Preparation of Halogenated Fluorescent Diaminophenazine Building Blocks

Abstract

A short, convenient, and scalable protocol for the one-pot synthesis of a series of fluorescent 7,8-dihalo-2,3-diaminophenazines is introduced. The synthetic route is based on the oxidative condensation of 4,5-dihalo-1,2-diaminobenzenes in aqueous conditions. The resulting diaminophenazines could be attractive intermediates for the preparation of polyfunctional phenazines and extended polyheteroacenes. We find that the undesired hydroxylation byproducts, typically obtained in aqueous conditions, are completely suppressed by addition of a stoichiometric amount of acetone during the oxidation step allowing for selective formation of 7,8-dihalo-2,2-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]phenazine derivatives with good to excellent yields. Under reductive conditions, the imidazolidine ring can be hydrolyzed into the desired 7,8-dihalo-2,3-diaminophenazines. Furthermore, we report a selective route under highly reducing conditions to monohydrodeaminate the 2,3-di(methylamino) phenazine derivatives, which allows for further structural variations of these phenazine building blocks. All of these derivatives are luminescent, with measured fluorescence quantum-yields of up to 80% in ethanol for the more rigid structures, highlighting the potential of such materials to provide new fluorophores.

Recent Advances in the Synthesis of Acridines and Phenazines

“…In 2015, Crabtree's group introduced a protocol for the one-pot synthesis of a series of 7,8-dihalo-2,3-diaminophenazines 188a-c, 189a-c, which is based on the oxidative condensation of 4,5-dihalo-1,2-diaminobenzenes under mild conditions (Scheme 23). 24 The oxidation of 4,5-dihalo-1,2-diaminobenzene analogues in the presence of acetone afforded phenazines 190a-c in moderate to good yields.…”

Efficient and Sustainable Synthesis of Spiroannulated Hybrid Molecules with Privileged Substructures using Nanostructured Heterogeneous Catalyst

“…[6] Phenazines are encountered in bioactive natural products [7] and synthetic pharmaceuticals [8] with antimalarial, [9] antiplasmodial, [10] antifungal, [11] cancer chemopreventive, [12] antichagasic [13] and antiparasitic activities. [14] (Figure 1) The fluorescent phenazines are used as bio-markers in biological systems [15] in addition to their use in photodynamic therapy (PDT) as photosensitizers. [16] Benzophenazines have been reported as inhibitors of topoisomerase I and II, which influence DNA topology in the cell cycle.…”

Strongly Coupled Phenazine–Porphyrin Dyads: Light-Harvesting Molecular Assemblies with Broad Absorption Coverage

“…Phenazines are highly conjugated heterocycles that can be structurally modified by many convenient synthetic methods. − For example, a simple condensation of o -phenylenediamine derivatives with functionalized o -quinones directly permits a variety of polyaromatic-based structures. ,, Accordingly, they are widely used as building blocks for a wide range of applications, including anticancer agents, − fluorescent markers in biological systems, − electroactive materials for organic light-emitting diodes, , organic electronics, conductive polymers, photoredox catalysts, and as photoactive materials for photocatalysis and dye-sensitized solar cells (DSSCs). − Phenazines are particularly attractive as light-absorbing molecules because their absorption bands can be systematically tuned by increasing the number of arene rings (Figure ). However, the majority of reported phenazines have limitations from their low extinction coefficients and their maximum absorption occurring in the green visible region.…”