Two monochloropyridine isomers, 2-chloropyridine (2-CP) and 3-chloropyridine (3-CP), are in need of a more effective separation method besides rectification. Herein we offer a facile and energy-saving adsorptive separation strategy using nonporous adaptive crystals of perethylated pillar[5]arene (EtP5), perethylated pillar[6]arene (EtP6), perbromoethylated pillar[5]arene (BrP5), and perbromoethylated pillar[6]arene (BrP6), which possess different cavity sizes and substituents and have never been employed in the separation of single-substituted heterocyclic aromatic compounds. BrP6 crystals show a marked preference for 2-CP in the equimolar mixture of 2-CP and 3-CP, affording it with 96.4% purity. Single crystal diffraction experiments demonstrate that BrP6 has stronger host-guest interactions with 2-CP than 3-CP. The cycling experiments demonstrate that BrP6 crystals can be used at least five times without losing their adsorption selectivity or capacity.