Catalytic trifluoromethylation of uracil to 5-trifluoromethyluracil by use of CF3I and its industrial applications
The catalytic trifluoromethylation of uracil using CF3I was investigated to find a new industrial process for the production of 5-trifluoromethyluracil. The catalytic system of FeSO4, H2O2 and H2SO4 in dimethylsulfoxide efficiently and selectively yielded 5-trifluoromethyluracil under mild conditions. FeSO4 exhibited the highest activity among the Fe(II) compounds tested. H2O2 was indispensable for the reaction and only Fe(II) compounds yielded the desired product. This characteristic of the reaction suggests that it proceeds in a Fenton oxidation manner. The reaction was applicable to large-scale production: 50 kg of 5-trifluoromethyluracil in a 600 L reactor. By the use of this catalytic system, selective trifluoromethylation at the 5-position was also performed with various uracil derivatives including uridines. Interestingly, Cp2Fe was superior to FeSO4 for several substrates.
Graphical abstractA catalytic system of FeSO4, H2O2 and H2SO4 in DMSO efficiently and selectively led to the formation of 5-trifluoromethyluracil from uracil and CF3I under mild conditions (at 40–50 °C for 40–120 min). This reaction could be applied to large-scale production: 50 kg of 5-trifluoromethyluracil. By the use of this catalyst system, the trifluoromethylation of various uracil derivatives including uridines was also performed at the 5-position selectively.Figure optionsDownload full-size imageDownload as PowerPoint slide
Journal: Applied Catalysis A: General - Volume 342, Issues 1–2, 30 June 2008, Pages 137–143