Li Lixin research group of Xinyang Normal University: green and efficient synthesis of brominated sulfur nitrogen heterocycles in aqueous phase

Lead nitrogen-containing heterocyclic compounds (thiazine) play an important role in natural products, drug molecules and material chemistry In recent years, many chemists have been interested in it, and many strategies have been developed to construct these compounds Among them, the direct ammoniation of C-H to construct C-N bond has a natural advantage, which effectively avoids the pre activation of substrate and the addition of guiding group, and also reduces the generation of waste, which has the advantage of green, efficient and rapid reaction synthesis For example, Wu group and Muniz group found that under the action of visible light, iodo benzothiazines can be rapidly constructed from sulfonamide substrate; Chen xuenian group of Henan Normal University reported that benzothiazines can be rapidly and efficiently synthesized directly from phenylthioether Recently, Li Lixin research group of Xinyang Normal University has made new progress in this field (DOI: 10.1021 / ACS Orglett 9b02131) Figure 1 Method strategy for construction of nitrogen-containing heterocyclic compounds (source: org Lett.) Li Lixin's introduction Li Lixin obtained his bachelor's degree and master's degree respectively from Henan University in 2006-2013 under the guidance of Professor Jiang Zhiyong From 2014 to 2018, he studied for a doctor's degree in Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, under the guidance of researcher Huang Hanmin In March 2018, he joined the school of chemistry and chemical engineering of Xinyang Normal University and engaged in free radical chemistry research Currently, he holds the position of lecturer and has published more than ten articles in Chem SOC Rev., J am Chem SOC., org Lett., chem Comm., org Synth., adv synth Catalyst In 2019, he won the "young scholars award plan" of South Lake scholars Since working independently, he has published many articles in organizational letters, advance Synthesis & catalysis The main research fields are asymmetric functionalization of olefins catalyzed by visible light and C-H activation catalyzed by transition metals Frontier scientific research achievements: the green and efficient synthesis of brominated sulfur nitrogen heterocycles in aqueous phase Due to the special biological activity and special skeleton structure of Thiazines, organic chemists have been interested in the synthesis of these compounds However, the methods reported in the literature to construct such molecular structures all need to react in organic solvents Based on the investigation of the previous work, the author found that the solvent of this kind of reaction is usually carried out in the solvent with large polarity The author thought whether the reaction substrate and reaction conditions could be optimized to realize the C-N / C-Br bonding reaction in the water phase and build a series of target products succinctly and efficiently Through a series of optimization conditions, the author found that when phi (OAC) 2 was used as oxidant, NaBr was used as bromine source, and water was used as solvent, the above transformation could be completed in a green and efficient way Fig 2 Development of sulfonamides (source: org Lett.) later, the author expanded the reaction substrate The results show that when the reaction substrate is sulfonamides (Fig 2), the mono brominated benzothiazines can be obtained The target product can be obtained by either electron donor or electron pulling substituent When the strong electron pulling substituent is introduced into the C-N bonded benzene ring, the bromination product is completely inhibited When the aliphatic sulfonamide is used as the substrate, the above transformation can also be successfully completed When the reaction substrate is thioimines, the dibromo Thiazines can be obtained efficiently Even when the electron withdrawing group is introduced on the C-N ring, the yield of the target product can be 89% (Fig 3) Fig 3 Development of thioimides (source: org Lett.) for the different brominated products, the author calculated and found that the electron cloud distribution on the benzene ring of the cycloamide framework and the thioimides framework was similar, excluding the difference of brominated products caused by the electrical enrichment Further studies show that when introducing isopropyl with large steric hindrance, the yield of dibromide decreases significantly, and the yield of mono bromine increases significantly, which proves that steric hindrance is the main factor for different bromination products (Fig 4) The author then studied the reaction mechanism and found that when NaBr was not added, only the product of C-N bonding could be obtained When the product was used as the substrate, it could be converted into the target product under the standard conditions, which proved that the conversion experienced the C-N and C-Br bonding relay conversion In a word, the author has constructed the heterocyclic compounds of sulfur and nitrogen by the method of atom economy and environment friendly, and realized the bond reaction of C-N and C-Br in one step The reaction can be successfully transformed in water, and the target product with high purity can be obtained by simple filtration The establishment of this method provides a way for the synthesis of a large number of Thiazines The research on other heterocyclic compounds is still in progress Figure 4 The research results of reaction mechanism (source: org Lett.) were published on org Lett (DOI: 10.1021 / ACS Orglett 9b02131) The work was completed under the hard work of Li Yong, Zhao Zhengguang and Luo Haotian, undergraduates of Xinyang Teachers College The above research results are supported by the start-up fund of Xinyang Normal University and the special fund of Nanhu scholars "Youth Award Program" Today, people and scientific research are getting 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.