Separations of azeotropic mixtures are typically carried out using energy-demanding processes (e.g., distillation). Here, we report the capacity of a self-assembled chlorinated boronic ester-based adduct to confine acetonitrile and benzene in channels upon crystallization. The solvent confinement occurs via a combination of hydrogen bonding and [π···π] interactions. Quantitative separation of benzene from an azeotropic 1:1 mixture of a benzene/acetonitrile (v/v), and methanol is achieved through crystallization with the chlorinated adduct by complementary [C-H···O] and [C-H···π] interactions. Inclusion behavior is rationalized by molecular modeling and crystallographic analysis. The chlorinated boronic ester adduct shows the potential of modularity via isosteric substitution for the separation of challenging chemical mixtures (e.g., azeotropes).