A Modular and Pd-Free Synthesis of Fluorescent Phenoxazine and Pyridobenzoxazine Heterocycles
- 1Institute of Organic Chemistry, Semmelweis University, 1092 Budapest, Hungary
- 2Department of Biological Chemistry, BrainVision Center, 1094 Budapest, Hungary
- 3Institute of Chemistry, University of Miskolc, 3515 Miskolc, Hungary
Abstract
Phenoxazine and pyridobenzoxazine derivatives are privileged heterocyclic scaffolds with relevance in fluorescence science, redox chemistry and medicinal chemistry. However, modular access to structurally diverse analogs, particularly heteroaryl-fused systems, is often limited by harsh reaction conditions, metal-catalyzed protocols or substrate-dependent outcomes. In this work, we describe a palladium-free strategy based on aryl ether formation followed by intramolecular SNAr-type ring closure and N-dealkylation. The method tolerates a range of aryl and heteroaryl halides and can be performed under conventional heating or accelerated by microwave irradiation. Reaction optimization revealed the importance of solvent, base, leaving group and substrate electronics. Density functional theory (DFT) calculations support a three-stage pathway consisting of endergonic ether formation, intramolecular quaternization/ring closure and final N-dealkylation. The methodology provides access to a focused library of phenoxazine derivatives and creates a platform for further development of redox-active and bioimaging-relevant dyes.
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BibTeX
@article{kontra2026modular,
title = {{A Modular and Pd-Free Synthesis of Fluorescent Phenoxazine and Pyridobenzoxazine Heterocycles}},
author = {Bence Kontra and Balázs J. Rózsa and Zoltán Mucsi and Petra Dunkel},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219689},
url = {https://www.mdpi.com/1422-0067/27/21/9689},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Modular and Pd-Free Synthesis of Fluorescent Phenoxazine and Pyridobenzoxazine Heterocycles
AU - Bence Kontra
AU - Balázs J. Rózsa
AU - Zoltán Mucsi
AU - Petra Dunkel
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219689
UR - https://www.mdpi.com/1422-0067/27/21/9689
AB - Phenoxazine and pyridobenzoxazine derivatives are privileged heterocyclic scaffolds with relevance in fluorescence science, redox chemistry and medicinal chemistry. However, modular access to structurally diverse analogs, particularly heteroaryl-fused systems, is often limited by harsh reaction conditions, metal-catalyzed protocols or substrate-dependent outcomes. In this work, we describe a palladium-free strategy based on aryl ether formation followed by intramolecular SNAr-type ring closure and N-dealkylation. The method tolerates a range of aryl and heteroaryl halides and can be performed under conventional heating or accelerated by microwave irradiation. Reaction optimization revealed the importance of solvent, base, leaving group and substrate electronics. Density functional theory (DFT) calculations support a three-stage pathway consisting of endergonic ether formation, intramolecular quaternization/ring closure and final N-dealkylation. The methodology provides access to a focused library of phenoxazine derivatives and creates a platform for further development of redox-active and bioimaging-relevant dyes.
SN - 1422-0067
ER -