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A scalable synthesis of 5,5′-dibromo-2,2′-bipyridine and its stepwise functionalization via Stille couplings

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Abstract

The synthesis of 5,5′-dibromo-2,2′-bipyridine and 5-bromo-2,2′-bipyridine, useful intermediates for elaboration into more complex ligands through metal-catalyzed coupling reactions, can be efficiently conducted on a multigram scale from inexpensive starting materials. The described procedure is reliably scalable and suitable for the synthesis of tens of grams of 5,5′-dibromo-2,2′-bipyridine. 5-Bromo-2,2′-bipyridine is produced as a minor product. The 5,5′-disubstituted-2,2′-bipyridine motif has excellent coordination properties and is a versatile building block for the synthesis of functional materials (including biodiagnostics, photovoltaics and organic light-emitting diodes) and complex molecular topologies (including catenanes and trefoil and pentafoil knots). The selective stepwise functionalization of 5,5′-dibromo-2,2′-bipyridine by consecutive Stille couplings is therefore illustrated and documented in detail. The synthesis of 5,5′-dibromo-2,2′-bipyridine takes 4–5 d: 1 d to prepare the key intermediate 2,2′-bipyridine dihydrobromide, 3 d for its reaction with bromine in a steel bomb reaction vessel and 8 h to isolate and purify the final product.

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Figure 1: A chloride-binding molecular pentafoil knot based on 5,5′-disubstituted-2,2′-bipyridine units (shown in blue) coordinating to Fe(II).
Figure 2: A molecular trefoil knot assembled through 5,5′-disubstituted-2,2′-bipyridine units (shown in blue) complexing Zn(II).
Figure 3
Figure 4: Stepwise functionalization of 3 by consecutive Stille couplings.
Figure 5: Experimental procedure and Equipment Setup for the synthesis of 5,5′-dibromo-2,2′-bipyridine 3 and 5-bromo-2,2′-bipyridine 4.

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Acknowledgements

This work was supported by the European Research Council (ERC) Advanced Grant WalkingMols and the UK Engineering and Physical Sciences Research Council (EPSRC). We thank the Deutsche Akademia der Naturforscher Leopoldina (BMBF LPD 9901/8-166) and Peter und Traudl Engelhorn–Stiftung for a postdoctoral fellowship to D.M.D.

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Authors and Affiliations

  1. School of Chemistry, The University of Edinburgh, Edinburgh, UK

    Daniel M D'Souza, David A Leigh, Marcus Papmeyer & Steffen L Woltering

  2. School of Chemistry, University of Manchester, Manchester, UK

    David A Leigh, Marcus Papmeyer & Steffen L Woltering

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  1. Daniel M D'Souza
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  2. David A Leigh
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  3. Marcus Papmeyer
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  4. Steffen L Woltering
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Contributions

D.M.D. designed and performed the experiments and analyzed the data. D.M.D., D.A.L., M.P. and S.L.W. wrote the manuscript.

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Correspondence to Daniel M D'Souza or David A Leigh.

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D'Souza, D., Leigh, D., Papmeyer, M. et al. A scalable synthesis of 5,5′-dibromo-2,2′-bipyridine and its stepwise functionalization via Stille couplings. Nat Protoc 7, 2022–2028 (2012). https://doi.org/10.1038/nprot.2012.122

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