Adsorptive C2H2/C2H4 separation using metal‐organic frameworks (MOFs) has emerged as a promising technology for the removal of C2H2 (acetylene) impurity (1%) from C2H4 (ethylene). The practical application of these materials involves the optimization of separation performance as well as development of scalable and green production protocols.Herein, we report the efficient C2H2/C2H4 separation in a MOF, Cu(OH)INA (INA: isonicotinate) which achieves a record C2H2 packing density of 351 mg cm‐3 at 0.01 bar through high affinity towards C2H2. DFT (density functional theory) calculations reveal the synergistic binding mechanism through pore confinement and the oxygen sites in pore wall.The weakly basic nature of binding sites leads to a relatively low heat of adsorption (Qst) of approximately 36 kJ/mol, which is beneficial for material regeneration and thermal management. Furthermore, a scalable and environmentally friendly synthesis protocol with a high space‐time yield of 544 kg m‐3 day‐1 has been developed without using any modulating agents. This material also demonstrates enduring separation performance for multiple cycles, maintaining its efficacy after exposure to water or air for three months.

Achieving Record C2H2 Packing Density for Highly Efficient C2H2/C2H4 Separation with a Metal‐Organic Framework Prepared by a Scalable Synthesis in Water