Abstract
Nitroarenes are readily accessible bulk chemicals and can serve as versatile starting materials for a series of synthetic reactions. However, due to the inertness of the CAr–NO2 bond, the direct denitrative substitution reaction with unactivated nitroarenes remains challenging. Chemists rely on sequential reduction and diazotization followed by the Sandmeyer reaction or the nucleophilic aromatic substitution of activated nitroarenes to realize nitro group transformations. Here we develop a general denitrative chlorination reaction under visible-light irradiation, in which the chlorine radical replaces the nitro moiety through the cleavage of the CAr–NO2 bond. This practical method works with a wide range of unactivated nitro(hetero)arenes and nitroalkenes, is not sensitive to air or moisture and can proceed smoothly on a decagram scale. This transformation differs fundamentally from previous nucleophilic aromatic substitution reactions under thermal conditions in both synthesis and mechanism. Density functional theory calculations reveal the possible pathway for the substitution reaction.
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Data availability
The data supporting the findings of this study are available within the paper and its Supplementary Information. Crystallographic data for compound 52 have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition number 2341039. These data can be obtained free of charge from the CCDC (http://www.ccdc.cam.ac.uk/data_request/cif).
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Acknowledgements
We thank J. Wang (PKU) for the high-resolution MS testing and Z. Luo (Central China Normal University (CCNU)) for the IR testing. We thank X. Meng (CCNU) for X-ray structure refinement. We thank L. Chen (CCNU) for electron paramagnetic resonance measurement. We also thank Y. Xu (Peking University) and G. Wu (Huazhong University of Science and Technology) for helpful discussion about the project. We are grateful to the Knowledge Innovation Program of the Wuhan-Shuguang Project (2023020201020308; F.Y.); the Cultivation Program of Wuhan Institute of Photochemistry and Technology (GHY2023KF003; F.Y.); the National Natural Science Foundation of China (22173077 and 22422110; G.-J.C.) and the Guangdong Basic and Applied Basic Research Foundation (2023B1515020052; G.-J.C.) for financial support; and CCNU for startup funding (F.Y.).
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T.L. developed the reaction methods and investigated the mechanism. T.L., Y.W. and W.Z. explored the substrate scope. Z.L. performed the DFT calculation. R.S, G.-J.C. and F.Y. prepared the paper. F.Y. directed the project.
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Supplementary Figs. 1–28, Tables 1–4, Discussion, experimental data, procedural details, synthesis and characterization data and NMR spectra.
Supplementary Data 1
Crystallographic data for compound 52; CCDC reference number 2341039.
Supplementary Data 2
Calculated coordinates of intermediates and transition states.
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Liang, T., Lyu, Z., Wang, Y. et al. Light-promoted aromatic denitrative chlorination. Nat. Chem. 17, 598–605 (2025). https://doi.org/10.1038/s41557-024-01728-1
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DOI: https://doi.org/10.1038/s41557-024-01728-1
