A Continuous Flow Synthesis and Derivatization of 1,2,4-Thiadiazoles

Publication date: Available online 23 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Marcus Baumann, Ian R. Baxendale
A continuous flow process is presented that enables the efficient synthesis and derivatization of 1,2,4-thiadiazole heterocycles. Special attention was given to the safe handling of the versatile yet hazardous trichloromethane sulfenylchloride reagent including its in-line quenching in order to eliminate malodourous and corrosive by-products. Based on this flow method gram quantities of 5-chloro-3-phenyl-1,2,4-thiadiazole were safely prepared allowing for further elaboration of this valuable building block by reaction with different nitrogen-, sulfur- and oxygen-based nucleophiles. This synthetic approach was subsequently applied to generate a series of bromophenyl-5-chloro-1,2,4-thiadiazoles providing a valuable entry towards further structural diversification on this important heterocyclic scaffold.

Graphical abstract

http://ift.tt/2iYKNBH