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.本研究报道了一种操作简便的一步法合成方案，可从邻醛基苯甲酸（phthalaldehydic acids）制备异构体纯的罗丹明染料（rhodamine dyes）。采用2,2,2-三氟乙醇与水的混合体系作为反应介质，能够干净高效地生成仅含单一异构体的各类罗丹明产物。该方法已成功应用于数种异构体纯罗丹明染料的克级规模合成，涵盖6-羧基四甲基罗丹明与6-羧基-X-罗丹明（6-carboxy-X-rhodamine, 6-CXR）。此外，本研究还报道了一种简便的钯催化羟基羰基化一步法路径，可由适当取代的二卤代苯甲醛合成邻醛基苯甲酸。