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.