows: 10.6 g (0.108 mol) of fluorinated phosgene (COF2) was introduced at a rate of 0.03 L / min, and the mixture was stirred at room temperature (25℃) for 30 min until COF3 was generated. - ( 19 (The characteristic peak was observed at δ=-89.4ppm by FNMR). The temperature was then raised to 50℃, the reaction pressure was adjusted to 0.2MPa, and 11.4g (0.114mol) of tetrafluoroethylene (C2F4) was introduced at a rate of 0.05L / min, and the reaction was continued for 3.5h.

[0041] Intermediate testing: The selectivity of perfluoropropionyl fluoride was improved to 98.8%, and the content of tetrafluoroethylene self-polymerization byproducts (oligomers) was <0.3% (the phase transfer catalyst promoted mass transfer efficiency and suppressed side reactions caused by local overconcentration).

[0042] Step S2: Preparation of 1-methoxyheptafluoropropane Preparation of the methylation system: The S1 reaction mixture was directly fed into another reactor, which was pre-filled with 50 mL of the same composite solvent as S1 (perfluorohexane-tetrahydrofuran 7:3) (water content <30 ppm), 15.1 g (0.119 mol) of dimethyl sulfate and 5.6 g (0.175 mol) of anhydrous methanol, and stirred until homogeneous; the reaction temperature was controlled at 40 °C and the pressure at 0.1 MPa, and the reaction was carried out for 2.5 h.

[0043] Product testing: After drying and distillation, 32.5 g of 1-methoxyheptafluoropropane was obtained, with a yield of 96.8% (based on tetrafluoroethylene) and a purity of 98.5% (GC-MS analysis showed that the content of CF4 byproduct was <0.5%, which was significantly lower than that of the single solvent system). Example 5:

[0044] This embodiment uses aluminum fluoride (AlF3) as a catalyst and anhydrous tetrahydrofuran (THF) as a solvent to verify the applicability of solid suspension catalysts.

[0045] Step S1: Preparation of perfluoropropionyl fluoride 1. Catalyst and solvent preparation: Add 200 mL of anhydrous THF to a 500 mL reaction vessel, add 8.4 g (0.1 mol) of solid fluorination catalyst AlF3, and stir to form a stable suspension.

[0046] 2. Reaction parameter control: 11.2 g (0.114 mol) of fluorinated phosgene (COF2) was introduced at a rate of 0.035 L / min, and the mixture was stirred at room temperature for 30 min until COF3 was generated. - The temperature was raised to 55℃, the pressure was adjusted to 0.2MPa, and 11.8g (0.118mol) of tetrafluoroethylene (C2F4) was introduced at a rate of 0.05L / min, and the reaction was continued for 4.2h.

[0047] Intermediate test: Perfluoropropionyl fluoride showed a selectivity of 98.0%, and the AlF3 suspension showed no significant sedimentation, indicating stable catalytic activity.

[0048] Step S2: Preparation of 1-methoxyheptafluoropropane Methylation system preparation: The S1 suspension reaction mixture was directly fed into another reactor, with 50 mL of anhydrous THF added beforehand, and 17.2 g (0.121 mol) of iodomethane and 8.0 g (0.174 mol) of anhydrous ethanol added; the reaction temperature was controlled at 42 °C and the pressure at 0.12 MPa, and the reaction was carried out for 2.8 h.

[0049] Product testing: After drying and distillation, 32.8 g of 1-methoxyheptafluoropropane was obtained, with a yield of 95.2% (based on tetrafluoroethylene) and a purity of 97.3% (GC analysis showed that the content of polymethylation byproducts was <0.5%). Example 6:

[0050] This embodiment uses cobalt fluoride (CoF2) as a catalyst and anhydrous diethyl ether as a solvent to verify the applicability of transition metal fluoride catalysts. The specific steps are as follows: Step S1: Preparation of perfluoropropionyl fluoride Catalyst and solvent preparation: Add 200 mL of anhydrous diethyl ether to a 500 mL reaction vessel, add 9.7 g (0.1 mol) of fluorinated catalyst CoF2, and stir until dissolved (some CoF2 is slightly soluble, forming a homogeneous clear liquid).

[0051] Reaction parameters were controlled as follows: 10.6 g (0.108 mol) of fluorinated phosgene (COF2) was introduced at a rate of 0.028 L / min, and the mixture was stirred at room temperature for 32 min until COF3 was generated. - The temperature was raised to 48℃, the pressure was adjusted to 0.18MPa, and 11.4g (0.114mol) of tetrafluoroethylene (C2F4) was introduced at a rate of 0.045L / min, and the reaction was continued for 3.8h.

[0052] Intermediate testing: Perfluoropropionyl fluoride selectivity was 97.2%, with no CoF2 hydrolysis byproducts (HF not detected).

[0053] Step S2: Preparation of 1-methoxyheptafluoropropane Methylation system preparation: The S1 reaction mixture was directly fed into another reactor, with 50 mL of anhydrous diethyl ether added beforehand, and 14.8 g (0.117 mol) of dimethyl sulfate and 5.5 g (0.172 mol) of anhydrous methanol added; the reaction temperature was controlled at 36 °C and the pressure at 0.1 MPa, and the reaction was carried out for 3.2 h.

[0054] Product testing: After drying and distillation, 31.6 g of 1-methoxyheptafluoropropane was obtained, with a yield of 94.4% (based on tetrafluoroethylene) and a purity of 96.3% (GC-MS verification showed that the characteristic peak of the target product accounted for ≥96.3%). Example 7:

[0055] This embodiment uses a CsF and KF mixed catalyst and perfluorodecane as a solvent to verify the applicability of the mixed catalyst to long-chain perfluoroalkane solvents. The specific steps are as follows: Step S1: Preparation of perfluoropropionyl fluoride Catalyst and solvent preparation: Add 200 mL of anhydrous perfluorodecane (water content <42 ppm) dried by molecular sieve to a 500 mL reaction vessel, add mixed fluorination catalyst (CsF to KF molar ratio 1:3, total amount of substance 0.1 mol: CsF 2.55 g, KF 8.78 g), and stir until completely dissolved.

[0056] Reaction parameters were controlled as follows: 11.5 g (0.117 mol) of fluorinated phosgene (COF2) was introduced at a rate of 0.032 L / min, and the mixture was stirred at room temperature for 28 min until COF3 was formed. - The temperature was raised to 65℃, the pressure was adjusted to 0.22MPa, and 12.2g (0.122mol) of tetrafluoroethylene (C2F4) was introduced at a rate of 0.055L / min, and the reaction was continued for 4.5h.

[0057] Intermediate testing: Perfluoropropionyl fluoride showed a selectivity of 98.5%, tetrafluoroethylene showed no self-polymerization, and the catalyst showed no signs of deactivation.

[0058] Step S2: Preparation of 1-methoxyheptafluoropropane Methylation system preparation: The S1 reaction mixture was directly fed into another reactor, with 50 mL of anhydrous perfluorodecane added beforehand, and 17.8 g (0.125 mol) of iodomethane and 8.3 g (0.18 mol) of anhydrous ethanol added; the reaction temperature was controlled at 48 °C and the pressure at 0.14 MPa, and the reaction was carried out for 2.6 h.

[0059] Product testing: After drying and distillation, 33.2 g of 1-methoxyheptafluoropropane was obtained, with a yield of 95.8% (based on tetrafluoroethylene) and a purity of 97.1% (GC analysis showed total impurity content <2.9%).

[0060] Comparative Example 1: Using toluene as a solvent Step S1: Preparation of perfluoropropionyl fluoride Solvent and catalyst preparation: Add 200 mL of anhydrous toluene (dried by molecular sieve, water content <30 ppm) to a 500 mL reaction vessel, add 15.2 g (0.1 mol) of cesium fluoride (CsF), stir to dissolve, and then purge with nitrogen to replace the air.

[0061] Reaction process: 10.8 g (0.11 mol) of fluorinated phosgene (COF2) was introduced. Upon stirring at room temperature, the solution rapidly turned yellow (due to the Friedel-Crafts fluorination side reaction between toluene and fluorinated phosgene). Samples were taken after 30 minutes for analysis; COF3... - Characteristic peaks ( 19 The FNMR intensity is extremely weak (δ=-89.5ppm) and it generates a large amount of toluene fluorination byproducts (such as o-fluorotoluene and p-fluorotoluene).

[0062] Tetrafluoroethylene reaction: The temperature was further increased to 50℃ and the pressure to 0.2MPa. 11.6g (0.116mol) of tetrafluoroethylene (C2F4) was introduced. After 4h of reaction, GC detection showed that the selectivity of perfluoropropionyl fluoride was only 62.3% (a large amount of tetrafluoroethylene polymerized with toluene byproducts).

[0063] Step S2: Preparation of 1-methoxyheptafluoropropane The S1 mixture was directly subjected to a methylation reaction, and the product was separated to obtain only 13.5g of 1-methoxyheptafluoropropane.

[0064] Test results: Total yield 39.8% (based on tetrafluoroethylene), purity 81.2% (containing a large amount of toluene-derived impurities), selectivity 68.5% (less than 70%).

[0065] Comparative Example 2: Using acetonitrile as a solvent Step S1: Preparation of perfluoropropionyl fluoride Solvent and catalyst preparation: Add 200 mL of anhydrous acetonitrile (water content <30 ppm) to a 500 mL reaction vessel, add 15.2 g (0.1 mol) of cesium fluoride (CsF), stir to dissolve, and then purge with nitrogen to replace the air.

[0066] Reaction process: 10.8 g (0.11 mol) of fluorinated phosgene (COF2) was introduced, and the mixture was stirred at room temperature for 30 min to generate COF3. - However, the cyano group (-CN) of acetonitrile is similar to COF3. -A nucleophilic reaction occurs, generating an unstable imide intermediate.

[0067] Tetrafluoroethylene reaction: After heating to 50℃ and pressurizing to 0.2MPa, tetrafluoroethylene was introduced. Due to the decomposition of the intermediate and the release of fluoride ions, tetrafluoroethylene underwent violent self-polymerization (a white polymer precipitate appeared on the inner wall of the reactor). After 4 hours, the selectivity of perfluoropropionyl fluoride was only 58.7%.

[0068] Step S2: Preparation of 1-methoxyheptafluoropropane Following the methylation reaction, 14.8 g of 1-methoxyheptafluoropropane was obtained.

[0069] Test results: Total yield 43.5% (based on tetrafluoroethylene), purity 79.6% (including polymer impurities), selectivity 65.2% (less than 70%).

[0070] Comparative Example 3: Using NaF as a catalyst (low-activity catalyst) Step S1: Preparation of perfluoropropionyl fluoride Catalyst and solvent preparation: Add 200 mL of the same anhydrous stable solvent as in Example 1 (perfluorohexane-tetrahydrofuran 7:3, water content <30 ppm) to a 500 mL reaction vessel, and add 4.2 g of sodium fluoride (NaF) (0.1 mol, the same amount as CsF). After stirring, NaF only partially dissolves (its solubility is much lower than that of CsF).

[0071] Reaction process: 10.8 g (0.11 mol) of fluorinated phosgene (COF2) was introduced, and the mixture was stirred at room temperature for 30 min. 19 No significant COF3 was detected by FNMR. - Characteristic peaks (NaF has low fluoride ion activity and is difficult to react with COF2 to generate active species).

[0072] Tetrafluoroethylene reaction: After heating to 50°C and pressing to 0.2 MPa, the reaction made almost no progress after the introduction of tetrafluoroethylene. After 4 hours, the amount of perfluoropropionyl fluoride produced was only 30% of that in Example 1. Moreover, due to insufficient NaF catalytic activity, fluorinated phosgene decomposed to produce a large amount of CF4 (accounting for 42% of the gas phase products).

[0073] Step S2: Preparation of 1-methoxyheptafluoropropane After methylation, 15.3 g of 1-methoxyheptafluoropropane was obtained.

[0074] Test results: Total yield 45.0% (based on tetrafluoroethylene), purity 82.1%, selectivity 69.8% (less than 70%).

[0075] Comparison of key data between the examples and comparative examples: Case Number Total yield (%) Selectivity (%) Product purity (%) Core Issues / Advantages Analysis Example 1 95.3 98.2 98.1 The basic process has achieved high yields, no side reactions, and excellent solvent and catalyst compatibility. Example 2 97.8 99.1 98.7 Mixed catalysts enhance activity, while phase-transfer catalysts promote mass transfer, further optimizing yield and selectivity. Example 3 93.6 99.0 99.0 Solid suspension catalysts exhibit excellent compatibility, online monitoring prevents over-reaction, and achieves maximum purity. Example 4 96.8 98.8 98.5 Even with a single KF catalyst plus a phase transfer catalyst, high yields are still maintained, demonstrating the versatility of the process for single catalysts. Example 5 95.2 98.0 97.3 Non-fluorinated single ether solvents are still suitable; the solid catalyst shows no precipitation and stable activity. Example 6 94.4 97.2 96.3 The transition metal fluoride catalyst is effective, the diethyl ether solvent has sufficient inertness, and the yield remains stable at over 94%. Example 7 95.8 98.5 97.1 Long-chain perfluoroalkanes exhibit excellent solvent compatibility; mixed catalysts suppress side reactions; and yield / selectivity is balanced. Comparative Example 1 39.8 68.5 81.2 Toluene undergoes a Friedel-Crafts side reaction with fluorinated phosgene, resulting in insufficient formation of active species and excessive byproducts. Comparative Example 2 43.5 65.2 79.6 <![CDATA[The cyano group of acetonitrile reacts with COF3 - to form an unstable intermediate, leading to the self-polymerization of tetrafluoroethylene and the product containing polymer impurities]]> Comparative Example 3 45.0 69.8 82.1 <![CDATA[The lattice energy of NaF is high, and its ability to release F⁻ is weak, making it unable to effectively generate COF3 - , and the decomposition of phosgene fluoride produces a large amount of CF4 by-products]]> Analysis conclusion: 1. The universality and stability of the process in the embodiments of the present invention As seen in Examples 1-7, regardless of whether a single catalyst or mixed catalyst is used, or whether a fluorinated-ether composite solvent or a single ether solvent is employed, or even with optimization techniques such as the introduction of phase transfer catalysts and online infrared monitoring, the overall yield remains consistently between 93.6% and 97.8%, with a selectivity ≥97.2% and a product purity ≥96.3%. This indicates that the core system of "inert anhydrous solvent + highly active fluorination catalyst" defined in this invention has strong universality, adaptable to different catalyst types, solvent combinations, and process optimization strategies, and can always avoid side reactions and maintain high-efficiency conversion. The fundamental reason is that the selected solvents (perfluoroalkanes and ethers) do not react with phosgene or COF3. - The reaction occurs, and the selected catalyst (KF, CsF, etc.) can efficiently release F. - To generate active species, the two work synergistically.

[0076] 2. The shortcomings of the comparative example and the targeted improvements of the present invention Comparing Examples 1-7 with Comparative Examples 1-3, it is clear that the low performance of the comparative examples all stems from the destruction of "solvent inertness" or "catalyst activity," while the present invention solves these problems at their root by precisely selecting raw materials.

[0077] 3. Additional gains from process optimization features Examples 2, 4, and 7 further demonstrate that, based on the "inert solvent + highly active catalyst" approach, the optimized features of this invention (mixed catalyst, phase transfer catalyst) can further enhance performance. For instance, Example 2, using a CsF-KF mixed catalyst (molar ratio 1:2), leverages the high dissociation of CsF and the low cost of KF to increase selectivity to 99.1%. Example 4, by adding the phase transfer catalyst TBAB, promotes the dispersion of F⁻ in the solvent, resulting in a 1.5% increase in yield compared to the system without TBAB. These optimizations not only do not compromise the stability of the core system but also further unlock the reaction potential, demonstrating the scalability of the process of this invention.

[0078] 4. Comparison of Industrial Adaptability From a production efficiency perspective, the continuous processes in Examples 1-7 require no intermediate separation and have a short production cycle. However, if the low-efficiency system in the comparative example is used, even with multiple purifications, the production cycle will be extended to more than 15 hours, and the yield will still be less than 45%, which completely fails to meet the industrial demand for "high efficiency and low cost". The stable high yield and short cycle characteristics of the embodiments of this invention can be directly adapted to large-scale continuous production and have significant industrial value.

[0079] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit it. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A process for the preparation of an asymmetric hydrofluoroether, characterized in that, The asymmetric hydrofluoroether is 1-methoxyheptafluoropropane, comprising two consecutive reaction steps without isolation and purification of the intermediate product: Step S1: under inert atmosphere, mix fluorophosgene with one or more fluorination catalysts in anhydrous stable solvent to saturation; then slowly introduce tetrafluoroethylene at a rate of 0.01-0.1 L / min, react at 10-100℃, 0-0.5 MPa to form perfluoropropionyl fluoride; Step S2: directly introduce the reaction mixture containing perfluoropropionyl fluoride from step S1 into a reactor, react with methylating reagent and optional alcoholic adjuvant in the same or similar solvent system at 10-100℃, 0-0.5 MPa to form 1-methoxyheptafluoropropane.

2. The process for the preparation of asymmetric hydrofluoroethers according to claim 1, characterized in that, The fluorination catalyst is selected from one or more than two combinations of potassium fluoride (KF), cesium fluoride (CsF), aluminum fluoride (AlF3), cobalt fluoride (CoF2).

3. The method for preparing asymmetric hydrofluoroether according to claim 1, characterized in that, When two catalysts are used, it is a mixture of CsF and KF, with a molar ratio of 1:1 to 1:

4.

4. The method for preparing asymmetric hydrofluoroether according to claim 1, characterized in that, The anhydrous stable solvent is a mixture of perfluoroalkane and ether, wherein the volume ratio of perfluoroalkane is 60-90%, and the water content of the mixture is less than 50 ppm.

5. The method for preparing asymmetric hydrofluoroethers according to claim 1, characterized in that, The perfluoroalkane is selected from one or more of perfluorohexane, perfluorononane, perfluorodecane; the ether is selected from one or more of diethyl ether, tetrahydrofuran, methyl tert-butyl ether.

6. The method for preparing asymmetric hydrofluoroether according to claim 1, characterized in that, In step S1, 0.5-2 mol% of phase transfer catalyst is added, which is selected from tetrabutylammonium bromide or polyethylene glycol dimethyl ether.

7. The method for preparing asymmetric hydrofluoroether according to claim 1, characterized in that, In step S2, the methylating reagent is dimethyl sulfate or iodomethane, the alcoholic adjuvant is methanol or ethanol, and the water content of the reaction system in step S2 is less than 50 ppm.

8. The method for preparing asymmetric hydrofluoroethers according to claim 1, characterized in that, In step S2, the change in the intensity of the C=O characteristic peak of perfluoropropionyl fluoride is monitored by online infrared, and the reaction is terminated when the peak intensity of the C=O characteristic peak of perfluoropropionyl fluoride decreases by ≥90% relative to the initial intensity in step S2.