Abstract
Polychlorinated biphenyls (PCBs) are environmental pollutants implicated in a variety of adverse health effects, including cancer and noncancer diseases in animals and humans. PCBs are metabolized to hydroxylated compounds, and some of these PCB metabolites are more toxic than the parent PCBs. Unfortunately, most PCB metabolites needed for toxicological studies are not available from commercial sources. Moreover, it is challenging to synthesize PCB metabolites because starting materials with suitable substitution patterns are not readily available. Here, we report the novel synthesis of a variety of mono- and dimethoxyarene derivatives from commercially available fluoroarenes via nucleophilic aromatic substitution with sodium methoxide. This reaction provided good to excellent yields of the desired methoxylated products. Suzuki coupling of selected mono- and dimethoxy haloarenes with chlorinated phenylboronic acids yielded methoxylated derivatives of PCB 11, 12, 25, 35, and 36 in low to good yields. Crystal structures of 3,3′-dichloro-2,5-dimethoxy-1,1′-biphenyl and 3′,5-dichloro-2,3-dimethoxy-1,1′-biphenyl confirmed the substitution pattern of both compounds. This synthesis strategy provides straightforward access to a range of mono- and dimethoxylated PCB derivatives that were not readily accessible previously.
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Acknowledgments
We thank Mr. Vic R. Parcell and Mr. Derek W. Simonsen for providing the GC-TOF-MS data.
Funding
This work was supported by grant ES013661 from the National Institute of Environmental Health Sciences/National Institutes of Health (NIEHS/NIH). Programmatic support was provided by grant ES05605 from NIEHS/NIH. The D8Venture diffractometer was funded by the NSF MRI program (CHE-1625732) and by the University of Kentucky (cost share). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences/National Institutes of Health or the National Science Foundation.
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Dhakal, R., Li, X., Parkin, S.R. et al. Synthesis of mono- and dimethoxylated polychlorinated biphenyl derivatives starting from fluoroarene derivatives. Environ Sci Pollut Res 27, 8905–8925 (2020). https://doi.org/10.1007/s11356-019-07133-3
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DOI: https://doi.org/10.1007/s11356-019-07133-3