Study On The Oiling Out In The Nucleation Process Of Pyraclostrobin

In the solution crystallization process,sometimes there is a new liquid phase that would appears first when the solution reaches supersaturation and then crystals crystallized,this special phenomenon is called oiling out.In general,after oiling out,impurities would gather in the viscous oil phase and because of the diffusion resistance,the crystal couldn’t grow up.Then it results in the coalescence of crystals and inclusion of impurities in solute aggregates,and eventually leads to the product purity,solvent residues and impurity can’t meet the requirements of product quality.Meanwhile,since the occurrence of oiling out disturbs the nucleation process,it is difficult to obtain the pure target crystal form in repeatably.In industrial production,therefore,we need to consider how to avoid the occurrence of oiling out in the crystallization process.However,at present the mechanism,the thermodynamics,the kinetics,and the process control of oiling out are still lack of systematic research.In order to solve problems discussed above,this paper takes green pesticide pyraclostrobin as the research model,investigates the thermodynamics behavior of oiling out in the nucleation process,and discusses the kinetic process of oiling out simply;meanwhile,we put forward a kind of mechanism of molecular cluster,successfully explained the influence of solvent on pyraclostrobin;Finally,we avoided the oiling out and obtained the stable target crystals by adjusting process parameters.Oiling out thermodynamics and dynamics in crystallization process is the basis of the oiling out research,thus in this paper,the oiling out in cooling crystallization process was monitored and analyzed by using process analytical technique,and three stages in oiling-out crystallization of pyraclostrobin were summarized.This paper identified the dynamics properties of oiling-out crystallization of pyraclostrobin and determined that the nucleation occurred in oil phase first by experiments.There are two kinds of polymorphs of pyraclostrobin in different low carbon alcohols: form II and form IV.In this paper,the solubilities of form II and form IV of pyraclostrobin in different lower alcohols were determined.The result showed that solubilities of two forms are positively correlated with the temperature,and solubilities in linear alcohols were greater than that in branched chain alcohols with the same carbon atom number.The solubility difference of pyraclostrobin in different alcohols was explained by using polarity,space steric hindrance and intermolecular interaction force.Based on the solubility of pyraclostrobin in isopropanol-cyclohexane mixed solvent,the phase diagram of pyraclostrobin – isopropanol-cyclohexane system was determined.In order to investigate the mechanism of oiling out of pyraclostrobin in cooling crystallization,the oiling out in pure solvents was investigated.The solubility parameter of the solvent system,the degree of supersaturation and solvation free energy function parameters were discussed.A hypothesis that there are two kinds of meso scale molecular clusters in phase separation system was put forward and proved the validity through the experiment.Finally,the mechanism of oiling out in pure solvents and mixed system were successfully revealed.In order to avoid the oiling out,cooling rate,initial concentration,stirring rate and seeding were investigated in oiling-out crystallization process.It was found that lower initial concentration,slowing down the cooling rate and stirring rate can reduce the occurrence of oiling out,but can not eliminate it.Seeding can not only eliminate the oiling out,but also control the polymorph.All the contents discussed above have never been reported by any other related literatures.