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Measurement and correlation of the solubility of 6-chloro-3-aminopyridazine in water and binary mixtures of water + ethanol from 293.55 K to 342.95 K
MOLLIQ-03936; No of Pages 6 Journal of Molecular Liquids xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Journal of Molecular Liquids
4Q1
Lei Wang ⁎
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School of Chemistry & Chemical Engineering, Linyi University, Linyi 276005, People's Republic of China
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Measurement and correlation of the solubility of 6-chloro-3-aminopyridazine in water and binary mixtures of water + ethanol from 293.55 K to 342.95 K
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a r t i c l e
i n f o
a b s t r a c t
Article history: Received 17 April 2013 Received in revised form 26 August 2013 Accepted 27 August 2013 Available online xxxx
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The solubility of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary system was measured from 293.55 K to 342.95 K using a synthetic method. The fusion point temperature and enthalpy of fusion were determined by differential scanning calorimetry. The experimental solubility data were regressed by modified Apelblat, λh and polynomial empirical equations. Apelblat and empirical polynomial equations are in good agreement with all experimental data with the root-mean-square deviation being less than 1.69%. In addition, the activity coefficients and molar enthalpy of dissolution 6-chloro-3-aminopyridazine were obtained. © 2013 Published by Elsevier B.V.
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1. Introduction
34 35
6-Chloro-3-aminopyridazine (C4H4ClN3, CAS Registry No. 5469-69-2) is a very important organic intermediate for synthesizing Cefozopran which is the fourth generation cephalosporin [1]. It is also a useful intermediate for synthesizing benzoylpyridazyl ureas which can exhibit larvicidal activities against the generation of chitin of insect larva, and lead to the death of the larvae [2–4]. In industry, the pure 6-chloro-3-aminopyridazine is mainly purified by crystallization and further recrystallization from the solvents such as water, ethanol or mixtures of those [4]. The solubility of 6-chloro-3aminopyridazine in solvents at different temperatures is important for optimizing the crystallization process. However, the solubility data of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures are not available in the previous publications [5]. In this work, the solubility of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures was measured from 293.15 to 338.15 K at atmospheric pressure. The modified Apelblat, λh (Buchowski) and polynomial empirical equations were chosen to regress the measured solid–liquid equilibrium data. The activity coefficients and molar enthalpy of dissolution of 6-chloro-3-aminopyridazine were estimated.
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Keywords: 6-Chloro-3-aminopyridazine Solubility Model Synthetic method Solid–liquid equilibrium
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journal homepage: www.elsevier.com/locate/molliq
⁎ Tel.: +86 539 8766300; fax: +86 539 8766600. E-mail address: [email protected].
2. Experimental
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2.1. Materials
54
6-Chloro-3-aminopyridazine (mass fraction purity N 0.98) supplied by Tongchuang Pharma Co., Ltd., China was purified by recrystallization from an (ethanol + water) mixture. The mass fraction purity of purified sample was analyzed by HPLC (type Shimadzu LC-10AT, Japan), and determined to be more than 0.995. The ethanol used in our experiments is analytical reagent grade, and provided by Tianjin Kewei Chemical Reagent Co., Ltd., China. Redistilled deionized water (specific resistivity N 5 MΩ ⋅ cm) was used throughout.
55 56
2.2. Fusion property measurements
63
The fusion point temperature Tfus and enthalpy of fusion ΔHfus of 6-chloro-3-aminopyridazine were obtained by DSC (differential scanning calorimetry) (Pyris-Diamond DSC, PerkinElmer, USA). The pre-calibration of the instrument was made by indium and tin (Tin: Tfus is 505.10 K, ΔHfus is 60.21 J g−1. Indium: Tfus is 429.75 K, ΔHfus is 28.45 J g−1.) before the equipment was used. About 5 mg of 6-chloro3-aminopyridazine crystalline powder was added to an aluminum crucible of DSC. And then the sample was heated under a nitrogen atmosphere at a heating rate of 2 K/min from 473.15 to 513.15 K. The DSC peak integration was achieved using Origin's Peak Analyzer. The DSC
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0167-7322/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.molliq.2013.08.013
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
57 58 59 60 61 62
65 66 67 68 69 70 71 72 73
The solubility of 6-chloro-3-aminopyridazine was determined by a synthetic method [5–8]. The experimental procedure was described in a previous publication [5], and was slightly improved in this experiment, as shown in Fig. 1. All experiments of measuring solubility were carried out in a 200 mL jacketed glass vessel. In order to prevent solvent evaporation, a condenser was linked directly to the vessel. At the outset of each experiment, a predetermined mass of 6-chloro-3-aminopyridazine and solvent were weighed on a precision electronic balance (type Sartorius BS210S, Germany) with an uncertainty of ±0.0001 g and then were put into the vessel. The mixture was heated slowly by the water circulating via the outer jacket provided by a thermostatically water bath (type CS501, China) to a fixed temperature with continuous stirring by a magnetic stirrer (type 85-2, China). A mercury-in-glass thermometer (type WLB, China) with uncertainty of ±0.05 K was used to measure the temperatures of the solid–liquid mixture. Equilibrium points of 6chloro-3-aminopyridazine were examined by a laser beam penetrating the glass vessel. When solid particles of 6-chloro-3-aminopyridazine just disappeared, the intensity of the laser beam penetrating the glass vessel reached a maximum, an additional 6-chloro-3-aminopyridazine [(2 to 5) mg] was added into the vessel. Repeating the process, until the last addition caused the light intensity being less than 90% of the maximum in 60 min, the mixture was considered as reaching phase equilibrium. The total amount of 6-chloro-3-aminopyridazine added was then recorded. All the solubility data points were determined three or more times, and the relative uncertainties of measurements were below 1 mol%.
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103
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3. Results and discussion
105
3.1. Property evaluation of pure components
106 107
The DSC of 6-chloro-3-aminopyridazine is shown in Fig. 2. The fusion point temperature Tfus and enthalpy of fusion ΔHfus are 493.9 ± 0.5 K[lit. (495.15–496.15) K[9]], and 36.3 ± 0.4 kJ/mol, respectively. Using the property of classical thermodynamics:
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104
ð1Þ
N
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ΔSfus ¼ ΔH fus =T fus
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108 109
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77 78
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2.3. Solubility measurements
Fig. 2. DSC curve of 6-chloro-3-aminopyridazine.
the entropy of fusion ΔSfus of 6-chloro-3-aminopyridazine is obtained, 110 111 and its value is 73.45 J/(mol·K). 112
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3.2.1. Modified Apelblat equation The absolute temperature T dependence of the experimental solubility x1 of 6-chloro-3-aminopyridazine in water and the binary mixtures of water + ethanol can be well correlated by the modified Apelblat equation [10–12]: ln x1 ¼ A þ
B þ ClnT T
114 115 116 117 118
ð2Þ
where A, B and C are adjustable empirical constants.
120 119
3.2.2. λh (Buchowski) equation Buchowski et al. [13,14] used the λh (Buchowski) equation originally to describe the solubility of solid solute in liquid–solid phase equilibrium systems. The model has an excellent effect for correlating the temperature and the solubility. The λh equation is given as:
121
λð1−x1 Þ 1 1 ln 1 þ ¼ λh − x1 T T fus
122 123 124 125
ð3Þ
where Tfus is the fusion point temperature of solid solute, and λ and h 126 127 are the two constants. 128 3.2.3. Polynomial empirical equation When the variable factors such as solute, solvent and pressure are defined, the solubility will change only when temperature changes. So the solubility of solute in solvents can be described by a 4th-order polynomial equation of absolute temperature as follows [15–17]: 2
3
x1 ¼ a þ bT þ cT þ dT þ eT
Fig. 1. Sketch of the experimental determinator for solubility: A, jacketed glass vessel; B, constant pressure funnel; C, mercurial thermometer transistor; D, condensation pipe; E, magnetic stirring apparatus; F, thermostat water bath; G, laser generator; H, photoelectric converter; I, control and digital display.
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3.2. Thermodynamic models
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experiments were repeated three times. The deviation in the temperature is ±0.5 K and in the enthalpy of fusion is no more than 1%.
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L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
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ð4Þ
where a, b, c, d, and e are adjustable equation parameters.
135 134
3.3. Solubility data of 6-chloro-3-aminopyridazine
136
The solubility data of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures at different temperatures are reported in Table 1 and shown in Fig. 3. It can be seen that whether in water or in (water + ethanol) binary mixtures, the solubility of 6chloro-3-aminopyridazine increases with the rise of temperature. At
137 138
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
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L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
Table 1 Solubility x1, activity coefficients γ1 of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol, and the relative deviations RDs of experimental solubility values with the calculated results. 103xλh
102RDλh
t1:4 Q2
T/K
t1:5 t1:6 Q3 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12
w=0 293.65 296.05 303.05 308.65 323.35 328.45 333.15
0.0628 0.0760 0.1335 0.1965 0.5563 0.7473 0.9364
0.0622 0.0762 0.1332 0.2023 0.5410 0.7349 0.9604
0.91 −0.21 0.24 −2.96 2.75 1.67 −2.56
0.0160 0.1044 0.1492 0.2239 0.5260 0.7359 0.9527
74.53 −37.37 −11.73 −14.23 5.44 1.49 −1.74
t1:13 t1:14 t1:15 t1:16 t1:17 t1:18 t1:19 t1:20 t1:21 t1:22 t1:23
w = 0.1001 293.65 298.15 303.35 308.65 313.15 317.85 322.65 327.75 332.95 338.55
0.2763 0.3506 0.4455 0.5793 0.7083 0.8569 1.023 1.251 1.502 1.797
0.2758 0.3482 0.4494 0.5746 0.7002 0.8521 1.031 1.248 1.501 1.810
0.19 0.70 −0.88 0.80 1.15 0.56 −0.70 0.23 0.06 −0.74
0.2985 0.3710 0.4583 0.5900 0.7144 0.8552 1.012 1.233 1.474 1.784
−8.04 −5.81 −2.87 −1.85 −0.86 0.19 1.13 1.46 1.86 2.07
t1:24 t1:25 t1:26 t1:27 t1:28 t1:29 t1:30 t1:31 t1:32 t1:33 t1:34 t1:35
w = 0.2043 293.55 298.55 303.45 307.75 312.65 317.85 322.75 328.05 333.15 339.25 342.95
0.2984 0.3878 0.4795 0.6039 0.7532 0.9773 1.162 1.409 1.716 2.127 2.389
0.2964 0.3862 0.4941 0.6070 0.7589 0.9501 1.161 1.427 1.721 2.126 2.401
0.68 0.40 −3.04 −0.51 −0.76 2.78 0.05 −1.27 −0.29 0.04 −0.51
0.3174 0.4050 0.4873 0.6142 0.7590 0.9855 1.159 1.397 1.698 2.100 2.354
t1:36 t1:37 t1:38 t1:39 t1:40 t1:41 t1:42 t1:43 t1:44 t1:45 t1:46
w = 0.3001 294.15 298.55 303.85 308.15 313.55 319.45 325.65 329.35 333.55 338.15
0.6576 0.8399 1.076 1.413 1.769 2.292 2.959 3.353 3.874 4.4960
0.6522 0.8385 1.113 1.380 1.777 2.292 2.930 3.357 3.884 4.509
0.82 0.16 −3.44 2.34 −0.43 0.00 0.98 −0.11 −0.25 −0.29
t1:47 t1:48 t1:49 t1:50 t1:51 t1:52 t1:53 t1:54 t1:55 t1:56 t1:57 t1:58 t1:59 t1:60 t1:61 t1:62 t1:63 t1:64 t1:65 t1:66 t1:67 t1:68
w = 0.3926 296.05 303.65 308.35 313.65 318.55 323.15 328.15 332.95 337.35
0.9771 1.3920 1.804 2.264 2.890 3.472 4.211 5.160 6.201
0.9703 1.422 1.782 2.279 2.838 3.463 4.269 5.185 6.162
w = 0.4991 293.65 299.25 303.25 307.35 313.25 317.85 324.55 328.15 334.35 338.15
1.548 2.021 2.349 2.873 3.658 4.530 5.717 6.705 8.186 9.468
t1:69 t1:70 t1:71 t1:72 t1:73
w = 0.5963 294.15 297.95 303.65 308.55
1.746 2.153 2.827 3.656
U
γ1
0.0612 0.0789 0.1314 0.1968 0.5572 0.7458 0.9369
2.58 −3.82 1.60 −0.16 −0.16 0.20 −0.05
38.49 35.89 28.71 25.33 17.02 15.62 15.04
0.2768 0.3478 0.4507 0.5781 0.7043 0.8552 1.032 1.247 1.501 1.822
−0.18 0.81 −1.16 0.20 0.57 0.19 −0.79 0.33 0.03 −0.03
8.75 8.63 8.73 8.59 8.61 8.75 8.98 9.07 9.30 9.66
−6.37 −4.44 −1.63 −1.71 −0.77 −0.84 0.27 0.91 1.06 1.28 1.45
0.3001 0.3800 0.4878 0.6044 0.7610 0.9548 1.165 1.425 1.714 2.115 2.395
−0.57 2.00 −1.73 −0.09 −1.04 2.30 −0.25 −1.17 0.15 0.54 −0.26
8.06 7.96 8.12 7.91 7.92 7.67 7.94 8.15 8.20 8.38 8.57
0.6576 0.8436 1.076 1.427 1.776 2.297 2.960 3.347 3.862 4.475
0.00 −0.44 0.03 −0.97 −0.40 −0.22 −0.05 0.17 0.32 0.46
0.6590 0.8311 1.104 1.377 1.783 2.304 2.939 3.360 3.878 4.494
−0.22 1.04 −2.64 2.54 −0.77 −0.51 0.67 −0.22 −0.10 0.04
3.77 3.67 3.70 3.44 3.51 3.50 3.52 3.61 3.69 3.80
0.70 −2.16 1.20 −0.67 1.81 0.27 −1.38 −0.48 0.63
0.9945 1.398 1.813 2.265 2.892 3.467 4.199 5.145 6.185
−1.78 −0.42 −0.50 −0.04 −0.07 0.14 0.29 0.28 0.26
0.9777 1.394 1.784 2.306 2.862 3.461 4.234 5.150 6.202
−0.06 −0.16 1.12 −1.88 0.98 0.32 −0.55 0.19 −0.02
2.79 2.83 2.72 2.75 2.67 2.70 2.74 2.71 2.67
1.541 2.003 2.400 2.872 3.685 4.442 5.770 6.607 8.277 9.458
0.47 0.86 −2.17 0.03 −0.73 1.93 −0.93 1.47 −1.11 0.10
1.559 2.030 2.350 2.877 3.658 4.533 5.709 6.701 8.172 9.455
−0.71 −0.48 −0.04 −0.14 0.02 −0.07 0.13 0.06 0.17 0.15
1.561 1.979 2.378 2.867 3.704 4.471 5.788 6.611 8.258 9.439
−0.81 2.08 −1.24 0.23 −1.26 1.30 −1.25 1.41 −0.88 0.31
1.56 1.58 1.65 1.63 1.67 1.65 1.74 1.72 1.80 1.80
1.736 2.149 2.890 3.651
0.52 0.16 −2.26 0.15
1.754 2.164 2.835 3.670
−0.47 −0.53 −0.31 −0.37
1.779 2.083 2.848 3.684
−1.91 3.21 −0.77 −0.76
1.42 1.39 1.40 1.36
E R
R
E T
103xPE
F
102RDPE
D
R O
P
102RDApel
C
103xApel
N C O
103x1
O
t1:1 t1:2 t1:3
3
(continued on next page)
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
4 t1:74
L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
Table 1 (continued) T/K
103x1
103xApel
102RDApel
103xλh
102RDλh
103xPE
102RDPE
t1:76 t1:77 t1:78 t1:79 t1:80 t1:81 t1:82 t1:83 t1:84 t1:85 t1:86 t1:87 t1:88 t1:89 t1:90 t1:91 t1:92 t1:93 t1:94 t1:95 t1:96 t1:97 t1:98 t1:99 t1:100 t1:101 t1:102 t1:103 t1:104 t1:105 t1:106
w = 0.5963 313.55 318.05 323.55 328.75 333.35 338.45
4.583 5.587 6.645 7.844 9.008 10.68
4.545 5.451 6.679 7.949 9.144 10.53
0.81 2.43 −0.51 −1.33 −1.51 1.40
4.594 5.598 6.641 7.828 8.981 10.64
−0.26 −0.19 0.06 0.21 0.31 0.33
4.624 5.512 6.654 7.837 9.040 10.66
−0.90 1.33 −0.14 0.09 −0.35 0.13
1.35 1.35 1.44 1.51 1.58 1.62
w = 0.6999 293.65 299.25 303.25 307.65 312.75 319.45 325.65 328.55 332.85 338.15
2.246 3.028 3.579 4.471 5.544 6.987 8.612 9.716 10.77 12.81
2.256 3.000 3.629 4.417 5.463 7.052 8.733 9.584 10.92 12.66
−0.45 0.92 −1.39 1.20 1.46 −0.93 −1.41 1.35 −1.39 1.16
2.240 3.034 3.582 4.483 5.557 6.991 8.608 9.715 10.75 12.79
0.26 −0.18 −0.09 −0.26 −0.23 −0.05 0.05 0.01 0.14 0.14
2.251 2.992 3.640 4.450 5.499 7.050 8.682 9.524 10.88 12.78
−0.26 1.22 −1.72 0.48 0.82 −0.90 −0.82 1.98 −1.09 0.17
1.08 1.05 1.08 1.06 1.08 1.15 1.21 1.21 1.29 1.33
w = 0.7859 293.95 298.15 303.85 308.35 312.95 317.95 323.35 328.55 333.05 338.15
2.532 3.108 3.975 4.739 5.509 6.741 8.210 9.647 11.22 12.73
2.551 3.084 3.936 4.721 5.635 6.762 8.145 9.644 11.08 12.86
−0.73 0.78 0.99 0.37 −2.28 −0.32 0.79 0.03 1.26 −0.96
2.529 3.112 3.982 4.745 5.508 6.744 8.213 9.644 11.21 12.72
0.15 −0.11 −0.17 −0.13 0.02 −0.04 −0.04 0.03 0.03 0.12
−0.73 0.78 0.99 0.37 −2.28 −0.32 0.79 0.03 1.26 −0.96
0.97 0.97 1.00 1.04 1.10 1.12 1.15 1.22 1.25 1.34
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P D
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Q2 t1:75
2.551 3.084 3.936 4.721 5.635 6.762 8.145 9.644 11.08 12.86
γ1
142
the same temperature, the solubility of solute increases with the increase of the mass fraction of ethanol in (water + ethanol) binary system, and the solubility value in pure water is the minimum.
145
3.4. Comparison among models
146
The relative deviations (RDs) between experimental solubility values and calculated solubility data are given in Table 1.
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x1;i
R
RD ¼
calcd x1;i −xi
:
R
147
The root-mean-square deviations (RMSDS) between experimental 150 solubility data and calculated values were calculated according to 151 Eq. (6), and are listed in Table 2. 152
T
143 144
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t1:107 w is the mass fraction of ethanol in mixture of ethanol + water; xApel, xλh, and xPE denote the solubility data of solute calculated by Apelblat, λh and empirical polynomial equations, t1:108 respectively; RDApel, RDλh, RDPE represent the relative deviations between experimental solubility values and calculated results regressed respectively by Apelblat, λh and empirical t1:109 polynomial equations.
O C N
0.014 0.013 0.012 0.011 0.010 0.009 0.008 0.007 0.006 0.005 0.004 0.003 0.002 0.001 0.000 290
U
x1
149 148
ð5Þ
2
N x1;i −x1;i 1X RMSD ¼ 4 N i¼1 x1;i calcd
!2 312 5
ð6Þ
where N denotes the number of solubility data points measured in one solvent; xcalcd and x1,i are the calculated solubility value and experimen1,i tal data, respectively. Tables 1 and 2 show that RDs of Apelblat and empirical polynomial equations are less than 3.82%, and RMSDS of the two equations are no more than 1.69%. So both the two models have satisfying fitting effects for all the experimental data. The λh equation can correlate well with the solubility data of solute in (ethanol + water) mixed solvents with the root-mean-square deviation being less than 3.33%, but it does not fit well for regressing the measured solubility data of 6-chloro-3aminopyridazine in pure water. It is conjectured that the reason for poor fitting effects is that the pure water, as the strong polar inorganic solvent, can form a comparatively strong non-ideal solution with 6chloro-3-aminopyridazine [13].
154 153
3.5. Prediction of dissolution properties
168
155 156 157 158 159 160 161 162 163 164 165 166 167
At phase equilibrium, there is a universal solubility model according 169 to basic thermodynamic theory [17,18]: 170 300
310
320
330
340
350
T/K Fig. 3. Solubility x1 of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol (w — the mass fraction of ethanol in mixture of ethanol + water). ■, w = 0; ●, w = 0.1001; ○, w = 0.2043; ★, w = 0.3001; ▲, w = 0.3926; □, w = 0.4991; ▽, w = 0.5963; ☆, w = 0.6999; ◆, w = 0.7859. calculated data based on the modified Apelblat equation. calculated data based on the λh equation. calculated data based on the polynomial empirical equation.
! ΔH tp 1 ΔC p T tp T tp 1 ΔV P−P tp ð7Þ ln − þ1 − − lnx1 γ 1 ¼ − T tp T R R R T T where γ1 represents the activity coefficient of solute and ΔV is the volume difference between phases of solid and liquid. Since the effects of the differences upon molar heat capacity under constant pressure ΔCp and pressure are very little, they can be ignored. The fusion temperature
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
172 171 173 174 175
lnx1 ¼
ΔHfus 1 1 − −lnγ 1 : T fus T R
ð8Þ 179 180 181
For the ideal solution, Eq. (8) can be written as: id
ln x1 ¼
ΔH fus 1 1 − T fus T R
ð9Þ
id
x1 ¼ γ1 x1 :
R O
O
F
where xid 1 denotes experimental mole fraction solubility of solute in ideal condition. The activity coefficient indicating the degree of deviation between real solution and ideal solution [19] is defined as:
P
D id
ΔH fus ΔS fus þ RT R
T C
184 185 186
187 188 189 190 191 192 193
ð11Þ 195 194
E
ln x1 ¼ −
183 182
ð10Þ
The values of activity coefficients of 6-chloro-3-aminopyridazine are shown in Table 1. It can be seen that, at the same temperature, the activity coefficient of 6-chloro-3-aminopyridazine decreases with the increase of the mass fraction of ethanol in the mixture of ethanol + water. Eq. (9) can also be written as:
For the real solution, taking into account the solvent effect, Eq. (13) 196 Q5 can be expressed as [21,22]: 197 lnx1 ¼ −
ΔHdis ΔSdis þ þc RT R
ð12Þ
where ΔHdis and ΔSdis denote enthalpy and entropy of dissolution, respectively; c is a constant. The logarithms of the saturated mole fraction solubility of 6-chloro3-aminopyridazine lnx1 and inverse of temperatures are presented in Fig. 4. The enthalpies of dissolution in Eq. (12) were obtained by regressing analysis on the experimental data, and are listed in Table 3. The positive values of ΔHdis in pure water and (water + ethanol) binary
-4
-5
-6
lnx1
R t2:14 t2:15
R
29.383 0.18666 0.26945 0.33825 0.63664 0.52682 0.82322 0.55757 0.41674 1.69 0.68 1.36 1.39 1.20 1.19 1.35 1.21 1.03
N C O
−29.873 −19.266 −18.110 −34.286 −3.1520 −3.6590 −45.111 −34.095 −17.019 −16114 −10235 −10004 −15175 −5465.8 −5200 −18272 −14584 −8998.4 214.94 136.14 128.86 239.14 29.463 32.026 312.18 237.31 121.37 0 0.1001 0.2043 0.3001 0.3926 0.4991 0.5963 0.6999 0.7859 t2:5 t2:6 t2:7 t2:8 t2:9 t2:10 t2:11 t2:12 t2:13
5
Tfus is close to triple point temperature Ttp, so Ttp and enthalpy of triple 176 point ΔHtp often be replaced by Tm and enthalpy of fusion ΔHfus. Eq. (7) 177 can be simplified as: 178
E
A, B and C are parameters of modified Apelblat model; λ and h are parameters of λh model; a, b, c, d and e are parameters of polynomial empirical equation model; RMSDApel, RMSDλh and RMSDPE denote the root-mean-square deviations between experimental solubility values and calculated results regressed respectively by Apelblat, λh and empirical polynomial equations.
1.15 0.56 1.23 1.26 0.83 1.19 1.34 1.10 0.71 0.04287 −0.00816 −0.01221 −0.00641 −0.18498 −0.07146 −0.33676 −0.10608 0.29954 −3.3545 0.63337 0.96630 0.55205 14.488 5.5915 26.594 8.3423 −23.488 340.11 25699 18711 13426 7620.3 8079.8 5471.7 7135.0 8873.9
32.35 3.33 2.70 0.41 0.65 0.29 0.33 0.17 0.10
−2.05 3.96 5.81 2.81 8.90 3.44 1.60 5.06 1.43
· · · · · · · · ·
10−4 10−5 10−5 10−5 10−4 10−4 10−3 10−4 10−3
4.34 −8.61 −1.24 −5.61 −1.89 −7.37 −3.37 −1.08 3.03
· · · · · · · · ·
10−7 10−8 10−7 10−8 10−6 10−7 10−6 10−6 10−6
−3.44 7.09 9.95 4.38 1.51 5.98 2.67 8.62 −2.40
· · · · · · · · ·
10−10 10−11 10−11 10−11 10−9 10−10 10−9 10−10 10−9
102RMSDPE e d c b
Polynomial empirical equation
a 102RMSDλh h
λh
λ 102RMSDApel C
U Modified Apelblat
A
w t2:4
t2:3
t2:1 t2:2
B
Table 2 Parameters of modified Apelblat, λh and polynomial empirical equations for 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol, and the RMSDs of experimental solubility values with the calculated results.
L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
-7
-8
-9
-10 0.0029
0.0030
0.0031
0.0032
0.0033
0.0034
K/T Fig. 4. Relations between the logarithm of solubility lnx1 of 6-chloro-3-aminopyridazine and absolute temperature T. ■, w = 0; ●, w = 0.1001; ○, w = 0.2043; ★, w = 0.3001; ▲, w = 0.3926; □, w = 0.4991; ▽, w = 0.5963; ☆, w = 0.6999; ◆, w = 0.7859.
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
199 198 200 201 202 203 204 205
6
Table 3 Dissolution enthalpy ΔHdis of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol. w=0
w = 0.1001
w = 0.2043
w = 0.3001
w = 0.3926
w = 0.4991
w = 0.5963
w = 0.6999
w = 0.7859
56.370
34.540
35.396
36.322
37.157
33.650
33.738
31.966
30.247
208
4. Conclusions
209
220 221
The experimental solubility data of 6-chloro-3-aminopyridazine in water and binary system of water + ethanol at temperatures ranging from 293.55 K to 342.95 K at atmospheric pressure. The fusion point temperature and enthalpy of fusion were determined by DSC. The activity coefficients and the molar enthalpy of dissolution of 6-chloro-3-aminopyridazine were obtained. The solubility of 6-chloro-3-aminopyridazine rises with the increase of temperature and the increase of the mass fraction of ethanol in the (water + ethanol) mixture. The modified Apelblat and polynomial empirical equations fit all the experimental solubility data of 6chloro-3-aminopyridazine well. But the measured solubility data of 6-chloro-3-aminopyridazine in pure water could not be regressed well by λh equation.
222 Q7
5. Uncited reference
212 213 214 215 216 217 218 219
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[1] B. Stanovnik, M. Tišler, Tetrahedron 23 (1967) 387–395. [2] I. Ishaaya, D. Degheele, Insecticides with Novel Modes of Action: Mechanism and Application, 1st ed., Springer-Verlag, Berlin, Germany, 1998. [3] H. Oberlander, D.L. Silhacek, Pestic. Sci. 54 (1998) 300–302. [4] R.F. Sun, Y.L. Zhang, F.C. Bi, Q.M. Wang, J. Agric. Food Chem. 57 (2009) 6356–6361. [5] X.X. Cao, J.Q. Liu, T.T. Lv, J.C. Yao, J. Chem. Eng. Data 57 (2012) 1509–1514. [6] X.H. Shi, M. Li, C.R. Zhou, Chin. J. Chem. Eng. 18 (2010) 654–658. [7] H. Matsuda, M. Fujita, K.J. Ochi, Chem. Eng. Data 48 (2003) 1076–1080. [8] K. Ochi, T. Saito, K. Kojima, J. Chem. Eng. Data 41 (1996) 361–364. [9] A. Apelblat, E. Manzurola, J. Chem. Thermodyn. 34 (2002) 1127–1136. [10] S. Polanc, Selective Reduction of Heterocyclic Azides and Hydrazino Compounds to Amines by Molybdenum(III) Species, synthesis, , 1980. 830–831. [11] A.T. Williamson, Trans. Faraday Soc. 40 (1944) 421–436. [12] F.X. Chen, M.R. Zhao, C.C. Liu, F.F. Peng, B.Z. Ren, J. Chem. Thermodyn. 50 (2012) 1–6. [13] H. Buchowski, A. Ksiazcak, S. Pietrzyk, J. Phys. Chem. 84 (1980) 975–979. [14] F.X. Chen, M.R. Zhao, C.C. Liu, F.F. Peng, B.Z. Ren, J. Chem. Thermodyn. 47 (2012) 341–345. [15] X.F. Ding, Q. Tan, Industry Crystallization, Chemical Industry Press, Beijing, China, 1985. [16] X.B. Sun, Study on Engineering Foundation of Comprehensive Utilization of Mixed Dibisic Acids, Zhengzhou University, Zhengzhou, China, 2007. [17] Y. Zhang, L.S. Wang, R.H. Zhou, X.M. Liu, J. Chem. Eng. Data 56 (2011) 2090–2094. [18] M. W. Stanley, Phase Equilibria in Chemical Engineering, Butterworth, New York, 1985. [19] E.M. Gonçalves, M.E. Minas da Piedade, J. Chem. Thermodyn. 47 (2012) 362–371. [20] J.R. Bourne, R.J. Davey, J. McCulloch, Chem. Eng. Sci. 33 (1978) 199–204. [21] H. Yan, Z. Wang, J.K. Wang, Ind. Eng. Chem. Res. 51 (2012) 2808–2813. [22] M. Mirmehrabi, S. Rohani, K.S.K. Murthy, B. Radatus, Int. J. Pharm. 282 (2004) 73–85.
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References
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mixtures reveal that 6-chloro-3-aminopyridazine being dissolved in all the solvents we tested is an entropy-driving process.
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Contents lists available at ScienceDirect
Journal of Molecular Liquids
4Q1
Lei Wang ⁎
5
School of Chemistry & Chemical Engineering, Linyi University, Linyi 276005, People's Republic of China
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Measurement and correlation of the solubility of 6-chloro-3-aminopyridazine in water and binary mixtures of water + ethanol from 293.55 K to 342.95 K
1Q4
6
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 17 April 2013 Received in revised form 26 August 2013 Accepted 27 August 2013 Available online xxxx
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The solubility of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary system was measured from 293.55 K to 342.95 K using a synthetic method. The fusion point temperature and enthalpy of fusion were determined by differential scanning calorimetry. The experimental solubility data were regressed by modified Apelblat, λh and polynomial empirical equations. Apelblat and empirical polynomial equations are in good agreement with all experimental data with the root-mean-square deviation being less than 1.69%. In addition, the activity coefficients and molar enthalpy of dissolution 6-chloro-3-aminopyridazine were obtained. © 2013 Published by Elsevier B.V.
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1. Introduction
34 35
6-Chloro-3-aminopyridazine (C4H4ClN3, CAS Registry No. 5469-69-2) is a very important organic intermediate for synthesizing Cefozopran which is the fourth generation cephalosporin [1]. It is also a useful intermediate for synthesizing benzoylpyridazyl ureas which can exhibit larvicidal activities against the generation of chitin of insect larva, and lead to the death of the larvae [2–4]. In industry, the pure 6-chloro-3-aminopyridazine is mainly purified by crystallization and further recrystallization from the solvents such as water, ethanol or mixtures of those [4]. The solubility of 6-chloro-3aminopyridazine in solvents at different temperatures is important for optimizing the crystallization process. However, the solubility data of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures are not available in the previous publications [5]. In this work, the solubility of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures was measured from 293.15 to 338.15 K at atmospheric pressure. The modified Apelblat, λh (Buchowski) and polynomial empirical equations were chosen to regress the measured solid–liquid equilibrium data. The activity coefficients and molar enthalpy of dissolution of 6-chloro-3-aminopyridazine were estimated.
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Keywords: 6-Chloro-3-aminopyridazine Solubility Model Synthetic method Solid–liquid equilibrium
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journal homepage: www.elsevier.com/locate/molliq
⁎ Tel.: +86 539 8766300; fax: +86 539 8766600. E-mail address: [email protected].
2. Experimental
53
2.1. Materials
54
6-Chloro-3-aminopyridazine (mass fraction purity N 0.98) supplied by Tongchuang Pharma Co., Ltd., China was purified by recrystallization from an (ethanol + water) mixture. The mass fraction purity of purified sample was analyzed by HPLC (type Shimadzu LC-10AT, Japan), and determined to be more than 0.995. The ethanol used in our experiments is analytical reagent grade, and provided by Tianjin Kewei Chemical Reagent Co., Ltd., China. Redistilled deionized water (specific resistivity N 5 MΩ ⋅ cm) was used throughout.
55 56
2.2. Fusion property measurements
63
The fusion point temperature Tfus and enthalpy of fusion ΔHfus of 6-chloro-3-aminopyridazine were obtained by DSC (differential scanning calorimetry) (Pyris-Diamond DSC, PerkinElmer, USA). The pre-calibration of the instrument was made by indium and tin (Tin: Tfus is 505.10 K, ΔHfus is 60.21 J g−1. Indium: Tfus is 429.75 K, ΔHfus is 28.45 J g−1.) before the equipment was used. About 5 mg of 6-chloro3-aminopyridazine crystalline powder was added to an aluminum crucible of DSC. And then the sample was heated under a nitrogen atmosphere at a heating rate of 2 K/min from 473.15 to 513.15 K. The DSC peak integration was achieved using Origin's Peak Analyzer. The DSC
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0167-7322/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.molliq.2013.08.013
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
57 58 59 60 61 62
65 66 67 68 69 70 71 72 73
The solubility of 6-chloro-3-aminopyridazine was determined by a synthetic method [5–8]. The experimental procedure was described in a previous publication [5], and was slightly improved in this experiment, as shown in Fig. 1. All experiments of measuring solubility were carried out in a 200 mL jacketed glass vessel. In order to prevent solvent evaporation, a condenser was linked directly to the vessel. At the outset of each experiment, a predetermined mass of 6-chloro-3-aminopyridazine and solvent were weighed on a precision electronic balance (type Sartorius BS210S, Germany) with an uncertainty of ±0.0001 g and then were put into the vessel. The mixture was heated slowly by the water circulating via the outer jacket provided by a thermostatically water bath (type CS501, China) to a fixed temperature with continuous stirring by a magnetic stirrer (type 85-2, China). A mercury-in-glass thermometer (type WLB, China) with uncertainty of ±0.05 K was used to measure the temperatures of the solid–liquid mixture. Equilibrium points of 6chloro-3-aminopyridazine were examined by a laser beam penetrating the glass vessel. When solid particles of 6-chloro-3-aminopyridazine just disappeared, the intensity of the laser beam penetrating the glass vessel reached a maximum, an additional 6-chloro-3-aminopyridazine [(2 to 5) mg] was added into the vessel. Repeating the process, until the last addition caused the light intensity being less than 90% of the maximum in 60 min, the mixture was considered as reaching phase equilibrium. The total amount of 6-chloro-3-aminopyridazine added was then recorded. All the solubility data points were determined three or more times, and the relative uncertainties of measurements were below 1 mol%.
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103
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3. Results and discussion
105
3.1. Property evaluation of pure components
106 107
The DSC of 6-chloro-3-aminopyridazine is shown in Fig. 2. The fusion point temperature Tfus and enthalpy of fusion ΔHfus are 493.9 ± 0.5 K[lit. (495.15–496.15) K[9]], and 36.3 ± 0.4 kJ/mol, respectively. Using the property of classical thermodynamics:
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ð1Þ
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C
ΔSfus ¼ ΔH fus =T fus
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108 109
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77 78
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2.3. Solubility measurements
Fig. 2. DSC curve of 6-chloro-3-aminopyridazine.
the entropy of fusion ΔSfus of 6-chloro-3-aminopyridazine is obtained, 110 111 and its value is 73.45 J/(mol·K). 112
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3.2.1. Modified Apelblat equation The absolute temperature T dependence of the experimental solubility x1 of 6-chloro-3-aminopyridazine in water and the binary mixtures of water + ethanol can be well correlated by the modified Apelblat equation [10–12]: ln x1 ¼ A þ
B þ ClnT T
114 115 116 117 118
ð2Þ
where A, B and C are adjustable empirical constants.
120 119
3.2.2. λh (Buchowski) equation Buchowski et al. [13,14] used the λh (Buchowski) equation originally to describe the solubility of solid solute in liquid–solid phase equilibrium systems. The model has an excellent effect for correlating the temperature and the solubility. The λh equation is given as:
121
λð1−x1 Þ 1 1 ln 1 þ ¼ λh − x1 T T fus
122 123 124 125
ð3Þ
where Tfus is the fusion point temperature of solid solute, and λ and h 126 127 are the two constants. 128 3.2.3. Polynomial empirical equation When the variable factors such as solute, solvent and pressure are defined, the solubility will change only when temperature changes. So the solubility of solute in solvents can be described by a 4th-order polynomial equation of absolute temperature as follows [15–17]: 2
3
x1 ¼ a þ bT þ cT þ dT þ eT
Fig. 1. Sketch of the experimental determinator for solubility: A, jacketed glass vessel; B, constant pressure funnel; C, mercurial thermometer transistor; D, condensation pipe; E, magnetic stirring apparatus; F, thermostat water bath; G, laser generator; H, photoelectric converter; I, control and digital display.
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3.2. Thermodynamic models
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experiments were repeated three times. The deviation in the temperature is ±0.5 K and in the enthalpy of fusion is no more than 1%.
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4
129 130 131 132 133
ð4Þ
where a, b, c, d, and e are adjustable equation parameters.
135 134
3.3. Solubility data of 6-chloro-3-aminopyridazine
136
The solubility data of 6-chloro-3-aminopyridazine in water and (water + ethanol) binary mixtures at different temperatures are reported in Table 1 and shown in Fig. 3. It can be seen that whether in water or in (water + ethanol) binary mixtures, the solubility of 6chloro-3-aminopyridazine increases with the rise of temperature. At
137 138
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139 140 141
L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
Table 1 Solubility x1, activity coefficients γ1 of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol, and the relative deviations RDs of experimental solubility values with the calculated results. 103xλh
102RDλh
t1:4 Q2
T/K
t1:5 t1:6 Q3 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12
w=0 293.65 296.05 303.05 308.65 323.35 328.45 333.15
0.0628 0.0760 0.1335 0.1965 0.5563 0.7473 0.9364
0.0622 0.0762 0.1332 0.2023 0.5410 0.7349 0.9604
0.91 −0.21 0.24 −2.96 2.75 1.67 −2.56
0.0160 0.1044 0.1492 0.2239 0.5260 0.7359 0.9527
74.53 −37.37 −11.73 −14.23 5.44 1.49 −1.74
t1:13 t1:14 t1:15 t1:16 t1:17 t1:18 t1:19 t1:20 t1:21 t1:22 t1:23
w = 0.1001 293.65 298.15 303.35 308.65 313.15 317.85 322.65 327.75 332.95 338.55
0.2763 0.3506 0.4455 0.5793 0.7083 0.8569 1.023 1.251 1.502 1.797
0.2758 0.3482 0.4494 0.5746 0.7002 0.8521 1.031 1.248 1.501 1.810
0.19 0.70 −0.88 0.80 1.15 0.56 −0.70 0.23 0.06 −0.74
0.2985 0.3710 0.4583 0.5900 0.7144 0.8552 1.012 1.233 1.474 1.784
−8.04 −5.81 −2.87 −1.85 −0.86 0.19 1.13 1.46 1.86 2.07
t1:24 t1:25 t1:26 t1:27 t1:28 t1:29 t1:30 t1:31 t1:32 t1:33 t1:34 t1:35
w = 0.2043 293.55 298.55 303.45 307.75 312.65 317.85 322.75 328.05 333.15 339.25 342.95
0.2984 0.3878 0.4795 0.6039 0.7532 0.9773 1.162 1.409 1.716 2.127 2.389
0.2964 0.3862 0.4941 0.6070 0.7589 0.9501 1.161 1.427 1.721 2.126 2.401
0.68 0.40 −3.04 −0.51 −0.76 2.78 0.05 −1.27 −0.29 0.04 −0.51
0.3174 0.4050 0.4873 0.6142 0.7590 0.9855 1.159 1.397 1.698 2.100 2.354
t1:36 t1:37 t1:38 t1:39 t1:40 t1:41 t1:42 t1:43 t1:44 t1:45 t1:46
w = 0.3001 294.15 298.55 303.85 308.15 313.55 319.45 325.65 329.35 333.55 338.15
0.6576 0.8399 1.076 1.413 1.769 2.292 2.959 3.353 3.874 4.4960
0.6522 0.8385 1.113 1.380 1.777 2.292 2.930 3.357 3.884 4.509
0.82 0.16 −3.44 2.34 −0.43 0.00 0.98 −0.11 −0.25 −0.29
t1:47 t1:48 t1:49 t1:50 t1:51 t1:52 t1:53 t1:54 t1:55 t1:56 t1:57 t1:58 t1:59 t1:60 t1:61 t1:62 t1:63 t1:64 t1:65 t1:66 t1:67 t1:68
w = 0.3926 296.05 303.65 308.35 313.65 318.55 323.15 328.15 332.95 337.35
0.9771 1.3920 1.804 2.264 2.890 3.472 4.211 5.160 6.201
0.9703 1.422 1.782 2.279 2.838 3.463 4.269 5.185 6.162
w = 0.4991 293.65 299.25 303.25 307.35 313.25 317.85 324.55 328.15 334.35 338.15
1.548 2.021 2.349 2.873 3.658 4.530 5.717 6.705 8.186 9.468
t1:69 t1:70 t1:71 t1:72 t1:73
w = 0.5963 294.15 297.95 303.65 308.55
1.746 2.153 2.827 3.656
U
γ1
0.0612 0.0789 0.1314 0.1968 0.5572 0.7458 0.9369
2.58 −3.82 1.60 −0.16 −0.16 0.20 −0.05
38.49 35.89 28.71 25.33 17.02 15.62 15.04
0.2768 0.3478 0.4507 0.5781 0.7043 0.8552 1.032 1.247 1.501 1.822
−0.18 0.81 −1.16 0.20 0.57 0.19 −0.79 0.33 0.03 −0.03
8.75 8.63 8.73 8.59 8.61 8.75 8.98 9.07 9.30 9.66
−6.37 −4.44 −1.63 −1.71 −0.77 −0.84 0.27 0.91 1.06 1.28 1.45
0.3001 0.3800 0.4878 0.6044 0.7610 0.9548 1.165 1.425 1.714 2.115 2.395
−0.57 2.00 −1.73 −0.09 −1.04 2.30 −0.25 −1.17 0.15 0.54 −0.26
8.06 7.96 8.12 7.91 7.92 7.67 7.94 8.15 8.20 8.38 8.57
0.6576 0.8436 1.076 1.427 1.776 2.297 2.960 3.347 3.862 4.475
0.00 −0.44 0.03 −0.97 −0.40 −0.22 −0.05 0.17 0.32 0.46
0.6590 0.8311 1.104 1.377 1.783 2.304 2.939 3.360 3.878 4.494
−0.22 1.04 −2.64 2.54 −0.77 −0.51 0.67 −0.22 −0.10 0.04
3.77 3.67 3.70 3.44 3.51 3.50 3.52 3.61 3.69 3.80
0.70 −2.16 1.20 −0.67 1.81 0.27 −1.38 −0.48 0.63
0.9945 1.398 1.813 2.265 2.892 3.467 4.199 5.145 6.185
−1.78 −0.42 −0.50 −0.04 −0.07 0.14 0.29 0.28 0.26
0.9777 1.394 1.784 2.306 2.862 3.461 4.234 5.150 6.202
−0.06 −0.16 1.12 −1.88 0.98 0.32 −0.55 0.19 −0.02
2.79 2.83 2.72 2.75 2.67 2.70 2.74 2.71 2.67
1.541 2.003 2.400 2.872 3.685 4.442 5.770 6.607 8.277 9.458
0.47 0.86 −2.17 0.03 −0.73 1.93 −0.93 1.47 −1.11 0.10
1.559 2.030 2.350 2.877 3.658 4.533 5.709 6.701 8.172 9.455
−0.71 −0.48 −0.04 −0.14 0.02 −0.07 0.13 0.06 0.17 0.15
1.561 1.979 2.378 2.867 3.704 4.471 5.788 6.611 8.258 9.439
−0.81 2.08 −1.24 0.23 −1.26 1.30 −1.25 1.41 −0.88 0.31
1.56 1.58 1.65 1.63 1.67 1.65 1.74 1.72 1.80 1.80
1.736 2.149 2.890 3.651
0.52 0.16 −2.26 0.15
1.754 2.164 2.835 3.670
−0.47 −0.53 −0.31 −0.37
1.779 2.083 2.848 3.684
−1.91 3.21 −0.77 −0.76
1.42 1.39 1.40 1.36
E R
R
E T
103xPE
F
102RDPE
D
R O
P
102RDApel
C
103xApel
N C O
103x1
O
t1:1 t1:2 t1:3
3
(continued on next page)
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4 t1:74
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Table 1 (continued) T/K
103x1
103xApel
102RDApel
103xλh
102RDλh
103xPE
102RDPE
t1:76 t1:77 t1:78 t1:79 t1:80 t1:81 t1:82 t1:83 t1:84 t1:85 t1:86 t1:87 t1:88 t1:89 t1:90 t1:91 t1:92 t1:93 t1:94 t1:95 t1:96 t1:97 t1:98 t1:99 t1:100 t1:101 t1:102 t1:103 t1:104 t1:105 t1:106
w = 0.5963 313.55 318.05 323.55 328.75 333.35 338.45
4.583 5.587 6.645 7.844 9.008 10.68
4.545 5.451 6.679 7.949 9.144 10.53
0.81 2.43 −0.51 −1.33 −1.51 1.40
4.594 5.598 6.641 7.828 8.981 10.64
−0.26 −0.19 0.06 0.21 0.31 0.33
4.624 5.512 6.654 7.837 9.040 10.66
−0.90 1.33 −0.14 0.09 −0.35 0.13
1.35 1.35 1.44 1.51 1.58 1.62
w = 0.6999 293.65 299.25 303.25 307.65 312.75 319.45 325.65 328.55 332.85 338.15
2.246 3.028 3.579 4.471 5.544 6.987 8.612 9.716 10.77 12.81
2.256 3.000 3.629 4.417 5.463 7.052 8.733 9.584 10.92 12.66
−0.45 0.92 −1.39 1.20 1.46 −0.93 −1.41 1.35 −1.39 1.16
2.240 3.034 3.582 4.483 5.557 6.991 8.608 9.715 10.75 12.79
0.26 −0.18 −0.09 −0.26 −0.23 −0.05 0.05 0.01 0.14 0.14
2.251 2.992 3.640 4.450 5.499 7.050 8.682 9.524 10.88 12.78
−0.26 1.22 −1.72 0.48 0.82 −0.90 −0.82 1.98 −1.09 0.17
1.08 1.05 1.08 1.06 1.08 1.15 1.21 1.21 1.29 1.33
w = 0.7859 293.95 298.15 303.85 308.35 312.95 317.95 323.35 328.55 333.05 338.15
2.532 3.108 3.975 4.739 5.509 6.741 8.210 9.647 11.22 12.73
2.551 3.084 3.936 4.721 5.635 6.762 8.145 9.644 11.08 12.86
−0.73 0.78 0.99 0.37 −2.28 −0.32 0.79 0.03 1.26 −0.96
2.529 3.112 3.982 4.745 5.508 6.744 8.213 9.644 11.21 12.72
0.15 −0.11 −0.17 −0.13 0.02 −0.04 −0.04 0.03 0.03 0.12
−0.73 0.78 0.99 0.37 −2.28 −0.32 0.79 0.03 1.26 −0.96
0.97 0.97 1.00 1.04 1.10 1.12 1.15 1.22 1.25 1.34
O
R O
P D
F
Q2 t1:75
2.551 3.084 3.936 4.721 5.635 6.762 8.145 9.644 11.08 12.86
γ1
142
the same temperature, the solubility of solute increases with the increase of the mass fraction of ethanol in (water + ethanol) binary system, and the solubility value in pure water is the minimum.
145
3.4. Comparison among models
146
The relative deviations (RDs) between experimental solubility values and calculated solubility data are given in Table 1.
C E
x1;i
R
RD ¼
calcd x1;i −xi
:
R
147
The root-mean-square deviations (RMSDS) between experimental 150 solubility data and calculated values were calculated according to 151 Eq. (6), and are listed in Table 2. 152
T
143 144
E
t1:107 w is the mass fraction of ethanol in mixture of ethanol + water; xApel, xλh, and xPE denote the solubility data of solute calculated by Apelblat, λh and empirical polynomial equations, t1:108 respectively; RDApel, RDλh, RDPE represent the relative deviations between experimental solubility values and calculated results regressed respectively by Apelblat, λh and empirical t1:109 polynomial equations.
O C N
0.014 0.013 0.012 0.011 0.010 0.009 0.008 0.007 0.006 0.005 0.004 0.003 0.002 0.001 0.000 290
U
x1
149 148
ð5Þ
2
N x1;i −x1;i 1X RMSD ¼ 4 N i¼1 x1;i calcd
!2 312 5
ð6Þ
where N denotes the number of solubility data points measured in one solvent; xcalcd and x1,i are the calculated solubility value and experimen1,i tal data, respectively. Tables 1 and 2 show that RDs of Apelblat and empirical polynomial equations are less than 3.82%, and RMSDS of the two equations are no more than 1.69%. So both the two models have satisfying fitting effects for all the experimental data. The λh equation can correlate well with the solubility data of solute in (ethanol + water) mixed solvents with the root-mean-square deviation being less than 3.33%, but it does not fit well for regressing the measured solubility data of 6-chloro-3aminopyridazine in pure water. It is conjectured that the reason for poor fitting effects is that the pure water, as the strong polar inorganic solvent, can form a comparatively strong non-ideal solution with 6chloro-3-aminopyridazine [13].
154 153
3.5. Prediction of dissolution properties
168
155 156 157 158 159 160 161 162 163 164 165 166 167
At phase equilibrium, there is a universal solubility model according 169 to basic thermodynamic theory [17,18]: 170 300
310
320
330
340
350
T/K Fig. 3. Solubility x1 of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol (w — the mass fraction of ethanol in mixture of ethanol + water). ■, w = 0; ●, w = 0.1001; ○, w = 0.2043; ★, w = 0.3001; ▲, w = 0.3926; □, w = 0.4991; ▽, w = 0.5963; ☆, w = 0.6999; ◆, w = 0.7859. calculated data based on the modified Apelblat equation. calculated data based on the λh equation. calculated data based on the polynomial empirical equation.
! ΔH tp 1 ΔC p T tp T tp 1 ΔV P−P tp ð7Þ ln − þ1 − − lnx1 γ 1 ¼ − T tp T R R R T T where γ1 represents the activity coefficient of solute and ΔV is the volume difference between phases of solid and liquid. Since the effects of the differences upon molar heat capacity under constant pressure ΔCp and pressure are very little, they can be ignored. The fusion temperature
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
172 171 173 174 175
lnx1 ¼
ΔHfus 1 1 − −lnγ 1 : T fus T R
ð8Þ 179 180 181
For the ideal solution, Eq. (8) can be written as: id
ln x1 ¼
ΔH fus 1 1 − T fus T R
ð9Þ
id
x1 ¼ γ1 x1 :
R O
O
F
where xid 1 denotes experimental mole fraction solubility of solute in ideal condition. The activity coefficient indicating the degree of deviation between real solution and ideal solution [19] is defined as:
P
D id
ΔH fus ΔS fus þ RT R
T C
184 185 186
187 188 189 190 191 192 193
ð11Þ 195 194
E
ln x1 ¼ −
183 182
ð10Þ
The values of activity coefficients of 6-chloro-3-aminopyridazine are shown in Table 1. It can be seen that, at the same temperature, the activity coefficient of 6-chloro-3-aminopyridazine decreases with the increase of the mass fraction of ethanol in the mixture of ethanol + water. Eq. (9) can also be written as:
For the real solution, taking into account the solvent effect, Eq. (13) 196 Q5 can be expressed as [21,22]: 197 lnx1 ¼ −
ΔHdis ΔSdis þ þc RT R
ð12Þ
where ΔHdis and ΔSdis denote enthalpy and entropy of dissolution, respectively; c is a constant. The logarithms of the saturated mole fraction solubility of 6-chloro3-aminopyridazine lnx1 and inverse of temperatures are presented in Fig. 4. The enthalpies of dissolution in Eq. (12) were obtained by regressing analysis on the experimental data, and are listed in Table 3. The positive values of ΔHdis in pure water and (water + ethanol) binary
-4
-5
-6
lnx1
R t2:14 t2:15
R
29.383 0.18666 0.26945 0.33825 0.63664 0.52682 0.82322 0.55757 0.41674 1.69 0.68 1.36 1.39 1.20 1.19 1.35 1.21 1.03
N C O
−29.873 −19.266 −18.110 −34.286 −3.1520 −3.6590 −45.111 −34.095 −17.019 −16114 −10235 −10004 −15175 −5465.8 −5200 −18272 −14584 −8998.4 214.94 136.14 128.86 239.14 29.463 32.026 312.18 237.31 121.37 0 0.1001 0.2043 0.3001 0.3926 0.4991 0.5963 0.6999 0.7859 t2:5 t2:6 t2:7 t2:8 t2:9 t2:10 t2:11 t2:12 t2:13
5
Tfus is close to triple point temperature Ttp, so Ttp and enthalpy of triple 176 point ΔHtp often be replaced by Tm and enthalpy of fusion ΔHfus. Eq. (7) 177 can be simplified as: 178
E
A, B and C are parameters of modified Apelblat model; λ and h are parameters of λh model; a, b, c, d and e are parameters of polynomial empirical equation model; RMSDApel, RMSDλh and RMSDPE denote the root-mean-square deviations between experimental solubility values and calculated results regressed respectively by Apelblat, λh and empirical polynomial equations.
1.15 0.56 1.23 1.26 0.83 1.19 1.34 1.10 0.71 0.04287 −0.00816 −0.01221 −0.00641 −0.18498 −0.07146 −0.33676 −0.10608 0.29954 −3.3545 0.63337 0.96630 0.55205 14.488 5.5915 26.594 8.3423 −23.488 340.11 25699 18711 13426 7620.3 8079.8 5471.7 7135.0 8873.9
32.35 3.33 2.70 0.41 0.65 0.29 0.33 0.17 0.10
−2.05 3.96 5.81 2.81 8.90 3.44 1.60 5.06 1.43
· · · · · · · · ·
10−4 10−5 10−5 10−5 10−4 10−4 10−3 10−4 10−3
4.34 −8.61 −1.24 −5.61 −1.89 −7.37 −3.37 −1.08 3.03
· · · · · · · · ·
10−7 10−8 10−7 10−8 10−6 10−7 10−6 10−6 10−6
−3.44 7.09 9.95 4.38 1.51 5.98 2.67 8.62 −2.40
· · · · · · · · ·
10−10 10−11 10−11 10−11 10−9 10−10 10−9 10−10 10−9
102RMSDPE e d c b
Polynomial empirical equation
a 102RMSDλh h
λh
λ 102RMSDApel C
U Modified Apelblat
A
w t2:4
t2:3
t2:1 t2:2
B
Table 2 Parameters of modified Apelblat, λh and polynomial empirical equations for 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol, and the RMSDs of experimental solubility values with the calculated results.
L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
-7
-8
-9
-10 0.0029
0.0030
0.0031
0.0032
0.0033
0.0034
K/T Fig. 4. Relations between the logarithm of solubility lnx1 of 6-chloro-3-aminopyridazine and absolute temperature T. ■, w = 0; ●, w = 0.1001; ○, w = 0.2043; ★, w = 0.3001; ▲, w = 0.3926; □, w = 0.4991; ▽, w = 0.5963; ☆, w = 0.6999; ◆, w = 0.7859.
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013
199 198 200 201 202 203 204 205
6
Table 3 Dissolution enthalpy ΔHdis of 6-chloro-3-aminopyridazine in pure water and binary mixtures of water + ethanol. w=0
w = 0.1001
w = 0.2043
w = 0.3001
w = 0.3926
w = 0.4991
w = 0.5963
w = 0.6999
w = 0.7859
56.370
34.540
35.396
36.322
37.157
33.650
33.738
31.966
30.247
208
4. Conclusions
209
220 221
The experimental solubility data of 6-chloro-3-aminopyridazine in water and binary system of water + ethanol at temperatures ranging from 293.55 K to 342.95 K at atmospheric pressure. The fusion point temperature and enthalpy of fusion were determined by DSC. The activity coefficients and the molar enthalpy of dissolution of 6-chloro-3-aminopyridazine were obtained. The solubility of 6-chloro-3-aminopyridazine rises with the increase of temperature and the increase of the mass fraction of ethanol in the (water + ethanol) mixture. The modified Apelblat and polynomial empirical equations fit all the experimental solubility data of 6chloro-3-aminopyridazine well. But the measured solubility data of 6-chloro-3-aminopyridazine in pure water could not be regressed well by λh equation.
222 Q7
5. Uncited reference
212 213 214 215 216 217 218 219
223
224
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[20]
E
210 211 Q6
References
F
mixtures reveal that 6-chloro-3-aminopyridazine being dissolved in all the solvents we tested is an entropy-driving process.
D
207
O
206
ΔHdis//kJ mol−1
R O
t3:3 t3:4
P
t3:1 t3:2
L. Wang / Journal of Molecular Liquids xxx (2013) xxx–xxx
U
N
C
O
R
R
E
C
T
255
Please cite this article as: L. Wang, J. Mol. Liq. (2013), http://dx.doi.org/10.1016/j.molliq.2013.08.013