Aqueous Electrochemical Synthesis of 5-Trifluoromethyluracil in Batch and Continuous Flow

Abstract

Without the use of chemical oxidants and metal catalysts, an aqueous electrochemical synthesis of 5trifluoromethyluracil in batch and continuous flow was reported. The green and economically friendly approach employing commercially available CF 3 SO 2 Na as a CF 3 source and cheap (NH 4 ) 2 SO 4 as a supporting electrolyte afforded the 5trifluoromethyluracil in 10 g scale in batch electrolysis. The continuous flow-electrolysis technique was employed to further facilitate the scale-up synthesis of 5-trifluoromethyluracil.

Overview of Recent Scale-Ups in Organic Electrosynthesis (2000–2023)

“…While examples of scaling up electrosynthesis have begun to emerge in the peer-reviewed literature, mostly in the last 5 years, these are still scarce. A range of additional transformations are emerging as opportunities toward scalable processes (e.g., electrochemical trifluoromethylation of heterocycles, hydrogenations − ) that may be of high interest to pharma. The electrosynthesis of catalysts , and ligands , for catalysis and the deployment of asymmetric electrocatalytic methods are also of interest, but examples of these on large scale are still scarce.…”

Harnessing photocatalytic and electrochemical approaches for C–H bond trifluoromethylation and fluoroalkylation

“…As the oxidation potential of electrolytic bromide is less than 71, bromide undergoes anodic oxidation to bromine which reacts with sulfinate salt to produce sulfonyl hypobro- In this context, Chen and colleagues also developed a method for the aqueous electrochemical synthesis of 5-trifluoromethyluracil 187, both in batch and continuous flow modes, utilizing the readily available CF 3 SO 2 Na 66 as the trifluoromethyl source and inexpensive (NH 4 ) 2 SO 4 as a supporting electrolyte (Scheme 112). 193 In the batch electrolysis, pure 5-trifluoromethyluracil was easily obtained on a 10 g scale due to the high conversion of uracil and the straightforward workup process. The continuous flow electrolysis demonstrated the potential for scaling up the production of 5-trifluoromethyluracil 188 even further.…”