Study On The Crystallization Of Pyrimethanil Pesticide

Pyrimethanil,as a special pyrimedine amine fungicide,is widely used due to its remarkable advantages of high efficiency,low toxicity and low residue.However,there is no systematical and profound study focused on effective control of known solid forms and comprehensive research on potential solid forms of pyrimethanil.It is of great significance to grasp the comprehensive solid form information of pesticides to achieve solid form control for the quality of pesticide products based on the theory of crystal engineering.Thus,this study aims to comprehensively understand the intermolecular interactions and packing modes of polymorphs,solvates and cocrystals,as well as their influence on crystal structures and properties.And this study provides a experimental and theoretical basis for solid form screening of pyrimidine amine pesticides.Firstly,the nonsolvated metastable polymorph(form II)was successfully prepared by melt crystallization or fast-cooling crystallization from the solution with high supersaturation for the first time.The solid-state phase transformation of form II was investigated by differential scanning calorimeter(DSC)and hot stage-polarized microscopy,and it was found that the two forms are monotropic systems.This study revealed that humidity and temperature are the main factors for inducing solid-to-solid transformation.And the structural information analysis showed that the molecular conformation and the weaker π-π stacking forces contribute to poor stability of form II.And the solubility of form I was determined in 7 pure solvents and two different mixed solvents from 283.15K to 323.151K by static equilibrium method,which provides the guidence for deciding the crystallization methods and the design of crystallization process.Secondly,the formation and desolvation behavior of pyrimethanil solvates were investigated.The solvate screening was carried out and six solvates were successfully prepared for the first time from acetonitrile,acetone,methyl acetate,DMF,DMA and NMP and the single crystal structures were obtained.The crystal structures were compared and analyzed from four aspects: unit cell parameters,hydrogen bonding,packing mode and molecular conformation.The above solid forms were characterized by SEM,DSC,TGA,HSM,FTIR and PXRD.The solvate formation and different desolvation behaviors are explained by solvent molecular properties and solvent-solute interactions in crystal structures.Finally,based on the studies on the “host-guest” intermolecular interactions and the corresponding molecular arrangement in the solvates,we performed rational synthesizer design of pyrimehanil co-crystals.And a new co-crystal of pyrimethanil and m-erythritol at the ration of 2:1 was successfully prepared for the first time,and its melting point is increased compared to form I.To prepare pure cocrystal products,the solubility of the solid phases in the ternary system was determined at 20 ℃ and a robust crystallization process by isothermal slurry conversion was developed based on the ternary phase diagram,which verified the accuracy of the data of the ternary phase diagram.And the binding energy was calculated to explain the formation of the cocrystal by using Materials Studio 6.0 software.All the contents discussed above have never been reported by any other related literatures.