Thermodynamic Parameters of Fluoxetine Estimated by Group Contribution Method

Abstract

Background: fluoxetine is a commonly used antidepressant in clinic. There are many synthetic methods, but the total yield is not very high. Physical property data of compounds are often used in scientific research, pharmaceutical process design, chemical and pharmaceutical production, synthesis and resolution of chiral drugs, etc., distinct and accurate estimation of physical property data will greatly save time and effort. In order to provide data support for industrial production of Fluoxetine, the thermodynamic parameters of fluoxetinewere estimated by Joback group contribution method which always used to estimated the thermodynamic parameters of industry product. In particular, thermodynamic parameters such as enthalpy, entropy and heat capacity are state functions, so in practical applications, a state of matter can be arbitrarily chosen as a reference state, and then calculated. Since the melting boiling point is generally related to the structure of the substance, it is found that the measured value is basically consistent with the estimated value by group contribution method. Based on the group contribution method, other thermodynamic properties such as molar melting, standard enthalpy of formation and residual entropy are also estimated to provide data support for the calculation in industrial production. Subjects and Methods: The structure of fluoxetine was divided by Joback group contribution method, and the group contribution value was calculated to get the standard enthalpy of formation, Standard molar isobaric heat capacity, and residual entropy of Fluoxetine. Results: the standard formation enthalpy of fluoxetineis202.09 kJ•mol^-1, standard molar isobaric heat capacity of fluoxetineis 54590 J•mol^-1•K^-1, and residual entropy of fluoxetineis 261.5 J•mol^-1•K^-1. The melting temperature of fluoxetinewas also estimated by Joback group contribution method at 825.94 K, which measured by experiment is 158°C, or 456 K, with average relative error ARD = 8.11%. The boiling point temperature of fluoxetine was estimated by Joback method is 733.87 K, which was 569.2°C (867.35K) by measured. The average relative error ARD is 15.38%. Conclusions: The results show that the thermodynamic parameters of fluoxetine can be estimated by Joback group contribution method. Joback method has a high accuracy in estimating the boiling point of Fluoxetine, and it quite fit with the melting point after revised.