Measurement and Correlation of Solubility of Two Isomers of

Article pubs.acs.org/jced

Measurement and Correlation of Solubility of Two Isomers of Cyanopyridine in Eight Pure Solvents from 268.15 K to 318.15 K Rui Zhang,† Zhengjie Feng,† and Hongbing Ji*,† †

Fine Chemical Industry Research Institute, School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China

ABSTRACT: Solubility of two isomers of cyanopyridine (CNP) in various solvents were determined by the gravimetric method in the temperature range from 268.15 K to 318.15 K at atmospheric pressure. The experimental results show that the solubility of 3-cyanopyridine increased dramatically over 298.15 K, whereas 4-cyanopyridine was more stable at the same state. The modified Apelblat model, polynomial equation, the Buchowski−Ksiazczak λh equation, and Wilson model were employed to correlate the experimental data. The Wilson model provides better agreement than the other models in terms of the 3- and 4-cyanopyridine. Moreover, molecular simulation was also used to present the interaction between 3-CNP, 4-CNP, and the solvent molecules, which can give an explanation for the solubility behavior in solvents.

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4-CNP have been reported in the literature,4,5 there was no details about solubility data. In this work, to better control the crystallization of a pair of cyanopyridine isomers, their solubility in various solvents (methanol, ethanol, 1-butanol, isobutyl alcohol, ethyl acetate, acetone, tetrachloromethane, 1-propanol) at temperatures from 268.15 K to 318.15 K under 0.1 MPa was determined by using the gravimetric method. The isomers were thermodynamically analyzed and correlated using four mathematical models, including the modified Apelblat equation, polynomial equation, Buchowski−Ksiazczak λh equation, and Wilson model. The interaction energy using DMol3 module in Materials Studio was obtained to understand the solubility of solute in various solvents.

INTRODUCTION Crystallization is an important operation widely used in industry to produce various particulate products such as pharmaceuticals and food additives.1 The thermodynamic information of a compound plays a vital role in the crystallization process. 3-Cyanopyridine and 4-cyanopyridine (3-CNP and 4-CNP) are a pair of isomer with a CN group (Figure 1),

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EXPERIMENTAL DETAILS Materials. 3-CNP and 4-CNP were purchased from Guangzhou Lonza Co., Ltd. (mass fraction purity > 99%) and Sigma-Aldrich Co. LLC. (mass fraction purity >98%), respectively. The analytic reagent grade methanol, ethanol, 1-butanol, isobutyl alcohol, ethyl acetate, acetone, tetrachloromethane, and 1-propanol (mass fraction purity > 99.5%) used in this work were purchased from Guangdong Guanghua Sci-Tech Co. Ltd.,

Figure 1. Molecular structure of cyanopyridine: (a) 3-cyanopyridine; (b) 4-cyanopyridine.

which are available commercially as a yellow crystalline solid.2,3 Currently, due to the synthetical process in industry, 3-CNP was commonly obtained impure with some 4-CNP residual. Therefore, it is essential to investigate the solubility properties of this pair of isomers in order to purify 3-CNP through crystallization process. Although the crystal structure of 3- and © 2017 American Chemical Society

Received: March 30, 2017 Accepted: September 13, 2017 Published: September 25, 2017 3241

DOI: 10.1021/acs.jced.7b00301 J. Chem. Eng. Data 2017, 62, 3241−3251

Journal of Chemical & Engineering Data

Article

Table 1. Details of Materials Used in This Work chemical name

mass fraction purity

3-cyanopyridine (CAS No: 100-54-9) 4-Cyanopyridine (CAS No: 100-48-1) ethanol methanol 1-butanol isobutyl alcohol ethyl acetate acetone tetrachloromethane 1-propanol

≥99 ≥98 ≥99.5 ≥99.5 ≥99.5 ≥99.5 ≥99.5 ≥99.5 ≥99.5 ≥99.5

polarity (water 100)28

formula weight

65.4 76.2 60.2 55.2 23.0 35.5 5.2 61.7

104.11 104.11 32.04 46.07 74.12 74.12 88.12 58.08 153.84 60.10

China. All chemicals were used directly as supplied by the manufacturers without further purification. The detailed information on the materials was listed in Table 1. Experimental Method and Procedure. The solubility of 3- and 4-CNP was determined using the gravimetric method.6−8 Excessive amounts of 3- and 4-CNP were added into various organic solvents in sealed glass jacketed cells (50 mL) with magnetic stirrer. The temperature from 268.15 K to 318.15 K was controlled by a Julabo FP51 thermostatic bath (±0.01 K). The solution was kept under magnetic stirring for at least 12 h, which was enough for thermodynamic equilibrium. Then the suspension was kept static for 4 h to ensure the crystal separated and equilibrium established. The empty weighting bottles were first weighed. After that, a preheated (or precooled) syringe was used to collect about 2 mL of upper clear portion of the solution, which was filtered by a 0.45 μm membrane into a preweighed weighting bottle and then weighed again quickly. Finally, the sample was dried in the vacuum oven at 303.15 K for 12 h until constant weight, and the ultimate weight was collected. All the weights were measured employing an analytical balance (MS104TS/02, Mettler Toledo) with an accuracy of ±0.1 mg. The mole fraction solubility of 3- and 4-CNP can be calculated as follows: x=

mA /MA mA /MA + mB /MB

source Guangzhou Lonza Co., Ltd. Sigma-Aldrich Co. LLC. Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech Guangdong Guanghua Sci-Tech

Co. Co. Co. Co. Co. Co. Co. Co.

Ltd. Ltd. Ltd. Ltd. Ltd. Ltd. Ltd. Ltd.

Figure 2. X-ray powder diffraction (XPRD) of 3-CNP and 4-CNP.

(1)

where mA and mB stand for the masses of solute (3-CNP, 4-CNP) and solvents (methanol, ethanol, 1-butanol, isobutyl alcohol, ethyl acetate, acetone, tetrachloromethane, 1-propanol), respectively, and MA and MB represent the molecular weight of 3-CNP, 4-CNP, and solvents, respectively. Each weight was carried out three times and the average value was chosen as the final result. The X-ray powder diffraction was used to characterize the solid residue to ensure to the polymorph during the measurement of solubility. Data collection was performed on a Rigaku D/MAX 2200 diffractometer (Cu Kα radiation, 1.5406 Å) at 100 mA and 40 kV. The measurements were performed at 2θ degrees from 5° to 50°, with a scanning rate of 10°/min. According to the XPRD patterns, the samples’ polymorph did not change during the measurement (Figure 2). Meanwhile, the melting temperature (Tm) and fusion enthalpy of 3- and 4-CNP were determined by differential scanning calorimetry (DSC-204 F1, Netzsch, Germany). About 5.0 mg of 3- and 4-CNP was used and the heating rate was 4 K/min under the protection of nitrogen. Indium was used for calibrating the instrument. (Figure 3).

Figure 3. DSC of 3-CNP and 4-CNP, the melting point and fusion enthalpy of them are 325.05 K, 16.73 kJ mol−1, and 353.55 K, 18.09 kJ mol−1, respectively. The standard uncertainties for the DSC measurements are typically u(T) ≈ 0.1 K and u(ΔfusH) ≈ 0.05ΔfusH.

Molecular Simulation. The molecular interaction between solute and solvent has an effect on the solubility of solute in solvent. Therefore, density functional theory (DFT) has been widely implemented in analyzing the experimental solubility of solute in different solvents. In this work the DMol3 module in Materials Studio was used to perform the calculations.9−11 The molecular of 3-CNP, 4-CNP, and eight pure solvents were optimized using the generalized gradient approximation (GGA)12 and the Perdew−Burke−Ernzerhof (PBE) function.11 A double numerical polarized (DNP) basis set was applied,11 which was equivalent to the 6-31G* basis set. The value of the 3242



Article

Table 2. Experimental (xexp) and Correlated (xcal) Mole Fraction Solubility of 3-CNP in Eight Different Pure Solvents (p = 0.1 MPa)a modified apleblat

λh

polynomial

T/K

102xexp

102xcal

102RD

102xcal

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

4.29 5.93 9.03 20.1 33.9 49.1 62.7

4.20 6.02 9.09 19.7 33.8 49.3 62.6

−2.18 1.42 0.64 −1.76 −0.52 0.56 −0.14 1.03

4.36 6.46 9.21 20.9 33.0 47.3 63.9

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

8.77 11.1 15.3 26.7 40.4 54.1 72.6

8.54 11.7 15.7 26.1 39.5 55.3 72.2

−2.57 5.95 2.50 −2.33 −2.20 2.32 −0.57 2.64

8.10 11.7 15.9 26.5 39.5 54.9 72.4

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

2.50 3.93 6.45 16.4 27.5 42.7 57.7

2.45 3.95 6.62 15.0 27.8 43.2 57.5

−1.67 0.66 2.76 −8.47 0.94 1.08 −0.38 2.28

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

2.80 3.96 7.02 17.0 30.0 43.5 60.0

2.88 4.09 7.56 17.2 29.1 44.6 59.6

2.77 3.33 7.73 1.15 −2.73 2.65 −0.64 3.00

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

20.9 24.7 28.2 37.5 47.8 63.0 80.3

21.2 24.5 28.2 37.1 48.4 62.6 80.3

1.23 −0.92 0.004 −0.98 −1.27 −0.52 0.071 0.71

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

24.7 29.0 32.9 43.8 54.1 66.4 83.3

25.1 28.9 33.1 42.7 54.1 67.4 82.8

1.56 −0.13 0.64 −2.55 0.063 1.52 −0.53 1.00

268.15 273.15 278.15 288.15 298.15

0.98 1.52 2.40 9.50 23.9

0.97 1.48 2.43 9.71 22.9

−0.77 −2.85 1.23 2.08 −4.28

−5.67 −1.89 −2.22 −0.38 0.74 −2.47 0.97 2.05 Isobutyl Alcohol 2.76 −1.39 4.11 3.70 7.23 2.98 17.3 1.51 28.9 −3.46 43.2 −0.63 60.4 0.72 2.06 Ethyl Acetate 21.4 2.17 24.4 −1.25 28.0 −0.72 37.0 −1.33 48.6 1.57 62.9 −0.089 80.1 −0.17 0.27 Acetone 25.0 1.10 28.8 −0.35 33.1 0.61 42.8 −2.35 54.2 0.30 67.5 1.62 82.7 −0.70 1.00 Tetrachloromethane 0.97 −0.24 1.53 0.91 2.40 0.08 9.51 0.043 24.0 0.43

Wilson

102RD

102xcal

102RD

102xcal

102RD

1.57 8.92 1.99 4.19 −2.65 −3.51 1.89 3.53

4.38 5.67 9.11 19.9 32.8 49.5 63.3

2.13 −4.45 0.90 −0.77 −3.51 0.79 0.95 1.93

4.28 5.92 9.01 20.0 33.8 49.2 62.6

−0.036 −0.066 −0.15 −0.055 −0.011 0.029 −0.027 0.054

−7.62 5.25 3.95 −0.87 −2.25 1.49 −0.26 3.10

8.11 11.6 16.1 26.3 39.6 52.7 71.9

−7.47 4.85 4.77 −1.44 −1.92 −2.53 −1.01 3.42

8.80 11.4 15.5 26.6 40.3 54.2 72.7

0.42 0.11 0.23 −0.087 −0.038 0.077 0.044 0.14

2.46 3.90 6.92 16.0 26.3 43.6 56.7

−1.29 −0.64 7.29 −2.15 −4.32 2.13 −1.83 2.74

2.48 3.91 6.44 16.3 27.4 42.6 57.8

−0.44 −0.54 −0.015 −0.061 −0.036 −0.047 0.018 0.17

2.77 4.04 6.91 17.1 29.5 43.8 60.7

−1.25 2.08 −1.57 0.47 −1.53 0.77 1.22 1.27

2.81 3.94 7.03 17.1 29.9 43.4 59.9

0.031 −0.25 0.14 0.059 −0.033 −0.023 −0.016 0.079

22.2 25.0 28.3 36.2 46.8 61.8 84.2

6.10 1.39 0.27 −3.50 −2.06 −1.82 4.85 2.86

20.8 24.6 28.1 37.4 47.7 62.9 80.2

−0.057 −0.033 −0.036 −0.025 −0.029 −0.016 −0.031 0.032

26.3 29.5 33.0 41.5 52.4 66.9 86.9

6.35 1.80 0.40 −5.32 −3.03 0.79 4.40 3.16

24.6 28.9 32.8 43.9 54.0 66.5 83.2

−0.074 −0.037 −0.036 0.021 −0.038 0.013 −0.010 0.032

0.98 1.50 2.42 9.48 23.6

0.60 −1.06 0.92 −0.27 −0.83

0.97 1.53 2.42 9.49 23.7

−0.31 0.56 0.67 −0.17 −0.40

Ethanol

Methanol

1-Butanol 2.35 3.85 6.30 16.3 27.7 41.6 58.3

3243



Article

Table 2. continued modified apleblat T/K

102xexp

102xcal

102RD

308.15 318.15 102RAD

39.3 56.8

40.3 56.5

2.52 −0.54 2.04

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

4.34 6.58 9.76 21.4 34.8 50.0 64.3

4.27 6.82 9.70 21.6 34.7 50.4 64.2

−0.59 3.67 −0.59 1.14 −0.15 0.81 −0.26 1.17

λh

polynomial 102xcal

102RD

Tetrachloromethane 38.8 −1.43 56.6 −039 0.50 1- Propanol 4.29 −1.13 6.96 5.72 9.61 −1.50 21.8 1.99 34.2 −1.79 48.6 −2.78 65.3 1.47 2.34

Wilson

102xcal

102RD

102xcal

102RD

39.7 56.3

1.11 −0.92 0.82

39.2 56.9

−0.24 0.16 0.36

4.13 6.10 10.4 19.8 32.9 45.1 63.7

−4.87 −7.28 6.57 −7.27 −5.50 −9.84 −1.02 6.05

4.33 6.57 9.75 21.3 34.7 50.1 64.4

−0.063 −0.017 −0.043 −0.057 −0.085 0.047 0.026 0.048

a Standard uncertainties u for temperature T and pressure P are u(T) = 0.01 K and u(P) = 0.5 kPa. The standard uncertainty is u(x) = 0.02x for the solubilities in ethyl acetate and acetone, u(x) = 0.16x for the solubilities in 1-butanol and iso-butanol, u(x)=0.22x for the solubility in tetrachloromethane, u(x) = 0.13x for the solubilities in ethanol and 1-propanol and u(x) = 0.07x for the solubility in methanol.

Table 3. Experimental (xexp) and Correlated (xcal) Mole Fraction Solubility of 4-CNP in Eight Different Pure Solvents (p = 0.1 MPa)a modified apleblat T/K

2

10 xexp

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

2

λh

polynomial

10 xcal

2

2

10 RD

10 xcal

0.65 1.60 1.79 3.67 7.06 13.6 27.3

0.67 1.65 1.82 3.67 6.99 13.7 27.2

3.00 3.06 1.87 0.20 −1.03 0.93 −0.11 1.46

0.66 1.65 1.78 3.61 7.16 13.6 27.2

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

2.45 3.02 3.61 6.20 9.54 17.3 30.4

2.44 2.99 3.71 5.94 9.90 17.1 30.4

−0.31 −1.13 2.83 −4.25 3.75 1.13 0.12 1.93

2.31 2.98 3.58 6.08 9.41 17.1 30.0

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

1.41 1.49 2.16 4.71 8.98 15.1 28.4

1.38 1.46 2.13 4.56 8.77 15.6 28.3

−2.31 −1.94 −1.84 −3.20 −2.32 2.90 −0.34 2.20

1.42 1.42 2.10 4.53 9.13 15.3 28.2

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

1.33 1.76 2.29 4.69 10.8 17.2 30.4

1.26 1.73 2.33 4.63 9.95 17.7 30.3

−5.76 −1.52 1.98 −0.47 −7.62 3.11 −0.35 2.97

268.15 273.15 278.15

10.6 12.1 14.2

10.3 12.3 14.5

−2.06 1.47 2.24

2

10 RD

2

Wilson

10 xcal

2

10 RD

2

10 xcal

102RD

1.99 2.71 −0.30 −1.52 1.31 0.31 −0.11 1.18

0.63 1.67 1.68 3.54 7.11 13.4 27.0

−2.78 4.43 −6.20 −3.39 0.63 −1.12 −1.16 2.81

0.65 1.59 1.76 3.63 7.04 13.7 27.1

0.18 −0.035 −1.07 −0.86 −0.25 0.094 −0.13 0.38

−5.73 −1.24 −0.81 −2.00 −1.39 −1.58 −1.34 2.01

2.52 2.87 3.36 5.84 9.31 18.2 29.6

2.84 −5.15 −7.05 −5.88 −2.45 5.16 −2.56 4.44

2.43 3.03 3.55 6.11 9.49 17.5 30.6

−0.44 0.022 −1.57 −1.47 −0.50 0.22 0.36 0.66

0.86 −4.81 −2.88 −3.76 1.66 1.25 −0.71 2.27 Isobutyl Alcohol 1.31 −1.56 1.74 −0.74 2.15 −6.09 4.71 0.47 10.4 −3.44 17.8 3.22 30.2 −0.78 2.33 Ethyl Acetate 10.4 −1.55 12.3 1.35 14.4 1.93

1.28 1.53 2.29 4.96 9.98 16.1 28.0

−9.10 2.50 5.85 5.42 9.04 6.06 −1.64 5.66

1.40 1.50 2.17 4.70 8.97 15.2 28.5

−0.081 0.051 0.089 −0.026 −0.018 0.094 0.045 0.058

1.38 1.82 2.39 5.04 12.5 18.4 30.3

3.44 3.66 4.27 7.68 2.29 6.76 −0.50 4.09

1.32 1.74 2.27 4.68 10.6 17.1 30.5

−0.088 −0.16 −0.11 −0.020 −0.26 −0.053 0.065 0.10

10.4 12.0 14.4

−0.18 −0.094 0.10

Ethanol

Methanol

1-Butanol

3244

10.6 12.4 14.5

0.15 2.64 2.52



Article

Table 3. continued modified apleblat T/K

102xexp

102xcal

102RD

288.15 298.15 308.15 318.15 102RAD

20.3 26.1 34.3 43.7

19.8 26.3 34.2 43.7

−2.42 0.96 −0.098 0.002 1.32

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

11.7 13.4 15.5 21.3 27.5 35.6 46.0

11.6 13.5 15.4 21.1 27.6 35.8 46.0

−0.79 0.88 −0.58 −1.01 0.029 0.56 0.044 0.56

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

1.29 1.94 2.92 3.96 8.39 15.1 28.7

1.35 1.90 2.91 4.06 8.33 15.1 28.7

4.94 −2.12 −0.57 2.47 −0.75 0.42 0.019 1.61

268.15 273.15 278.15 288.15 298.15 308.15 318.15 102RAD

2.46 2.71 3.96 7.00 12.9 19.0 29.8

2.35 2.89 4.08 7.25 12.1 19.5 29.7

−4.32 6.58 2.93 3.48 −5.38 2.50 −0.36 3.65

λh

polynomial 102xcal

102RD

Ethyl Acetate 19.7 −2.57 26.3 1.04 34.3 0.021 43.7 0.072 1.22 Acetone 11.7 0.025 13.5 0.55 15.6 0.67 20.9 1.97 27.6 0.31 35.9 0.94 45.8 −0.39 0.69 Tetrachloromethane 1.24 −3.82 1.88 −3.16 2.85 −2.35 3.83 −3.16 8.95 6.61 15.1 0.18 28.5 −0.57 2.83 1- Propanol 2.44 −0.82 2.90 7.20 3.82 −3.67 7.05 0.71 12.3 −4.32 19.6 3.01 29.5 −0.99 2.96

Wilson

102xcal

102RD

102xcal

102RD

19.6 26.0 34.0 44.1

−3.23 −0.16 −0.68 0.77 1.45

20.2 26.0 34.2 43.8

−0.035 −0.044 −0.058 0.040 0.080

11.5 13.5 15.7 21.0 27.6 35.8 45.8

−1.22 0.72 1.39 −1.49 0.19 0.59 0.28 0.84

11.5 13.3 15.6 21.4 27.6 35.5 45.9

−0.17 −0.096 0.058 0.049 0.054 −0.033 −0.037 0.071

1.18 1.85 2.88 4.11 8.38 16.0 28.2

−8.45 −4.93 −1.29 9.29 −0.091 5.94 −1.75 4.53

1.28 1.95 2.93 3.95 8.40 15.1 28.6

−0.072 0.040 0.013 −0.034 0.017 0.11 −0.057 0.049

2.39 2.81 4.16 7.23 12.5 19.3 29.9

−2.63 3.64 5.08 3.18 −2.52 1.76 0.065 2.70

2.43 2.72 3.94 7.02 12.8 19.1 29.9

−0.26 0.064 −0.13 0.11 −0.079 0.034 0.036 0.10

a Standard uncertainties u for temperature T and pressure P are u(T) = 0.01 K and u(P) = 0.5 kPa. The standard uncertainty is u(x) = 0.02x for the solubilities in ethyl acetate and acetone, u(x) = 0.12x for the solubilities in 1-butanol and isobutyl alcohol, u(x) = 0.11x for the solubility in tetrachloromethane, u(x) = 0.17x for the solubility in ethanol, and u(x) = 0.08x for the solubilities in methanol and 1-propanol.

convergence criteria was 10−5 Hartree in the self-consistentfield calculation and the tolerances of energy, maximum force, and maximum displacement were 1.0 × 10−4 au, 0.02 au, and 0.05 au in the geometry optimization, respectively. After the geometries of all involving molecules were optimized at this level,13 the interaction energy Einter was defined as E inter = ECNP − sol − ECNP − Esol

Table 4. Interaction Energy Einter and the Hydrogen Bonds Distance between 3-CNP, 4-CNP, and Solvents (1 Å = 0.1 nm) solvent ethanol methanol 1-butanol isobutyl alcohol ethyl acetate acetone tetrachloromethane 1-propanol

(2)

where ECNP, Esol and ECNP‑sol are the total energies of CNP (3-CNP, 4-CNP), solvent and CNP with each solvent, respectively. The larger absolute value of Einter illustrates the stronger interactions between CNP and solvent molecules.

■

THEORETICAL MODELS Modified Apelblat Equation. The Apelblat model is commonly employed for estimation of solubility in solvents, which is expressed as eq 3:14,15 ln x = a +

b + c ln T T

ethanol methanol 1-butanol isobutyl alcohol ethyl acetate acetone tetrachloromethane 1-propanol

(3)

where x is the mole fraction solubility of 3- and 4-CNP, T is an absolute temperature (K), and a, b, and c are empirical constants, which are obtained by least-squares analysis.

Einter/kJ mol−1a 3-CNP −18.832 −19.794 −18.063 −18.542 −20.156 −21.227 −16.621 −18.883 4-CNP −18.535 −19.219 −18.391 −17.863 −19.760 −20.947 −16.335 −18.058

bond distance/Å (OH···N) 1.714 1.671 1.785 1.762

1.683 1.706 1.695 1.774 1.818

1.792

a

Einter and the hydrogen bonds between the N atom in the pyridine cycle and the H atom in the hydroxyl group 3245



Article

Table 5. Regressed Coefficients of Modified Apeblat Equation between 268.15 K and 318.15 K 3-CNP

4-CNP

solvent

a(×10−3)

b(×10−5)

c(×10−3)

RMSD (×103)

R2

a(×10−3)

b(×10−5)

c(×10−3)

RMSD (×103)

R2


0.7798 0.3346 0.6832 0.7457 −0.0451 0.0125 0.9872 0.7197

−0.3821 −0.1777 −0.2563 −0.3710 0.0005 −0.0231 −0.0462 −0.0354

−0.1146 −0.0484 0.3104 −0.1093 0.0077 −0.0009 −0.3357 −0.1056

1.92 3.13 5.70 5.97 3.23 3.26 5.56 2.13

0.9997 0.9990 0.9988 0.9982 0.9997 0.9990 0.9989 0.9996

−0.3173 −0.4078 −0.1662 0.1154 0.0272 −0.0235 −0.3533 0.1142

0.0892 0.1400 0.0264 −0.0991 −0.0335 −0.0103 0.1100 −0.0890

0.0499 0.0629 0.0271 −0.0148 −0.0034 0.0045 0.0551 −0.0151

0.61 1.89 1.97 3.75 2.63 0.29 0.58 3.45

0.9994 0.9996 0.9989 0.9979 0.9995 0.9998 0.9991 0.9985

Table 6. Regressed Coefficients of Polynomial Equation between 268.15 K and 318.15 K solvent

B0

103B1


0.8049 7.2070 1.0382 0.2449 0.5797 0.7499 9.1231 0.2186 B0

−5.521 −135.9 6.5976 6.82 6.57 −0.0433 −114.6 0.3742 103B1


0.1782 0.8962 0.9504 0.7241 0.7428 0.6158 0.8051 0.5439

18.52 16.76 16.75 19.74 −2.5550 −3.2410 16.26 12.69

104B2 3-CNP −0.0440 3.8660 −0.8746 −1.1550 −1.1600 −0.5010 5.1825 −0.6110 103B2 4-CNP −0.1775 −0.1739 −0.1746 −0.1862 −0.0358 −0.0407 −0.1847 −0.1310

106B3

103B4

103RMSD

R2

0.1690 −0.3020 0.1283 0.2810 0.2830 0.1580 −0.1032 0.1850 106B3

622.5 7322 1304 824.7 751.6 50.07 8054 528 103B4

9.42 6.23 4.56 4.58 4.09 6.22 2.32 7.14 103RMSD

0.9967 0.9992 0.9992 0.9983 0.9996 0.9990 0.9984 0.9974 R2

0.3510 0.3521 0.3525 0.3680 0.0117 0.0131 0.3770 0.2680

865.6 385.9 347.4 288.7 366.6 765.9 869.4 295

0.48 2.06 1.41 2.73 0.40 0.22 2.27 3.35

0.9993 0.9983 0.9990 0.9991 0.9995 0.9996 0.9983 0.9984

Table 7. Regressed Coefficients of λh Equation between 268.15 K and 318.15 K 3-CNP −4

4-CNP

solvent

λ

10 h

10 RMSD

R


0.3834 0.5425 0.3386 0.2984 0.3039 2.1156 0.5062 0.4252

0.7007 0.4851 0.7215 0.8779 0.3759 0.3073 1.6485 0.6515

5.39 7.23 4.53 3.55 5.27 7.98 2.67 8.29

0.9985 0.9979 0.9976 0.9994 0.9982 0.9971 0.9995 0.9948

3

(4)

where B0, B1, B2, B3, and B4 are semiempirical constants, which can be calculated by least-squares analysis. Buchowski−Ksiazczak λh equation. The Buchowski− Ksiazczak λh equation can be used to describe the thermodynamic behavior of liquid−solid systems as follow: ⎛1 ⎛ 1 − x ⎞⎟ 1 ⎞ ln⎜1 + λ = λh⎜ − ⎟ ⎝ x ⎠ Tm ⎠ ⎝T

−4

λ

10 h

103RMSD

R2

2.6679 1.6685 1.7405 1.8872 0.7934 0.8201 2.3006 1.2256

0.2608 0.3163 0.3221 0.2925 0.2893 0.2721 0.2758 0.3644

7.64 8.74 8.44 7.48 3.44 1.85 4.14 2.71

0.9973 0.9949 0.9956 0.9975 0.9992 0.9997 0.9981 0.9988

where λ and h are two variable parameters, and λ represents the nonideality of the solution system, and h estimates the enthalpy of solution. Tm is the melting temperature of 3- and 4-CNP. As shown in Figure 3, Tm and the melting enthalpy of 3- and 4- CNP is 325.05 K (51.9 °C), 16.73 kJ mol−1 and 353.55 K (80.4 °C), 18.09 kJ mol−1, respectively. The melting point for 3-CNP and 4- CNP was 49.1 °C (onset point), 52.8 °C (maximum point), and 77.4 °C (onset point), 81.3 °C (maximum point), respectively. The melting points of 3- and 4-cyanopyridine are reported as 50−52 °C and 76−79 °C in the literature.18,19 The relative deviations (RD, RD = |experimental data − literature data|/(literature data)) for 3- and 4- CNP were 3.8%, 0.1% and 5.7%, 0.2%, respectively, which shows the accuracy and reliable of the measurement result. Wilson Model. On the basis of a binary system, the Wilson model20 was used to describe the solubility of a solute in liquid

Polynomial Equation. The fourth-order polynomial eq (eq 4)16,17 was always used to describe the relationship between solubility and absolute temperature at specific solute, solvent, and pressure. x = B0 + B1T + B2 T 2 + B3T 3 + B4 T 4

2

(5) 3246



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where γ1 is the liquid-phase activity coefficient of solute; ΔfusHtp is the molar enthalpy of fusion at the triple point; ΔCp denotes the molar heat capacity difference of the solute between the solid and the liquid; ΔV represents the volume difference between the solid and liquid phases; Ttp and Ptp represent the temperature and pressure of the triple point; P is the absolute pressure and R is the universal gas constant. Generally, the negligible difference between triple point and normal melting point makes it suitable to replace ΔfusHtp and Ttp by enthalpy of melting ΔfusHm and melting point Tm. Furthermore, the last two terms including ΔCp and ΔV are the correction of heat capacity and pressure difference, which are often minor and also negligible. Thus, eq 6 can be expressed simply as

Table 8. Regressed Parameters of Wilson Model in the Temperatures from 268.15 K to 318.15 K solvent

Δλ12


1142.3 1999.1 −56.8 −49.8 −70.6 579.9 −30.6 548.6


1176.9 2053.7 100.1 −66.6 −56.8 606.3 −27.4 573.5

Δλ21 3-CNP −1141.8 −1997.7 71.3 52.5 70.5 −588.7 82.4 −550.5 4-CNP −1187.1 −2051.2 −103.2 71.0 56.9 −606.1 27.5 −573.3

104 RMSD

R2

1.10 3.01 1.36 0.93 1.36 1.34 6.62 1.65

0.99999 0.99999 0.99999 0.99999 0.99999 0.99999 0.99999 0.99999

2.16 6.28 0.073 1.31 1.52 1.43 0.91 0.75

0.99999 0.99999 0.99999 0.99999 0.99999 0.99999 0.99999 0.99999

ln xγ1 =

ΔfusHtp ⎛ 1 1⎞ ⎜⎜ − ⎟⎟ R ⎝ Ttp T⎠ ⎞ ΔV ΔCp ⎛ Ttp Ttp − − + 1⎟ − (P − Ptp) ⎜ln R ⎝ T T RT ⎠

(7)

To use eq 7, a thermodynamic model is demanded to represent activity coefficients as a function of temperature and composition at constant pressure. In this paper, the Wilson model, a local composition model initially proposed by Wilson, was used to derive γ1, which can be shown as eq 8 in the binary system:21,22

solvents as follow ln xγ1 =

ΔfusHm ⎛ 1 1⎞ − ⎟ ⎜ R ⎝ Tm T⎠

⎛ Λ12 Λ 21 ⎞ ln γ1 = −ln(x + Λ12x1) + x1⎜ − ⎟ x1 + Λ 21x ⎠ ⎝ x + Λ12x1 (6)

(8)

Figure 4. Experimental and fitted solubility of 3-CNP in eight pure solvents through the modified Apelblat (a), polynomial equation (b), λh equation (c), Wilson model (d) (the dash line): □, ethanol; ○, methanol; △, 1-butanol; ▽, isopropyl alcohol; ◁, ethyl acetate; ▷, acetone; ◇, tetrachloromethane; ☆, 1- propanol. 3247



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Figure 5. Experimental and fitted solubility of 4-CNP in eight pure solvents through modified Apelblat (a), polynomial equation (b), λh equation (c), Wilson model (d) (the dash line): □, ethanol; ○, methanol; △, 1-butanol; ▽, isopropyl alcohol; ◁, ethyl acetate; ▷, acetone; ◇, tetrachloromethane; ☆ 1- propanol.

interaction. It can be found from Figure 1 that 3-CNP and 4-CNP with a CN bond were both hydrogen acceptors, meaning they can form hydrogen bonds with the solvent molecules. Figures 6 and 7 present the calculated hydrogen bonds at different locations between 3-CNP, 4-CNP, and solvents (ethanol (a), methanol (b), 1-butanol (c), isobutyl alcohol (d), and 1-propanol (e)) excluding acetone, ethyl acetate, and tetrachloromethane without hydrogen donor, respectively. As shown in Table 4, the order of absolute value of Einter for 3-CNP was acetone > ethyl acetate > methanol > ethanol > 1-butanol > 1-propanol > isobutyl alcohol > tetrachloromethane, while the order of Einter for 4-CNP was acetone > ethyl acetate > methanol > 1-propanol > ethanol > isobutyl alcohol > 1-butanol > tetrachloromethane, and all the Einter for 3-CNP were higher than that for 4-CNP. The location of hydrogen bond in their molecular structure may also influence the interaction energy. Therefore, the interaction energy Einter and hydrogen bond at different points between the N atom in the pyridine and H atom in the hydroxyl group in solvents were calculated (seen Table 4). It can be clearly found from Table 4 that the interaction energy Einter is less and OH···N is stronger than that because of OH···NC, which indicates that the interaction between solute and solvents with the hydroxyl group in solution forms through the N atom in the pyridine cycle and H atom in the hydroxyl group. Additionally, the Einter between the solute and three solvents (ethyl acetate, acetone, and tetrachloromethane) is still constant as a result of no influence from the hydrogen bond. The hydrogen bonds between acetone, ethyl acetate, and solute were not formed, but Einter was strong, which may result in the higher solubility of solute in two solvents.25 It can

where Λ12 =

⎡ Δλ ⎤ ⎡ λ − λ11 ⎤ V2 V2 exp⎢ − 12 exp⎢ − 12 ⎥ ⎥⎦ = ⎣ RT ⎦ ⎣ V1 RT V1

(9)

Λ 21 =

⎡ Δλ ⎤ ⎡ λ − λ 22 ⎤ V1 V = 1 exp⎢ − 21 ⎥ exp⎢ − 21 ⎥ ⎣ RT ⎦ ⎣ V2 RT ⎦ V2

(10)

where γ1 is the liquid-phase activity coefficient of solute; x and x1 are the mole of fraction of solutes and the selected solvent, respectively. In eq 9 and eq 10, Δλ12 and Δλ21 are the model parameters; V1 and V2 represent the molar volumes of solute and solvent, respectively. The values of V2 are obtained from the literature and that of 3-CNP and 4-CNP are calculated from its density at 298.15 K,23 that is, the molar volume value of CNP denoted the molar volume at the solid state rather than the liquid state.

■

RESULTS AND DISCUSSION The experimental and correlated results of 3-CNP and 4-CNP were shown in Tables 2 to 8 and graphically in Figures 4 and 5, respectively. It can be found in Table 1 that the solubility of both isomers of CNP increased with the temperature increase. The polarity order of all solvents was methanol > ethanol > 1-propanol >1-butanol > isobutyl alcohol > acetone > ethyl acetate > tetrachloromethane, which was not consistent with the solubility of 3- and 4-CNP order in Figures 4 and 5. Polarity may have a main influence on the strength of solute− solvent van der Waals interactions.24 However, the hydrogen bond was also a critical factor impacting the solute−solvent 3248



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Figure 7. Interactions between 4-CNP and ethanol (a), methanol (b), 1-butanol (c), isobutyl alcohol (d), and 1-propanol (e), respectively. (Left) OH···N between the N atom in pyridine cycle and the H atom in the hydroxyl group; (right) OH···NC. Figure 6. Interactions between 3-CNP and ethanol (a), methanol (b), 1-butanol (c), isobutyl alcohol (d), and 1-propanol (e), respectively. (Left) OH···N between the N atom in the pyridine cycle and the H atom in the hydroxyl group; (Right) OH···NC.

where n is the number of experimental points, and xical and xiexp are the calculated and experimental solubility values, respectively. It is seen from Tables 2 and 3 that the calculated solubility of 3-CNP and 4-CNP through four models is well consistent with the experimental data. Additionally, the relative average RAD of the four models is no more than 5%. Therefore, these models are suitable for correlating the solubility of 3-CNP and 4-CNP in these pure organic solvents. Additionally, several thermodynamic models were used to describe the solid−liquid equilibrium, and the following four equations were then selected to correlate the experimental solubility data in pure solvents, including the modified Apelblat equation, polynomial equation, λh equation, and Wilson model. These results indicate that all models were appropriate for correlating the solubility of 3- and 4-CNP in different solvents with changing temperature. On the basis of the error analysis (RD, RAD, RMSD, and R2), it is found that the Wilson model for isomers of CNP was little better than the other equations.

be seen from Tables 2 to 4 that the larger absolute value of Einter has contributed to higher solubility. It is noted that the solubility of 3-CNP was higher than 4-CNP in these pure solvents, and the variation with temperature was more obvious, which was also consistent with the Einter shown in Table 3. Therefore, on the basis of the difference of solubility, cooling crystallization may be an effective method to separate them to improve the purity of product. To investigate the reliability and robustness of the experimental solubility, the solubility of 3- and 4-CNP in the solvents studied was correlated by the four different thermodynamic models. The relative deviation (RD), relative average deviation (RAD), and the root-mean square deviation (RMSD) were used to evaluate the difference between the measured and correlation results, which are defined as eqs 11 to 13.8,24,26,27 RD =

RAD =

i i xcal − xexp i xexp

1 n

n

∑ i=1

■

(11) i xcal

−

CONCLUSION The solubility of two isomers of CNP in eight different pure solvents was determined by a gravimetric method at temperatures ranging from 268.15 K to 318.15 K. The data shows that the solubility of both isomers of CNP has a strong dependence on temperature in these solvents. The modified Apelblat equation, polynomial equation, the λh equation, and Wilson model were used to analyze the experimental data. The results

i xexp

i xexp

⎡ n (x i − x i )2 ⎤1/2 cal exp ⎥ RMSD = ⎢∑ ⎢⎣ i = 1 ⎥⎦ n

(12)

(13) 3249



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(4) Laing, M.; Sparrow, N.; Sommerville, P. The crystal structure of 4-cyanopyridine. Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. 1971, 27, 1986−1990. ́ (5) Kubiak, R.; Janczak, J.; Sledź , M. Crystal structures of 2- and 3cyanopyridine. J. Mol. Struct. 2002, 610, 59−64. (6) Zhang, R.; Ma, J.; Li, J.; Jiang, Y.; Zheng, M. Effect of pH, temperature and solvent mole ratio on solubility of disodium 5′guanylate in water + ethanol system. Fluid Phase Equilib. 2011, 303, 35−39. (7) Aniya, V.; De, D.; Mohammed, A. M.; Thella, P. K.; Satyavathi, B. Measurement and Modeling of Solubility of para-tert-Butylbenzoic Acid in Pure and Mixed Organic Solvents at Different Temperatures. J. Chem. Eng. Data 2017, 62, 1411−1421. (8) Hao, J.; Yang, W.; Li, H.; Fan, S.; Zhao, W.; Hu, Y. Solubility of 4-Methylsulfonylacetophenone in Nine Pure Solvents and (Ethyl Acetate + n-Hexane) Binary Solvent Mixtures from 278.15 to 328.15 K. J. Chem. Eng. Data 2017, 62, 236−242. (9) Delley, B. An all-electron numerical method for solving the local density functional for polyatomic molecules. J. Chem. Phys. 1990, 92, 508−517. (10) Delley, B. Fast Calculation of Electrostatics in Crystals and Large Molecules. J. Phys. Chem. 1996, 100, 6107−6110. (11) Delley, B. From molecules to solids with the DMol3 approach. J. Chem. Phys. 2000, 113, 7756−7764. (12) Perdew, J. P.; Burke, K.; Ernzerhof, M. Generalized Gradient Approximation Made Simple. Phys. Rev. Lett. 1996, 77, 3865−3868. (13) Zhu, P.; Chen, Y.; Fang, J.; Wang, Z.; Xie, C.; Hou, B.; Chen, W.; Xu, F. Solubility and solution thermodynamics of thymol in six pure organic solvents. J. Chem. Thermodyn. 2016, 92, 198−206. (14) Apelblat, A.; Manzurola, E. Solubilities of L-aspartic, DLaspartic, DL-glutamic, p-hydroxybenzoic, o-anisic, p-anisic, and it aconic acids in water from T = 278 K to T = 345 K. J. Chem. Thermodyn. 1997, 29, 1527−1533. (15) Apelblat, A.; Manzurola, E. Solubilities of o-acetylsalicylic, 4aminosalicylic, 3,5-dinitrosalicylic, and p-toluic acid, and magnesiumDL-aspartate in water from T = (278 to 348) K. J. Chem. Thermodyn. 1999, 31, 85−91. (16) Zhang, Y.; Wang, L.; Zhou, R.; Liu, X. Measurement and Correlation for the Solubilities of Dihydrocapsaicin in n-Heptane, nHexane, n-Pentane, Ethyl Acetate, Acetone, Ethanol, and Water. J. Chem. Eng. Data 2011, 56, 2090−2094. (17) Wang, L. Measurement and correlation of the solubility of 6chloro-3-aminopyridazine in water and binary mixtures of water + ethanol from 293.55 to 342.95 K. J. Mol. Liq. 2013, 188, 55−60. (18) Zou, T.; Yu, X.; Feng, X.; Bao, M. An efficient transformation of primary halides into nitriles through palladium-catalyzed hydrogen transfer reaction. Chem. Commun. 2015, 51, 10714−10717. (19) Leggio, A.; Belsito, E. L.; Gallo, S.; Liguori, A. One-pot conversion of aldehydes to nitriles mediated by TiCl4. Tetrahedron Lett. 2017, 58, 1512−1514. (20) Wilson, G. M. Vapor-Liquid Equilibrium. XI. A New Expression for the Excess Free Energy of Mixing. J. Am. Chem. Soc. 1964, 86, 127−130. (21) Liu, J. Q.; Chen, S. Y.; Ji, B. Solubility and Thermodynamic Functions of Isatin in Pure Solvents. J. Chem. Eng. Data 2014, 59, 3407−3414. (22) Zhang, Y.; Wei, S.; Wang, H. H.; Liu, J. Q.; Wang, W. Solubility Measurement and the Correlation of 1-Naphthaleneacetic Acid in Pure and Methanol + Water Binary Solvents from T = (278.25 to 323.55) K. J. Chem. Eng. Data 2017, 62, 1292−1301. (23) Casteel, J. F.; Sears, P. G. Dielectric constants, viscosities, and related physical properties of five cyano- and halopyridines at several temperatures. J. Chem. Eng. Data 1975, 20, 10−13. (24) Tong, Y.; Wang, Z.; Yang, E.; Pan, B.; Jiang, J.; Dang, L.; Wei, H. Determination and correlation of solubility and solution thermodynamics of ethenzamide in different pure solvents. Fluid Phase Equilib. 2016, 427, 549−556.

show that the Wilson model for both 3-CNP and 4-CNP shows better agreement with experimental data. In addition, the molecular simulation results show that the solubility sequence of two isomers in eight pure solvents is consistent with the strength of interactions between the solute and solvent molecules.

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AUTHOR INFORMATION

Corresponding Author

*Tel: +86 20 8411 3658. Fax: +86 20 8411 3654. E-mail: jihb@ mail.sysu.edu.cn. ORCID

Hongbing Ji: 0000-0003-1684-9925 Funding

The financial support by National Science Fund for Distinguished Young Scholars (21425627), Guangdong collaborative innovation, and platform for the construction of special funds (2014B090902006), Guangdong Technology Research Center for Synthesis and Separation of Thermosensitive Chemicals (2015B090903061) is acknowledged. Notes

The authors declare no competing financial interest.

■

NOMENCLATURES solubility of the solute (mol mol−1) calculated solubility of the solute (mol mol−1) experimental solubility of the solute (mol mol−1) mA the mass of the solute (g) mB the mass of the solvent (g) MA the molecular mass of the solute (g mol−1) MB the molecular mass of the solvent (g mol−1) Einter the interaction energy between CNP and solvents ECNP the total energies of CNP (3-CNP or 4-CNP) Esol the total energies of each solvent ECNP‑sol the total energies of CNP with each solvent a,b,c parameters for the modified Apelblat equation T absolute temperature (K) B0,B1,B2,B3,B4 semiempirical constants of polynomial equation λ empirical constant for the λh equation h empirical constant for the λh equation (K) Tm melting temperature of the solute (K) R gas constant (8.314 J mol−1 K−1) RAD the relative average deviation RD the relative deviation RMSD standard deviation Δλ12, Δλ21 empirical constant for the Wilson model V1 mole volume of the solute (cm3 mol−1) V2 mole volume of the solvent (cm3 mol−1) x xcal xexp

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REFERENCES

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(25) Sun, H.; Liu, P.; Xin, Y.; Liu, B.; Wu, S. Thermodynamic analysis and correlation of solubility of Cefaclor in different solvents from 278.15 to 313.15 K. Fluid Phase Equilib. 2015, 388, 123−127. (26) Liang, A.; Wang, S.; Qu, Y. Determination and Correlation of Solubility of Phenylbutazone in Monosolvents and Binary Solvent Mixtures. J. Chem. Eng. Data 2017, 62, 864−871. (27) Lv, P.; Wang, H.; Tong, Y.; Dang, L.; Sun, C.; Pang, S.-P. Measurement and Correlation of the Solubility of ε-CL-20 in 12 Organic Solvents at Temperatures Ranging from 278.15 to 318.15 K. J. Chem. Eng. Data 2017, 62, 961−966. (28) Smallwood, I. M. Handbook of Organic Solvent Properties; Butterworth-Heinemann: London, 1996.

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Measurement and Correlation of Solubility of Two Isomers of

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