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In recent years, the application of difluoromethyl containing compounds in medicine and pesticides has become more and more extensive The cheap reagent for direct introduction of difluoromethyl Zui is chf2cl (Freon 22) The production of chf2cl is huge, and it is often used to produce fluoropolymer with relatively low cost However, as chf2cl is a strong ozone depleting gas and controlled by the Montreal Protocol, the production and use of the substance has become increasingly limited and expensive CHF3 (Freon 23) can also be directly introduced into difluoromethyl as a by-product generated in the production of chf2cl (Figure 1) CHF3 is a non-toxic and non ozone depleting gas, but its greenhouse effect is 15000 times greater than CO2, and its emission to the environment is limited by the Kyoto protocol Currently, it can only be treated by incineration Figure 1 The synthesis of chf2cl will produce a large number of CHF3 Because the activity of CHF3 reaction is very low, only recently has the literature reported that CHF3 is used for the synthesis of difluoromethyl compounds in the laboratory In response to this problem, European continuous flow experts, Professor C Oliver Kappe of Graz University in Austria and others have carried out a series of studies on this subject, and the research results Zui has recently been published on Green Chemistry (green Chem, 2018, 20, 108-112) Professor Kappe and others tried to use CHF3 to synthesize and amplify difluoromethylamino acids under continuous flow conditions Difluoromethylamino acids are used as irreversible inhibitors of efficient selective amino acid decarboxylase At present, Zui is a representative of ilonide, an anticancer drug, which is located in the list of World Health Organization basic drug standards It is also used in the treatment of African sleep diseases and Pneumocystis carinii pneumonia, a common opportunistic infection of Zui related to AIDS There are two main methods to synthesize difluoromethylamino acids (Fig 2) The direct synthesis of difluoromethylamino acids by CHF3 has not been reported in literature Fig 2 Method for synthesis of difluoromethylamino acids The author first tested it in a kettle with diethyl phenylmalonate (Table 1) Table 1 Difluoromethylation reaction of diethyl phenylmalonate and CHF3 through screening different organic bases, combined with literature, it is found that only using LiHMDS as organic base can make the reaction produce corresponding products The author then used LiHMDS as an organic base to screen the reaction of CHF3 under the condition of continuous flow (Table 2) Table 2 Under continuous flow conditions, the difluoromethylation of methyl dibenzoacetate can significantly improve the conversion and selectivity of the reaction by reducing the reaction temperature and increasing the pressure of the reaction system Subsequently, the author tried to use the reaction conditions for different substrates (Fig 3) Fig 3 The results of CHF3 difluoromethylation under continuous flow condition show that except that the yield of 2C is lower than that of the reactor condition, the yield of other substrates is higher than that of the reactor condition or the preparation methods of some compounds have not been reported in the literature In addition, the two-step yield of ilonide (2k) increased from 37% - 40% of the previously reported use of chf2cl to 76% Conclusion: CHF3, a by-product of polytetrafluoroethylene production, is used as starting material to synthesize difluoromethylamino acids directly by continuous flow, which are highly selective and powerful inhibitors of pyridoxal phosphate decarboxylase The raw material needed for the reaction is cheap and easy to obtain The product can obtain good yield and purity through simple hydrolysis and precipitation Because atom economy, sustainability, reagent cost and reagent availability are important factors for industrial reference, the process shows a good prospect of industrial application