Investigation Of 4-Hydroxycoumarin Crystallization Process

As a kind of important coumarin compounds,4-hydroxycoumarin and its derivatives are widely used in many fields such as medicine, dyes and spices due to their excellent biological activity, optical activity and chemical activity. At present, the production of 4-hydroxycoumarin in China are still not comparable with that out of China due to the low yield and low purity as well as the poor crystallinity. Therefore, in this paper the crystallization process of 4-hydroxycoumarin was studied systemically.First of all, the 4-hydroxycoumarin samples were characterized and tested in terms of several analyzation techniques, such as FT-IR, XRD, DSC, DTA-TG, SEM. Then the XRD data of 4-hydroxycoumarin was resolved using Materials Studio software so that its unit cell parameters, crystal system, space group and cell structure could be obtained. Based on the above results, the crystal form of 4-hydroxycoumarin was predicted according to BFDH and AE theoretical models, the latter got better result.In this paper, the solubility of 4-hydroxycoumarin in five pure solvents (acetone, methyl acetate, acetic acid, water and isopropanol) and two binary mixed solvents (acetone+water and isopropanol+water) were determined by laser detection technique respectively. The experimental solubility data were fitted and correlated by using different solubility models, such as Apelblat empirical model, Van’t Hoff empirical model, (CNIBS)/Redlich-Kister model and new modified Jouyban-Acree model. In addition, thermodynamic properties in the process of dissolution were also studied according to Van’t Hoff equation.Based on studies of the crystal morphology and crystallization thermodynamics, a diluting-cooling crystallization process of 4-hydroxycoumarin was put forward in order to improve the yield and crystallization habit. The effects of the operating conditions in the diluting-cooling crystallization process on the yield and crystal habit were investigated. A set of optimal conditions for the diluting-cooling crystallization process of 4-hydroxycoumarin was obtained:stirring speed was 150rpm, flow speed rate was 0.7mL/min, cooling rate was 0.7℃/min and end temperature was 15℃ and breeding time was 1.0h. The results obtained in this paper provide the theoretical guidance for the industrial production of 4-hydroxycoumarin and are practically significant.