Estimation of Melting Points of Organic Compounds

Abstract

Melting point finds applications in chemical identification, purification and in the calculation of a number of other physicochemical properties such as vapor pressure and aqueous solubility. Despite the availability of enormous amounts of experimental data, no generally applicable methods have been developed to estimate the melting point of a compound from its chemical structure. A quick estimation of melting point can be a useful tool in the design of new chemical entities.In this dissertation, a simple means of estimating the melting points for a large variety of pharmaceutically and environmentally relevant organic compounds is developed. Melting points are predicted from the separate calculation of the enthalpy and entropy of melting directly from the chemical structure. The entropy of melting is calculated using a semi-empirical equation based on only two non-additive molecular parameters. This equation is validated and refined using a large collection of experimental entropy of melting values. The enthalpy of melting is calculated by additive group contributions.Melting points are estimated from the ratio of the enthalpy of melting and the entropy of melting. All of the methods and group contributions developed in this study are compatible with the UPPER (Unified Physical Property Estimating Relationships) scheme. The predicted melting points are compared to experimental melting points for over 2200 organic compounds collected from the literature. The average absolute error in melting point prediction is 30.1 °. This is a very reasonable estimate considering the size and diversity of the dataset used in this study.