title: Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation.
abstract: A continuous process strategy has been developed for the preparation of α-thio-β-chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts.
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Olga C
authors.initials: OC
authors.lastname: Dennehy
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Valérie M Y
authors.initials: VM
authors.lastname: Cacheux
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Deadman
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Denis
authors.initials: D
authors.lastname: Lynch
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Collins
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Humphrey A
authors.initials: HA
authors.lastname: Moynihan
authors.affiliation: Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
authors.forename: Anita R
authors.initials: AR
authors.lastname: Maguire
keywords: cascade reactions; flow chemistry; α-thio-β-chloroacrylamides