The heterogeneous palladium-catalyzed Suzuki reactions between model aryl bromides (4-bromoanisole, 4-bromoaniline, 4-amino-2-bromopyridine, and 2-bromopyridine) and phenylboronic acid have been successfully conducted in water with no added ligand at the 100-mL scale using 20-40 millimoles of aryl bromide. The product yields associated with these substrates were optimized and key reaction parameters affecting the yields were identified. The results clearly indicate that the reaction parameters necessary to achieve high yields are substrate dependent. In addition, it is demonstrated that aqueous Suzuki reactions of substrates containing basic nitrogen centers can produce quantitative yields of desired products in the absence of added ligand.KEYWORDS: palladium catalysis without added ligand, Suzuki reactions in water, heterogeneous catalysis, scale-up, green and sustainable Suzuki reactions.
The Suzuki coupling reaction of basic nitrogen containing substrates (2-bromo- and 2-chloro-4-aminopyridine, and 2-bromo and 2-chloropyridine) with phenylboronic acid using Pd(TPP)2Cl2/K3PO4 in acetonitrile-water biphasic solvent systems under a CO2 or a N2 atmosphere is discussed. It was observed that 2-halo-4-aminopyridine produced quantitative yields of coupled products under a CO2 atmosphere while the yields for the 2-halopyridines were poor. In contrast, the yields of coupled products for the 2-halopyridines substrates were quantitative under a N2 atmosphere while only poor yields were realized for the 2-halo-4-aminopyridines under the same conditions. Evidence is presented which suggests that the presence of CO2 alters the pH of the aqueous phase of the reaction system and the accompanying efficiency of the coupling process. Using a series of buffers to adjust the pH of the aqueous phase, the pH dependence associated with the efficiency of the coupling process is illustrated.
As green chemistry and engineering are being integrated into chemical
processes in academia and industry, it becomes equally important to
equip students with the relevant tools in the fields of sustainable
chemistry and processes. In this context, continuous flow technology
has been identified as one of the promising strategies. Herein, we
describe an approach which unites flow chemistry, undergraduate research,
and chemical education research. Teams of undergraduate students designed,
developed, validated, and implemented batch and flow experiments for
an upper-level organic chemistry laboratory. The research to develop
the experiment, which was part of an undergraduate research course
(Vertically Integrated Project course, VIP), the pedagogic implementation,
and the outcome in the instruction laboratory are reported.
A series of aqueous heterogeneous Suzuki coupling reactions of substrates containing basic nitrogen centers with phenylboronic acid in the absence of added base and ligand is presented. High yields of products were obtained by employing aryl bromides containing aliphatic 1°, 2°, and 3° amine substituents, and good to high yields were obtained by employing a variety of substituted bromopyridines. In the former series, the pH of the aqueous phase changed from basic to acidic during the course of the reaction, while in the latter series the aqueous phase was on the acidic side of the pH scale throughout the entire course of reaction. A mechanistic interpretation for these observations, which generally preserves the oxo palladium catalytic cycle widely accepted in the literature, is presented.
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