Synthesis and Spectrophotometric Studies of 9‐Substituted‐4,5‐dimethoxyacridine Multifunctionalizable Fluorescent Dyes and Their Macrocyclic Derivatives

• Published in: European journal of organic chemistry 2021-05, Vol.2021 (17), p.2485-2497
• Main Authors: Golcs, Ádám, Ádám, Bálint Árpád, Vezse, Panna, Huszthy, Péter, Tóth, Tünde
• Format: Article
• Language: English
• Subjects: Acridines; Antibiotics; Antiseptics; Chemical compounds; Chemical reactions; Coupling (molecular); Cross coupling; Dyes/Pigments; Fluorescence; Fluorescent dyes; Optical measuring instruments; Precursors; Sensors; Spectrophotometry; Substitutes; Synthetic methods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202100291

Acridine derivatives are widely used as antiseptics, disinfectants, antibiotics, and fluorescent dyes as well as a subunit of optical sensor molecules of various analytical applications. We reported here the synthesis of several new 9‐substituted‐4,5‐dimethoxyacridine derivatives (9‐bromo‐, 9‐(p‐methylphenyl)‐, 9‐(p‐benzyloxyphenyl)‐, 9‐azido‐, 9‐phenyltriazole‐, 9‐[(trimethylsilyl)ethynyl]‐, 9‐nitrile‐) as potential multifunctionalizable fluorescent precursors of sensor molecules, indicators or dyes including optimized procedures for preparation of 9‐haloacridines and their cross‐coupling reactions. Improved stability of several new compounds could be achieved by the synthetic modification at position 9 of the acridine unit compared to their unsubstituted acridine analogs. The basic spectroscopic characteristics of these useful intermediates were also determined. The new fluorescent compounds showed promising photochemical properties for optochemical‐based applications in the future. The extremely large Stokes‐shifts (above 15500 cm−1) should especially be emphasized. Moreover, the effects of the substituents at position 9 of the acridine unit on fluorescence signaling were studied by the examples of new precursors and their macrocyclic derivatives as known optical sensor molecules. Some interesting relationships between quantum yield and structural features were reported. The synthesis of several new easy‐to‐functionalize acridine fluorophores as precursors of optochemical sensor molecules or dyes is reported. The possibilities for modifying position 9 of the proposed acridine intermediates are discussed. Studies on chemical stability and fluorescence signaling were carried out as a function of the 9‐substituent. Photophysical characterization of the new dyes shows outstanding properties.