Synthesis of Fluorescent Rhodols from Fluorescein Derivatives via Smiles Rearrangement

Julia Shoemaker

OAI: oai:digitalcommons.ursinus.edu:chem_hon-1078

The xanthene family of fluorophores, such as fluorescein and rhodamines, is commonly used as a scaffold in many different chemical tools because of the tunability of their photophysical properties and reactivity. Hybrid fluoresceins in which the xanthene hydroxyl group is replaced with an amino group result in a subclass of xanthene fluorophores named rhodols. Rhodols retain many strengths of fluoresceins while possessing red-shifted absorbance and emission, less pH sensitivity, and broader tunability. Despite these improved properties, rhodols remain underutilized when developing chemical tools due to current synthetic routes requiring multiple steps, precious metals, and high temperatures often resulting in limited substrate scopes. The present work describes a new method to produce rhodols from available fluorescein derivatives. The process proceeds via a tandem alkylation, Smiles rearrangement, hydrolysis sequence to effect a direct amination of widely available fluoresceins with an amine source under metal-free, mild conditions.

Organic chemistry Fluorophore Rhodol Chemistry Physical Sciences and Mathematics