Synthesis of 8-hydroxyquinolines with amino and thioalkyl functionalities at position 4

Six 8-hydroxyquinolines with amino and thioalkyl functionalities at position 4 have been prepared. The synthesis starts with chlorination of the readily available 4-hydroxy-8-tosyloxyquinoline to give 4-chloro8-tosyloxyquinoline in 94% yield. Treatment of the 4-chloro-8-tosyloxyquinoline with sulphur and nitrogen nucleophiles produces the target 4-amino and 4-thioalkyl-8-hydroxyquinolines in more than 70% yield. In case of sulphur nucleophiles and pyrrolidine, the removal of the protecting tosyl group at position 8 occurs simultaneously with the substitution of chlorine at position 4.