Application of preferential crystallization for racemic compound integrating thermodynamics, kinetics and optimization 2

[...]... negative for both of mandelic acid and ketoprofen The enthalpies of fusion difference between (RS) and (S) were 59 also positive for both of them In addition, their ∆Tf were all far away from -30 oC which implies that the racemic species is likely to be a conglomerate All these thermal analysis suggest that the mandelic acid and ketoprofen are in form of racemic compound But for the case of mandelic... temperature and eutectic temperature of different mole fraction of (S)-Kp Experiment data Mole fraction of (S)-Kp o TE( C) 0.50 o Calculated Tf(oC) Tf( C) 94.54 94.54 0.65 72. 64 92. 82 92. 61 0.75 72. 42 88.86 88.73 0.86 71. 92 81.15 80.13 0.88 72. 61 78.34 77.66 0.90 73. 12 78.59(uncertain) 74.70 0. 92 71. 62 (uncertain) 71.76 0.94 70. 62 (uncertain) 72. 69 0.96 70.75 (uncertain) 73. 62 75.41 75. 42 1.00 The binary... and thermodynamic calculation From the spectroscopic techniques, such as FTIR, Raman and PXRD, the spectra were different between the pure enantiomer and racemate for the mandelic acid and ketoprofen It indicates that the mandelic acid and ketoprofen all belong to the racemic compound Through the thermal analysis and calculation, it was found that the Gibbs free energy of formation of the racemic compound. .. Schröder-Van Laar equation and the Prigogine-Defay equation The calculated results were in good agreement with the DSC experiment data for both mandelic acid and ketoprofen Their shape of binary phase diagram both show the typical shape of racemic compound system, just the more favorable racemic compound system for mandelic acid and unfavorable racemic compound system for ketoprofen From the binary phase.. .racemic compound 120 00 S-Kp 10000 RS-Kp I 8000 6000 4000 20 00 0 10 20 30 40 50 60 2Theta Fig 3.6 PXRD patterns of (RS)-Kp and (S)-Kp 3.3 .2 Characterization by thermal analysis and binary phase diagram Construction of the binary phase diagram from simple measurements of melting temperatures of racemic species and of their corresponding enantiomers has traditionally been used for identifying... by DSC is given in Table 3.1 The melting temperature of (S)- and (RS)-MA reached to 1 32. 5 and 119.5 o C respectively The enthalpy of fusion of (S)- and (RS)-MA were 27 678 and 28 375 J/mol respectively All these results are comparable to those found in reference (Lorenz and Seidel-Morgerstern, 20 02) For the majority of chiral species that are racemic compound, their stability can be defined through the... 115.6 115.60 0. 72 115.9 117.6 116.89 0.75 115.8 119.0 118.76 0.80 115.9 121 .2 121 .76 0.85 115.7 124 .0 124 . 62 0.90 115.4 126 .9 127 .36 0.95 115.5 129 .8 129 .98 1 32. 5 1 32. 50 1.00 53 liquidus line from equation melting temperature from DSC solidus line from equation eutectic temperature from DSC Temperature ( oC) 130 125 120 115 110 0 0.1 0 .2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Mole fraction of S-MA Fig 3.8 The... temperature of racemate is lower than that of enantiomer It indicates that the mandelic acid may be a kind of more favorable racemic compound On the contrary, the melting temperature of racemate is higher than that of enantiomer for ketoprofen, which suggests ketoprofen could be an unfavorable racemic compound The binary melting phase diagrams were constructed for the mandelic acid and ketoprofen based... results indicate the formation of racemic compound of ketoprofen In addition, the melting temperature of Kp racemate is higher than that of enantiomer It suggests that the ketoprofen should be a kind of unfavorable racemic compound The liquidus curve also can be calculated from the melting point and the enthalpy of fusion of the pure enantiomer and racemate by the Schröder-Van Laar equation and the Prigogine-Defay... racemic compound forming system, which can further verify that the mandelic acid is a kind of more favorable racemic compound 52 Table 3 .2 The melting temperature and eutectic temperature of different mole fraction of (S)-MA Experiment data Mole fraction of (S)-MA o TE( C) 0.50 o Calculated Tf(oC) Tf( C) 119.5 119.50 0.55 115.7 119.3 119 .27 0.60 115.9 118.8 118.58 0.65 116.0 118.3 117.38 0.68 116.2 . 0. 72 115.9 117.6 116.89 0.75 115.8 119.0 118.76 0.80 115.9 121 .2 121 .76 0.85 115.7 124 .0 124 . 62 0.90 115.4 126 .9 127 .36 0.95 115.5 129 .8 129 .98 1.00 1 32. 5 1 32. 50 54 110 115 120 125 130 0. of fusion and melting temperature of both the racemic compound and enantiomers, which can be obtained by DSC measurement. When a racemic compound is formed, the equations for the enthalpy and. lattice of (S)- and (RS)-MA and suggest that the mandelic acid should be a racemic compound. From the Fig. 3 .2, the peak positions and shape of the FTIR spectrum for the (RS)-Kp and (S)-Kp