Study On Solid-Liquid Equilibrium Of Three Hydroxyacetophenone Compounds

Hydroxyacetophenones are important intermediates in pharmaceutical and chemical industry.Hydroxyacetophenones can be obtained by Friedel-Crafts acylation reaction with phenol as raw material and acetic acid as acylating agent.However,the solubility data required for crystallization separation of the synthesized products have not been reported yet.The solid-liquid equilibrium study provides basic data for the crystallization process and guides the screening of crystallization solvents.The thermodynamic model was studied and the solubility was predicted.In addition,the analysis of intermolecular forces at the micro level has certain significance in the prediction of solubility sequence.In this paper,three hydroxyacetophenones,m-hydroxyacetophenone,2,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone,are taken as the research objects.The following research works were carried out:（1）The solubility data of hydroxyacetophenones in conventional mono-solvents and binary solvents,including proton solvents（methanol,ethanol,n-propanol,isopropanol,n-butanol,isobutanol and water）and aprotic solvents（methyl acetate,ethyl acetate,n-propyl acetate and benzene）was determinated by static equilibrium method from 20°C to 60°C.Binary solvents include methanol+water,ethanol+ethyl acetate,ethanol+methyl acetate,n-propanol+ethyl acetate;（2）Based on the van’t Hoff equation,the thermodynamic properties of dissolution of the three compounds in pure and binary solvents were calculated by slope method,including dissolution enthalpyΔH_sol^o,dissolution entropyΔS_sol^o and Gibbs free energyΔG_sol^o.The results show that the dissolution process of the three acetophenone compounds is an endothermic,entropic increasing,non-spontaneous and enthalpy driven process;（3）The empirical models and activity coefficient models were used to fit the solubility data,and the obtained model parameters can be used for solubility prediction.The average relative deviations of the empirical models were less than that of the activity coefficient models,and the three-parameter Apelblat model had the smallest deviation of less than 4%except for the methanol+water special system,so it was the best thermodynamic model;（4）The dissolution mechanism of three hydroxyacetophenone compounds in different solvents were investigated by KAT-LSER model and preferential solvation effect,which provided convenience for the screening of crystallization solvents.