Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Published in: Beilstein journal of organic chemistry Vol. 12; no. 1; pp. 2511 - 2522
• Main Authors: Dennehy, Olga C, Cacheux, Valérie M Y, Deadman, Benjamin J, Lynch, Denis, Collins, Stuart G, Moynihan, Humphrey A, Maguire, Anita R
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 24.11.2016; Beilstein-Institut
• Subjects: cascade reactions; Chemistry; flow chemistry; Full Research Paper; α-thio-β-chloroacrylamides; cascade reactions; α-thio-β-chloroacrylamides; flow chemistry
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.12.246

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.