Paper
Organic & Biomolecular Chemistry
the 2-halo-4-aminopyridines reduces the rate of Pd insertion
into the carbon–halogen bond. In contrast, under a CO2
atmosphere, at a pH of 8, a small steady-state concentration of
protonated 4-amino-2-halopyridine (approximately 0.1%) is
present which, in essence, activates the carbon–halogen bond
toward the Pd insertion process. This is nothing more than a
conjecture, but it suggests that the rate of Suzuki coupling for
the 2-chloro-4-amino substrate should be much slower that the
corresponding rate for 2-chloropyridine. This conjecture is
consistent with the rate profiles reported here for the 2-chloro-
4-aminopyridine (Fig. 3) and 2-chloropyridine (Fig. 4). The
former requires up to 24 hours reaching completion whereas
the latter is complete in just two hours.
The pH of the aqueous phase can, in principle, also affect
the substrate, product, and catalyst partitioning between the
organic-rich and water-rich phases. As we noted before, the
reactions with 40% water were typically liquid–liquid biphasic
system whereas a substantial solid phase was present when
25% water was employed. We specifically investigated the sub-
Notes and references
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Acknowledgements
We thank Dow Chemical Company for their collaboration and
financial support.
7602 | Org. Biomol. Chem., 2014, 12, 7598–7602
This journal is © The Royal Society of Chemistry 2014