Atom‐ and Mass‐economical Continuous Flow Production of 3‐Chloropropionyl Chloride and its Subsequent Amidation

Abstract

3-Chloropropionyl chloride is a chemically versatile building block with applications in the field of adhesives, pharmaceuticals, herbicides and fungicides. Its current production entails problems concerning safety, prolonged reaction times and the use of excessive amounts of chlorinating reagents. We developed a continuous flow procedure for acid chloride formation from acrylic acid and a consecutive 1,4-addition of hydrogen chloride generating 3-chloropropionyl chloride, as presented in this paper. Up to 94 % conversion was reached in 25 minutes at mild temperatures and pressures. This continuous flow method offers a safer alternative and is highly efficient in terms of consumption of starting product and shorter residence time. Valorization of this building block is exemplified by the synthesis of beclamide, a compound with sedative and anticonvulsant properties. Over 80 % conversion towards this drug was achieved in 1 minute in a continuous flow setup. Further research is needed to telescope the synthesis of 3-chloropropionyl chloride and subsequent beclamide formation without intermediate purification.

Post‐synthetic ‘Click’ Synthesis of RAFT Polymers with Pendant Self‐immolative Triazoles

“…We were perplexed by the consistently low yield of the esterification reaction with acryloyl chloride, which was initially ascribed to degradation of the monomer via olefin hydrochlorination. [18] However, TLC analysis did not indicate significant formation of side products (SI, Figure S10), and we did not identify plausible side-products by MS during the reaction. Nonetheless, purification of the monomer by silica gel chromatography afforded a highly pure monomer that was characterized in full by NMR and HRMS (SI, Section S3).…”