Establishing Structure–Activity Relationships in Heterogeneous Catalysis of Three-Component Organic Coupling Reactions by Lewis Acidic Metal Sites and Polar Moieties

The
postpandemic surge in demand for antimicrobial drugs has accelerated
the customization of suitable catalysts, fostering a synergy between
their structure and activity in promoting the multicomponent organic
coupling reactions. In this work, we have successfully constructed
two new polar metal–organic frameworks, viz., Co-bpaipa and Ni-bpaipa, where bpaipa2– = 5-(bis(pyridin-2-ylmethyl)amino)isophthalate,
embedded with catalytically active Co/Ni Lewis acidic metal sites
and polar moieties (such as O/N heteroatoms) for a critical evaluation
of their role in the synthesis of an important category of antimicrobial
drugs, oxazolidinones, from a three-component coupling reactions.
Both frameworks feature a rare 2D fes topology and
possess high thermal (up to 380 °C) and water stability. Microscopic
analysis revealed block- and octagon-shaped surface images of Co and
Ni analogs, respectively, at the micrometer scale. Their chemical
state and elemental composition were further examined using X-ray
photoelectron spectroscopy. For the solvent-free synthesis of 2-aryl
oxazolidinones, the use of CO2 gas as a direct feedstock
ensures a sustainable process that also involves epoxides and aromatic
amines. The vital aspect of this study is to optimize conditions that
are critical for high yields of products under a comparatively milder
temperature, a lower catalyst loading, and a shorter reaction time.
Interestingly, depending on the metal center, the epoxide-to-aniline
ratio influences the formation of oxazolidinones such that the maximum
conversion (∼90%) is obtained with Co-bpaipa and Ni-bpaipa using 3:1 and 1:1 ratios, respectively. Such an
outcome through a comparison of two catalysts with a difference in
the single metal site conducted for the first time is fully supported
by investigating the nature and strength of interactions between the
reactants and catalysts through comprehensive theoretical simulations,
including QTAIM and CBMC analysis. A wide spectrum of substrates with
diverse electronic, steric, and polarizing effects is tested to obtain
bioactive precursors, particularly tedizolid and delpazolid, achieving
high conversion rates (65–94%) and turnover numbers. The postcatalysis
analysis of both Co-bpaipa and Ni-bpaipa demonstrates their structural stability and nonleachability, even
after multiple catalytic runs.