Efficient synthesis of 5′-fluoroalkoxythiazoles via α-bromo-α-fluoroalkoxyacetophenones Hantzsch type cyclization with thioureas or thioamides

Novel α-fluoroalkoxyacetophenones were synthesized by addition of the readily available 2,2-dimethoxy-2-phenylethanol to fluoroolefins. α-Bromination yielded α-bromo-α-fluoroalkoxyacetophenones, which on treatment with thioureas or thioamides gave thiazoles with fluoroalkoxy groups at the 5′-position by the Hantzsch-type cyclization. This provides a versatile methodology for the construction of heterocycles from aliphatic fluoroalkoxy containing building blocks.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Thiazoles with fluoroalkoxy groups at the 5′-position were prepared by the Hantzsch-type cyclization. ► Addition of α-hydroxyacetophenone to fluoroolefins yields α-polyfluoroalkoxyacetophenones. ►α-Perfluoroalkoxyacetophenones were synthesized by nucleophilic displacement of bromide with a perfluoroalcoholate anion.