A continuous flow synthesis and derivatization of 1,2,4-thiadiazoles.
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.
Department of Chemistry, University of Durham, South Road, DH1 3LE Durham, United Kingdom. Electronic address: marcus.baumann@durham.ac.uk.
Marcus
M
Baumann
Department of Chemistry, University of Durham, South Road, DH1 3LE Durham, United Kingdom.
Ian R
IR
Baxendale
D018360:Crystallography, X-Ray; D015386:Hazardous Substances / Q000737:chemistry; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry*
D015386:Hazardous Substances; D013830:Thiadiazoles; D013455:Sulfur; D009584:Nitrogen; D010100:Oxygen
Flow synthesis; Heterocycles; Medicinal chemistry; Microreactors; Thiadiazoles