Method for synthesizing silver trifluoromethane mercaptide based on sodium trifluoromethanesulfinate
The synthesis of trifluoromethanethiol silver by using a double-chamber reaction tube method of sodium trifluoromethylsulfinate, triphenylphosphorium and diphenylphosphorium chloride and silver fluoride has solved the problem of high cost in the prior art, and achieved a low-cost and simplified operation synthesis route, which is suitable for industrial applications.
Patent Information
- Application Number
- CN202410228861.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-02-29
- Publication Date
- 2025-08-29
AI Technical Summary
The existing synthesis of trifluoromethanethiol silver is expensive, mainly due to the expensive cost of silver fluoride and the generation of by-product silver sulfide, which limits its industrial application.
Sodium trifluoromethylsulfinate, triphenylphosphorus and diphenylphosphorus chloride were used to react with silver fluoride in acetonitrile solution, and the product and by-product were separated through a double-chamber reaction tube, reacted at room temperature and filtration, distillation under reduced pressure and recrystallization to obtain silver trifluoromethanethiol.
It significantly reduces synthesis costs, simplifies operating procedures, reduces energy consumption, and is suitable for industrial production.
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Figure CN120554259A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthesis and relates to a method for synthesizing silver trifluoromethanethiol (AgSCF3) based on sodium trifluoromethanesulfinate. Background Art
[0002] Due to its high Hansch constant (π=1.44), the electron-withdrawing trifluoromethylthio (CF3S - ) has long been considered one of the most lipophilic substituents and a unique moiety capable of improving the pharmacokinetics and physicochemical properties of drug molecules, such as lipophilicity and metabolic stability. It is well known that the addition of a trifluoromethylthio group to small molecules can significantly enhance their ability to cross lipid membranes and their in vivo absorption rate. Furthermore, the high electronegativity of the trifluoromethylthio group significantly enhances the stability of small molecules in acidic environments. Consequently, trifluoromethylthio groups have garnered significant attention not only from academia but also from the pharmaceutical and agrochemical industries due to their potential for allele-based drug design.
[0003] Silver trifluoromethanethiol is an important nucleophilic trifluoromethylsulfiding reagent. Currently, a variety of reactions including trifluoromethylsulfiding have been achieved, but its synthesis cost is too high, which greatly limits its application range.
[0004] Document 1 (Xu C, Ma B, Shen Q, N-Trifluoromethylthiosaccharin: An EasilyAccessible, Shelf-Stable, Broadly Applicable Trifluoromethylthiolating Reagent [J]. Angew.Chem.Int.Ed.2014, 53, 9316-9320.); Document 2 (Li H, Liu S, Huang Y, Xu XH, Qing FL,Tandemtrifluoromethylthiolation / aryl migration of aryl alkynoates totrifluoromethylthiolatedalkenes[J].Chem.Commun.,2017,53,10136-10139.); Document 3(Das D,Ghosh KG,ChanduP,Sureshkumar D,Ammonium Chloride-MediatedTrifluoromethylthiolation of p-QuinoneMethides[J].J.Org.Chem.2020,85,21,14201-14209.), the methods used in the above documents all utilize the reflux reaction of silver fluoride and carbon disulfide in acetonitrile to prepare silver trifluoromethanethiol, but two-thirds of the silver fluoride only plays a fluorination role and is finally consumed as a by-product silver sulfide. Due to the expensive cost of silver fluoride, the price of silver trifluoromethanethiol is very high. Therefore, finding cheap and readily available substitutes to improve the existing synthesis process is the key to further industrial application of silver trifluoromethanethiol. Summary of the Invention
[0005] The present invention aims to provide a method for synthesizing silver trifluoromethanethiol based on sodium trifluoromethanesulfinate with low toxicity, low cost and simple process.
[0006] The technical solutions for achieving the purpose of the present invention are as follows:
[0007] The method for synthesizing silver trifluoromethanethiol based on sodium trifluoromethanesulfinate comprises the following steps:
[0008] Under nitrogen protection, silver fluoride (AgF) and solvent acetonitrile (MeCN) are first added to one reaction chamber of a sealed double-chamber reaction tube, and then sodium trifluoromethanesulfinate (CF3SO2Na) and triphenylphosphine (Ph3P) are added to the other reaction chamber, and an acetonitrile solution of diphenylphosphine chloride (Ph2PCl) is slowly added dropwise. The reaction is fully reacted at room temperature. After the reaction is completed, it is filtered, distilled under reduced pressure under light-shielding conditions, and recrystallized to obtain silver trifluoromethanethiol (AgSCF3).
[0009] Preferably, the molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, silver fluoride and diphenylphosphine chloride is 2-4:3-6:1:3-6.
[0010] Preferably, the concentration of diphenylphosphonium chloride in the acetonitrile solution is 0.5 to 1.0 mmol / mL.
[0011] Preferably, the reaction time is more than 8 hours.
[0012] Preferably, the filtration method is to filter the reaction liquid in the reaction chamber where the silver fluoride is located using diatomaceous earth; the recrystallization method is to redissolve the reaction liquid after reduced pressure distillation with acetonitrile, then add ether, and let it stand at -20°C for 24 hours under light-proof conditions.
[0013] Compared with the prior art, the present invention has the following significant advantages:
[0014] (1) Using cheap and readily available sodium trifluoromethanesulfinate as the starting material significantly reduces the amount of silver fluoride used, greatly reducing costs and making it more suitable for industrialization.
[0015] (2) The two-chamber reaction can separate the product from the by-product, facilitating subsequent purification.
[0016] (3) The operation is simple and safe, and the reaction at room temperature does not require heating, which reduces energy consumption. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 Schematic diagram of the synthesis method of the present invention.
[0018] Figure 2 It is silver trifluoromethanethiol 19 F NMR spectrum. DETAILED DESCRIPTION
[0019] The present invention will be further described below in conjunction with specific embodiments and accompanying drawings.
[0020] The present invention is based on the method for synthesizing silver trifluoromethanethiol from sodium trifluoromethanesulfinate, and its synthesis route is:
[0021]
[0022] Example 1
[0023] Under nitrogen protection, a dual-chamber reaction tube was used. Silver fluoride (0.13 g, 1 mmol) and 2 mL of MeCN were added to one chamber, while triphenylphosphine (1.18 g, 4.5 mmol) and sodium trifluoromethanesulfinate (0.47 g, 3 mmol) were added to the other chamber. Diphenylphosphine chloride (0.99 g, 4.5 mmol) was then dissolved in 6 mL of MeCN and slowly added dropwise to the reaction chamber under nitrogen. The mixture was stirred for 8 h in a sealed container at room temperature. After the reaction was complete, the reaction solution in the AgF reaction chamber was filtered through celite and distilled under reduced pressure in the dark. The resulting solid was redissolved in a minimal amount of MeCN, and a large amount of ether was added to the solution. The vial was wrapped in aluminum foil and placed in a -20°C refrigerator for 24 h. Finally, the product, silver trifluoromethanethiol, was removed and filtered while still cold to obtain a 70% yield.
[0024] Example 2
[0025] Under nitrogen protection, a dual-chamber reaction tube was used. Silver fluoride (0.13 g, 1 mmol) and 2 mL of MeCN were added to one chamber, while triphenylphosphine (0.79 g, 3 mmol) and sodium trifluoromethanesulfinate (0.31 g, 2 mmol) were added to the other chamber. Diphenylphosphine chloride (0.66 g, 3 mmol) was then dissolved in 4 mL of MeCN and slowly added dropwise to the chamber under nitrogen. The mixture was stirred for 8 h in a sealed container at room temperature. After the reaction was complete, the reaction solution in the AgF chamber was filtered through celite and distilled under reduced pressure in the dark. The resulting solid was redissolved in a minimal amount of MeCN, and a large amount of ether was added to the solution. The vial was wrapped in aluminum foil and placed in a -20°C refrigerator for 24 h. Finally, the product, silver trifluoromethanethiol, was removed and filtered while still cold to obtain a 65% yield.
[0026] Example 3
[0027] Under nitrogen protection, a dual-chamber reaction tube was used. Silver fluoride (0.13 g, 1 mmol) and 2 mL of MeCN were added to one chamber. Triphenylphosphine (1.18 g, 4.5 mmol) and sodium trifluoromethanesulfinate (0.47 g, 3 mmol) were added to the other chamber. Diphenylphosphine chloride (0.99 g, 4.5 mmol) was then dissolved in 9 mL of MeCN and slowly added dropwise to the reaction chamber under nitrogen. The mixture was stirred for 8 h in a sealed container at room temperature. After the reaction was complete, the reaction solution in the AgF reaction chamber was filtered through celite and distilled under reduced pressure in the dark. The resulting solid was redissolved in a minimal amount of MeCN, and a large amount of ether was added to the solution. The vial was wrapped in aluminum foil and placed in a -20°C refrigerator for 24 h. Finally, the product, silver trifluoromethanethiol, was removed and filtered while still cold to obtain a 60% yield.
[0028] Silver trifluoromethanethiol prepared in each embodiment 19 F NMR Figure 2 .
[0029] 19 F NMR (470MHz, CD3CN) δ-22.93 (s).
[0030] Comparative Example 1
[0031] This comparative example is substantially the same as Example 1, except that the molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, silver fluoride, and diphenylphosphine chloride is 5:7.5:1:7.5. Because the molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, and diphenylphosphine chloride relative to silver fluoride is too high, while the production of the intermediate thiocarbonyl fluoride is increased, the excess is significantly excessive, increasing the potential for side reactions and increasing costs.
[0032] Comparative Example 2
[0033] This comparative example is substantially the same as Example 1, except that the molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, silver fluoride, and diphenylphosphine chloride is 1:1.5:1:1.5. Because the molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, and diphenylphosphine chloride to silver fluoride is too low, too little thiocarbonyl fluoride intermediate is produced, the silver fluoride reaction is incomplete, and the yield is reduced.
[0034] Comparative Example 3
[0035] This comparative example is substantially the same as Example 1, except that the concentration of diphenyl phosphonium chloride in the acetonitrile solution is 1.5 mmol / mL. Due to the excessively high concentration of diphenyl phosphonium chloride, the reaction with sodium trifluoromethanesulfinate is vigorous, resulting in increased exotherm and overheating, which causes phosphorus-fluorine byproducts to be carried into the silver fluoride reaction chamber, complicating post-processing and reducing yield.
[0036] Comparative Example 4
[0037] This comparative example is substantially the same as Example 1, except that the concentration of diphenyl phosphine chloride in the acetonitrile solution is 0.25 mmol / mL. Since the concentration of diphenyl phosphine chloride is too low, the reaction is too mild, and the intermediate thiocarbonyl fluoride produced cannot fully enter the silver fluoride reaction chamber, resulting in incomplete reaction of silver fluoride and a reduced yield.
Claims
1. A method for synthesizing silver trifluoromethanethiol based on sodium trifluoromethanesulfinate, characterized in that: The steps include: Under nitrogen protection, silver fluoride and solvent acetonitrile are first added to one reaction chamber of a sealed double-chamber reaction tube, and then sodium trifluoromethanesulfinate and triphenylphosphine are added to the other reaction chamber, and an acetonitrile solution of diphenylphosphine chloride is slowly added dropwise. The reaction is fully reacted at room temperature. After the reaction is completed, the mixture is filtered, distilled under reduced pressure under light-proof conditions, and recrystallized to obtain silver trifluoromethanethiol.
2. The method according to claim 1, characterized in that The molar ratio of sodium trifluoromethanesulfinate, triphenylphosphine, silver fluoride and diphenylphosphine chloride is 2-4:3-6:1:3-6.
3. The method according to claim 1, wherein The concentration of diphenylphosphonium chloride in acetonitrile solution is 0.5~1.0 mmol / mL.
4. The method according to claim 1, wherein The reaction time is more than 8 hours.
5. The method according to claim 1, characterized in that The filtration method is to filter the reaction liquid in the reaction chamber where the silver fluoride is located with diatomaceous earth; the recrystallization method is to redissolve the reaction liquid after vacuum distillation with acetonitrile, then add ether, and stand at -20°C for 24 hours under light-proof conditions.