Rapid Synthesis of Unsymmetrical Sulforhodamines Through Nucleophilic Amination of a Monobrominated Sulfoxanthene Dye

• Published in: European journal of organic chemistry 2015-01, Vol.2015 (1), p.152-165
• Main Authors: Chevalier, Arnaud, Renault, Kevin, Boschetti, Frédéric, Renard, Pierre-Yves, Romieu, Anthony
• Format: Article
• Language: English
• Subjects: Chemical Sciences; Cheminformatics; Fluorescence; Macrocyclic li­gands; Medicinal Chemistry; Nucleophilic substitution; or physical chemistry; Organic chemistry; Rhodamine dyes; Theoretical and
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201403165

A transition‐metal‐free method for the synthesis of N‐substituted unsymmetrical sulforhodamine fluorophores from an unusual monobrominated sulfoxanthene dye and primary or secondary amines by direct SNAr‐type reactions is presented. The simplicity and effectiveness of this “postamination” procedure were demonstrated through the rapid preparation of a library of multifunctional red‐emitting rhodamine analogues. Some of these analogues are equipped with a reactive handle and retain the two water‐solubilizing sulfonic acid moieties of the starting halogenated derivative; this makes them ideal candidates for biolabeling applications. The potential utility of this expeditious strategy to finely tune the photophysical (Stokes shift) and physicochemical properties (amphiphilic character and water solubility) of the sulforhodamine scaffold was also demonstrated through the appendage of a fluorescent amine to create a fluorescence resonance energy transfer (FRET) pair, a long‐chain amine, and tetraazamacrocycles derived from cyclen. Simplicity and diversity! A range of primary and secondary functionalized amines were easily introduced onto a sulfoxanthene dye through simple metal‐free SNAr reactions to provide original sulforhodamine fluorophores with promising properties.