Study Towards Benzylic Mono-difluorination Of Nitrogen Heterocyclic And [3+2] Cycloaddition To Construct Pyrazolone Ring

The fluorine atom is a unique atom with a small radius and strong electronegativity.It has good applications in medicinal chemistry,agrochemicals and daily necessities.In the past few decades,the more prominent advances are the catalysis of organometallics and transition metals in the field of fluorine chemistry.The most prominent and difficult is the construction of C-F bonds,because a series of unavoidable problems such as of the high hydration energy,the formation of metal compounds that have strong bond energy and the formation of polar bonds with other atoms.With the continuous exploration of researchers,the emergence of positron emission tomography scanners has largely solved the above problems.This brings fluorine chemistry to a new development.The continuous emergence of fluorine positive reagents makes it easy to construct C-F bonds.Various types of fluorides are already available for purchase and the applicability of the products has been greatly improved.Papers on the relationship between monofluoro and difluorination of alkyl groups are rarely reported.On the one hand,harsh conditions such as strong bases and metal catalysts are required,and on the other hand,the applicability of substrates is also low.By consulting a large number of related literatures,we tried to obtain monofluoride and difluorination by solvent effect instead of adding base and catalyst,and the final result also obtained high yield of monofluoro and difluorinated products.The study of diazo compounds can be traced back to the 1960 s and 1970 s.Under the conditions of light or high temperature,the compound will form an intermediate of ketene.The intermediate has good electrophilicity,the formed compounds have good application value in many fields.The intermediate can also be [3+2] cyclized with a fluorenyl derivative to form a pyrazolone derivative.The reaction can be carried out at a high temperature with concentrated sulfuric acid as a catalyst,and the yield is only 56%.And we can get a pyrazolone derivative with an 83% yield through a low-cost metal catalyst at temperatures below 100°C.The optimization of the conditions of the reaction has been completed and the substrate expansion is still being further refined.