Optimization of the Synthesis of Koser's Reagent Using Electron Deficient Arenes

Koser’s reagent ([hydroxyl(tosyloxy)iodo]benzene), and derivatives thereof, can be used for many different kinds of reactions, such as the synthesis of diaryl iodane tosylates which are useful aryl electrophiles.  The preparation of Koser’s reagent depends on the nucleophilicity of the iodine atom in the aryl iodide precursors.  Accordingly, derivatives of Koser’s reagent with electron deficient arenes are more difficult to synthesize than electron rich arenes along with extended reaction times (multiple hours) and expensive 2,2,2-trifluoroethanol as a co-solvent are required for synthetically useful yields (57 – 83%). A greener, cost effective and efficient reaction would ideally be conducted in short reaction time and without the need for the fluorinated co-solvent, while maintaining high chemical yields.  Experiments were conducted using microwave and conventional heating at varying temperature, time, and reaction concentration to determine which variable had the greatest influence on reaction yield using the highly electron-deficient aryl iodides 1-iodo-4-trifluromethylbenzene and 1-iodo-4-nitrobenzene. It was found that the most influential variable was reaction concentration. The koser’s reagent using 1-iodo-4-trifluromethyl-benzene was prepared in 85% yield in only 2 minutes at 40°C in dichloromethane at 0.67 M in aryl iodide. Using the 1-iodo-4-nitro-benzene, the reaction was optimized at 40°C for 30 minutes in dichloromethane at 0.67 M for 88% yield. Future experiments will test the breadth of this effect across a diverse range electron deficient arenes.