Study On The Model Of Solid-Liquid Equilibrium And Crystallization Process For Maem

2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic, thiobenzothiazole ester (MAEM) was the main intermediate for synthesis of the broad-spetrum cephalosporin. Systematic studies have been performed to resolve the problems occurred in the home industry manufacture of MAEM, such as low yield and significant quality difference between batches. In this paper, the crystallization of MAEM was studied systematically both in experiment and theory, including crystallization thermodynamics, the cosolvency models and crystallization process.Firstly, the solid-liquid equilibrium of MAEM was researched to select the suitable solvents. The solubility of MAEM in dichloromethane, acetonitrile, tetrahydrofuran,1,2-dichloroethane, acetone and binary mixtures of tetrahydrofuran+dichloromethane, tetrahydrofuran+1,2-dichloroethane and dichloromethane+acetonitrile was measured using a laser monitoring observation technique. The temperature and solvents ratio have an effect on the solubility of MAEM. The metastable zone for crystallization of MAEM in dichloromethane in different temperature was measured by the laser monitoring observation technique. The Modified Apelblat equation was used to correlate the experimental solubility data.When the Jouyban-Acree model was used to descript the solubility in binary solvent mixtures, the solubility in the pure solvents were required. In this paper, the solubility in pure solvents were descripted by the modified Apelblat model, then the modified Jouyban-Acree model was proposed to correlate the solubility of a solute with the variation of both temperature and initial composition of binary solvent mixtures. When the modified Jouyban-Acree model was used to correlated 39 solubility sets obtained from references. The overall mean percentage deviation of the modified Jouyban-Acree model was 3.65(±0.15). The linearly modified Jouyban-Acree model that has 9 parameters can be simplified based on the p-value of the parameters, then the most simplified equations were obtained by the stepwise regression method. Study on decimal digits of the model parameters can be converted to integer programme. When the decimal digits of parameters was same, The model obtained by integer programme was obviously superior to that obtained by directly cut off method. The overall mean percentage deviation of the most simplified equation with integral parameters was 4.32(±0.26). The modified Jouyban-Acree model was used to correlate the experimental solubility of MAEM in the binary mixtures of tetrahydrofuran+ dichloromethane, tetrahydrofuran+1,2-dichloroethane and dichloromethane+ acetonitrile. The most simplified equations with integral parameters can be produced by the simplification and optimization method. These equations can well descript the solubility of MAEM with both temperature and initial composition of the mixed solvents.According to the researches of crystallization thermodynamics, the cooling-crystallization process was adopted to purify the MAEM. The effect of agitation rate, the rate of water content of the solvents, the solvent ratio, etc on the purity, yeied, crystal and CSD of the crystallized products have been experimentally studied in detail. The optimum process conditions can be determined, and the product quality, yield and size are enhanced obviously.