Chiral Separation Of 1,2-Cyclohexanediamine And Study Its Solid-liquid Equilibrium System

(-)-1,2-DACH and?+?-1,2-DACH are important pharmaceutical intermediate,which has a wide range of applications in the fields of medicine,asymmetric catalysis,and molecular recognition.What's more the optically pure tartaric acid is used for the chiral resolution of?�?-1,2-DACH due to its low price and easy availability.A mixed solution of 1R,2R-cyclohexanediamine-D-tartrate salt and1S,2S-cyclohexanediamine-D-tartrate salt was obtained after chiral resolution of?�?-1,2-DACH.The separated of optically pure1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt from the mixed solution was the key steps,which affected the chiral resolution effect of?�?-1,2-DACH.This article study the aspect of solid-liquid equilibrium,thermodynamic quality,the phase diagram and their application in chiral resolution.In this paper,1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartratesalt were synthesized with the?-?-1,2-DACH,D-?-?tartaric acid and?+?-1,2-DACH,D-?-?tartaric acid.The yield of the two salts can reach 99.20%and 96.67%,respectively.The nuclear magnetic resonance,elemental analysis,infrared spectroscopy,and melting point determination was used to qualitative detection to confirm the 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt.The result indicates that the purity of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt can reach 99%.And the purity of the two salts meets the requirements of solute purity in the solid-liquid equilibrium.The researchers found that it is an advantageous tool for the separation and purification of two salts in their aqueous solution when study the solid-liquid equilibrium and ternary solid-liquid phase diagram of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt in binary and ternary solvents.They are used for the selection of the optimal separation solvent,separation and purification of?�?-1,2-DACH.The solubility data and phase equilibrium data are provided as the theoretical basis for the analysis.In this work we survey the solubility of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt in H₂O,?H₂O+methanol?,?H₂O+ethanol?,?H₂O+n-propyl alcohol?,?H₂O+isopropanol?,?H₂O+n-butyl alcohol?pure solvent and binary solvent mixtures.These experiments were measured at temperatures from?297.55 to 348.15?K using the dynamic method under atmospheric pressure.The Apelblat equation,?h equation Wilson model and NRTL model were applied to correlate the experimental results.And the apparent thermodynamic properties of the dissolution process,including enthalpy,entropy and Gibbs energy,were calculated by applying of the van't Hoff analysis and Gibbs equation.Experimental results indicates that 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt has a greater solubility in water than other binary mixed solvents.What's more,the solubility of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt is increasing with the temperature,which makes H₂O possible for the extraction of1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt.It is obvious that the solubility decreases with the rising of the ratio of alcohol.In addition,the values relative average deviation?RAD?is less than 0.0381,0.2338,0.1187,0.0051 and 0.3789,1.8080,0.3219,0.0415 for 1R,2R-cyclohexanediamine-D-tartrate and 1S,2S-cyclohexanediamine-D-tartrate between experimental and calculated with the use of Apelblat model,?h model,Wilson model and NRTL model to regression.The calculated values show good agreement with the experimental results and the computational results show that the Wilson model is superior to the?h model,Apelblat model,and NRTL model.In the use of van't Hoff analysis,the apparent thermodynamic properties of the solution process were calculated including enthalpy,entropy and Gibbs.The apparent thermodynamic parameters values proved that the solution process of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt in the H₂O,?H₂O+methanol?,?H₂O+ethanol?,?H₂O+n-propyl alcohol?,?H₂O+isopropanol?,?H₂O+n-butyl alcohol?pure solvent and binary solvent mixtures are endothermic and the main contributor to the positive standard molar Gibbs energy of solution is the positive enthalpy.The solid-liquid phase equilibrium for the ternary system of?1R,2R-cyclohexanediamine-D-tartrate salt+1S,2S-cyclohexanediamine-D-tartrate salt+H₂O?was measured at 298.15 K,308.15 K,318.15 K and 328.15 K by the isothermal solution saturation method under 101.3 k Pa.The corresponding ternary phase diagrams were built based on the mutual solubility data.And the dependence of temperature and phase diagram also be demonstrated.What's more,correlate the liquid-solid equilibrium with NRTL model and Wilson model.And obtained the interaction parameters for the two system.All experiments results correlated well with Wilson model,the ternary phase diagrams were plotted and correlated by Wilson model.At the given temperature,the crystalline zone of 1R,2R-cyclohexanediamine-D-tartrate salt was larger than that of 1S,2S-cyclohexanediamine-D-tartrate salt,and increased with the temperature.The ternary phase diagrams were correlated and evaluated via the NRTL model and the Wilson model.The results show that the relative average deviation?RAD?is smaller between the calculated value and the actual measured value of the Wilson model which is suitable than that of the NRTL model.Two separation paths for two salts in a mixed salt solution of 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt was proposed based on the solid-liquid equilibrium phase diagrams.The phase diagram analysis method was used to calculate and analyzed the yields in the first cycle and the stable cycle of the two separation routes,respectively.The calculation results show that 1R,2R-cyclohexanediamine-D-tartrate salt and 1S,2S-cyclohexanediamine-D-tartrate salt can be separated high-efficiency from the solution in the two separation methods.