Process for the synthesis of olafluor and its use

Abstract

This invention provides a synthesis process for olafron and its application, comprising the following steps: mixing a solvent, octadecylamine, and triethylamine, then pumping the mixture with 2-bromo-1-ethanol into a continuous flow reactor; extracting the reaction solution after the reaction and purifying it to obtain OLF-A1; mixing OLF-A1, a solvent, and potassium carbonate, heating the mixture and adding 3-bromo-1-chloropropane to react; extracting the reaction solution after the reaction and purifying it with silica gel to obtain OLF-A2; mixing OLF-A2, a solvent, and potassium carbonate, heating the mixture and adding diethanolamine; extracting the reaction solution after the reaction and purifying it to obtain OLF-A3; mixing OLF-A3 and a dehydrating agent, then adding hydrofluoric acid, heating and stirring, concentrating the mixture, and purifying it to obtain the finished product, olafron. This invention solves the problems of excessive impurities and low yield in conventional processes by optimizing the reaction apparatus and purification methods for intermediate synthesis, providing technical support for the efficient synthesis of olafron.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to a synthesis process of olaflu and its application. Background Technology

[0002] Oraflu, as a high-performance fluorinated surfactant, combines the high stability and low surface tension of fluorine with the hydrophobicity of long-chain alkyl groups. It has broad application prospects in oral care, industrial cleaning, and material modification. Optimizing its synthesis process is crucial for improving product quality and market competitiveness.

[0003] The existing olaflue synthesis process requires multiple steps and involves numerous intermediates. However, current technologies typically employ conventional reactors for conversion, which presents several technical drawbacks: Firstly, the mass and heat transfer efficiency of conventional reactors is limited, leading to localized uneven conditions and non-target conversions of raw materials. This results in frequent side reactions and the generation of various structurally similar, difficult-to-separate impurities. These impurities directly affect the selectivity of subsequent fluorination reactions, making it difficult to achieve the required purity for the final olaflue product. Secondly, the generation of numerous impurities severely restricts the conversion efficiency of the target intermediates. In existing processes, the yield of the target intermediates typically only reaches 60%-75%, and subsequent purification requires complex methods such as multiple distillations and recrystallization. This not only increases the number of process steps and production costs but also results in high energy consumption and large wastewater discharge.

[0004] Furthermore, in traditional purification processes, distillation is prone to intermediate decomposition due to high temperatures, while recrystallization is limited by solvent selection and crystallization condition control, making it difficult to effectively remove structurally similar alkylation byproducts, further exacerbating the process difficulty of subsequent olafron synthesis. Therefore, how to reduce impurity generation during intermediate synthesis, improve reaction yield, and simplify the purification process has become a critical technical challenge that urgently needs to be addressed in existing olafron synthesis processes.

[0005] In conclusion, a new technical solution is urgently needed to address the problems existing in the current technology. Summary of the Invention

[0006] To address the shortcomings and deficiencies in the existing technology, this invention provides a synthesis process for olafron and its applications. This invention proposes an olafron synthesis process based on a combination of microchannel reaction and silica gel purification. By optimizing the reaction apparatus and purification methods for intermediate synthesis, it solves the core problems of excessive impurities and low yields in conventional processes, providing technical support for the efficient and green synthesis of olafron.

[0007] One object of the present invention is to provide a synthesis process for olaflu, the synthesis process of olaflu comprising the following steps: S1. Mix the solvent, octadecylamine and triethylamine, and then pump 2-bromo-1-ethanol into a continuous flow reactor for reaction. After the reaction, extract the reaction solution and purify it to obtain the intermediate OLF-A1. S2. The intermediate OLF-A1, solvent and potassium carbonate are mixed, and 3-bromo-1-chloropropane is added to the mixture under high temperature to carry out the reaction. After the reaction, the reaction solution is extracted and purified with silica gel to obtain intermediate OLF-A2. S3. The intermediate OLF-A2, solvent and potassium carbonate are mixed, and diethanolamine is added at a higher temperature to react. After the reaction, the reaction solution is extracted and purified to obtain intermediate OLF-A3. S4. The intermediate OLF-A3 and the dehydrating agent are mixed, and then hydrofluoric acid is added at low temperature. After heating and stirring, the mixture is concentrated. After concentration, the product Olarflu is obtained by purification.

[0008] Furthermore, in step S1, the reaction temperature is 90-100℃ and the reaction time is 6-8 h.

[0009] Furthermore, in step S2, the reaction temperature is 75-85℃ and the reaction time is 6-8 h.

[0010] Furthermore, in step S3, the reaction temperature is 110-120℃, and the reaction time is 6-8 h.

[0011] Furthermore, in step S1, the reaction is carried out in a continuous flow manner, which has the advantages of fast reaction speed, low impurity generation and high yield, which is conducive to improving the reaction efficiency and yield.

[0012] Further, in step S1, the mass ratio of octadecylamine, triethylamine and 2-bromo-1-ethanol is 100:(30-50):(30-50).

[0013] Further, in step S2, the mass ratio of the intermediate OLF-A1 to 3-bromo-1-chloropropane is (95-100):(40-70).

[0014] Further, in step S3, the mass ratio of the intermediate OLF-A2 to diethanolamine is (100-105):(50-60).

[0015] Further, in step S4, the mass ratio of the intermediate OLF-A3 to hydrofluoric acid is (110-120):(20-30), and the concentration of the hydrofluoric acid is 30-50 wt%.

[0016] Further, in steps S1-S3, water and methyl tert-butyl ether (MTBE) are added for extraction.

[0017] Further, in step S2, the amount of silicone is 15-25 wt% of OLF-A1, preferably 20 wt%.

[0018] Furthermore, the silica gel has a particle size of 50-400 mesh, preferably 200-300 mesh.

[0019] Furthermore, in step S4, the dehydrating agent is selected from alcohol compounds.

[0020] Furthermore, the dehydrating agent is preferably isopropanol.

[0021] Another object of the present invention is to provide the application of the above-mentioned synthesis process of olaflurium in oral care products.

[0022] The present invention has the following beneficial effects: (1) In the synthesis process of oraflu provided by the present invention, step S1 is carried out in a continuous flow reactor. Compared with the traditional batch reactor reaction, it has the advantages of fast speed, less impurities and high yield, which can effectively improve the reaction efficiency. (2) In step S2 of the present invention, a specific silica gel is used for purification, which can efficiently adsorb highly polar impurities and solve the problem that OLF-A2 (the product is a high-boiling oil) cannot be purified by crystallization or distillation. (3) In step S4 of the present invention, the reaction product (OLF-A4) is purified by alcohol crystallization to obtain high-purity olaf. Attached Figure Description

[0023] Figure 1 The overall synthetic process route of the present invention is shown.

[0024] Figure 2 The HNMR spectrum of OLF-A3 obtained in Example 1 is shown.

[0025] Figure 3 The LCMS-positive ion spectrum of olaflurium obtained in Example 1 is shown. Detailed Implementation

[0026] To more clearly illustrate the technical solution of the present invention, the following embodiments are provided. Unless otherwise stated, the raw materials, reactions, and post-processing methods appearing in the embodiments are all commercially available raw materials and technical methods well known to those skilled in the art.

[0027] The terms "preferred," "more preferably," and "more suitable" used in this invention refer to embodiments of the invention that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this invention.

[0028] It should be understood that, except in any operational instance or otherwise indicated, the amounts or all figures representing ingredients used, for example, in the specification and claims, should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical parameters set forth in the following specification and appended claims are approximate values ​​varying according to the desired performance to be obtained according to the invention.

[0029] The silica gel used in this embodiment of the invention is Qingdao marine chromatography silica gel, 200-300 mesh.

[0030] Example 1 A process for synthesizing olaflu, the process comprising the following steps: S1. Add component A: 200 kg DMF (N,N-dimethylformamide), 100 kg octadecylamine and 45 kg triethylamine to reaction vessel 1 and mix, heat to 100-110℃, set aside; add component B: 48.68 kg 2-bromo-1-ethanol to reaction vessel 2 and heat to 80-90℃, set aside; The materials in reactors 1 and 2 are pumped into a continuous flow reactor through metering pumps 1 and 2. The flow rate of pump 1 is controlled at 57.5 kg / h and the flow rate of pump 2 is controlled at 8.11 kg / h. The reaction time is 6 hours and the reaction temperature is controlled between 90-100℃. After cooling to 25°C, add 300 kg of water and 500 kg of MTBE, stir for 1 h, then let stand for 1 h, and separate the layers after separation. Add 100 kg of 10 wt% sodium chloride aqueous solution to the organic phase for washing, stir for 0.5 h, let stand, and separate the layers. Add 100 kg of 10 wt% sodium chloride aqueous solution to the organic phase for washing, then let stand and separate the layers. 20 kg of anhydrous sodium sulfate was added to the organic phase and dried for 2 h. After filtration, the organic phase was concentrated at 45 °C until 1 / 10 of the liquid volume remained. The concentration was then reduced to 0 °C, and crystals were precipitated. The mixture was stirred for 2 h, filtered, and dried under vacuum at 35 °C to obtain a white solid, namely intermediate OLF-A1, totaling 99.27 kg with a yield of 85.33%. S2. Mix 198.54 kg DMF, 99.27 kg intermediate OLF-A1, and 65.64 kg potassium carbonate, heat to 75°C, and slowly add 59.81 kg 3-bromo-1-chloropropane dropwise, maintaining the temperature at 75°C for 6 h. After the reaction is complete, perform TLC for 2 h. Sample preparation: take 1 mL of reaction solution + 0.2 mL of water + 0.2 mL of MTBE; developing solvent: EA:methanol = 3:1, v / v, iodine fumigation. After cooling to 25℃, 27.81 kg of water and 496.35 kg of MTBE were added, stirred for 1 h, and then allowed to stand for 1 h. After separation, the liquid was separated. 99.27 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, stirred for 0.5 h, allowed to stand, and then separated. 99.27 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, and then allowed to stand and separated. 19.85 kg of anhydrous sodium sulfate was added to the organic phase and dried for 1 h. Then 20 kg of silica gel was added and stirred for 1 h. After filtration, the filtrate was concentrated under reduced pressure at 45 °C until no effluent flowed out. The concentration was then continued under reduced pressure for 3 h to obtain a pale yellow oily liquid, namely intermediate OLF-A2, totaling 104.32 g, with a yield of 88.32%. S3. Mix 208.64 kg DMF, 104.32 kg intermediate OLF-A2, and 58.79 kg diethanolamine, stir and heat to 110℃, maintain this temperature, add potassium carbonate every 1 h, 11.6 kg each time, for a total of 5 times; after the potassium carbonate addition is complete, keep warm for 6 h, after which TLC can be used for central control. Sample preparation: take 1 mL of reaction solution + 0.2 mL of water + 0.2 mL of MTBE, developing solvent: EA:methanol = 3:1, v / v, iodine fumigation; After cooling to 25℃, 312.96 g of water and 521.6 kg of MTBE were added, stirred for 1 h, and then allowed to stand for 1 h. After separation, the liquid was separated. 104.32 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, stirred for 0.5 h, allowed to stand, and then separated. 104.32 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, and then allowed to stand and separated. 20.86 kg of anhydrous sodium sulfate was added to the organic phase and dried for 1 h. After filtration, the organic phase was concentrated until the moisture content was less than 0.5%. The concentration was complete, yielding a white paste-like solid, namely intermediate OLF-A3, totaling 117.31 kg, with a yield of 91.45%. S4. At 20℃, 586.55 kg of isopropanol and 117.31 kg of intermediate OLF-A3 were added to the R206 reactor. Then, 25.57 kg of 40 wt% HF solution was added dropwise at 0℃ for 2 h. After the pH of the system reached 4-5, it was slowly raised to room temperature and stirred for another 2 h. The reaction solution was concentrated at 45°C until about 1 / 5 of the volume remained. Then, 117 kg of isopropanol was added to further concentrate the water content until the water content was ≤1.5%. After concentration, another 117 kg of isopropanol was added, and the mixture was cooled to 0°C. After crystals precipitated, the mixture was stirred for another 2 hours. The mixture was then filtered and dried under vacuum at 30°C to obtain a paste-like solid, which is the finished product, oraflu, weighing a total of 119.18 kg with a yield of 93.45%.

[0031] Figure 1 The overall synthetic process route of the present invention is shown.

[0032] Figure 2 The HNMR spectrum of OLF-A3 obtained in Example 1 is shown (Note: the three active hydroxyl hydrogens are not integrated).

[0033] Figure 3 The LCMS-positive ion spectrum of olaflurium obtained in Example 1 is shown.

[0034] Example 2 A process for synthesizing olaflu, the process comprising the following steps: S1. Add component A: 200 kg DMF, 100 kg octadecylamine and 45 kg triethylamine to reaction vessel 1 and mix, heat to 100-110℃, set aside; add component B: 48.68 kg 2-bromo-1-ethanol to reaction vessel 2 and heat to 90℃, set aside; The materials in the reactors 1 and 2 are pumped into the continuous flow reactor through metering pump 1 and metering pump 2. The flow rate of pump 1 is controlled at 43.125 kg / h and the flow rate of pump 2 is controlled at 6.085 kg / h. The reaction time is 8 hours and the reaction temperature is controlled between 90-100℃. After cooling to 25°C, add 300 kg of water and 500 kg of MTBE, stir for 1 h, then let stand for 1 h, and separate the layers after separation. Add 100 kg of 10 wt% sodium chloride aqueous solution to the organic phase for washing, stir for 0.5 h, let stand, and separate the layers. Add 100 kg of 10 wt% sodium chloride aqueous solution to the organic phase for washing, then let stand and separate the layers. Continue to add 20 kg of anhydrous sodium sulfate to the organic phase and dry for 2 h. After filtration, concentrate the organic phase at 45 °C. When the liquid volume is reduced to 1 / 10, cool to 0 °C. After crystals precipitate, stir for 2 h, then filter and dry under vacuum at 35 °C to obtain a white solid, namely intermediate OLF-A1. S2. Mix 198.54 kg DMF, 99.27 kg intermediate OLF-A1, and 65.64 kg potassium carbonate, heat to 85℃, and slowly add 59.81 kg 3-bromo-1-chloropropane dropwise, maintaining the temperature at 75℃ for 6.5 h. After the reaction is complete, perform TLC for intermediate control 2 h later. Sample preparation: take 1 mL of reaction solution + 0.2 mL of water + 0.2 mL of MTBE; developing solvent: EA:methanol = 3:1, v / v, iodine fumigation. After cooling to 25℃, 27.81 kg of water and 496.35 kg of MTBE were added, stirred for 1 h, and then allowed to stand for 1 h. After separation, the liquid was separated. 99.27 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, stirred for 0.5 h, allowed to stand, and then separated. 99.27 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, and then allowed to stand and separated. Continue to add 19.85 kg of anhydrous sodium sulfate to the organic phase and dry for 1 h. Then add 22 kg of silica gel, stir for 1.5 h, filter, and concentrate the filtrate under reduced pressure at 55 °C until there is no effluent. Continue to concentrate under reduced pressure for 3 h to obtain a pale yellow oily liquid, namely intermediate OLF-A2. S3. Mix 208.64 kg DMF, 104.32 kg intermediate OLF-A2, and 58.79 kg diethanolamine, stir and heat to 120℃, maintain this temperature, add potassium carbonate every 1 h, 11.6 kg each time, for a total of 5 times; after the potassium carbonate addition is complete, keep warm for 6 h, after which TLC can be used for central control. Sample preparation: take 1 mL of reaction solution + 0.2 mL of water + 0.2 mL of MTBE, developing solvent: EA:methanol = 3:1, v / v, iodine fumigation; After cooling to 25℃, 312.96 g of water and 521.6 kg of MTBE were added, stirred for 1 h, and then allowed to stand for 2 h. After separation, the liquid was separated. 104.32 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, stirred for 0.5 h, allowed to stand, and then separated. 104.32 kg of 10wt% sodium chloride aqueous solution was added to the organic phase for washing, and then allowed to stand and separated. Continue to add 20.86 kg of anhydrous sodium sulfate to the organic phase and dry for 1 h. After filtration, concentrate the organic phase until the moisture content is less than 0.5% to obtain a white paste-like solid, namely intermediate OLF-A3. S4. At 30℃, 586.55 kg of isopropanol and 117.31 kg of intermediate OLF-A3 were added to the R206 reactor. Then, 25.57 kg of 40 wt% HF solution was added dropwise at 5℃ for 2 h. After the pH of the system reached 5-6, it was slowly raised to room temperature and stirred for another 2 h. The reaction solution was concentrated at 55℃ until about 1 / 5 of the volume remained. Then, 117 kg of isopropanol was added to concentrate the water until the water content was ≤1.5%. After concentration, another 117 kg of isopropanol was added, and the temperature was lowered to 0℃. After crystals precipitated, the mixture was kept warm and stirred for 2 hours. The mixture was then filtered and dried under vacuum at 35℃ to obtain a paste-like solid, which is the finished product, oraflu.

[0035] Comparative Example 1 The difference between this comparative example and Example 1 is that in step S1, the materials in reactor 1 and reactor 2 are directly added to a conventional reactor and reacted at 90-100℃ for 6 h. The subsequent extraction and purification steps are the same as in Example 1, and intermediate OLF-A1 is obtained with a yield of 72.5%.

[0036] Comparative Example 2 The difference between this comparative example and Example 1 is that in step S2, the silica gel is replaced with 60-100 mesh silica gel, and the resulting intermediate OLF-A2 is applied to step S3, with a yield of 89.5% in step S3.

[0037] As can be seen from the above, Comparative Example 1 uses a conventional reactor, resulting in a product with more impurities, lower purity, and lower yield. Comparative Example 2 uses silica gel for impurity removal, but the impurity content is high, affecting product quality and reducing subsequent yield.

[0038] In summary, this invention utilizes a continuous flow reactor for reaction, employs silica gel adsorption for impurity removal, and alcohol crystallization for purification, effectively improving reaction efficiency and product purity. It solves the problems existing in the prior art and has promising application prospects.

[0039] In summary, the synthesis process of olaflu provided by this invention effectively reduces the content of impurities, improves the purity of olaflu, has a high yield, overcomes the problems existing in the prior art, and has good application prospects.

[0040] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0041] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A process for the synthesis of olafluor, characterized in that, The synthesis process of the olafluor includes the following steps: S1. The solvent, octadecylamine and triethylamine are mixed, and then pumped into a continuous flow reactor for reaction with 2-bromo-1-ethanol. After the reaction, the reaction solution is extracted, and the intermediate OLF-A1 is obtained by purification; S2. The intermediate OLF-A1, solvent and potassium carbonate are mixed, and 3-bromo-1-chloropropane is added for reaction after being heated. After the reaction, the reaction solution is extracted, and the intermediate OLF-A2 is obtained by purification with silica gel; S3. The intermediate OLF-A2, solvent and potassium carbonate are mixed, and diethanolamine is added for reaction after being heated. After the reaction, the reaction solution is extracted, and the intermediate OLF-A3 is obtained by purification; S4. The intermediate OLF-A3 and water-carrying agent are mixed, and then hydrofluoric acid is added at low temperature. After being heated and stirred, concentration is performed, and the finished product olafluor is obtained by purification after the concentration is completed.

2. The process for synthesis of olafluor according to claim 1, wherein, In step S1, the reaction temperature is 90-100℃, and the reaction time is 6-8 h; In step S2, the reaction temperature is 75-85℃, and the reaction time is 6-8 h; In step S3, the reaction temperature is 110-120℃, and the reaction time is 6-8 h.

3. The process for synthesis of olafluor according to claim 1, wherein, In step S1, the mass ratio of octadecylamine, triethylamine and 2-bromo-1-ethanol is 100:(30-50):(30-50).

4. The process for synthesis of olafluor according to claim 1, wherein, In step S2, the mass ratio of intermediate OLF-A1 and 3-bromo-1-chloropropane is (95-100):(40-70).

5. The process for synthesis of olafluor according to claim 1, wherein, In step S3, the mass ratio of intermediate OLF-A2 and diethanolamine is (100-105):(50-60).

6. The process for synthesis of olafluor according to claim 1, wherein, In step S4, the mass ratio of intermediate OLF-A3 and hydrofluoric acid is (110-120):(20-30).

7. The process of claim 1, wherein the process is carried out at a temperature of about 20 °C to about 30 °C. In steps S1-S3, water and methyl tert-butyl ether are added for extraction.

8. The process of claim 1, wherein, In step S2, the amount of silica gel used is 15-25 wt% of OLF-A1.

9. The process of claim 1, wherein, In step S4, the water-carrying agent is selected from alcohol compounds.

10. The use of the synthesis process of olafluor according to any one of claims 1-9 in oral care products.

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