Synthesis method of 1-adamantane acetic acid-2, 2-difluoro-2-ethyl sulfonate
Through a multi-step synthesis method, the reaction conditions and temperature were controlled, and the high-purity 1-adamantane acetic acid-2,2-difluoro-2-ethylsulfonate was successfully prepared, which solved the preparation of high-purity products in the prior art The problem has achieved an efficient and simple synthesis process and is suitable for industrial production.
Patent Information
- Application Number
- CN202411520082.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-29
- Publication Date
- 2025-02-25
AI Technical Summary
The prior art is difficult to effectively prepare high-purity 1-adamantane acetic acid-2,2-difluoro-2-ethylsulfonate, which has problems such as harsh reaction conditions, low yield and low purity, making it difficult to meet photoelectric materials and high-end Demand in the chemical industry.
A multi-step synthesis method is adopted, including the synthesis of intermediate I and intermediate II and the corresponding reaction steps, and the preparation of high-purity products is gradually realized by controlling the temperature and reaction conditions.
The high yield and high purity of 1-adamantane acetic acid-2,2-difluoro-2-ethylsulfonate (purity up to 99.5% or more) was achieved, and new ideas were opened for its synthesis, ensuring reaction efficiency, and suitable for industrial applications.
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Figure CN119504515A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic chemistry, and particularly relates to a method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate. Background Art
[0002] In the field of optoelectronic materials, photoacid generators play a pivotal role. They can efficiently generate acidic substances under the action of light, thereby initiating a series of chemical reactions, providing strong support for the synthesis and preparation of optoelectronic materials. As a new type of anion part of photoacid generator, 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate has attracted extensive attention and research due to its unique chemical structure and excellent performance.
[0003] With the continuous advancement of science and technology and the rapid development of the optoelectronic industry, the requirements for photoacid generators are becoming higher and higher. High-purity 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate has become an ideal choice for synthesizing optoelectronic materials due to its high thermal stability, excellent solubility and high acid production efficiency. In the preparation process, high purity not only means improved product quality, but also reduces the interference of impurities on chemical reactions, thereby ensuring the performance and stability of the final product.
[0004] However, how to prepare high-purity 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate is a challenging topic. Traditional preparation methods often have problems such as harsh reaction conditions, low yield, and low purity, which are difficult to meet the needs of large-scale industrial production. Therefore, researchers in this field have been constantly exploring new preparation methods and processes to improve the purity and yield of the product and meet the urgent needs of optoelectronic materials and high-end chemical industries for high-purity 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate. Summary of the invention
[0005] In order to solve the above technical problems, the present invention provides a method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate.
[0006] Specifically, the above synthesis method mainly includes the following steps:
[0007] S1: Add methyl fluorosulfonyl difluoroacetate and methanol to a three-necked flask, stir for 20 minutes, mix evenly, then add sodium methoxide, heat at 60°C for 12 hours, after completion, add tetrahydrofuran, methanol and sodium borohydride to the material in the three-necked flask, stir and react at 60°C for 4 hours, concentrate, add 16wt% sodium hydroxide solution dropwise to the obtained concentrated solution, stir and react for 4 hours, adjust the pH to 3.5-4.5 with 37% hydrochloric acid, and filter to obtain a white solid intermediate I;
[0008] S2: Add 1-adamantaneacetic acid and dichloromethane into a three-necked flask. After the 1-adamantaneacetic acid is completely dissolved, maintain the temperature at 20°C, then add thionyl chloride dropwise, heat the resulting mixture to 65°C in an oil bath for 9 hours, and cool to 30°C after completion. Vacuum evaporate the dichloromethane to dry the excess thionyl chloride to obtain a white solid intermediate II.
[0009] S3: In a three-necked flask, add the white solid intermediate II obtained in S2 and acetonitrile, stir to dissolve completely, heat to 70°C, first dropwise add the white solid intermediate I obtained in S1, then dropwise add triethylamine, after the dropwise addition is complete, react at 80°C for 24h; after the reaction is complete, filter to obtain a solid and acetonitrile organic phase;
[0010] Methyl tert-butyl ether was added to the above acetonitrile organic phase and the mixture was rotary evaporated to dryness twice to completely remove the white solid intermediate I to obtain a light yellow liquid, which was dissolved by adding methyl tert-butyl ether. The obtained solution was washed with water and separated into phases. The organic phase was concentrated to obtain a white solid 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate.
[0011] Preferably, in S1, the dropping speed of the 16 wt % sodium hydroxide solution is 5 mL / min.
[0012] Preferably, in S1, the mass volume ratio of methyl fluorosulfonyl difluoroacetate and methanol added to the three-necked flask is 1 g:9 mL;
[0013] The molar ratio of methyl fluorosulfonyl difluoroacetate and sodium methoxide added to the three-necked flask is 1:1.9-2.1;
[0014] The mass ratio of methyl fluorosulfonyl difluoroacetate: sodium borohydride: tetrahydrofuran: methanol in the three-necked flask is 1:2.9-3.1:20-21:18-19;
[0015] Adjust pH to 4.0.
[0016] Preferably, in S2, the mixture is heated to 65°C in an oil bath and reacted at this temperature for 9 hours.
[0017] Preferably, in S2, the mass ratio of 1-adamantaneacetic acid to dichloromethane added to the three-necked flask is 1:2.03.
[0018] Preferably, in S3, the mass ratio of the white solid intermediate II and acetonitrile added to the three-necked flask is 1:10;
[0019] The molar ratio of white solid intermediate II: white solid intermediate I: triethylamine is 1:10:1.
[0020] Preferably, in S1, the white solid intermediate I is 1,1-difluoro-2-hydroxyethanol;
[0021] In S2, the white solid intermediate II is 1-adamantanacetyl chloride.
[0022] Preferably, in S3, the mass ratio of the added white solid intermediate I to acetonitrile is 1:10.
[0023] The beneficial effects of the present invention are:
[0024] (1) The 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate prepared by the preparation method of the present invention has a high yield, a purity of more than 99.5%, and a novel structure;
[0025] (2) A new idea is provided for the preparation of 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate, thereby ensuring the reaction efficiency;
[0026] (3) The preparation method provided by the present invention has the advantages that the temperature conditions of the entire reaction process are easy to control, the method is simple and easy to implement, there are few intermediate impurity products, the preparation cost is saved and the purity of the product is improved, and it is suitable for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] Figure 1 The target product is 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate 1 H NMR spectrum;
[0028] Figure 2 The target product is 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate 12 C NMR spectrum;
[0029] Figure 3 The target product is 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate 19 F NMR spectrum. DETAILED DESCRIPTION
[0030] In order to enable those skilled in the art to better understand the present invention, the present invention is further described in conjunction with specific implementation methods.
[0031] 1.1 Reagents and drugs
[0032] Table 1 Reagent and drug information
[0033]
[0034] Example 1
[0035] The overall reaction formula of a method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate is as follows:
[0036]
[0037] The above-mentioned synthesis method comprises the following steps:
[0038] (1) Synthesis of 1,1-difluoro-2-hydroxyethanol
[0039] Add 5 g (26.03 mmol) of methyl fluorosulfonyl difluoroacetate and 45 mL of methanol into a three-necked flask, stir for 20 min, mix evenly, then add 2.8 g (51.83 mmol) of sodium methoxide, heat at 60 °C for 12 h to synthesize the compound 2,2-difluoro-2-(methoxysulfonyl)acetic acid methyl ester;
[0040] Afterwards, 40 mL of tetrahydrofuran, 10 mL of methanol and 2.95 g (78.03 mol) of sodium borohydride were added to the material in the three-necked flask, and the reaction was stirred at 60°C for 4 h. The concentrated solution was added with 16.5 mL of 16 wt% sodium hydroxide solution, and the reaction was continued with stirring for 4 h. The solution was acidified with 37 wt% hydrochloric acid to a pH of about 4, and filtered and dried to obtain 3.2 g of white solid intermediate I, i.e., 1,1-difluoro-2-hydroxyethanol, with a yield of 66.8%.
[0041] (2) Synthesis of 1-adamantanacetyl chloride
[0042] In a 250 mL three-necked flask, add 30.5 g (20.8 mmol) of 1-adamantane acetic acid and 15 g of dichloromethane. When the 1-adamantane acetic acid is completely dissolved and turns brown, maintain the temperature at 20°C, then add 29.7 g (249.66 mmol) of thionyl chloride dropwise, heat the resulting mixture to 65°C in an oil bath, and react at this temperature for 9 hours. Monitor the reaction progress by gas chromatography.
[0043] After the reaction was completed, the temperature was lowered to 30°C, and the solvent dichloromethane was evaporated by vacuum, and the excess thionyl chloride was dried to obtain 37.5 g of white solid intermediate II, i.e., 1-adamantaneacetyl chloride, with a yield of 94.9%. The content was detected by gas chromatograph and was 99.9%.
[0044] (3) Synthesis of 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate
[0045] In a 500 mL three-necked flask, add 18.5 g (86.9 mmol, 99.9%) of 1-adamantaneacetyl chloride obtained in (2) and 185 g of acetonitrile, stir until completely dissolved, first add 16 g (8.69 mmol) of the white solid intermediate I obtained in (1) into the three-necked flask, then add 8.8 g (86.9 mmol) of triethylamine dropwise, white smoke is visible at the beginning of the dropwise addition, and then a white solid is formed. After the dropwise addition is completed, react at 80°C for 24 h; after the reaction is completed, filter to obtain a solid and acetonitrile organic phase;
[0046] 60 g of methyl tert-butyl ether was added to the above acetonitrile organic phase and the mixture was dried twice by rotary evaporation to completely remove the white solid intermediate I, and a light yellow liquid was obtained. 100 g of methyl tert-butyl ether was added to dissolve the mixture, and the obtained solution was washed with water for phase separation. The organic phase was concentrated to obtain 24.52 g of white solid 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate, with a yield of 78.25%. The content was detected by gas chromatograph and was 99.9%.
[0047] The structural analysis of the obtained product is as follows Figure 1 , Figure 2 As shown in: 1 H NMR (400MHz, DMSO) δ4.58-4.47(m,2H),2.12(s,2H),1.91(s,3H),1.70-1.34(m,12H). 13 C NMR (400MHz, DMSO) δ170.43 (s), 61.15 (t, J = 20.9Hz), 48.34 (s), 42.01 (s), 36.73 (d, J = 15.3Hz), 32.73 (s), 28.42 (s). 19 FNMR(500MHz,DMSO)δ-113.83(s).
[0048] In summary, the present invention provides a method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate, which not only achieves the preparation of products with high yield and high purity (purity of more than 99.5% and novel structure), but also opens up new ideas for the synthesis of this compound and ensures the efficient conduct of the reaction. At the same time, the temperature conditions of the entire preparation process are easy to control, the method is simple and practical, and the generation of intermediate impurity products is effectively reduced, thereby reducing the preparation cost while further improving the purity of the product, which is very suitable for industrial production applications.
[0049] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. All equivalent changes and modifications made within the scope of the present invention should still fall within the scope of the present invention.
Claims
1. A method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate, characterized in that: The main steps include: S1: Add methyl fluorosulfonyl difluoroacetate and methanol to a three-necked flask, stir for 20 minutes, mix evenly, then add sodium methoxide, heat at 60°C for 12 hours to synthesize compound 2,2-difluoro-2-(methoxysulfonyl)acetic acid methyl ester. After completion, add tetrahydrofuran, methanol and sodium borohydride to the material in the three-necked flask, stir at 60°C for 4 hours, concentrate, add 16 wt% sodium hydroxide solution to the obtained concentrated solution, stir and continue to react for 4 hours, adjust the pH to 3.5-4.5 with 37 wt% hydrochloric acid, and filter and dry to obtain a white solid intermediate I; S2: Add 1-adamantaneacetic acid and dichloromethane into a three-necked flask. After the 1-adamantaneacetic acid is completely dissolved, maintain the temperature at 20°C, then add thionyl chloride dropwise, and react at 65°C for 9h. After the reaction is completed, the temperature is lowered to 30°C, and the dichloromethane is evaporated under vacuum to dry the excess thionyl chloride to obtain a white solid intermediate II; S3: Add the white solid intermediate II obtained in S2 and acetonitrile to a three-necked flask, stir until completely dissolved, first add the white solid intermediate I obtained in S1 to the three-necked flask, then drop triethylamine, after the dropwise addition is complete, react at 80°C for 24h; after the reaction is complete, filter to obtain a solid and acetonitrile organic phase; Methyl tert-butyl ether was added to the above acetonitrile organic phase and the mixture was rotary evaporated to dryness twice to completely remove the white solid intermediate I to obtain a light yellow liquid, which was dissolved by adding methyl tert-butyl ether. The obtained solution was washed with water and separated into phases. The organic phase was concentrated to obtain a white solid 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate.
2. A method for synthesizing 1-adamantaneacetic acid-2,2-difluoro-2-ethylsulfonate according to claim 1, characterized in that: The overall reaction formula of the synthetic method is as follows:
3. The synthesis method according to claim 1, characterized in that In S1, the dropping speed of 16 wt % sodium hydroxide solution is 5 mL / min.
4. The synthesis method according to claim 1, characterized in that In S1, the mass volume ratio of methyl fluorosulfonyl difluoroacetate and methanol added to the three-necked flask is 1 g:9 mL; The molar ratio of methyl fluorosulfonyl difluoroacetate and sodium methoxide added to the three-necked flask is 1:1.9-2.1; The mass ratio of methyl fluorosulfonyl difluoroacetate: sodium borohydride: tetrahydrofuran: methanol in the three-necked flask is 1:2.9-3.1:20-21:18-19; Adjust pH to 4.
0.
5. The synthesis method according to claim 1, characterized in that In S2, the mixture was heated to 65°C in an oil bath and reacted at this temperature for 9 h.
6. The synthesis method according to claim 1, characterized in that In S2, the mass ratio of 1-adamantaneacetic acid and dichloromethane added to the three-necked flask is 1:2.
03.
7. The synthesis method according to claim 1, characterized in that In S3, the mass ratio of the white solid intermediate II and acetonitrile added to the three-necked flask is 1:10; The molar ratio of white solid intermediate II: white solid intermediate I: triethylamine is 1:10:
1.
8. The synthesis method according to claim 1, characterized in that In S1, the white solid intermediate Ⅰ is 1-adamantanacetyl chloride; In S2, the white solid intermediate II is 1,1-difluoro-2-hydroxyethanol.
9. The synthesis method according to claim 1, characterized in that In S3, the mass ratio of the added white solid intermediate I and acetonitrile is 1:10.