Scalable Regioselective Synthesis of Rhodamine Dyes

A one-step, operationally
simple protocol for the synthesis of
isomerically pure rhodamine dyes from phthalaldehydic acids is reported.
Using a mixture of 2,2,2-trifluoroethanol and water as reaction media
allows for clean and efficient formation of various rhodamines as
a single isomer. This method was successfully applied to the synthesis
of several isomerically pure rhodamines, including 6-carboxytetra­methyl­rhodamine
and 6-carboxy-X-rhodamine (6-CXR) on gram scale. A simple, one-step,
Pd-catalyzed hydroxy­carbonylation approach to phthalaldehydic
acids from appropriately substituted dihalo­benzadehydes is also
described.