Study On Solid-liquid Equilibrium And Crystallization Of Thiamethoxam

Thiamethoxam is a new generation of nicotinic insecticide,which has the advantages of low toxicity,high activity,strong safety,wide insecticide spectrum,fast action rate,long duration and little environmental pollution.However,the research on thiamethoxam is mainly focused on the synthesis process,and there is no research on drug crystallization,which leads to the problems of low yield,small particle size and uneven particle size distribution of existing thiamethoxam products.Based on this,this study studied the crystallization process of thiamethoxam,and discussed the crystallization thermodynamics and crystallization technology respectively.The research results can provide basic data and theoretical guidance for the industrial crystallization process of thiamethoxam.The solubility of thiamethoxam in nine pure organic solvents,as well as two mixed solvents,DMSO-water and methanol-acetonitrile,was determined by dynamic method.The order of solubility from large to small in pure solvent is: DMSO >DMA > acetic acid > acetonitrile > 2-methoxyethanol > 2-ethoxyethanol >1,4-dioxane > propionic acid > methanol,it can be concluded that the solubility of thiamethoxam in the solvents conforms to the principle of similar phase dissolution.If the groups are identical,the greater the polarity,the greater the solubility.The modified Apelblat equation,?h equation,NRTL equation,Wilson model and J-A model were used to model the solubility data.The Apelblat equation and ?h equation have better fitting effect.The mixed thermodynamic properties of gibbs free energy,entropy and enthalpy were calculated and the thermodynamic behavior was analyzed.Based on the study of crystallization thermodynamics,the dissolution and crystallization process of thiamethoxam in DMSO-water was optimized.In view of the factors affecting the yield of crystallization and the size of particle size,seven factors: drop dosage of solvent,the crystallization time,the initial concentration of solution,the crystallization temperature,the drop acceleration of the dissolution agent,the amount of seed addition,and the stirring speed were selected.The appropriate crystallization conditions of thiamethoxam were determined as follows: the dosage of solubilizer was 4.4 m L/m L,the droplet acceleration rate of solubilizer was 1.5 m L min,the dosage of seed was 0.5 %,the stirring rate was 250 r/min,the aging time was 6 h,the initial concentration of solute was 0.33 g/m L,and the crystallization temperature was 25 ?.Under these conditions,the yield of thiamethoxam was 69%,the average grain size was 19.45 ?m and the coefficient of variation was 0.9325.