Functionalizable 1H-Indazoles by Palladium Catalyzed Aza-Nenitzescu Reaction: Pharmacophores to Donor-Acceptor Type Multi-Luminescent Fluorophores

Abstract

Development of small-molecule-based multi-luminescent fluorophores utilizing simple synthetic methodologies, as well as easily available starting materials, has gained much attention in recent years. Herein, we disclose an efficient protocol for the synthesis of N-protected 1H-indazole derivatives with diverse substituents at their 3- and 5-positions via palladium-catalyzed reactions of hydrazones and p-benzoquinones. The obtained 1H-indazole derivatives can be easily modified into donor-acceptor (D?A)-type chromophores (Indazo-Fluors) with tunable emission properties in both solid and solution state. Owing to the extent of intramolecular charge transfer, Indazo-Fluors exhibit positive solvatochromic emission spanning from blue-green to orange-red. Theoretical studies were undertaken to rationalize the observed trends in the optical properties of Indazo-Fluors. Finally, a triethylene glycol (TEG) appended Indazo-Fluor exhibiting a large Stokes shift and low cytotoxicity allowed us to use it for cell imaging. 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim