Improved Synthetic Procedures for 4,7,2‘,7‘-Tetrachloro- and 4‘,5‘-Dichloro-2‘,7‘-dimethoxy-5(and 6)-carboxyfluoresceins

Literature syntheses of 4,7,2',7'-tetrachloro-5(and 6)-carboxy-fluorescein ("5 and 6 TET") 1 and 4',5'-dichloro-2',7'-dimethoxy-5(and 6)-carboxyfluorescein ("5 and 6 JOE") 2 are reviewed, and new, preparatively useful methods are presented. A three-step synthesis of 1 was developed, which proved to be more efficient than the published seven step synthesis of this compound. The published synthesis of 2 also proved difficult to reproduce, and a better workup of the key intermediate 2-chloro-4-methoxy resorcinol was devised. Isolation of purified single isomers of both dyes is described.