PhD Scientific Days 2025

Poster Session II. - G: Pharmaceutical Sciences and Health Technologies

Unexpected Cyclizations of 2-(2-vinyl)phenoxy-tert-anilines

Name of the presenter

Kontra Bence

Institute/workplace of the presenter

Institute of Organic Chemistry

Authors

Bence Kontra^1,2, Zoltán Mucsi², Petra Dunkel¹

1: Institute of Organic Chemistry, Semmelweis University
2: Department of Biological Chemistry, Brain Vision Center

Text of the abstract

Introduction:
In the course of our studies on the cyclizations of 2-(2-vinyl)phenoxy-tert-anilines, we observed an unexpected reaction pathway, leading to a phenoxazine product (1). Phenoxazine is an important building block in organic chemistry, and can be found in more than 50000 molecules, including biomolecules and pharmaceuticals (2). It is important to have effective and economic synthetic tools to prepare these versatile building blocks. In our previous work (1), we obtained phenoxazine products under simple conditions, without any additional reagents or catalysts. Because of its simplicity, this new cyclization of appropriately substituted starting materials has the potential to scale up to multigram levels.

Aims:
Our goal was to study the applicability of the reaction, to optimize it, and test it on additional substrates, including further heterocyclic examples.

Method:
For our studies, standard synthetic organic chemical methods were applied. We synthetized several viable starting materials and analyzed the results of the cyclization test reactions using chromatographic methods. We tested the reactions in different solvents and temperatures, with microwave irradiation for higher temperature ranges.

Results:
Based on our results with the first set of starting materials under different conditions, we established this new cyclization as an efficient new tool for preparing phenoxazine derivatives. We plan to extend the cyclization to more complex substrates and rationalize our results by computational chemistry.

Conclusion:
We have identified and optimized a new protocol to prepare diversely substituted phenoxazine building blocks, without using additional reagents or catalysts.

Funding:
Supported by 2020-1.1.5-GYORSÍTÓSÁV-2021-00004, 2020-2.1.1.-ED-2022-00208 from the NKFIH, the EKÖP-2024-209 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.

[1]: Dunkel, P.; Kontra, B. et al. RSC Adv., 2024, 14, 16784–16800.
[2]: Sadhu, C.; Mitra, A.K. Mol Divers 2024, 28, 965–1007.