Professor Yi Wenbin, Nanjing University of technology research group: cf3so2na and rfso2na one pot synthesis of trifluoromethylamine and perfluoroalkylamine

Introduction organic fluorine chemistry has always been a hot topic Among the fluorine-containing functional groups, CF 3 group has been studied and practiced most because of its high lipophilicity and electricity absorption Because perfluorocarbon chain can stabilize the parent molecule, perfluoroalkyl RFs (rf4 = c4f9, c8f17, etc.) are also concerned In view of the wide existence of nitrogen in drug molecules, the realization of trifluoromethylation of amines is of great significance for pharmaceutical and agrochemical industries Recently, Professor Yi Wenbin's research group of Nanjing University of science and technology has developed a cf3so2na based secondary amine trifluoromethylation method, which has been successfully extended to the synthesis of perfluoroalkylamine of rfso2na and improved the existing synthesis strategy of trifluoromethylamine The method has the advantages of good functional group tolerance, mild conditions, low cost of raw materials and easy operation Relevant research results were published in Chem Commun (chem Commun 2019, 55, 8536-8539) Brief introduction to the research group of Professor Yi Wenbin of Nanjing University of science and technology since its establishment, the research group has been committed to the basic research on the principle, design and application of fluorine-containing functional groups in the field of fine chemicals and medicine for a long time In recent years, the research focus is mainly on the reduction of trifluoromethyl sulfide Relevant achievements were published in such internationally renowned journals as angelw Chem Int ed., org Lett., chem Commun., J org Chem., adv synth Catalyst., chem EUR J At present, the research group has 10 doctors and 8 masters Brief introduction to Professor Yi Wenbin, male, born in 1979, professor and doctoral supervisor of Nanjing University of technology The main research fields are organic fluorine chemistry, sodium sulfite and the application of sulfonyl chloride In recent years, as the first author or corresponding author, he has published more than 30 papers in the journals of angelw Chem Int ed., green Chem., org Lett., chem Commin., etc Won the third prize of Jiangsu Science and Technology Progress Award (ranking first) Young and middle-aged academic leaders of blue project in Jiangsu Province and high-level talents of "six talent peaks" in Jiangsu Province Cutting edge scientific research achievements: one pot synthesis of trifluoromethylamine and perfluoroalkylamine organic fluorine chemistry by cf3so2na and rfs2na has been regarded as a hot topic, because the fat solubility, metabolic stability and biological activity of drug molecules can be significantly changed by introducing one or a small amount of fluorine-containing substituents Because of its high lipophilicity and electricity absorption, CF 3 group is one of the most studied and practiced groups Perfluoroalkyl RF (R F = C 4f 9, C 8F 17, etc.) is also very important, because perfluorocarbon chain can stabilize the parent molecule Although the significance of CF 3 group in improving drug efficacy is significant, the study of n-cf 3 compounds is rare In view of the wide existence of nitrogen in drug molecules, the realization of trifluoromethylation of amines is of great significance for pharmaceutical and agrochemical industries Traditional n-cf 3 compounds can be prepared by the oxidation and transformation of dithiocarbamate or the halogen fluorine exchange reaction However, these methods often have the problems of dangerous reagents, harsh reaction conditions and poor functional group compatibility In recent years, schoenebeck group and Xiao Jichang group reported the one pot synthesis of trifluoromethylamine with (me 4N) SCF and pdfA respectively Although both strategies are effective, the reagents used are relatively expensive and the synthesis is cumbersome Langlois reagent (cf3so2na), as a cheap material on the market, has been widely used in trifluoromethylation, trifluoromethylthiosulfoxide, trifluoromethylsulfonation and trifluoromethylsulfonation Before that, Yi Wenbin group realized its application in the electrophilic trifluoromethyl mercaptanization of indole, pyrrole and enamine by using diethyl phosphite This time, they developed a new use of CF 3so2na: trifluoromethylation of free amine (Figure 1) Figure 1 Construction of n-cf3 group (source: chem Commun.) after preliminary study, the author optimized the reaction conditions with N-methylaniline 1a and cf3so2na2a as template substrates After a series of screening, the author determined the best reaction conditions: the molar ratio of amine to cf3so2na and PPh3 is 1:1.5:3, MeCN is the solvent, the reaction is carried out at room temperature for 1 h, and then 4.5 equivalent AGF is added, the reaction yield can reach 84% Next, the range of substrate was investigated A series of secondary amines (Fig 2), including power supply groups (n-butyl, benzyl and methoxy) and electricity absorption groups (bromine, cyano, nitro, ketone and ester) have good yields A variety of secondary amines, such as N-phenyl, N-benzyl and n-alkylamine, can also be converted into trifluoromethylated products Heterocyclic amines and aliphatic secondary amines have also successfully obtained corresponding products By increasing CF 3so2na The substrate with two amino groups can also be converted into corresponding products Figure 2 Secondary amine reaction substrate expansion (source: chem Commun.) further, the authors studied n-trifluoromethylation of drug like molecules, including amoxapine, paroxetine, maprotiline, sertraline and fluoxetine in antidepressants, and tetracaine as an anesthetic (Figure 3) Fig 3 It is worth mentioning that the corresponding products are obtained by increasing the temperature to 50 ℃ and adding diphenylphosphine chloride, c2f5so2na, c3f7so2na, c4f9so2na, c6f13so2na and c8f17so2na, with the yields of 49% - 81% At the same time, amoxapine, a drug like molecule, also provides a corresponding product (Fig 4) Figure 4 Perfluoroalkane substrate development (source: chem Commin.) finally, the mechanism of this reaction was studied (Figure 5) CF 3sna is reduced by PPH 3 to form CF 3sna, which is then decomposed into thiofluoro phosgene 5A and fluoride Rfso2na also undergoes a series of rearrangement and decomposition under the action of phosphine reducing agent to produce thiofluorophosgene analogue 5B Then, thiofluorophosgene reacts with amine to form intermediate and final product under the action of silver fluoride Figure 5 Formation mechanism of intermediates (source: chem Commun.) Yi Wenbin's research group used cheap CF 3so2na to prepare trifluoromethylamine, and extended it to perfluoroalkylamine, improving the established synthesis method of trifluoromethylamine Considering the cheap raw materials, mild conditions and the compatibility of high functional groups, this method is expected to be used in the synthesis of bioactive compound amines The research results were recently published on chemical communications and selected as the cover article (chem Commun 2019, 55, 8536-8539) Liang Shuai, Ph.D graduate student and Wei Jing, master's graduate student, Nanjing University of technology, were the co first authors of the 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: Professor Yi Wenbin, Nanjing University of science and technology research group: new use of sulfonyl chloride direct chlorination sulfurization of Alkynes Nowadays, people and scientific research have been paid more and more attention in the 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 website, chembeangoapp, chembeango official micro blog, CBG information wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the representative research groups in China, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit