Article pubs.acs.org/IECR
Thermodynamics of the Solubility of KF in N,N-Dimethyl Ethanolamine, Pyridine, Diethanolamine, and Sulfolane from 308.73 to 367.37 K Hua Li,*,† Juan Liu,† Xiaoshuang Chen,‡ and Tiantian Ren† †
School of Chemical Engineering and Energy, Zhengzhou University, Zhengzhou 450001, China School of Energy and Power Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China
‡
S Supporting Information *
ABSTRACT: The solubilities of potassium fluoride (KF) in the different nonproton polar solvents N,N-dimethyl ethanolamine, pyridine, diethanolamine, and sulfolane have been determined using a dynamic method at temperatures ranging from 308.73 to 367.37 K. The experimental data were correlated with the modified Apelblat equation, and the solubilities correlated by the Apelblat model showed good agreement with the experimental data. It provided the basic data for preparation of 2,3,4,5tetrafluorobenzoic acid.
■
INTRODUCTION 2,3,4,5-tetrafluorobenzoic acid is an important pharmaceutical intermediate, commonly used in the preparation of antibacterial agents of quinolone, such as lomefloxacin, sparfloxacin, fleroxacin, ofloxacin, levofloxacin, and rufloxacin, and so forth, which is characterized by broad-spectrum antimicrobial activity, high-efficiency, and low cytotoxicity to humans. Quinolone drug is clinically recognized to be a powerful and safe weapon for the treatment of various bacterial infections and has become a blockbuster drug, with annual sales of around 3 billion dollars worldwide. In the halogen-exchange fluorination reaction for preparation of 2,3,4,5-tetrafluorobenzoic acid, KF is the commonly adopted raw material.1 Because the element fluorine has extreme electronegativity, the fluorination reaction must be carried out in nonproton polar solvents under anhydrous condition to prevent the side reactions such as fluorine hydrolysis and so forth. In liquid−solid heterogeneous fluorination reaction, the solubilities of KF in the nonproton polar solvents have great effect on the rate of fluorination reaction.2 Therefore, to increase the rate of fluorination reaction, it is necessary to know the solubilities of KF in the solvents, but the fundamental data which have been published for KF in the nonproton polar solvents is sparse.3 This work reports solubility data of KF in the four solvents using a dynamic method at temperatures ranging from 308.73 to 367.37 K. The chemical names of the four solvents are N,Ndimethyl ethanolamine (DMEA), pyridine, diethanolamine, and sulfolane respectively. The solubility data were correlated by the modified Apelblat equation. The solubilities correlated by the Apelblat model showed good agreement with the experimental data.
Shanghai Chemical Reagent Co. and have mass fraction purities of 0.995. Solubility Measurements. The solubilities of KF in N,Ndimethyl ethanolamine (DMEA), pyridine, diethanolamine, and sulfolane were measured by a dynamic method described previously.4,5 The laser monitoring observation technique was used to determine the dissolution temperature of the solid− liquid mixture. The laser monitoring system consisted of a laser generator, a photoelectric transformer, and a light intensity display. The experiments were carried out in a 50 mL jacketed glass vessel with a magnetic stirrer; a constant temperature (±0.02 K) was maintained at the required temperature by circulating water through the outer jacket from a thermoelectric controller. A glass sleeving with a mercury glass thermometer was inserted into the inner chamber of the vessel for the measurement of the temperature. The uncertainty of temperature was ±0.02 K. Predetermined amounts of KF and the solvents were weighed using an electronic balance with an uncertainty of ±0.0001 g and transferred into the vessel. The contents of the vessel were heated very slowly at a rate of 1 K h−1 when the system was in equilibrium. When the last portion of KF just disappeared, the intensity of the laser beam penetrating the vessel reached the maximum, and the temperature was recorded. The solubility expressed by the mole fraction was calculated as follows6 x=
(1)
where m1 and m2 represent the mass of the solute and the solvent, respectively. M1 and M2 are the molecular mass of the solute and the solvent, respectively.
■
EXPERIMENTAL SECTION Materials. Potassium fluoride, N,N-dimethyl ethanolamine (DMEA), pyridine, diethanolamine, and sulfolane were all of analytical reagent (AR) grade, and they were obtained from © 2012 American Chemical Society
m1/M1 m1/M1 + m2 /M 2
Received: Revised: Accepted: Published: 5592
July 28, 2011 March 23, 2012 March 27, 2012 March 27, 2012 dx.doi.org/10.1021/ie201633v | Ind. Eng. Chem. Res. 2012, 51, 5592−5595
Industrial & Engineering Chemistry Research
Article
Test of Apparatus. To prove the feasibility and the uncertainty of the measurement, the solubilities of NaCl in water were measured and compared with the values reported in the literature.7 The experimental measurements agreed with the reported values with a mean relative deviation of 0.23%. The measured values are listed in Table 1.
The relative average deviations (RAD) calculated by equations are listed in Table 2. The RAD is defined as RAD =
NaCl 293.15 0.0996 0.0998 −0.20
313.15 0.1015 0.1013 0.20
333.15 0.1033 0.1030 0.29
353.15 0.1061 0.1058 0.28
N
∑ i=1
xi − xci xi
(5)
RD between the calculated solubilities and the experimental data are less than 10%, which indicates that the calculated solubilities show good agreement with the experimental data. From Table 2, it can be found that the values of correlation coefficient R2 are more than 0.995, which shows that the models agree very well with the experimental data, and the overall rmsd of the 31 data points which are correlated with the modified Apelblat equation for KF in solvents N,N-dimethyl ethanolamine (DMEA), pyridine, diethanolamine, and sulfolane is 0.49 × 10−5. The relative average deviations are 1.06%, 2.72%, 0.63%, and 2.86% for DMEA, pyridine, diethanolamine, and sulfolane, respectively, which indicates that the modified Apelblat equation is suitable to correlate the solubility data of KF in these nonproton polar solvents. By using the experimental data, the solubility curves for the studied systems by the modified Apelblat equation are plotted in Figure 1; it is evident that the solubility for KF in the four
Table 1. Solubility of NaCl in 100 g of Water T/K m m (lit)7 100 RD
1 N
373.15 0.1090 0.1092 −0.18
■
RESULTS AND DISCUSSION Solubility. The solubility data of KF in different nonproton polar solvents at different temperatures was obtained. The temperature dependence of the solubility for KF in the different solvents is described by the modified Apelblat equation,8−10 B ln x = A + + C ln(T /K ) (2) T /K
where x is the mole fraction solubility of KF, T is the absolute temperature, and A, B, and C are the model parameters; the physical meanings of A, B, C are described in ref 10. The adjustable parameters A, B, C can be obtained from simple optimization. The object function F is defined as follows: F = min ∑|xci−xi|2, the values of parameters A, B, C are listed in Table 2. The calculated solubility xc of KF is given in the Supporting Information. The root-mean-square deviation (rmsd) is defined as ⎡1 RMSD = ⎢ ⎢⎣ N
⎤1/2 2⎥ ( x x ) − ∑ ci i ⎥⎦ i=1
Figure 1. Solubility of KF in N,N-dimethyl ethanolamine (DMEA), pyridine, diethanolamine and sulfolane ▼, DMEA; ●, pyridine; ■, diethanolamine; ◆, sulfolane; solid line calculated from the Apelblat equation.
N
(3)
where N is the number of the experimental points, xci represents the solubilities calculated from the equations, and xi represents the experimental solubility values. The model parameters and the rmsd are listed in Table 2. The relative deviations between the experimental value and the calculated value are also given in the Supporting Information. Relative deviations (RD) are calculated according to x − xc RD = (4) x
nonproton polar solvents is small, and the solubility increases with the increase of temperature. From Figure 1, it can be found that at the same temperature, the solubility of KF in the four nonproton polar solvents follow the order DMEA > pyridine > diethanolamine > sulfolane. The molecular structures for KF, N,N-dimethyl ethanolamine, pyridine, diethanolamine, and sulfolane are shown in Figure 2. The phenomenon is based on comprehensive effects of several factors, such as molecular weight, molecular diameter, molecular structure and space conformations, and polarization of the solvents. If the interaction of solute particles and solvent
where x represents the experimental solubility values.
Table 2. Parameters of KF in N,N-Dimethyl Ethanolamine (DMEA), Pyridine, Diethanolamine, And Sulfolane solvent
A
B
C
R2
105 rmsd
102 RAD
DMEA pyridine diethanolamine sulfolane
168.23 236 148.15 −174.70
−13195.89 −16988.78 −11846.19 5219.31
−23.45 −33.27 −20.87 25.83
0.9995 0.9991 0.9999 0.9964
0.62 0.75 0.21 0.39
1.06 2.72 0.63 2.86
5593
dx.doi.org/10.1021/ie201633v | Ind. Eng. Chem. Res. 2012, 51, 5592−5595
Industrial & Engineering Chemistry Research
Article
⎡ ∑n (x − x )2 ⎤0.5 ci i ⎥ SEP = ⎢ i = 1 ⎢⎣ ⎥⎦ n−1
(9)
The square of the correlation coefficient (R2) indicates the quality of the fit of all the data to a straight line and is calculated to check the test set; it is calculated as follows:
Figure 2. Molecular structure of DMEA, pyridine, diethanolamine, and sulfolane.
n
∑i = 1 (xci − x ̅ )2 R = n ∑i = 1 (xi − x ̅ )2 2
where xi is the experimental value, xci represented the predicted value, x̅ is the mean of the experimental value in the prediction set, and n is the total number of samples used in the prediction set. Then the five general statistical parameters were used to evaluate the model, and the results are shown in the Table 3. From Table 3, it is found that five general statistical parameters, especially PRESS and R2 values, are satisfactory, which indicates that the model shows good agreement with the experimental data.
particles is similar to the interaction of solvent particles, then there will be a larger solubility. It is the same rule for molecular structure and space conformations, and polarization of solute and solvent. KF has little solubility in sulfolane because the space obstacles of the five-membered ring of sulfolane and its distortion to the plane. Test of the Model. For evaluation of the predictive power of the modified Apelblat equation, the optimized model was applied for prediction of the x values at 31 data points. For the constructed model, five general statistical parameters were selected to evaluate the predictive ability of the model for x values.11 In this case, the predicted x of each sample in the prediction step was compared with the experimental data. The PRESS (predicted residual sum of squares) statistic appears to be the most important parameter accounting for a good estimate of the real predictive error of the models. Its small value indicates that the model predicts better than chance and can be considered statistically significant.
■
CONCLUSIONS The solubilities of KF in the nonproton polar solvents were measured using the dynamic method and the laser monitoring observation technique, and the experimental data were correlated with the modified Apelblat equation. The overall rmsd deviation is 0.49 × 10−5. The calculated results show good agreement with the experimental data. The experimental solubility and correlation equation in this work can be used as essential data for the preparation of 2,3,4,5tetrafluorobenzoic acid.
n
PRESS =
∑ (xci − xi)2
■
(6)
i=1
The root mean square error of prediction (RMSEP) is a measurement of the average difference between predicted and experimental values, at the prediction step. RMSEP can be interpreted as the average prediction error, expressed in the same units as the original response values. The RMSEP was obtained by the following formula ⎡1 RMSEP = ⎢ ⎢⎣ n
n i=1
The solubility data of KF in different nonproton polar solvents at different temperatures, and also the relative deviations (RD) between the experimental value and calculated value are given in a table. This material is available free of charge via the Internet at http://pubs.acs.org.
■
⎤0.5 ⎥⎦
(7)
⎤0.5 2⎥ ∑ (xci − xi) ⎥⎦ i=1
AUTHOR INFORMATION
Corresponding Author
*Phone: 0086-371-67781712. Fax: 0086-371-63886154. E-mail:
[email protected].
The third statistical parameter was the relative error of prediction (REP) that shows the predictive ability of each component, and is calculated as 100 ⎡⎢ 1 REP(%) = x ̅ ⎢⎣ n
ASSOCIATED CONTENT
S Supporting Information *
2⎥
∑ (xci − xi)
(10)
Notes
The authors declare no competing financial interest.
■
n
(8)
REFERENCES
(1) Li, H.; Wang, H. K.; Zhao, R. J.; Liu, J.; Zhao, Z. G.; Hu, G. Q. Preparation of 2, 3, 4, 5-Tetrafluorobenzoic Acid. J. Korean Chem. Soc. 2010, 54, 744−748. (2) Li, B. D.; Lv, B. D. Synthesis of Sevoflurane by the Halogenexchange Fluorinating Reaction in the Ionic Liquid. Applied Chem. 2009, 26, 1126−1128.
The predictive applicability of a regression model is described in various ways. The most general expression is the standard error of prediction (SEP) which is given in the following formula Table 3. Results of the Five General Statistical Parameters solvent DMEA pyridine diethanolamine sulfolane
PRESS
RMSEP −10
3.0299 × 10 4.5207 × 10−10 1.1266 × 10−10 1.20486 × 10−10
6.15417 7.51723 3.75267 4.14876
× × × ×
REP(%) −6
10 10−6 10−6 10−6 5594
1.142119 1.955702 1.116989 2.340929
R2
SEP −6
6.5791 × 10 8.03626 × 10−6 4.01177 × 10−6 4.48118 × 10−6
0.9983 0.9859 0.9989 0.9976
dx.doi.org/10.1021/ie201633v | Ind. Eng. Chem. Res. 2012, 51, 5592−5595
Industrial & Engineering Chemistry Research
Article
(3) Wynn, D. A.; Roth, M. M.; Pollard, B. D. The solubility of Alkalimetal Fluorides in Nnon-aqueous Solvents with and without Crown Ethers, as Determined by Flame Emission Spectrometry. Talanta 1984, 31 (11), 1036−1040. (4) Nie, Q.; Wang, J. K. Solubility of 16α,17α-Epoxyprogesterone in Six Different Solvents. J. Chem. Eng. Data 2005, 50, 1750−1752. (5) Li, H.; Zhu, J.; Hu, G. Q.; Jiang, P. L.; Zhao, L.; Zhang, Y. D. Measurement and Correlation of Solubility of Pimelic Acid in Ether, THF, Ethanol and Methanol. J. Chem. Eng. Data 2009, 54, 2986− 2990. (6) Li, H.; Guo, F.; Hu, G. Q. Measurement and Correlation for Solubility of Thiourea in Triglycol + Water at Temperatures from (292.05 to 357.75) K. J. Chem. Eng. Data 2009, 54, 2100−2102. (7) Xue, C. M.; Fan, Y. Common Chemistry Handbook; Geophysics Press: Peking, China, 1997. (8) Apelblat, A.; Manzurola, E. Solubility of Ascorbic, 2Furancarboxylic, Glutaric, Pimelic, Salicylic, and o-Phthalic Acids in Water from 279.15 to 342.15K, and Apparent Molar Volumes of Ascorbic, Glutaric, and Pimelic Acids in Water at 298.15K. J. Chem. Thermodyn. 1989, 21, 1005−1008. (9) Apelblat, A.; Manzurola, E. Solubilities of o-Acetylsalicylic, 4Aminosalicylic, 3,5-Dinitrosalicylic, and p-Toluic Acid, and Magnesium-DLaspartatein Water from T = (278 to 348) K. J. Chem. Thermodyn. 1999, 31, 85−91. (10) Zhao, C. X.; He, C. H. Solubility of Atractylenolide III in Hexane, Ethyl Acetate, Diethyl Ether, and Ethanol from (283.2 to 323.2) K. J. Chem. Eng. Data 2007, 52, 1223−1225. (11) Ghasemi, J.; Saaidpour, S.; Brown, S. D. QSPR study for estimation of acidity constants of some aromatic acids derivatives using multiple linear regression (MLR) analysis. J. Mol. Struct., THEOCHEM 2007, 805, 27−32.
5595
dx.doi.org/10.1021/ie201633v | Ind. Eng. Chem. Res. 2012, 51, 5592−5595
