Molecular symmetry significantly affects organic compounds' phase transition temperature (Tm and Tb) and solubility. As a general rule , crystals of symmetrical molecules have higher melting temperatures but are less soluble than crystals of less symmetrical molecules with similar structures. A prevalent explanation is based on Gibbs free energy at the thermal equilibrium regarding the relationship between the enthalpy (ΔH), entropy (ΔS), and phase transition temperature. The higher temperature implies the smaller ΔS because the enthalpy is usually related to the molecular interactions such as the ionic, polar, and hydrogen bond interactions. Isomers have the same functional groups; thus, the enthalpy should be equal. Hence, entropy dominates the difference of isomers' phase transition temperature. Walden showed that the average entropy of melting for many "coal tar" derivatives, which consist mainly of aromatic hydrocarbons, is constant, 13.5 cal/(deg•mol) . In contrast, for small spherical molecules, it is 3 cal/(deg•mol) . The boiling entropy of non-hydrogenbonding organic compounds generally follows Trouton's rule, 88 J/(deg•mol) - . However, conventional thermodynamics infers that molecules have a large degree of rotational and conformational freedom in both the liquid and the gas; the entropy associated with changes in these parameters upon boiling is small. Conversely, liquid molecules gain tremendous translational freedom upon entering the gas phase. The entropy of boiling is almost entirely the result of this increase in translational motion. In contrast, the entropy of melting is primarily due to rotational and conformational factors and only slightly due to translational factors. Therefore, the factor of molecular symmetry gradually faints in the studies of boiling entropy. Instead, Joback quantified the contributions of functional groups to the enthalpy to predict the boiling point and solubility. After that, this method dominated the studies on the boiling point. - The intimate connection between molecular symmetry and melting temperature is quantified by Yalkowsky et al. . A high enthalpy of melting implies considerable bonding energies. Molecular symmetry may contribute to tighter crystal packing via shape-cohesion effects. The molecular rotational symmetry number (σ) is introduced to express the impact of molecular symmetry on the entropy of melting: the number of indistinguishable positions that can be obtained by rigidly rotating the molecule about its center of mass. The greater the molecular rotational symmetry number, the higher the probability of the molecule being in the correct orientation. In the solid phase, the symmetry of a molecule results in a residual amount of molar entropy of magnitude Rlnσ above that of a similar but non-symmetrical molecule. Consequently, the difference in entropy between the liquid and solid phases will be negligible for the more symmetrical molecule. This, in turn, means that symmetry in a molecule reduces the entropy gained upon melting for that compound (ΔSm). Either of the two effects listed above, not to mention a combination of the two, would result in a higher melting temperature for a symmetrical molecule over a non-symmetrical one.