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

ix 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‐chloro‐8‐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.