Study Of Crystallization Process Of D-p-Hydroxyphenylglycine

DL-p-hydroxyphenylglycine (DL-p-HPG) is important materials for the preparation of various medicines. D-p-hydroxyphenylglycine (D-p-HPG) is a useful intermediate for the preparation of semisynthetic amoxicillin, ceforperazone, and so on. And L-p-hydroxyphenylglycine (L-p-HPG) is the active ingredient of oxphenicine, a new medicine for the treatment of heart diseases. The concentration of D-p-HPG that obtained by enzyme method is low. In order to determine good production, the crystallization process researched, including crystal structure, crystallization thermodynamics, optimization of hybrid models, simulating calculation and crystallization process.The crystal structure of D-p-HPG was obtained by the XRD spectra and JADE5.0. The dissertation is devoted to the study of conformations and properties of D-p-HPG in the gas phase using the DFT and ab initio calculations. The optimized geometry, frequency and intensity of the vibrational bands of D-p-HPG were obtained by the ab initio and DFT. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental IR and Raman spectra. The observed and the calculated frequencies are found to be in good agreement.Crystallization thermodynamics is the basic of crystallization process. Based on the project, the solubility of L-p-HPG in different solvents was measured using a laser monitoring observation technique at atmospheric pressure. The solubility data were accurately correlated by the modified Apelblat equation, the calculated results of which were proved to show fine representation of experimental data. In order to meet the process required, the metastable zone of D-p-HPG in water was determined. The data provide the theory basis for the crystallization process and have the instruction significance with optimization of crystallization process.Based on the Crystallization thermodynamics, the solubility of D-p-HPG and L-p-HPG in binary water-ethanol solvents was measured. The two hybrid modes were obtained, which were mathematically represented with the component of solvent and temperature. Based on the p-values of the parameters, the terms that were insignificant were selected and were omitted from the models, so that the two hybrid models could be simplified. Furthermore, to reduce the number of decimal digits of the parameter values without influence on the precision of the models, discrete programming with GA was used to optimize the parameters. Comparison with the experiment data and calculation values, the results indicated that the hybrid models were feasible to describe the solubility of L-p-HPG in binary water-ethanol solvent mixtures. The final models are not only convenient for wide use but also provide a method to optimize the parameters of models.Finally, the crystallization process was optimized experimentally. The effects of parameters, such as evaporation speed, agitation speed, temperature decreasing rate, water output, final temperature and so on, on the product quality were studied. And the better operation conditions of crystallization were determined.