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    Home > Professor Yi Wenbin, Nanjing University of science and technology research group: the new use of sodium trifluoroethylsulfite -- promoting direct electrophilic trifluoroethylsulphurization reaction in the absence of metal

    Professor Yi Wenbin, Nanjing University of science and technology research group: the new use of sodium trifluoroethylsulfite -- promoting direct electrophilic trifluoroethylsulphurization reaction in the absence of metal

    • Last Update: 2018-07-25
    • Source: Internet
    • Author: User
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    In the family of organic fluorides, the high lipophilicity and electron absorption properties of fluoroalkylthiol group have attracted extensive attention in academia and pharmaceutical industry The compounds containing trifluoroethylthiol (SCH 2cf 3) have been widely used in medicine, pesticide and other fields The research of new methods and reagents for introducing Sch 2cf 3 into bioactive molecules has also become a research difficulty and hotspot in the field of organic chemistry Recently, the research group of Professor Yi Wenbin, School of chemical engineering, Nanjing University of science and technology has successfully realized the new use of sodium trifluoroethylsulfite (naso2cf2cf3) for direct electrophilic trifluoroethylsulphurization under the condition of no metal (DOI: 10.1021 / ACS JOC 8b00676) Professor Yi Wenbin ', The direct introduction of Sch 2cf 3 into heterocycles and aromatics is very limited The initial work is the polar nucleophilic substitution reaction of sodium thiophenol to trifluoroethyliodide reported by Ghirardelli group In 1998, Chen Qingyun and his colleagues reported the srnl reaction of 2,2,2-trifluoroethylhalide with mercaptan ion under ultraviolet irradiation In 2016, Weng Zhiqiang and his colleagues reported the copper catalyzed trifluoroethylmercaptanization of arylhalides In the same year, Gouverneur group developed a method of inserting 1-aryl-2,2,2-trifluoro-1-diazolane with mercaptan to form Trifluoroethyl substituted sulfide However, these indirect methods have a common disadvantage: the sulfur atom comes from the substrate itself (such as sodium Thiophenol and mercaptan) or other sulfur sources (such as s 8) Therefore, the development of effective methods for direct trifluoroethylmercaptanization is still very challenging The main goal of Professor Yi Wenbin's research group is to develop naf2och2cf3 as a direct trifluoroethylmercaptan reagent (Figure 1) Figure 2 Optimization of reaction conditions (source: J.Org Chem.) the research team selected indole 2A as the model substrate to optimize the reaction conditions (Figure 2) It was found that the type of solvent, the type of reducing agent and the amount of naso2ch2cf3 had great influence on the yield of the reaction After a series of screening, the best yield (94%) was obtained when the molar ratio of indole, naso2ch2cf3, tmscl and (ETO) 2p (o) h was 1:2:2:3 Fig 3 The study on the substrate applicability of trifluoroethylthiolation reaction of indole and other heterocycles (source: J.Org Chem.) shows that (Fig 3), the yield of indole with electron donor group is higher than that of indole with electron acceptor group, which is also one of the typical characteristics of electrophilic reaction Indole derivatives of various substituents, including methyl, methoxy, halogen, ester group and nitrile group, are converted into corresponding trifluoroethylmercaptan products with good to excellent yields It should be noted that the yield of N heterocyclic bioactive compounds reached 85% In addition, the product of Sch 2cf 3 can be obtained by trifluoroethylmercaptanization of pyrrole Fig 4 Expansion of trifluoroethylthiol reaction substrate of active aromatics (source: J.Org Chem.) in order to further prove the applicability of this method, based on the successful reaction of indole and other heterocycles, the author also studied trifluoroethylthiol of active aromatics (Fig 4) When toluene is used as solvent, the yield of the target product can be medium or higher In addition to active aromatics, naphthol, which is rich in electrons, can also react smoothly in this system Fig 5 Development of Trifluoroethyl thiol reaction substrate of mercaptan (source: J.Org Chem.) fluoroalkyldisulfide is an important precursor of bioactive trifluoromethylthiosulfonate In order to further expand the substrate range of this reaction, the author expanded the substrate of Trifluoroethyl mercaptan (Fig 5) Figure 6 Control experiment and possible reaction mechanism (source: J.Org Chem.) then, the author explored the reaction mechanism (Figure 6) In order to understand the mechanism of tmscl promoting trifluoroethylmercaptanization, the author carried out a control experiment and 19 F NMR monitoring According to the previous report of the research group, when naso2ch2cf3 reacts with (ETO) 2p (o) h, only a new peak of δ - 65.8 ppm appears, which is considered as cf3ch2s (o) H In the absence of tmscl, the reaction of indole with naso2ch2cf3 and (ETO) 2p (o) h can also produce trifluoroethylmercaptan with a yield of only 32%, which shows that tmscl does promote trifluoroethylmercaptan Then, in the absence of indole, the author reacts with naso2ch2cf3, (ETO) 2p (o) H and tmscl (Fig 2, I) to get another δ - 64.7 PPM signal The results of 19F NMR analysis of indole reaction under optimized conditions show that both intermediates reduce and contribute to the formation of products (Fig 2, II) Based on the previous reports that naso2cf3 and NCS lead to in-situ formation of cf3scl, the author speculates that cf3ch2scl (δ - 64.7 ppm) can be generated in-situ with the help of tmscl and used as the main electrophilic reagent in trifluoroethylmercaptanization Based on the above analysis, the author thinks that naso2ch2cf3 is reduced by (ETO) 2p (o) h to form cf3ch2soh, and then the intramolecular nucleophilic attack is carried out to form cf3ch2soh Cf3ch2soh can produce cf3ch2s + to form a small amount of products In addition, cf3ch2soh can produce more reactive cf3ch2scl in the presence of tmscl The electrophilic attack of CF 3CH 2soh or CF 3CH 2scl on indole is helpful to the formation of the product Figure 7 Oxidation of trifluoroethylmercaptan (source: J.Org Chem.) in addition, the author found that in addition to some molecules containing Sch 2cf 3 group, some molecules containing so 2CH 2cf 3 and soch 2cf 3 group also have some biological activities Therefore, the author further expanded the product of trifluoroethylmercaptan of indole, and obtained the products of double oxidation and single oxidation respectively (Fig 7) Conclusion: Professor Yi Wenbin's research group has successfully realized the new use of sodium trifluoroethylsulfite for direct electrophilic trifluoroethylsulfination reaction under the condition of no metal, which provides an important supplementary method for the Fluoroalkane sulfination reaction This method is efficient, simple and suitable for all kinds of heterocycles, active aromatics and mercaptans The research results were recently published in J org Chem (DOI: 10.1021 / ACS JOC 8b00676) Wang Rongkang, Ph.D student, School of chemical engineering, Nanjing University of science and technology, and Jiang Luqi, Ph.D., lecturer, were the co first authors of this paper The research work has been strongly supported by the National Natural Science Foundation, Jiangsu Natural Science Foundation, Jiangsu blue project, Jiangsu "six talent peaks" and other projects Review of previous reports of Professor Yi Wenbin's research group: new use of CF 3so2cl: promoting direct chlorination of alkenes and alkynes - trifluoromethylthiolation Today, science and technology elements are increasingly valued in economic life, China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.
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