Solid-liquid Equilibrium Research On Seperation Process Of Nitroacetanilide Isomers Via Solvent Crystallization

Nitroacetanilide contains three isomers of 2-nitroacetanilide,3-nitroacetanilide and 4-nitroacetanilide.They are all important fine chemical intermediates and widely used in organic synthesis,printing and dyeing,medicine,organic nonlinear optical materials and other industries.At present,the 4-nitroacetanilide is mainly produced by nitration of acetanilide in industry,and a small amount of 2-nitroacetanilide and 3-nitroacetanilide is produced at the same time.Solvent crystallization has the advantages of low energy consumption and simple operation,which can effectively separate the nitroacetanilide isomers.Solvent crystallization is based on solubility data,but they are relatively lacking at present.In this dissertation,the solid-liquid equilibrium of nitroacetanilide isomers in different systems was studied.The results provide the basis for the separation processes of nitroacetanilide isomers.The solubility data of 2-nitroacetanilide,3-nitroacetanilide and 4-nitroacetanilide in methanol,ethanol,isopropanol,n-propanol,acetonitrile,ethyl acetate,cyclohexane,n-butanol,ethylene glycol(EG),isobutanol,n-heptanol,1,4-dioxane,N,N-dimethylformamide(DMF),water,and N-methylpyrrolidone(NMP)were measured by using isothermal dissolution method.The solubility of nitroacetanilide isomers increased with a rise of temperature,and obeyed the sequence from high to low in different solvents for 2-nitroacetanilide at the certain temperature:NMP>DMF>1,4-dioxane>ethyl acetate>methanol(acetonitrile)>ethanol>n-propanol>n-butanol>isobutanol>isopropanol>n-heptanol>EG>cyclohexane>water;the mole faction solubility of 3-nitroacetanilide ranked as NMP>DMF>1,4-dioxane>ethyl acetate>methanol>acetonitrile>ethanol>n-propanol>isopropanol>n-butanol>isobutanol>n-heptanol>EG>water>cyclohexane and the mole faction solubility of 4-nitroacetanilide ranked as NMP(DMF)>1,4-dioxane>ethyl acetate>n-heptanol>acetonitrile>n-butanol>n-propanol>ethanol>isopropanol>methanol>isobutanol>EG>water>cyclohexane.Moreover,the obtained solubility values were correlated by the modified Apelblat model,?h model,NRTL model and Wilsonmodel.The maximum values of relative average deviation(RAD)and root-mean-square deviation(RMSD)acquired with the four models were no more than 8.95%and 80.65×10-4,respectively,and the modified Apelblat model provided better results than the other three models.In addition,the influence of solvent effect on the solubility of nitroacetanilide isomers was discussed and the dissolution Gibbs energy,dissolution enthalpy,and dissolution entropy were calculated.The solubility data of nitroacetanilide isomers in(ethanol+water),(n-propanol+water),(1,4-dioxane+water)and(DMF+water)solvent mixtures were measured by using isothermal dissolution method.The solubility of 2-nitroacetanilide,3-nitroacetanilide and 4-nitroacetanilide increased with increasing temperature and mass fraction of ethanol(n-propanol,1,4-dioxane,DMF)for the binary systems studied and no solubilization phenomenon was found during entire experiments.Moreover,the Jouyban-Acree model,Van't Hoff-Jouyban-Acree model,Apelblat-Jouyban-Acree model were used to correlate the solubility data that obtained the corresponding model parameters.The RAD and RMSD were no more than 6.08%and 7.17×10-3,respectively,and the Jouyban-Acree model achieved best correlation results.In the meanwhile,the standard enthalpy of dissolution and transfer properties of nitroacetanilide isomers in mixed solvents were calculated.The solid-liquid phase equilibria of 2-nitroacetanilide+3-nitroacetanilide+ethanol/ethyl acetate and 2-nitroacetanilide+4-nitroacetanilide+ethanol/ethyl acetate at 293.15 K,303.15 K and 313.15 K were measured by Schreinemaker's method,and the ternary phase diagrams were obtained.The co-crystallization regions were decreased with increasing temperature.The crystallization region of 3-nitroacetanilide and 4-nitroacetanilide was larger than that of 2-nitroacetanilide at a given temperature,especially in 2-nitroacetanilide+3-nitroacetanilide+ethyl acetate and 2-nitroacetanilide+4-nitroacetanilide+ethyl acetate system,and ethyl acetate was more favorable in separation of nitroacetanilide isomers.In addition,the solubility data was correlated with the NRTL model and Wilson model.The RAD were 3.80×10-2 and 7.51×10-2 respectively,the RMSD were 6.655×10-3 and 9.205×10-3 respectively,which illustrated that the NRTL model could correlate the 2-nitroacetanilide+ 3-nitroacetanilide+ethanol/ethyl acetate and 2-nitroacetanilide+4-nitroacetanilide+ethanol/ethyl acetate ternary systems accurately.