Studies On The Thermodynamic Properties Of Nitrogenous Heter Ocyclic Drug Intermediates

In recent years, the development of new drugs will continue to progress and innovation inorder to avoid drug resistance using a drug long-term, and new diseases emerging. In addition, thesynthesis and development of new drugs can not do without the production of pharmaceuticalintermediates, thus stimulating the market demand of medicine intermediates. Due to the increasingcomplex structure of new drugs, the special organic pharmaceutical intermediates often have beenneeded. Such as some high efficiency and good performance of new drugs, are mostly synthesizedby the heterocyclic compounds used as pharmaceutical intermediates. As an important part of RNA,uracil widely exists in living organisms and is widely used in medicine and biochemical researchfield. The halogen derivatives of uracil are also widely used in the field of pharmaceutical synthesisbecause their structures are similar to uracil. The great progression has been made for synthesis andcharacterization of structure and properties about uracil and the halogen derivatives of uracil.However, the domestic and foreign research on the thermodynamic properties of uracil and itshalogenated uracil derivatives are rarely.This paper have reported that the heat capacities of uracil,6-chlorouracil,5-chlorouracil and5-bromouracil have been measured using a Quantum Design Physical Property Measurement System(PPMS) in the temperature range from (1.9~300)K. The heat capacities were fitted usingtheoretical models and the thermodynamic functions were calculated based on the curve fitting. Thestandard molecular entropies at298.15K were determined to be132.48J·K1·mol1,156.89J·K1·mol1,154.98J·K1·mol1and165.39J·K1·mol1for uracil,6-chlorouracil,5-chlorouraciland5-bromouracil. And the effects of halogen substituents and substituted position for uracil and itshalogenated capacities have been studied in this paper. In addition, the four kinds of pharmaceuticalintermediates thermal stability were measured using the TG, and the effects of halogen substituentsand substituted position for uracil and its halogenated thermal stability have been explored, theresults were as follows:The experimental results indicates that the heat capacities of four compounds increase with thetemperature increasing and no any thermal anomalies are observed in the whole temperature region;and also the heat capacity values of halogenated uracil derivatives are larger than that of uracil atdue to a higher molecular weight with a similar molecular structure. However, the thermalstabilities of halogenated uracil derivatives are lower than that of uracil. According to the data obtained from thermal analysis, the rule of thermodynamic properties of the compounds withsimilar structure was discussed from the point of view of molecular structure.The results of this research have provided important basic thermodynamic data and theoreticalresearch for these four kinds of pharmaceutical intermediates. This research not only deepens theunderstanding about the properties of the uracil and its derivatives, but also a meaningful work forthe synthesis and development of new drugs.