Systematic study of synthesizing various heteroatom-substituted rhodamines from diaryl ether analogues

The dye rhodamine, as the most popular scaffold to construct fluorescent labels and probes, has been explored extensively on its structure-fluorescence relationships. Particularly, the replacement of the oxygen atom in the 10th position with heteroatoms obtained various new rhodamines with improved photophysical properties, such as brightness, photostability, red-shifted emission and fluorogenicity. However, the applications of heteroatom-substituted rhodamines have been hindered by difficult synthetic routes. Herein, we explored the condensation strategy of diaryl ether analogues and o-tolualdehyde to synthesize various heteroatom-substituted rhodamines. We found that the electron property and steric effect in the rhodamine 10th position determined the synthetic yield. It's concluded that this condensation method was more suitable for the synthesis of heteroatom-substituted rhodamines with small or electron-donating groups like rhodamine, S-rhodamine and Si-rhodamine. We hope these results will benefit the design and synthesis of heteroatom-substituted rhodamines.