Decoding Melting Point Mechanisms in Positional Isomers: From Steric Rule to Competing Interactions

The applicability of organic crystals is largely dictated by their melting behavior; however, a robust, microscopic mechanism that explains the substantial melting point variations among positional isomers is still lacking. Here, by constructing a model system encompassing approximately 20 classes of nitrobenzene derivatives and integrating experimental characterization with theoretical calculations, we systematically decipher the melting point modulation mechanism. For disubstituted benzenes, while the para-isomer consistently exhibits the highest melting point due to superior symmetry, we unveil a steric rule dictating the position of the minimum melting point isomer: ortho-isomers prevail for small substituents (e.g., −NH₂, −OH), whereas meta-isomers are favored for bulky groups (e.g., −NO₂, −COOH). In polysubstituted benzenes, the topology of hydrogen-bonding networks can override global molecular symmetry, emerging as the dominant factor. Energy decomposition analysis quantifies that within an isomeric series, a stronger net intermolecular attraction correlates with a higher melting point, while conformational entropy exerts a significant modulating effect. This work establishes a definitive “position-structure-energy-melting point” relationship, providing a fundamental basis for the rational design of functional molecular crystals.