Using a Hierarchical Molecular Structure-Based Method to Estimate the Physicochemical Properties of Halogen/Cyano-Substituted Alkanes

In this work, molecular descriptors of halogen/cyano-substituted alkanes (HCSAs), RX (X = F, Cl, Br, I and CN), were extracted using a hierarchical molecular structure method. They are divided into three hierarchies: number of vertices, vertex skeleton, and functional group, including the vertex number (<i>m</i>), sum of vertex number effect (<i>S</i> _VNE), odd-even index (OEI), intramolecular polarization effect index (IMPI), polarization effect index (PEI) of group, and group influencing factor (<i>G</i> _n). The properties (such as boiling point and refractive index) of each series of HCSAs can be quantitatively correlated well using these six molecular descriptors. The results show that the average absolute percentage error (APPE) between the experimental and calculated values for each series of HCSAs is less than 1%. However, some properties (such as critical temperature and critical volume) of HCSAs lack sufficient experimental data to develop class-specific estimation equations. Instead, they can be incorporated into a general estimation equation by adding the functional group characteristic parameter (Δ<i>P</i> _X) and the electronegativity (χ_X) of the group for all five series of HCSAs. These general quantitative correlation equations exhibit good estimation accuracy with APPE values all below 4%. Using the obtained estimation equations, the properties of HCSAs without experimental values were predicted, which include more than 1000 values of boiling point, density, refractive index, critical temperature, critical pressure, standard enthalpy of formation, and critical volume. This study provides a novel approach for establishing general equations to estimate the properties of monosubstituted alkanes with different functional groups.