Article pubs.acs.org/jced
Measurement and Correlation of the Solubility of 2,6-Diaminohexanoic Acid Hydrochloride in Aqueous Methanol and Aqueous Ethanol Mixtures Hua Sun,† Min Li,‡ Jingtan Jia,§ Fengkui Tang,‡ and Erhong Duan*,‡ †
College of Chemical & Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei, 050018, People's Republic of China ‡ School of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei, 050018, People's Republic of China § Huayang Chemical Co., Ltd., Jizhou, Hebei, 053200, People's Republic of China ABSTRACT: The solubility of 2,6-diaminohexanoic acid hydrochloride in three pure and aqueous alcohols (methanol and ethanol) was measured by a dynamic method with a laser monitoring technique in the temperature range from 283.15 K to 333.15 K. The solubility in the different solvents increases in the following order: water > methanol > ethanol. In binary solvents, the solubility decreases with increasing alcohol concentration. The solubility data were correlated with the combined nearly ideal binary solvent/Redlich−Kister (CNIBS/R-K) model and a modified Jouyban−Acree model. For the five solvents studied, the CNIBS/R-K model was found to provide a more accurate mathematical representation of the experimental data, while the modified Jouyban−Acree model contained provisions for correlating both solvent composition and temperature.
■
INTRODUCTION As one of the eight essential amino acids, (2S)-2,6-diaminohexanoic (L-lysine) acid is necessary for human health but can be obtained only from diet. Compared to (2S)-2,6-diaminohexanoic acid, which is unstable and has a bad smell, 2,6-diaminohexanoic acid hydrochloride (L-lysine hydrochloride, HCl) is relatively stable and easy to preserve. Therefore, it is available commercially as 2,6-diaminohexanoic acid hydrochloride. Figure 1 shows the
experimental solubility data in aqueous ethanol solvents were available. In this paper, the solubility data of 2,6-diaminohexanoic acid hydrochloride in aqueous methanol and aqueous ethanol mixtures were measured via a laser monitoring observation technique. By this method, solubility data can be obtained much faster than with an analytical method.6,7 The experimental solubility and correlation equations in this work can be used as essential data and models in the purification process of 2,6diaminohexanoic acid hydrochloride.
■
EXPERIMENTAL SECTION Materials and Reagents. 2,6-Diaminohexanoic acid hydrochloride (C6H14N2O2·HCl, CAS No.: 657-27-2) was prepared by recrystallization from water solution three times, dried at 378.15 K for 24 h, and stored in a desiccator. Its purity was measured by high-performance liquid chromatography (HPLC) to be 0.995 in mass fraction, according to USP27.8 The mass fraction purities of alcohols (methanol and ethanol) obtained from Tianjin Chemical Reagent Co., China, determined by gas chromatography, are higher than 99.5 %. Distilled HPLC grade deionized water was used. Apparatus and Procedure. The solubility was measured using an apparatus similar to that described in the literature.9 A laser monitoring observation technique was used to monitor
Figure 1. Chemical structure of 2,6-diaminohexanoic acid hydrochloride.
molecular structure. 2,6-Diaminohexanoic acid hydrochloride is widely used in food, food additives, and drugs.1,2 In industry, (2S)-2,6-diaminohexanoic acid can be generated through fermentation.3 2,6-Diaminohexanoic acid hydrochloride is separated and purified by extraction, decolorization, and crystallization. In the final purification step, the product is recrystallized from solution by antisolvent crystallization.4 The binary aqueous and ethanol mixtures are usually used as solvents for the crystallization of 2,6-diaminohexanoic acid hydrochloride. It is necessary to know the solubility data in the related solvents for the purification and refining process. A review of the literature of L-lysine, however, indicated that only some solubility data were reported.5 No systematic © 2012 American Chemical Society
Received: December 16, 2011 Accepted: March 27, 2012 Published: April 5, 2012 1463
dx.doi.org/10.1021/je300173v | J. Chem. Eng. Data 2012, 57, 1463−1467
Journal of Chemical & Engineering Data
Article
the disappearance of the last crystal particles in the liquid + solid mixtures. The solubility was measured with 100 mL jacked glass vessel at constant temperature through a thermostatted bath with an uncertainty of ± 0.05 K. A condenser was used in the vessel to prevent the evaporation of the solvent. The dissolution of the solute was examined by a laser beam penetrating the vessel. An analytical balance (Metler Toledo AB204-N, Switzerland) with an uncertainty of ± 0.0001 g was used. The solubilities of 2,6-diaminohexanoic acid hydrochloride in aqueous and alcohol mixture were measured by the laser method.9 An additional experiment was done in our previous work5 to verify the uncertainty of the measurement. The uncertainty in the solubility values are less than 3 %. The same experiments were measured at least three times. The mean values were calculated and used to get the molar fraction solubility, x1, based on eq 1. The compositions of solvent mixtures, x2, were defined in eq 2 x1 =
m1/M1 m1/M1 + m2 /M 2 + m3 /M3
x2 =
m2 /M 2 m2 /M 2 + m3 /M3
Table 1. Mole Fraction Solubility (x1) of 2,6Diaminohexanoic Acid Hydrochloride in Binary Methanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K
(1)
(2)
where m1, m2, and m3 represent the mass of the solute, alcohols (methanol and ethanol), and water, respectively, and M1, M2, and M3 are the molecular weights of the solute, alcohols (methanol and ethanol), and water, respectively.
■
RESULTS AND DISCUSSION Solubility Data. The solubilities of 2,6-diaminohexanoic acid hydrochloride in pure and aqueous alcohols (methanol and ethanol) were shown in Tables 1 and 2, with the temperature range from 293.15 K to 323.15 K. To compare clearly the experimental values, the solubilities of 2,6-diaminohexanoic acid hydrochloride in the binary alcohols (methanol and ethanol) and water solvent mixtures in the temperature range from 293.15 K to 323.15 K were presented in Figures 2 and 3. The solubilities we measured in this paper are close to the solubility value reported in literature.5 From the experimental values (Tables 1 and 2), we could know that the solubility of 2,6-diaminohexanoic acid hydrochloride in binary alcohols (methanol and ethanol) and water solvent mixtures was a function of temperature and solvent composition. Specifically, the solubility of 2,6-diaminohexanoic acid hydrochloride in binary alcohols (methanol and ethanol) and water solvent mixtures increases with increasing temperature, while it decreases with the increase of alcohol (methanol and ethanol) content in the solvent mixture. At the same conditions, the solubility in the different solvents increases in the following order: water > methanol > ethanol, which could be well-explained by the principle that the similar substance is more likely to be dissolved by each other. In binary solvents, the solubility decreases with increasing alcohol concentration. Water is a good solvent for the dissolution 2,6-diaminohexanoic acid hydrochloride, and alcohol will be a good antisolvent for the recrystallization of 2,6-diaminohexanoic acid hydrochloride. The solubility data can be used as fundamental data for the solvent selection for the purification process. Data Correlation. There are some mathematical models that accurately describe the solubility data. The combined nearly ideal binary solvent/Redlich−Kister (CNIBS/R-K) model was proposed by Acree and co-workers.10−12 This model describes
x2
x1
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.0520 0.0470 0.0183 0.0058 0.0023 0.0001
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.0609 0.0629 0.0285 0.0088 0.0027 0.0002
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.0732 0.0775 0.0400 0.0136 0.0033 0.0004
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.0931 0.0909 0.0531 0.0194 0.0043 0.0005
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.1157 0.1046 0.0687 0.0264 0.0058 0.0006
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
0.1289 0.1205 0.0895 0.0344 0.0081 0.0007
x1calc (eq 4) T = 283.15 K 0.0515 0.0495 0.0164 0.0064 0.0022 0.0001 T = 293.15 K 0.0605 0.0652 0.0265 0.0095 0.0026 0.0002 T = 303.15 K 0.0730 0.0785 0.0390 0.0139 0.0033 0.0004 T = 313.15 K 0.0930 0.0913 0.0526 0.0196 0.0042 0.0005 T = 323.15 K 0.1154 0.1059 0.0668 0.0271 0.0057 0.0006 T = 333.15 K 0.1281 0.1242 0.0842 0.0366 0.0079 0.0007
x1calc (eq 7) 0.0454 0.0458 0.0222 0.0080 0.0017 0.0001 0.0588 0.0590 0.0291 0.0109 0.0025 0.0002 0.0748 0.0747 0.0376 0.0145 0.0034 0.0003 0.0937 0.0932 0.0477 0.0189 0.0047 0.0004 0.1157 0.1147 0.0597 0.0242 0.0062 0.0006 0.1411 0.1394 0.0737 0.0306 0.0081 0.0009
the solubility of the crystalline solute dissolved in the mixture solvents; N
ln x1 = x 2 ln(x1)2 + x3 ln(x1)3 + x 2x3 ∑ Si(x 2 − x3)i i=0
(3)
where Si is the model constant and N can vary from 0 to 3. x2 and x3 are mole fractions of the components in binary solvent calculated in the absence of solute. (x1)i is the saturated mole fraction solubility of the solute in pure solvent i. When N = 2, eq 3 can be rearranged into eq 4. ln x1 = B0 + B1x 2 + B2 x 22 + B3x 2 3 + B4 x 2 4
(4)
B0, B1, B2, B3, and B4 are parameters of this model, which were obtained by least-squares analysis. 1464
dx.doi.org/10.1021/je300173v | J. Chem. Eng. Data 2012, 57, 1463−1467
Journal of Chemical & Engineering Data
Article
Table 2. Mole Fraction Solubility (x1) of 2,6Diaminohexanoic Acid Hydrochloride in Binary Ethanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K x2 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000 0.0000 0.1989 0.4011 0.6090 0.7867 1.0000
x1
x1calc (eq 4)
x1calc (eq 7)
T = 283.15 K 0.0545 0.0172 0.0069 0.0015 0.0002 4.1315·10−6 T = 293.15 K 0.0609 0.0631 0.0423 0.0356 0.0092 0.0130 0.0039 0.0027 0.0003 0.0004 8.7330·10−6 8.4453·10−6 T = 303.15 K 0.0732 0.0730 0.0611 0.0618 0.0247 0.0241 0.0050 0.0051 0.0007 0.0007 1.0531·10−5 1.0557·10−5 T = 313.15 K 0.0931 0.0920 0.0811 0.0860 0.0419 0.0373 0.0065 0.0074 0.0009 0.0008 1.4453·10−5 1.4618·10−5 T = 323.15 K 0.1157 0.1140 0.0983 0.1054 0.0577 0.0502 0.0083 0.0096 0.0011 0.0010 1.8845·10−5 1.9103·10−5 T = 333.15 K 0.1289 0.1274 0.1032 0.1095 0.0628 0.0558 0.0098 0.0112 0.0012 0.0011 2.1214·10−5 2.1459·10−5 0.0520 0.0216 0.0043 0.0024 0.0001 4.3210·10−6
0.0341 0.0260 0.0113 0.0023 0.0002 3.6148·10−6 0.0500 0.0370 0.0159 0.0032 0.0003 5.9373·10−6
Figure 2. Solubilities of 2,6-diaminohexanoic acid hydrochloride in binary methanol (2) + water (3) solvent mixtures: ■, 0.00; red ●, 0.20; green ▲, 0.40; blue ▼, 0.59; pink □, 0.80; yellow ◀, 1.00; the molar fraction of methanol in mixed solvents (solid free).
0.0715 0.0514 0.0219 0.0045 0.0005 9.4378·10−6 0.0998 0.0700 0.0294 0.0062 0.0007 1.4565·10−5 0.1366 0.0934 0.0389 0.0082 0.0010 2.1881·10−5
Figure 3. Solubilities of 2,6-diaminohexanoic acid hydrochloride in binary ethanol (2) + water (3) solvent mixtures: ■, 0.00; red ●, 0.20; green ▲, 0.40; blue ▼, 0.59; pink □, 0.80; yellow ◀, 1.00; the molar fraction of ethanol in mixed solvents (solid free).
0.1834 0.1225 0.0506 0.0108 0.0013 3.2079·10−5
The substitution of (1 − x2) for x3 in eq 5 with N = 2 and subsequent rearrangements result in eq 6.
The CNIBS/R-K model can be used to describe the solubility data and to predict solubility data for different concentrations of a mixed solvent at a fixed temperature. In 1998, Jouyban-Gharamaleki and his co-workers proposed a model which describes the effect of both solvent composition and temperature on the solubility data. This model is one of the theoretical models for calculating the solubility of solute in binary solvents at various temperatures and the different concentration of solvents; it is also called the Jouyban−Acree model:13,14 N
ln x1 = x 2 ln(x1)2 + x3 ln(x1)3 + x 2x3 ∑ i=0
ln x1 = ln(x1)3 + (ln(x1)2 − ln(x1)3 )x 2 + +
T
+
T ( − 2J1 + 8J2 )x 2 3 T
+
( − 4J2 )x 2 4 T
(6)
Equation 6 could be rearranged to eq 7 by introducing a constant term and simplified: T ln x1 = A 0 + A1T + A 2 Tx 2 + A3x 2 + A4 x 2 2 + A5x 2 3
Ji (x 2 − x3)i T
( − J0 + 3J1 − 5J2 )x 2 2
(J0 − J1 + J2 )x 2
+ A 6x 2 4 (5)
(7)
where A0, A1, A2, A3, A4, A5, and A6 are parameters of this model, which were calculated by regressing T ln x1 against T, Tx2, x2, x22, x23, and x24 by least-squares analysis.
where Ji is a model constant, T is the absolute temperature, and the other symbols denote the same meanings as eq 3. 1465
dx.doi.org/10.1021/je300173v | J. Chem. Eng. Data 2012, 57, 1463−1467
Journal of Chemical & Engineering Data
Article
Table 3. Regression Parameters and MD of Equation 4 for 2,6-Diaminohexanoic Acid Hydrochloride in Binary Methanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K T/K
B0
B1
B2
B3
283.15 293.15 303.15 313.15 323.15 333.15
−2.9668 −2.8057 −2.6169 −2.3752 −2.1596 −2.0548
6.1654 5.2050 3.4001 1.3782 0.3058 0.5609
−44.5777 −32.1898 −18.9838 −7.9699 −3.2553 −3.2946
70.0104 43.8712 20.2629 2.9096 −2.4337 −1.5306
B4
MD
−37.7219 −22.4492 −9.9526 −1.5067 0.1146 −0.9309 overall MD = 2.79
6.48 3.91 1.29 0.46 1.40 3.21
Table 4. Regression Parameters and MD of Equation 7 for 2,6-Diaminohexanoic Acid Hydrochloride in Binary Methanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K x2
A0
A1
A2
A3
A4
A5
A6
0.0000 0.1975 0.3984 0.5919 0.7959 1.0000
MD 4.73 6.69 11.70 15.28 8.60 16.00
−2137.43
−0.65
4.46
−5816.85
1092.39
7278.05
−4068.09 overall MD = 10.50
Table 5. Regression Parameters and MD of Equation 4 for 2,6-Diaminohexanoic Acid Hydrochloride in Binary Ethanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K T/K
B0
B1
B2
B3
283.15 293.15 303.15 313.15 323.15 333.15
−2.9092 −2.7632 −2.6170 −2.3862 −2.1712 −2.0607
−8.2122 −1.6970 2.0710 1.9496 0.9236 −0.2160
17.1972 −6.7250 −18.1910 −13.0711 −5.8742 −0.6523
−27.6252 5.0079 20.6714 9.2244 −3.8831 −11.1589
B4
MD
9.1526 −5.5046 −13.3932 −6.8499 0.1392 3.3385 overall MD = 11.37
26.33 19.46 1.40 6.57 7.83 6.62
Table 6. Regression Parameters and MD of Equation 7 for 2,6-Diaminohexanoic Acid Hydrochloride in Binary Ethanol (2) + Water (3) Solvent Mixtures in the Temperature Range from 283.15 K to 333.15 K x2
A0
A1
A2
A3
A4
A5
A6
0.0000 0.1989 0.4011 0.6090 0.7867 1.0000
MD 20.38 14.33 54.65 8.21 26.94 21.14
−3172.72
7.83
−5.81
1657.73
Compared to the CNIBS/R-K model, the Jouyban−Acree model can calculate the solubility with respect to solvent composition and temperature simultaneously. The experimental solubility data of 2,6-diaminohexanoic acid hydrochloride was correlated with eqs 4 and 7. The experimental solubility data (x1) and back-calculated solubility data from these models (x1calc) are listed in Table 1. The ability of the CNIBS/R-K model and the modified Jouyban−Acree model to represent mathematically the experimental solubility of 2,6-diaminohexanoic acid hydrochloride in alcohols (methanol and ethanol) and water mixtures at different temperatures and solvent compositions is summarized in Tables 1 and 2, respectively, in the form of regression parameters and mean deviations in back-calculated solubility.
−2149.42
1090.68
−1623.40 overall MD = 24.28
To evaluate the accuracy and predictability of models, the mean deviation (MD) was introduced and calculated by eq 8: MD = 100
∑ |x1 − x1calc| /x1 N
(8)
where N is the number of experimental points and x1calc denotes the calculated solubility. The solubility data of 2,6-diaminohexanoic acid hydrochloride in binary solvent mixtures at different temperatures with different solvent compositions were well-simulated by the two models according to Tables 3 to 6. Compared to the CNIBS/R-K model, which can only be used for the prediction of solubility for different concentrations of a mixed solvent at one fixed temperature, the modified 1466
dx.doi.org/10.1021/je300173v | J. Chem. Eng. Data 2012, 57, 1463−1467
Journal of Chemical & Engineering Data
Article
(10) Acree, W. E., Jr.; McCargar, J. W.; Zvaigzne, A. L.; Teng, L.-L. Mathematical representation of thermodynamic properties. Carbazole solubilities in binary alkane + dibutyl ether and alkane + tetrahydropyran solvent mixture. Phys. Chem. Liq. 1991, 23, 27−35. (11) Acree, W. E., Jr.; Zvaigzne, A. L. Thermodynamic properties of nonelectrolyte solutions. Part 4. Estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the NIBS and modified Wilson equation. Thermochim. Acta 1991, 178, 151−167. (12) Acree, W. E., Jr. Mathematical representation of thermodynamic properties. Part 2. Derivation of the combined nearly ideal binary solvent (NIBS)/Redlich-Kister mathematical representation from a two-body and three-body interactional mixing model. Thermochim. Acta 1992, 198, 71−79. (13) Jouyban-Gharamaleki, A.; Acree, W. E., Jr. Comparison of Models for Describing Multiple Peaks in Solubility Profiles. Int. J. Pharm. 1998, 167, 177−182. (14) Jouyban-Gharamaleki, A.; Acree, W. E., Jr. In Silico Prediction of Drug Solubility in Water-Ethanol Mixtures Using Jouyban-Acree Model. J. Pharm. Pharm. Sci. 2006, 9, 262−269.
Jouyban−Acree model can be used for the prediction of solubility at different temperatures and different concentrations. The overall MD of the CNIBS/R-K and the modified Jouyban− Acree models indicate that the CNIBS/R-K model can provide a more accurate mathematical representation than the modified Jouyban−Acree model.
■
CONCLUSION The solubility of 2,6-diaminohexanoic acid hydrochloride in binary alcohols (methanol and ethanol) and water solvent mixtures decreased with decreasing temperature and increased with increasing water content in the solvent mixture. The solubility in pure water was the highest, and the solubility in pure ethanol was the lowest. The experimental data can be well-regressed by the CNIBS/R-K model for each temperature, and the modified Jouyban−Acree model can be used at various temperatures and solvent compositions. Furthermore, the CNIBS/R-K model was found to provide a more accurate mathematical representation of the experimental data, while the modified Jouyban− Acree model allowed the calculation of solubility of 2,6diaminohexanoic acid hydrochloride in binary solvent mixtures at an arbitrary mixture composition and arbitrary temperature in the temperature range from 283.15 K to 333.15 K and solvent composition (x2) range from 0.0000 to 1.0000.
■
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Fax: +86-311-88632210. Funding
This research is supported by the Natural Science Foundation of China (No. 21106033), Natural Science Foundation of Hebei (No. 10276736), and Hebei University of Science and Technology (Project No. QD201044). Notes
The authors declare no competing financial interest.
■
REFERENCES
(1) Fitz, D.; Jakschitz, T.; Rode, B. M. The catalytic effect of L- and d-histidine on alanine and lysine peptide formation. J. Inorg. Biochem. Data 2008, 102, 2097−2102. (2) Kimura, E.; Asakura, Y.; Uehara, A.; Inoue, S.; Kawahara, Y.; Yoshihara, Y.; Nakamatsu, T. U.S. Patent 5846790, 1998. (3) Anastassiadis, S. L-Lysine fermentation. Recent Patents Biotechnol. 2007, 1, 11−24. (4) Kalaiselvi, D.; Mohan, K. R.; Jayavel, R. Crystal growth, thermal and optical studies of semiorganic nonlinear optical material: L-Lysine hydrochloride dehydrate. Mater. Res. Bull. 2008, 43, 1829−1835. (5) Zhao, D.; Li, Q.; Duan, E.; Li, H.; Shen, X. Solubility of L-lysine hydrochloride in dimethyl sulfoxide, methanol, ethanol, water, and glycol between (283 and 323) K. J. Chem. Eng. Data 2009, 54, 2126− 2127. (6) Zhao, D. S.; Duan, E. H.; Zhang, X. L. Solubility of triethylenediamine in methanol, ethanol, isopropanol, 1-butanol, and ethyl acetate between 276.15 K and 363.15 K. J. Chem. Eng. Data 2007, 52, 1483−1485. (7) Cheng, F. Q.; Bai, Y.; Liu, C. Thermodynamic analysis of temperature dependence of the crystal growth rate of potassium sulfate. Ind. Eng. Chem. Res. 2006, 45, 6266−6271. (8) The United States Pharmacopeia XXVII; United States Pharmacopeial Convention Inc.: Rockville, MD, 2004; pp 1109−1110. (9) Haitao, Z.; Jingkang, W.; Qiang, N. Solubiliy of sodium cefotaxime in aqueous 2-Propanol mixtures. J. Chem. Eng. Data 2006, 51, 2239−2241. 1467
dx.doi.org/10.1021/je300173v | J. Chem. Eng. Data 2012, 57, 1463−1467
