Based On The Application Expansion Of Sodium Trifluoromethanesulfinate In Direct Trifluoromethylation Of Aromatic Rings

Organic compounds containing trifluoromethyl(CF₃)groups have been widely used in pesticide,medicine,and materials science.Therefore,how to introduce trifluoromethyl into the target compound by a new,economical,convenient and efficient method has always been a research hotspot.Because trifluoromethyl has the characteristics of lipophilicity,strong electron withdrawing and stable carbon-fluorine bond,the introduction of trifluoromethyl into organic compounds can significantly change the acid-base,dipole distance,Polarity and lipophilicity make it have better chemical and metabolic stability.The trifluoromethylation reaction is mainly realized by using trifluoromethylation reagents.Trifluoromethylating reagents can be divided into three types:Nucleophilic trifluoromethylating reagents(such as Rupper reagent),electrophilic trifluoromethylating reagents(such as Umemoto reagent,Togni reagent),and free radical trifluoromethylating reagents(such as CF₃SO₂Na).Because the raw materials for preparing the above-mentioned Rupper reagent,Umemoto reagent and Togni reagent are relatively expensive or the synthesis steps require two to three steps,these trifluoromethylation reagents cannot be produced and used in large quantities in industry.The common methods of introducing trifluoromethyl groups on aromatic hydrocarbons through trifluoromethylating reagents can be divided into the following three types:the trifluoromethylation of aromatic(hetero)hydrocarbons by the catalysis of transition metals;Metal catalysis can directly trifluoromethylate aromatic(hetero)hydrocarbons;aromatic(hetero)hydrocarbons that do not require metals can be directly trifluoromethylated.This thesis is a horizontal topic.The partner company selected 15 trifluoromethyl compounds with market potential through market research.Using sodium trifluoromethanesulfinate(Langlois reagent)as the source of trifluoromethyl,and under the condition of tert-butyl hydroperoxide(TBHP)as the oxidant,trifluoromethyl is introduced into aromatic compounds by changing The variables of mixed solvent,feeding amount,stirring rate and reaction temperature determine the optimal process conditions for the experiment and provide a method for the preparation of such compounds.In this thesis,a total of 15 target compounds have been synthesized.Among the 15compounds,there are eleven pyridine rings,two pyrazine rings,one pyridazine ring and one pyrrole ring.A total of 19 trifluoromethyl compounds have been synthesized.Some of the aromatic ring substrates are synthesized by this method to obtain a mixture,and some of the substrates have relatively low yields,so this method cannot be used in the pilot scale-up of these target compounds.The 19 trifluoromethyl compounds synthesized were analyzed by hydrogen nuclear magnetic resonance spectroscopy(¹H NMR),high-resolution mass spectrometry(HRMS)and infrared spectroscopy(IR)and other characterization methods to determine their structures.Analyzing the structure of the target compound shows that when there is a power-supplying group on the aromatic ring(such as an amino group),the reaction yield is higher and the synthesized products are basically ortho-para-position products,such as the yield ratio of A₆ and A₇ is 2.55:1.The steric hindrance also has a certain influence on the reaction yield.For example,A₁₀ and A₁₁ are affected by steric hindrance,and the trifluoromethyl group is preferentially substituted at the 5position of pyridine,and the resulting A₁₁ continues to react to obtain A₁₀.The yield ratio of A₁₀ and A₁₁ is about 1:3.98.The halogen contained in the aromatic ring substrate also affects the position of trifluoromethyl substitution.Halogen is an electricity-attracting group,but it belongs to the first type of positioning group,and the substitution easily occurs in ortho and para position,such as A₈.This thesis not only lays a market foundation for the pilot scale-up of this compound,but also lays a chemical foundation for the research and development of fine chemicals such as related new medicines and pesticides.