Direct Atrifluoromethylthiolation Of Aromatics And Base-promoted Amination Of Halogenated Aromatics

Aromatic amine compounds are widely present in pharmaceutical molecules,natural products,and functional materials.Therefore,the preparation of aromatic amines has become a hot topic in the field of organic synthesis,which attracted the attention of many researchers.The traditional methods for preparing aromatic amines were mainly achieved by reductive alkylation of nitro groups,which require transition metal catalysis,equivalent reductant.In recent years,the amination of halogenated aromatics to aromatic amines has been reported,most of whichused transition metal catalysts.The reaction conditionsfor transition-metal-free reactions are harsh,need more solvents,and the reaction mechanism is S_NAr mechanism.Therefore,it is significant to develop a base-promotedamination reaction of halogenated aromatics with equivalent aminating agent,and to study its mechanism.The trifluoromethylthio group has strong electron absorption and high lipophilicity,which has a great effect on the absorption and penetration for organic molecules.Therefore,Trifluoromethylthiolated aromatics have good application prospects in the fields of medicine,materials and biological agents.The reported aromatic trifluoromethylthiolation reactions are mainly electrophilic trifluoromethylthiolation and nucleophilic trifluoromethylthiolation,most of which require special trifluoromethylthiolation reagents,such as metals or lewis acid catalysis.Herein,it is still of great significance to obtain trifluoromethylthiolated aromatics by a free radical process with sulfur powder and CF₃SO₂Na as a trifluoromethylthiolation reagent.Specific research work is divided into the following two parts:1.A base-promoted amination reaction of electron-deficient halogenated aromatics is developed.The method has the advantages of transition-metal-free,limited amount solvent,air atmosphere,mild reaction temperature,and expandability to gram scale.We provide a simple and efficient way to synthesize electron-deficient arylamine compounds.The reactivity of the four halogenated aromatics is inconsistent with the S_NAr and S_N2 mechanisms.We have speculated that the reaction may not be proceded with radical process or benzyne mechanism through a series of control experiments.The reaction mechanism is still unclear and needs further investigation.2.The K₂S₂O₈-promoted aromatic trifluoromethylthiolation reaction was conducted using electron-rich aromatics as substrates,sulfur powder and CF₃SO₂Na as trifluoromethylthiolation reagent,acetonitrile as solvent,and 10 mol%of pivalic acid as additive.The method has the advantages of transition-metal-free and compatibility with air.Direct perfluoroalkyl thiolation of aromatics can also be achieved by using Substituted perfluoroalkyl sulfonate sodium.