Measurement and Correlation of Solubilities of 4-Amino-3, 6

Apr 10, 2014 - Jin-Qiang Liu,* Qiao-Yun Bai, Xin-Xiang Cao,* Dong-Feng Hong, Yao-Yao Li, Sha Wu, and Li-Yue Zhang. College of Chemistry and Chemical ...
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Measurement and Correlation of Solubilities of 4‑Amino-3,6dichloropyridazine in Ethanol + Water Mixtures from (303.15 to 323.15) K Jin-Qiang Liu,* Qiao-Yun Bai, Xin-Xiang Cao,* Dong-Feng Hong, Yao-Yao Li, Sha Wu, and Li-Yue Zhang College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang, 471022 P. R. China ABSTRACT: The solubilities of 4-amino-3,6-dichloropyridazine (ADCP) in an ethanol + water mixture were determined from (303.15 to 323.15) K with an interval of 2.5 K at atmospheric pressure using the synthetic method with a laser monitoring observation technique. The solubility of ADCP was found to increase with the rise of temperature and the mole fraction of ethanol. The experimental solubilities were regressed with different models including the modified Apelblat equation, combined nearly ideal binary solvent/Redlich−Kister (CNIBS/R-K) model, and the hybrid model. For the six mixture solvents studied, all of the mean percentage deviations with Apelblat equation are less than 1.7 %.

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INTRODUCTION Pyridazines are of great organic1,2 and inorganic3−7 interests as well as an important intermediate in the synthesis of pharmaceuticals. 8 − 2 1 4-Amino-3,6-dichloropyridazine (C4H3N3Cl2, CAS registry no. 823-58-5, molecular weight 164.0), with its chemical structure shown in Figure 1, is

synthesis with high purity. Because the initial reaction solvent is ethanol and the recrystillization solvent is water, we hypothesized that ethanol and water mixture is suitable solvent for the recrystillization of ADCP for ethanol and water are miscible. However, to the best knowledge of us, no accurate solubilities of ADCP in ethanol and water mixtures had been reported in literatures. In this study, the solubilities of ADCP in several different proportions of binary ethanol + water mixtures are measured at temperatures ranging from (303.15 to 323.15) K with 2.5 K interval, obtained by a synthetic method employing laser monitoring observation technique. The measured experimental solubility data are correlated by the modified Apelblat equation, the combined nearly ideal binary solvent/Redlich−Kister (CNIBS/R-K, General Single) model, and the hybrid model.

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EXPERIMENTAL SECTION Materials. A white crystalline of ADCP was purchased from J&K Chemical Co., Ltd. and synthesized following literature procedure.22 It was further purified by twice recrystallization from the solution of ethanol, and its purity was determined by high-performance liquid chromatography (HPLC) to be 0.998 in mass fraction. Urea of analytically pure grade (> 99.5 % in mass fraction) was purchased from Tianjin Damao Chemical Reagent Co., Ltd. of China. Double-distilled water was used in our experiment. Analytically pure anhydrous ethanol (> 99.5 % in mass fraction) was purchased from Tianjin Kermel Chemical Reagent Co., Ltd. of China, dried, and stored over 3 Å

Figure 1. Chemical structure of 4-amino-3,6-dichloropyridazine.

synthesized from the amination of 3,4,6-trichloropyridazine in ethanol solution saturated with NH3.22 This process requires anhydrous ethanol solution. Pure ADCP is obtained from the recrystallization of crude product in water.22 However, the solubility of ADCP in water is so little that plentiful water is necessary for the purification of crude product, which means a great waste of water. Due to the crucial role of ADCP in the synthesis of medicals, it is very necessary to find a suitable solvent for its separation and subsequent recrystillization to realize the industrial scale © 2014 American Chemical Society

Received: November 6, 2013 Accepted: April 4, 2014 Published: April 10, 2014 1448

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molecular sieves and was used without further purification. The mass fraction of water in ethanol was less than 0.002, as determined by the Karl Fischer method. Apparatus and Procedure. The solubility is measured by a synthetic method. All of the apparatuses including composition and type are exactly the same as our previous work.23−25 Briefly, all experiments were carried out in an about 200 mL jacketed glass vessel with a magnetic stirrer (type 85-3, China), and a mercury-in-glass thermometer (type WLB, China) with uncertainty of ± 0.05 K. A condenser was introduced to the apparatuses to prevent the evaporation of the solvent. Predetermined masses of ADCP and solvent were weighted on a precision electronic balance (type Sartorius BS210S, Germany) with the uncertainty of ± 0.0001 g, and introduced into the vessel. A laser beam was employed to observe the dissolution of the solid. The solid + liquid mixture was continuously stirred, and was heated slowly by the circulating water via the outer jacket provided by a thermostatically water bath (type CS501, China) to a fixed temperature. Along with the increase of the temperature of the mixture, solid particles dissolved continuously, and the intensity of the laser beam penetrating the glass vessel gradually increased. The light signal transmitted through the vessel was collected by a detector to guarantee the dissolution of the last crystal. When ADCP just disappeared, the intensity of the laser beam reached a maximum. Then an additional portion of ADCP (2 to 5) mg was transferred into the vessel. Repeat 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 consumption of ADCP was recorded. Every solubility data point was repeated at least three times, and the relative uncertainties of measurements were lower than 1 % mole percent. The saturated mole fraction solubility (x1) is calculated from eq 1 while the initial mole faction composition of ethanol (x2) can be obtained from eq 2. x1 =

m1/M1 ∑ mi /Mi

(1)

x2 =

m2 /M 2 m2 /M 2 + m3 /M3

(2)

OMPD =

x1 − x1cal x1

100 N

∑

RESULTS AND DISCUSSION Experimental Solubility Data. The accuracy of the experimental method described above was confirmed by comparing our solubility data of urea in water with those in literature.26 As seen in Table 1, great agreement of our experimental data with reported values demonstrated that our experimental method was accurate and reliable. Table 1. Comparison of the Solubility Data of Urea in Water between Literature (xref) and Our Experiments (x), at Temperature T and Pressure p = 0.1 MPaa T/°C

x/g (100 g water)−1

xref/g (100 g water)−1

100RD

MPD

1.8 10.3 15.5 21.0 25.5 30.5 39.7 50.1 60.0

70.21 85.95 96.88 110.1 120.8 135.1 164.1 205.0 259.2

70.12 85.86 97.00 109.6 121.0 135.4 163.9 205.2 258.9

0.11 0.083 −0.096 0.34 −0.12 −0.16 0.082 −0.060 0.065

0.124

a

Standard uncertainties u are u(T) = 0.05 K, u(x) = 0.001.

The measured solubility data of ADCP in different binary solvents at temperature ranging from (303.15 to 313.15) K with 2.5 K interval were presented in Table 2 with the ideal solubility in mole fraction of the solute calculated from eqs 6, 8, and 11, where T represents the absolute temperature. To show the experimental values clearly, the plot of the solubility data of ADCP in these binary solvents at the temperature range of (303.15−323.15) K was drawn in Figure 2. From Table 2 and Figure 2, it can be seen that the solubility of ADCP with given initial solvent composition increases with increasing temperature, which means that the process of ADCP dissolving in binary ethanol + water mixtures in the experimental temperature range are endothermic. At a certain constant temperature, the solubility of ADCP increases with the increase of the mole fraction of ethanol in the solvent mixtures, which indicates that the subtle variation of physical properties of water and ethanol were done after some content of ethanol added and that ethanol + water mixture was suitable cosolvent for the recrystillization of ADCP. Data Correlation. Modified Apelblat Equation. The relationship between mole fraction solubility and temperature is described by the modified Apelblat equation, which has been widely used in the correlation of solubility data of different substances.27,28 The temperature dependence of solubility of ADCP in different binary ethanol + water mixtures was correlated with the modified Apelblat eq 6: B ln x1 = A + + C ln(T /K ) (6) T /K

(3)

x1 − x1cal x1

(5)

1

■

The mean percentage deviation (MPD) defined in eq 4 was employed to evaluate the agreement between the experimental data and the model predictions. MPD =

N

∑ MPD

where n is the number of MPDs.

where mi and Mi (i = 1, 2, and 3) represent the mass and molecular weight of the solute ADCP, ethanol, and water, respectively. The relative deviation (RD) between the calculated and experimental values is calculated from eq 3. RD =

1 N

(4)

where x1 is the calculated mole fraction solubility of the solute in binary mixtures; T is the absolute temperature; A, B, and C are the empirical model parameters. The values of A, B, and C are listed in Table 3, together with MPD and OMPD.

To evaluate the accuracy and predictability of the three models, the mean value of MPDs was denoted as overall MPD (OMPD) and is defined by eq 5. 1449

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Table 2. Experimental Mole Solubilities of 4-Amino-3,6-dichloropyridazine (x1) in Binary Ethanol + Water Mixtures at a Temperature Ranging from 303.15 to 323.15 K at 0.1 MPa and Calculated Solubility (xcal 1 ) Obtained from eqs 6, 8, and 11 T/K

103x1b

c 103xcal,1 1

d 103xcal,2 1

100RD

100RD

e 103xcal,3 1

100RD

f

x2 = 0.1979 303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

0.049 0.118 0.243 0.436 0.695 0.987 1.279 1.439 1.513

0.050 0.118 0.243 0.441 0.709 1.013 1.292 1.476 1.516

−2.92 −0.23 0.13 −1.06 −1.94 −2.64 −1.03 −2.61 −0.16

0.047 0.113 0.234 0.421 0.672 0.962 1.251 1.412 1.494

4.65 4.00 3.81 3.56 3.41 2.54 2.21 1.84 1.29

0.074 0.121 0.197 0.314 0.496 0.771 1.185 1.799 2.697

−50.74 −3.08 19.10 27.92 28.70 21.85 7.34 −25.02 −78.26

0.189 0.371 0.648 1.047 1.594 2.175 2.829 3.445 4.034

−11.20 −9.51 −9.04 −8.41 −8.03 −5.90 −5.10 −4.22 −2.94

0.282 0.414 0.599 0.852 1.197 1.657 2.264 3.053 4.065

−65.89 −22.11 −0.66 11.74 18.90 19.33 15.91 7.64 −3.73

5.088 6.551 8.322 10.167 11.926 13.285 14.062 15.196 16.098 x2f = 0.7018 12.274 14.132 15.990 17.612 18.820 20.231 20.567 21.084 21.558 x2f = 0.8119 9.715 11.343 12.642 13.933 15.274 17.043 18.340 19.553 21.047 x2f = 1 17.439 18.189 18.819 19.475 20.538 21.455 22.174 23.133 24.111

14.25 12.34 11.79 11.05 10.59 7.97 6.95 5.82 4.11

5.535 6.970 8.610 10.440 12.432 14.546 16.733 18.934 21.085

6.72 6.73 8.73 8.66 6.80 −0.77 −10.73 −17.35 −25.59

−25.37 −21.36 −20.25 −18.78 −17.88 −12.98 −11.17 −9.21 −6.37

9.408 11.210 13.032 14.794 16.412 17.804 18.901 19.648 20.014

3.90 3.74 1.99 0.23 −2.80 0.57 −2.16 −1.78 1.24

13.96 12.08 11.54 10.81 10.36 7.80 6.80 5.69 4.03

11.264 13.219 15.090 16.770 18.158 19.171 19.752 19.876 19.546

0.24 −2.47 −5.59 −7.35 −6.56 −3.71 −0.38 4.14 10.87

−1.97 −1.69 −1.60 −1.50 −1.43 −1.06 −0.92 −0.76 −0.54

15.042 17.465 19.613 21.324 22.471 22.972 22.804 22.003 20.652

12.04 2.36 −5.89 −11.13 −10.98 −8.20 −3.79 4.16 13.89

x2f = 0.2854 303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

0.170 0.339 0.595 0.966 1.475 2.054 2.692 3.305 3.919

0.176 0.338 0.598 0.979 1.487 2.101 2.764 3.397 3.905

−3.38 0.48 −0.51 −1.38 −0.81 −2.28 −2.70 −2.77 0.35

303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

5.933 7.473 9.434 11.429 13.338 14.435 15.112 16.135 16.789

5.944 7.653 9.489 11.340 13.080 14.575 15.708 16.391 16.575

−0.17 −2.42 −0.58 0.78 1.94 −0.97 −3.95 −1.59 1.27

303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

9.790 11.645 13.297 14.828 15.964 17.906 18.501 19.305 20.266

9.890 11.529 13.178 14.776 16.264 17.582 18.678 19.510 20.048

−1.02 0.99 0.90 0.35 −1.88 1.81 −0.96 −1.06 1.07

303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

11.291 12.901 14.291 15.622 17.040 18.484 19.677 20.733 21.930

11.357 12.783 14.230 15.670 17.076 18.421 19.678 20.820 21.826

−0.58 0.91 0.43 −0.31 −0.22 0.34 0.00 −0.42 0.48

303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

17.102 17.887 18.522 19.188 20.248 21.230 21.972 22.957 23.983

17.098 17.810 18.562 19.354 20.188 21.068 21.995 22.971 24.000

0.02 0.43 −0.22 −0.86 0.29 0.76 −0.10 −0.06 −0.07

x2f = 0.5007

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Table 2. continued a

b c cal,1 standard uncertainties u are u(T) = 0.05K, u(x1) = 0.001, u(xcal 1 ) = 0.001, and u(x2) = 0.001. x1 represents the experimental solubility data. x1 d cal,2 represents back-calculated solubility data by variant 1 of the modified Apelblat equation. x1 represents back-calculated solubility data by variant 2 represents back-calculated solubility data by variant 3 of the hybrid model. fx2 is the mole fraction of of the general single (CNIBS/R-K) model. excal,3 1 ethanol in a mixed solvent.

in which x1 stands for the mole fraction solubility of the solute in binary mixtures. Bi (i = 0, 1, 2, 3, and 4) are the model parameters and the values of Bi are collected in Table 4, together with MPD and OMPD. x2 represents the initial mole fraction composition of the binary solvent mixtures. The Hybrid Model. Replacing ln(x1)B,T and ln(x1)C,T in eq 7 with the corresponding values from the modified Apelblat equation as follows:

ln(x1)C,T = a 2 +

b2 + c 2 ln T T

(10)

x0 A2 (x 0)2 + A3 ln T + A4 x 20 + A5 2 + A 6 2 T T T 0 3 0 4 (x ) (x ) + A 7 2 + A8 2 + +A 9x 20 ln T (11) T T

where Ai (i = 1 to 9) are the model parameters calculated by a least-squares analysis, are listed in Table 5, together with MPD and OMPD. It is seen from Tables 2 to 5 that the calculated solubilities by the modified Apelblat eq 6 are in good agreement with the experimental values in most cases, while both CNIBS/R-K model (8) and the Hybrid model (11) always give worse correlation results than modified Apelblat equation. The MPD is always less than 2 % with modified Apelblat equation, and the OMPDs of eqs 8 and 11 are 7.67 and 12.08, respectively, which means they are not suitable for the calculation of the solubility data.

ln x1 = x0B ln(x1)B,T + x0C ln(x1)C,T + x0Bx0C N

(7)

where Si is a constant and N is the number of solvents and equals 2 in this work. xB0 and xC0 represents to the initial mole fraction composition of the binary solvent calculated as if the solute was not present. (x1)B,T and (x1)C,T denote the mole fraction solubility of the solute in monosolvent B and C, respectively. Equation 7 can be simplified as eq 8 called the general single model30 as follows: ln x1 = B0 + B1x 2 + B2 x 22 + B3x 23 + B4 x 24

(9)

ln x1 = A1 +

Combined Nearly Ideal Binary Solvent/Redlich−Kister (CNIBS/R-K) Model. The relationship between mole fraction solubility and mole fraction of binary solvent at constant temperature in the solid−liquid equilibrium is described with CNIBS/R-K model, which was proposed by Acree and Zvaigzne29 and had the equation formula as follows:

i=0

b1 + c1 ln T T

The hybrid model can be obtained from combining eqs 7, 9, and 10 together and further rearrangements, which was proposed by Zhou31 and had the equation formula as follows:

Figure 2. Mole fraction solubilities x1 in different ethanol + water mixtures: w ■, 0.1979; ●, 0.2854; ▲, 0.5007; ▼, 0.7018; ⧫, 0.8119; ◀, 1; ―, solubility curve calculated from the modified Apelblat equation.

∑ Si(x0B − x0C)i

ln(x1)B,T = a1 +

■

CONCLUSIONS The solubilities of ADCP in ethanol + water mixture ranging from 0.2 to 1 have been determined from (303.15 to 323.15) K with an interval of 2.5 K by a synthetic method. The solubilities in all solvent mixtures increase with the rise of temperature.

(8)

Table 3. Parameters of the Modified Apelblat Equation for ADCP in Different Solvent Mixturea parameters x2b

A/103

B/104

C/102

R2

MPDc

OMPDd

0.1979 0.2854 0.5007 0.7018 0.8119 1

11.776 ± 0.161 7.1198 ± 0.194 3.445 ± 0.256 1.7642 ± 0.177 9.4293 ± 0.069 −0.11492 ± 0.063

−56.082 ± 0.749 −34.351 ± 0.900 −16.430 ± 1.19 −8.4976 ± 0.821 −46.656 ± 0.321 0.37350 ± 0.294

−17.389 ± 0.239 −10.492 ± 0.288 −5.0896 ± 0.380 −2.6048 ± 0.262 −1.3887 ± 0.103 0.17243 ± 0.094

0.99988 0.99978 0.99661 0.99649 0.99935 0.99795

1.41 1.63 1.52 1.11 0.41 0.31

1.07

a

Standard uncertainties u are u(x2) = 0.001, u(MPD) = 0.01, and u(OMPD) = 0.01. bx2 represents the mole fraction of ADCP in the ethanol + water mixture. cMPD denotes the mean percentage deviation. dOMPD denotes the mean value of MPDs. 1451

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Table 4. Parameters of the CNIBS/R-K Model for ADCP at Temperatures Ranging from (303.15 to 323.15) Ka parameters T/K 303.15 305.65 308.15 310.65 313.15 315.65 318.15 320.65 323.15

B0

B1

B2

B3

B4

R2

MPDb

OMPDc

−10.062 ± 4.6163 −8.9279 ± 3.9525 −7.8531 ± 3.7653 −7.2979 ± 3.5139 −7.3030 ± 3.3592 −7.2922 ± 2.4923 −7.7789 ± 2.162 −8.6622 ± 1.7995 −9.7894 ± 1.2617

−19.339 ± 41.124 −18.938 ± 35.211 −20.205 ± 33.543 −18.349 ± 31.303 −12.693 ± 29.926 −8.2522 ± 22.203 −0.290 59 ± 19.260 9.2223 ± 16.031 20.268 ± 11.240

137.02 ± 121.59 124.94 ± 104.11 120.92 ± 99.173 109.36 ± 92.550 87.866 ± 88.478 69.971 ± 65.645 42.614 ± 56.944 14.125 ± 47.397 −18.414 ± 33.232

−205.33 ± 145.40 −184.88 ± 124.50 −176.26 ± 118.60 −159.73 ± 110.68 −132.25 ± 105.81 −108.12 ± 78.503 −73.597 ± 68.098 −40.264 ± 56.681 −2.1690 ± 39.741

93.661 ± 60.433 83.800 ± 51.744 79.430 ± 49.293 72.075 ± 46.001 60.496 ± 43.977 49.854 ± 32.628 35.243 ± 28.304 21.812 ± 23.558 6.3796 ± 16.517

0.982 11

11.90

7.67

0.982 43

10.16

0.978 99

9.67

0.976 31

9.02

0.972 57

8.62

0.981 71

6.37

0.983 62

5.52

0.987 65

4.59

0.993 70

3.21

a

standard uncertainties u are u(T) = 0.05 K, u(MPD) = 0.01, and u(OMPD) = 0.01. bMPD denotes the mean percentage deviation. cOMPD denotes the mean value of MPDs.

Funding

Table 5. Parameters of the Hybrid Model for ADCP in the Selected Solvent Mixtures at the Temperatures Ranging from (303.15 to 323.15) Ka parameters

nonlinear regression values

A1 A2 A3 A4 A5 A6 A7 A8 A9 (O)MPDb

−30.1367 −34676.1 −44.8118 3177.54 −29601.7 −177 390 134 389 −40223.2 −466.386 12.08

This work was financially funded by the National Natural Science Foundation of Henan Province (21172105) and The Low Carbon Fatty Amine Engineering Research Center of Zhejiang Province (2012E10033). Notes

The authors declare no competing financial interest.

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a

Standard uncertainties u are u(T) = 0.05 K, and u((O)MPD) = 0.01. MPD denotes the mean percentage deviation or the mean value of the mean percentage deviation.

b

The modified Apelblat, General Single (CNIBS/R-K) model and the hybrid model based on solid−liquid phase equilibrium principles is used to correlate the solubility data of ADCP in these ethanol−water mixtures. The MPD among these values does not exceed 1.7 % for modified Apelblat equation, and the solubility calculated by the model shows satisfactory agreement with the experimental data.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. Fax: +86-379-65523821. *E-mail: [email protected]. Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. J.-Q.L. measured and correlated the data and wrote this paper; X.-X.C. correlated the data, Q.-Y.B., Y.-Y.L., S.W., and L.-Y.Z. measured the data. D.-F.H. synthesized and purified ADCP, discussed the data, and read this paper. 1452

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dx.doi.org/10.1021/je401053y | J. Chem. Eng. Data 2014, 59, 1448−1453