RAFT unchained - Scalable manufacturing of thiocarbonyl chain transfer agents

Here, we report an efficient approach for the manufacturing of chain-transfer agents (CTA) for RAFT polymerization using non-volatile organic compounds (VOC) in one pot with only water-washing as a work-up. Although the RAFT process is scientifically mature, nearly all RAFT CTAs are still produced through multi-step syntheses involving material- and energy-intensive separations. Today's commercially available RAFT agents are high-value specialty products available only from fine chemical vendors, limiting RAFT's industrial success. The current work illustrates a single-step one-pot approach to synthesize ethyl (3-oxo-2-butyl) carbonotrithioate and O-ethyl S-(3-oxobutan-2-yl) carbonodithioate at up to 10 L scale in various non-VOC solvents with varied degrees of potential for cross-reactivity: diethyl succinate, tributyl acetyl citrate, castor oil glycidal ether, and glycerol triglycidyl ether. We studied the purity and yield of these CTAs using NMR and LC-MS, and then conducted rigorous polymerization and kinetic studies to evaluate the efficacy of these molecules in maintaining the RAFT equilibrium. We found that the use of these non-VOC solvents impedes neither the synthesis of these molecules nor the RAFT control, thus enabling scalable and low-impact pathways to RAFT CTA manufacturing.