Solubility Measurement and Thermodynamic Model Correlation and

Article pubs.acs.org/jced

Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Solubility Measurement and Thermodynamic Model Correlation and Evaluation of 2‑Chloro-5-nitroaniline in 12 Pure Solvents Renjie Xu† and Jian Wang*,‡ †

Guangling College, Yangzhou University, YangZhou, Jiangsu 225009, P. R. China College of Chemistry & Chemical Engineering, YangZhou University, YangZhou, Jiangsu 225002, P. R. China

‡

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S Supporting Information *

ABSTRACT: The solubility data of 2-chloro-5-nitroaniline in pure methanol, ethanol, n-propanol, isopropanol, 1-butanol, acetonitrile, acetone, 2-butanone, ethyl acetate, 1,4-dioxane, toluene, and N-methylpyrrolidone (NMP) were obtained. The solubility in mole fraction of 2-chloro-5-nitroaniline in the selected solvents increased with a rise of temperature. Moreover, at a certain temperature, they decreased according to the following order: NMP > acetone > 2-butanone > 1,4dioxane > ethyl acetate > acetonitrile > toluene > ethanol > npropanol > methanol > 1-butanol > isopropanol. The achieved solubility values were correlated by the modified Apelblat equation, λh equation, Wilson model, and NRTL model. The maximum values of root-mean-square deviation and relative average deviation were 17.31 × 10−4 and 2.55%, respectively. In order to choose the best model for 2-chloro-5-nitroaniline, the Akaike information criterion was discussed. Furthermore, the results of thermodynamic property of Gibbs energy indicated that the mixing process of 2-chloro-5-nitroaniline in solvents was spontaneous and favorable.

1. INTRODUCTION Aromatic aminonitro compounds with metapositions of amino and nitro groups occupy a unique and distinctive role in pharmaceuticals, agrochemicals, fine chemicals, and dyes.1,2 2Chloro-5-nitroaniline (CAS No. 6283-25-6) is an important chemical product and is mainly used for coupler intermediates, color film imaging agent, and new dyestuff.3,4 With the continuous development of the pharmaceutical industry, a Chinese Patent No.108358848 reports the preparation of intermediate of bendamustine hydrochloride by acylation of 2chloro-5-nitroaniline with glutaric anhydride in the past year.5 This is an intermediate for the total synthesis of a very promising therapeutic agent (bendamustine hydrochloride), and the solubility data presented here could facilitate translational work that would streamline the manufacturing of this pharmaceutical. Compared with other patents6,7 for the production of bendamustine hydrochloride, this patent has the advantages of simple synthetic route, high yield, and less wastewater. The expansion of downstream product research and development will inevitably lead to an increase in demand for 2-chloro-5-nitroaniline. In industry, 2-chloro-5-nitroaniline is mainly obtained from 2,4-dinitrochlorobenzene using the method of their regioselective reduction; however, the products contain isomer mixtures such as 4-chloro-3-nitroaniline.8−11 The synthetic route is shown in Figure 1. The separation of 2-chloro-5-nitroaniline from isomer mixtures is the first process in the whole synthesis of bendamustine hydrochloride. Thus, systematic research about solubility is of great significance. © XXXX American Chemical Society

Figure 1. Synthetic route of 2-chloro-5-nitroaniline according to ref 11.

In this work, the solubility of 2-chloro-5-nitroaniline in 12 pure organic solvents was determined from 278.15 to 318.15 K. The Apelblat equation, λh equation, Wilson model, and NRTL model were used to correlate the solubility data, and the applicability of these models was evaluated by Akaike information criterion (AIC). Afterward, the mixing property of Gibbs energy for the solution process of 2-chloro-5-nitroaniline in pure solvents was calculated by Wilson model.

2. EXPERIMENTAL SECTION 2.1. Materials. 2-Chloro-5-nitroaniline (the mass fraction is 0.996) and the solvents were purchased from Sinopharm Chemical Reagent Co., Ltd., China and used without further purification. These solvents selected in the experiment are the most commonly used organic solvents in our laboratory. The Received: October 15, 2018 Accepted: February 28, 2019

A

DOI: 10.1021/acs.jced.8b00931 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Detailed Information on the Materials Used in the Work chemicals

molar mass/ (g·mol−1)

melting point/K

melting enthalpy/ (kJ·mol−1)

2-chloro-5-nitroaniline

172.57

393.39a

27.026a

methanol n-propanol isopropanol ethanol toluene ethyl acetate acetonitrile 1,4-dioxane 1-butanol acetone 2-butanone N-methyl-2-pyrrolidone

32.04 60.06 60.06 46.07 92.14 88.11 41.05 88.11 74.12 58.05 72.11 99.13

density/ (kg·m−3) (295 K) 1494c

source Sinopharm Chemical Reagent Co., Ltd., China

mass fraction purity

analysis method

0.996

HPLCe

0.997 0.994 0.995 0.995 0.996 0.995 0.994 0.996 0.996 0.995 0.995 0.995

GCf GC GC GC GC GC GC GC GC GC GC GC

394.15b 786.5d 805.3d 803.5d 789.3d 871.0d 900.3d 776.8d 1033.7d 809.8d 784.5d 806.2d 1028d

a This work, determined at 101.2 kPa. The standard uncertainties u are u(T) = 0.5 K, u(p) = 0.45 kPa, and u(ΔfusH) = 0.4 kJ·mol−1. bTaken from ref 12. cCalculated with the Advanced Chemistry Development (ACD/Laboratories) Software V11.02 (1994−2016 ACD/Laboratories). dTaken from ref 16. eHigh-performance liquid phase chromatography. fGas chromatography.

the measured peak area and x is the concentration of solute). The representative chromatogram with the retention time was presented in Supporting Information Figure S1. The results showed that 10 h was enough to make the solution equilibrium for all the studied systems. After that, the magnetic stirrer was stopped and any solid was allowed to precipitate out from the mixture. Then about 2 mL (standard uncertainty, 0.01 mL) of the upper equilibrium liquor was taken out with the 2 mL syringe preheated or cooled in the thermostatic water bath. The sample was transferred instantaneously to a 25 mL flask covered with a rubber stopper and weighed using the analytical balance. It was diluted to the mark with corresponding solvent, and then 2 μL of the solution was gotten out to analyze by HPLC. During the experiment process, the atmospheric pressure was about 101.2 kPa. The mole fraction solubility (xe) of 2-chloro-5-nitroaniline in pure solvents can be calculated with eq 1.

detailed information on solute and solvents was presented in Table 1. 2.2. Melting Properties Measurement. The melting temperature (Tm ) of 2-chloro-5-nitroaniline has been determined by previous work;12 however, the fusion enthalpy (ΔfusH) has not been reported so far. Due to the need of thermodynamic model calculation, ΔfusH was measured by differential scanning calorimetric (DSC) instrument (PyrisDiamond, PerkinElmer), and the process is under a nitrogen atmosphere. Moreover, the DSC of excessive solids in solvents was measured as well. The instrument was recalibrated with indium. About 5 mg solid samples was added into a DSC pan and heated with a heating rate of 5 K·min−1 from 303 to 420 K. The standard uncertainty of temperature was 0.5 K, and 400 J· mol−1 for enthalpy of fusion. 2.3. Solubility Determination. The solid−liquid equilibrium for the pure systems of (solute + solvent) was determined by using the isothermal saturation method in the temperature range of 273.15−313.15 K.13,14 The reliability of verification of experimental apparatus was verified in our previous work.15 First, about 60 mL of solvent and some excess 2-chloro-5nitroaniline were added into the 100 mL glass vessel for each experiment. The temperature was maintained by circulating water through the outer jacket from the thermostatic watercirculator bath. The true temperature was displayed via a mercury glass microthermometer inserted in the inner chamber of the glass vessel, of which standard uncertainty was 0.02 K. A magnetic stirrer was used to mix the solid and solvent adequately. The liquid phase was taken out at intervals of 2 h using a 2 mL preheated syringe connected with a pore syringe filter (PTFE, 0.2 μm), and then tested by the highperformance liquid chromatography (HPLC, Agilent-1260). LP-C18 (250 mm × 4.6 mm) reversed-phase column was used in the detection process. The temperature was 303 K, and the wavelength of ultraviolet detector was 254 nm. The mobile phase was methanol/water = 4:1 in volume fraction, and the flow rate was 1.0 mL·min−1. The calibration curve of 2-chloro5-nitroaniline within the concentration range studied was linear, and the coefficient of determination (R2) value was 0.998. The calibration curve equation was y = 18937.3x (y is

xe =

m1/M1 m1/M1 + m2 /M 2

(1)

where m1 is the mass of solute and m2 is those of corresponding solvents. Besides, M1 and M2 are molar masses of solute and solvent.

3. RESULTS AND DISCUSSION 3.1. DSC of 2-Chloro-5-nitroaniline. The results of the DSC curve were shown in Figure 2. From the analysis of the DSC curve, in this study, Tm and ΔfusH are 393.39 K and 27.026 kJ·mol−1, respectively. Moreover, the Tm obtained is close to the data reported by ref 12. The DSC of excessive solids in solvents was measured as well and shown in Figure S2 in the Supporting Information. The results of melting point and enthalpy data were almost identical. 3.2. Solubility Data. Since the melting point of 1,4dioxane is about 285 K, only the temperature higher than that is studied in the determination of solubility. The determined mole fraction solubility (x) of 2-chloro-5-nitroaniline in methanol, ethanol, n-propanol, isopropanol, 1-butanol, acetonitrile, acetone, 2-butanone, ethyl acetate, 1,4-dioxane, toluene, and NMP at the temperature from 273.15 to 313.15 K are B



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absolute temperature T. As expressed in eq 3, it is a semiempirical equation.18,19 ln x = A + B /(T /K) + C ln(T /K)

(3)

where x represents the solubility of 2-chloro-5-nitroanilin in mole fraction in 12 pure organic solvents at studied temperature T in kelvin; A, B, and C are the model parameters. Wilson Model. For a solid−liquid system arriving at equilibrium at a certain temperature and pressure, a universal (solid−liquid) phase equilibrium model may be described as20 ln(xγ ) = Figure 2. DSC curve of 2-chloro-5-nitroaniline.

Ttp ΔHtp ijj 1 y 1 zy ΔCp ijj Ttp jj − zzzz − − + 1zzzz jjln j R j Ttp Tz R k T T { k { ΔV (p − ptp ) − (4) RT

where R is the universal gas constant having a value of 8.314 J· K−1·mol−1; x is solubility of the solute (in mole fraction), and γ is the activity coefficient of solute; ΔV and ΔCp are the difference of volume and heat capacity of solute in solid phase and liquid phase at the melting temperature. The simple equation describing the solubility of a solute in different solvents can be deduced from eq 5.20

listed in Table 2 and shown graphically in Figure 3. As can be seen, the result of solubility increases with increasing temperature. At a given temperature, the mole fraction solubility of 2-chloro-5-nitroaniline is largest in NMP and lowest in isopropanol. At 313.15 K, the mole solubility values of NMP and isopropanol are 0.0226 and 0.2092, respectively. Figure 3 also indicates that the value in different solvents decrease according to the following order: NMP > acetone > 2-butanone > 1,4-dioxane > ethyl acetate > acetonitrile > toluene > ethanol > n-propanol > methanol > 1-butanol > isopropanol. Solubility in alcoholic solvents was significantly lower than that in other solvents. Some properties of the studied solvents, which correspond to polarities, dipole moments (μ), dielectric constants (ε), and Hildebrand solubility parameters (δH),16 are presented in Table 3. It can be seen, in 2-chloro-5-nitroaniline + alcohol at 298.15 K, the sequence of the solubility data in mass fraction (w(methanol) = 0.0830, w (ethanol) = 0.0704, w (n‑propanol) = 0.0492, w (isopropanol) = 0.0370, w (1‑butanol) = 0.0427) is consistent with the polarities and Hildebrand solubility parameters (δH), except for isopropanol and 1-butanol. For other solvents, the order of them from high to low is in accordance with the polarities and dipole moments (μ) except for acetonitrile and ethyl acetate. In these studied solvents, the polarities seem to be more important, but the polarity of solvents is not the only factor. Besides, van der Waals force should also be taken into consideration. 3.3. Solubility Correlation and Calculation. The solubility behavior for 2-chloro-5-nitroaniline in pure solvents was correlated by four different thermodynamic models (λh equation,17 modified Apelblat equation,18,19 Wilson model,20 and NRTL model21). As expressed in eq 2, λh equation is a function of solubility data and absolute temperature (T), which is proposed by Buchowski and co-workers.17 However, the melting point of the solute is needed in the calculation. ÄÅ É λ(1 − x) ÑÑÑÑ 1 zyz ÅÅÅ ji 1 lnÅÅ1 + − ÑÑ = λhjjj z j ÅÅÇ Ñ x Tm/K zz{ ÑÖ (2) k T /K For many solid−liquid equilibrium systems, this model can well be used to describe the experimental solubility by changing the values of adjustable parameters λ and h. As described, Tm represents the melting temperature of 2-chloro5-nitroanilin in kelvin. Modified Apelblat Equation. The modified Apelblat equation is another function of mole fraction solubility and

ln(xiγi) =

ΔfusH ijj 1 1 yzz − jjj z R k Tm/K T /K zz{

(5)

In order to correlate the solubility (x) of 2-chloro-5nitroaniline with thermodynamic models, the activity coefficient (γ) is needed in advance. For binary mixtures, the expressions of Wilson model describing the activity coefficient ln γ are presented as eqs 6−-8.22 ÅÄÅ ÑÉÑ Λ12 Λ 21 Å ÑÑ ÑÑ ln γ1 = −ln(x1 + Λ12x 2) + x 2ÅÅÅÅ − ÅÅÇ x1 + Λ12x 2 x 2 + Λ 21x1 ÑÑÑÖ i Δλ12 yzz V2 i λ − λ11 yz V2 zz = expjjj− 12 expjjjj− zz V1 RT { V1 k k R(T /K) {

Λ12 =

Λ 21 =

i Δλ 21 yzz V1 V i λ − λ11 zy zz = 1 expjjjj− expjjj− 21 zz V2 RT { V2 k k R(T /K) {

(6)

(7)

(8)

In eqs 6−8, x1 and x2 are the compositions of solute and solvent in mole fraction. V1 is the molar volume of the solute, and V2, for the solvent. Δλij are model parameters (J·mol−1). NRTL Model. Based on the local composition concept, the NRTL model is applied to correlate the results of solubility as well.21 The vapor−liquid, liquid−liquid, and liquid−solid phase equilibrium are usually described by this function. The calculated process is provided as eqs 9−12. N ÅÄ ÑÉ N N ∑j = 1 τjiGjixj ∑i = 1 xiτijGij ÑÑÑÑ xjGij ÅÅÅÅ ln γi = +∑ N ÅÅÅτij − ÑÑ N N Å ∑i = 1 Gijxi ∑i = 1 Gijxi ÑÑÑÑ j = 1 ∑i = 1 Gijxi Å ÅÇ Ö (9)

Gji = exp( −αjiτji)

(10)

αij = αji = α

(11)

τij = C

gij − g jj R(T /K)

=

Δgij R(T /K)

(12) DOI: 10.1021/acs.jced.8b00931 J. Chem. Eng. Data XXXX, XXX, XXX−XXX


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Table 2. Experimental Mole Fraction Solubility (x) of 2-Chloro-5-nitroaniline in 12 Pure Solvents at the Temperature Range from T = 273.15 to 313.15 K under 101.2 kPaa T/K 273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

xexp

xNRTL

T/K

Methanol 0.0071 0.0071 0.0085 0.0085 0.010 0.01 0.0119 0.0119 0.014 0.014 0.0165 0.0165 0.0193 0.0193 0.0226 0.0226 0.0263 0.0264

0.0071 0.0085 0.0101 0.0119 0.0141 0.0165 0.0193 0.0226 0.0262

0.0071 0.0085 0.0101 0.0119 0.014 0.0165 0.0193 0.0226 0.0263

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

0.37

0.49

0.39

100RAD

0.0097 0.0112 0.0129 0.0149 0.0173 0.0198 0.0227 0.0258 0.0297

0.38 Ethanol 0.0097 0.0097 0.0112 0.0112 0.0130 0.013 0.0149 0.0149 0.0172 0.0172 0.0198 0.0197 0.0227 0.0226 0.0259 0.0259 0.0296 0.0297

0.0096 0.0112 0.013 0.015 0.0173 0.0198 0.0227 0.0259 0.0295

0.0096 0.0112 0.013 0.015 0.0172 0.0198 0.0227 0.0259 0.0296

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

0.43

0.37

100RAD

0.0080 0.0094 0.0110 0.0129 0.0152 0.0177 0.0209 0.0246 0.0283

0.30 0.34 n-Propanol 0.0079 0.0079 0.0094 0.0094 0.0110 0.0111 0.0130 0.0130 0.0152 0.0153 0.0178 0.0179 0.0209 0.0209 0.0244 0.0243 0.0284 0.0283

0.0079 0.0094 0.0111 0.0131 0.0153 0.0179 0.0209 0.0242 0.0281

0.0079 0.0094 0.0111 0.013 0.0153 0.0179 0.0209 0.0243 0.0282

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

0.99

0.80

100RAD

0.0047 0.0059 0.0074 0.0091 0.0109 0.0132 0.0158 0.0188 0.0226

0.45 0.67 Isopropanol 0.0048 0.0048 0.0059 0.0059 0.0073 0.0073 0.0090 0.0089 0.0109 0.0108 0.0132 0.0131 0.0158 0.0158 0.0189 0.019 0.0225 0.0228

0.0048 0.0059 0.0073 0.0089 0.0109 0.0132 0.0158 0.019 0.0227

0.0048 0.0059 0.0073 0.0089 0.0108 0.0131 0.0158 0.019 0.0228

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

0.87

1.06

100RAD

0.0055 0.0069 0.0086 0.0104 0.0128 0.0153 0.0182 0.0213 0.0252

0.75 1.03 1-Butanol 0.0055 0.0057 0.0069 0.0069 0.0086 0.0085 0.0105 0.0103 0.0127 0.0125 0.0153 0.015 0.0182 0.0181 0.0215 0.0216 0.0251 0.0258

0.0056 0.0069 0.0085 0.0103 0.0125 0.0151 0.0181 0.0216 0.0257

0.0056 0.0069 0.0085 0.0104 0.0126 0.0151 0.0181 0.0216 0.0255

288.15 293.15 298.15 303.15 308.15 313.15

0.44

1.33

1.06

100RAD 273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 100RAD 273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 100RAD 273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 100RAD 273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 100RAD

xλh

xWilson

0.0071 0.0085 0.0100 0.0118 0.0141 0.0165 0.0193 0.0227 0.0263

xapelblat

1.55

xexp 0.0118 0.0134 0.0153 0.0174 0.0199 0.0231 0.0268 0.0309 0.0352

xapelblat

xλh

xWilson

xNRTL

Toluene 0.0117 0.0115 0.0134 0.0133 0.0153 0.0154 0.0175 0.0177 0.0201 0.0203 0.0231 0.0233 0.0266 0.0267 0.0307 0.0305 0.0354 0.0349

0.0115 0.0133 0.0154 0.0178 0.0204 0.0234 0.0267 0.0304 0.0345

0.0115 0.0133 0.0154 0.0177 0.0204 0.0233 0.0267 0.0304 0.0347

0.54

1.17

1.59

1.38

0.1557 0.1607 0.1661 0.172 0.1784 0.1855 0.1932 0.2017 0.2111

0.1549 0.1606 0.1665 0.1727 0.1793 0.1861 0.1934 0.201 0.2091

0.1558 0.1608 0.1662 0.1721 0.1784 0.1854 0.193 0.2015 0.2108

0.06

0.38

0.1028 0.1124 0.1226 0.1333 0.1445 0.1563 0.1688 0.1819 0.1958

0.1035 0.1126 0.1223 0.1327 0.1437 0.1556 0.1685 0.1824 0.1975

0.21

0.30

0.0884 0.0976 0.1074 0.1178 0.1288 0.1404 0.1528 0.1659 0.1798

0.089 0.0978 0.1071 0.1172 0.1281 0.1398 0.1525 0.1663 0.1814

0.51

0.92

0.1095 0.1198 0.1306 0.1422 0.1544 0.1675

0.1099 0.1197 0.1303 0.1417 0.1544 0.1681

0.55

0.32

0.0767 0.0837

0.0773 0.0838

NMP 0.1550 0.1605 0.1664 0.1729 0.1794 0.1862 0.1931 0.2010 0.2092

0.06

0.1032 0.1123 0.1225 0.1332 0.1444 0.1561 0.1682 0.1818 0.1969

0.38 Acetone 0.1033 0.1038 0.1125 0.1127 0.1224 0.1222 0.1329 0.1324 0.1441 0.1435 0.156 0.1555 0.1687 0.1684 0.1822 0.1825 0.1965 0.1979

0.0877 0.0973 0.1079 0.1186 0.1296 0.1409 0.1529 0.1650 0.1787

0.18 0.43 2-Butanone 0.0879 0.0892 0.0975 0.0978 0.1076 0.107 0.1183 0.117 0.1294 0.1279 0.141 0.1397 0.1531 0.1525 0.1655 0.1665 0.1783 0.1818

0.1104 0.1194 0.1297 0.1417 0.1540 0.1689

0.19 1.05 1,4-Dioxane 0.1103 0.1099 0.1195 0.1196 0.1298 0.1302 0.1413 0.1418 0.1543 0.1544 0.1688 0.1682

0.0765 0.0836

0.12 0.30 Ethyl Acetate 0.0766 0.0774 0.0837 0.0838

100RAD 273.15 278.15 D

0.155 0.1606 0.1665 0.1727 0.1793 0.1862 0.1934 0.2011 0.2091



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Table 2. continued T/K 283.15 288.15 293.15 298.15 303.15 308.15 313.15

xexp 0.0915 0.0991 0.1073 0.1157 0.1256 0.1354 0.1450

Ethyl Acetate 0.0912 0.0908 0.0991 0.0983 0.1074 0.1065 0.1162 0.1153 0.1254 0.125 0.1351 0.1357 0.1452 0.1473

0.0222 0.0277 0.0342 0.0413

0.18 0.72 Acetonitrile 0.0223 0.0232 0.0278 0.028 0.0341 0.0337 0.0413 0.0402

100RAD 273.15 278.15 283.15 288.15

xλh

xapelblat

xWilson

xNRTL

T/K

0.0911 0.099 0.1073 0.116 0.1253 0.1351 0.1456

0.0909 0.0985 0.1066 0.1154 0.125 0.1355 0.1471

293.15 298.15 303.15 308.15 313.15

0.23

0.61

0.0231 0.028 0.0337 0.0403

0.0232 0.028 0.0336 0.0402

xexp

xapelblat

0.0495 0.0579 0.0671 0.0770 0.0877

100RAD

xλh

xWilson

xNRTL

Acetonitrile 0.0492 0.0478 0.0579 0.0565 0.0673 0.0666 0.0772 0.0781 0.0876 0.0914

0.0479 0.0567 0.0667 0.0781 0.091

0.0477 0.0565 0.0667 0.0784 0.0919

0.22

2.20

2.55

2.47

a

x denotes the experimental mole fraction solubility of 2-chloro-5nitroaniline at the studied temperature T; RAD denotes the relative deviation and the relative average deviation, respectively. Standard uncertainties u are u(T) = 0.02 K, u(p) = 400 Pa; relative standard uncertainty ur is ur(x) = 0.018. xexp, experiment data; xApelblat, calculated by Apelblat model; xλh, calculated by λh model; xWilson, calculated by Wilson model; xNRTL, calculated by NRTL model.

Figure 3. Solubility (x) of 2-chloro-5-nitroaniline in mole fraction in 12 pure solvents at different temperatures: (A) ■, methanol; ●, ethanol; ▲, n-propanol; ▼, isopropanol; ◆, 1-butanol; ★, toluene; (B) ◇, 1,4-dioxane; ○, acetone; ▽, ethyl acetate; □, acetonitrile; ☆, NMP; Δ, 2-butanone.

Table 3. Physical Properties for the Selected Solventsa solvent

polarity (water, 100)

μ(298 K)/D

ε(293 K)/ (F·m−1)

δH(298 K)/ (cal1/2·cm−3/2)

ethanol methanol n-propanol acetonitrile ethyl acetate isopropanol toluene 1-butanol 1,4-dioxane acetone 2-butanone NMP

65.4 76.2 61.7 46 23 54.6 9.9 60.2 16.4 35.5 32.7 36

1.7 1.7 1.7 3.2 1.7 1.66 0.4 1.66 0.4 2.9 2.8 4.1

22.4 32.6 20.1 37.5 6.02 18.3 2.38 18.2 2.21 20.6 18.5 32.2

13.4 14.5 11.9 11.9 9.1 11.5 8.9 24.1 10.0 10.0 19.62 23.2

τij = aij +

bij (14)

T

where aij and bij are adjustable model parameters relating to energy interaction between component i and component j. The two parameters are independent upon temperature and composition. The experimental solubility of 2-chloro-5-nitroaniline in the selected pure solvents are correlated and calculated by using the method of nonlinear regression.24 During the regression process, the objective function is defined as F=

∑ (ln xie − ln xic)2 i=1

(15)

where ln xei and ln xci are the logarithm of experimental and calculated solubility data in mole fraction, respectively. In this work, these four solubility models are evaluated by relative average deviation (RAD) and root-mean-square deviation (RMSD), which are expressed as eqs 16 and17, respectively.

a

Taken from ref 16.

where Δgij are model parameters (J·mol−1). α exhibits the nonrandomness of the solution (varies from 0.20 to 0.47). Assuming that the binary cross-interaction parameters in the Wilson model (Δλij) and NRTL model (Δλij) are a linear relationship with temperature, as described in the previous works;23 the Λij in Wilson model and τij in NRTL model can be expressed as eqs 13 and 14, respectively. ÄÅ É bij yzÑÑÑÑ Vj ÅÅÅ ij expÅÅÅ−jjjaij + zzzÑÑÑ Λ ij = ÅÅ j T z{ÑÑÑÖ Vi (13) ÅÇ k

RAD =

1 N

i |xic − xie| yz zz zz e k xi {

∑ jjjjj

(16)

N

RMSD = E

∑i = 1 (xic − xie)2 N

(17) DOI: 10.1021/acs.jced.8b00931 J. Chem. Eng. Data XXXX, XXX, XXX−XXX


Article

Table 4. Parameters of the Modified Apelblat Equation and λh Equation for 2-Chloro-5-nitroaniline in Different Solvents λh equation

modified Apelblat equation solvent

A

B

C

104RMSD

λ

h

104RMSD


−59.529 −46.619 −86.574 185.87 −7.374 −3.759 −139.078 76.723 −127.444 −27.216 30.346 −40.75

390.738 −535.722 1286.967 −10757.407 −938.494 −2847.4 3904.237 −6305.001 4312.531 −63.426 −2705.024 1163.93

9.529 7.777 13.73 −26.79 1.469 1.576 21.45 −10.488 19.471 4.488 −4.077 6.172

0.68 0.58 1.03 1.34 2.50 0.83 1.45 0.74 2.02 3.07 2.76 1.50

0.083 0.113 0.112 0.524 0.10 0.156 0.095 0.165 0.16 0.174 0.213 −0.111

24296.128 22275.644 21622.008 5350.639 7005.672 20094.712 20813.621 18390.021 5593.508 4706.132 4844.206 7409.557

0.73 0.69 1.30 15.78 9.88 1.21 2.65 2.65 4.59 6.76 15.74 8.64

Table 5. Parameters of the Wilson and NRTL Models for 2-Chloro-5-nitroaniline in Different Solvents Wilson model

NRTL model

solvent

a12

b12/K

a21

b21/K

10 RMSD

a12

b12/K

a21

b21/K

α

104RMSD


2.886 1.307 1.948 −0.485 4.561 0.455 3.416 0.748 3.639 3.682 3.558 6.244

−969.96 −560.03 −645.12 −319.30 −1873.18 −40.09 −1000.81 −115.64 −1679.29 −1797.97 −1667.04 −2534.87

57.536 19.338 62.604 15.526 14.597 94.004 102.115 17.055 58.311 289.669 448.685 11.794

−5219.056 21091.388 −4656.058 2111.898 1259.778 32180.101 −5341.885 2391.839 1820.745 −50320.342 −100550.90 −2427.501

1.02 0.77 1.39 14.33 2.96 1.05 3.89 2.36 8.34 4.53 7.02 1.27

289.69 754.575 366.906 −189.826 −547.655 1149.677 213.99 7.415 10887.624 1825.351 −390.766 −220.083

4012.515 98393.226 16788.181 796.53 −367772.221 −627916.441 82218.638 7.675 −3300582.77 −755577.023 210074.588 −29978.464

4.888 3.668 3.891 1.681 6.229 2.121 4.875 −0.027 5.453 5.284 4.992 8.592

−1054.171 −636.574 −727.214 −422.383 −2035.41 −107.957 −1099.633 −27.851 −1854.342 −1882.654 −1747.175 −2954.358

0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2

0.72 0.64 1.54 17.31 8.55 1.33 3.31 1.83 4.99 4.64 13.69 8.24

4

Table 6. Value of the Akaike Information Criterion of the the Modified Apelblat Equation, λh Equation, Wilson Model, and NRTL Model in the Selected Solvents model Apelblat equation λh equation Wilson model NRTL model

RSS −6

3.25 × 10 6.725 × 10−5 3.222 × 10−5 6.264 × 10−5

N

no. of params

AIC

e((AICmin − AICi)/2)

105 105 105 105

3 2 4 4

−11.291 −10.261 −6.997 −6.332

1.0000 0.5975 0.1168 0.0838

a

ωi

0.5561 0.3323 0.0650 0.0466

ωi = Akaike weight.

a

where xci stands for the calculated solubility values of 2-chloro5-nitroaniline, and xei , experimental ones. N is the number of experimental data points. During the process of regression using the activity coefficient equation, the density of 2-chloro-5-nitroaniline is calculated with Advanced Chemistry Development (ACD/Laboratories) Software V11.02 (1994−2016 ACD/Laboratories). While in solvent, it is taken from the ref 16. Furthermore, the Tm and ΔfusH of 2-chloro-5-nitroaniline are taken from this work. The results of model parameters of these four functions along with the RMSD values are presented in Tables 4 and 5, In addition, the difference between the experimental and calculated solubility values were compared, the calculated solubility data of 2-chloro-5-nitroaniline with four models along with calculated RAD values are presented in Table 2. Moreover, in Tables 4 and 5, the largest RMSD value is 17.31 × 10−4, which is obtained with the NRTL model in the system of solute + acetonitrile. The RAD values are all less than 2.55%. All of these models show satisfactory correlation results with

the experimental values and can help to understand the relationship between the solubility and temperature as well as solvent composition. All the results could be an auxiliary guide in the separation and purification process of 2-chloro-5nitroaniline. The obtained solubility and thermodynamic studies would be very helpful for optimizing the purification process of 2-chloro-5-nitroaniline. 3.4. Akaike Information Criterion of Four Models. The Akaike Information criterion (AIC)25 was used to compare the relative applicability of these models. Generally, the model with the lowest value of AIC can be supposed to be the best-fit model. The value of AIC for the four models is given as follows: AIC = −2 ln L(θ ) + 2k

(18)

Here L(θ) is the maximized likelihood value for the estimated model, and k is the number of estimable parameters in the model. F



2-butanone acetone

AICi )/2)

(23)

where x1 denotes the mole fraction of solute, and x2, the solvent; the superscript id denotes the ideal state. The excess mixing properties can be evaluated by using eq 24 in terms of the Wilson model. The mixing properties are described as eqs 24 according to the Wilson model.26 GE = RT (x1 ln γ1 + x 2 ln γ2) = −RT[x1 ln(x1 + x 2 Λ12) + x 2 ln(x 2 + x1Λ 21)] (24)

ΔmixG is calculated by Wilson model, presented in Table 7, and graphically plotted in Figure 4. For different solution, the dissolution ability of a solute can be inflected by the mixing Gibbs energy (ΔmixG). According to Table 7 and Figure 4, the values of ΔmixG are all negative and decrease with the increase in temperature. We can conclude that the dissolution process in the selected pure solvents is spontaneous and favorable. G

NMP toluene

−123.24 −136.55 −151.67 −167.66 −185.75 −207.59 −231.26 −255.76 −279.72 −58.07 −70.47 −84.83 −99.52 −117.98 −136.49 −156.95 −177.94 −202.74

1-butanol isopropanol

−49.58 −60.25 −72.97 −86.79 −100.96 −118.09 −136.59 −156.88 −180.94 −83.76 −95.81 −109.03 −124.02 −141.24 −159.07 −180.49 −203.71 −225.65

Δmix Gid = RT (x1 ln x1 + x 2 ln x 2)

n-propanol

For an ideal solution, the mixing Gibbs energy in pure solvents are expressed as 37

ethanol

(22)

−101.73 −114.25 −127.83 −143.04 −160.32 −177.38 −196.03 −214.81 −236.85

Δmix G = GE + Δmix Gid

Table 7. Calculated Values of Mixing Gibbs Free Energy (ΔmixG/(J·mol−1)) in Studied Solution

Here M is the number of the selected models in the comparison; AICmin is the minimum value of AIC for the selected models; AICi is the AIC value of the ith model. The value of Akaike weights is also presented in Table 6. The lowest AIC value and the highest Akaike weight value indicate that the Apelblat equation can be used to correlate the solubility data of 2-chloro-5-nitroaniline best among these four models. 3.5. Thermodynamic Analysis of Gibbs Energy. According to the Lewis−Randall rule, the thermodynamic property of Gibbs energy can be obtained. For real solution, the mixing properties may be calculated by using eqs 22 and 23.

−1628.7 −1637.42 −1646.23 −1656.01 −1662.29 −1666.89 −1668.41 −1671.53 −1671.79

(21)

−74.52 −86.6 −99.08 −113.38 −130.63 −147.83 −166.82 −188.47 −210.11

− AICi )/2)

methanol

exp((AICmin − M ∑i = 1 exp((AICmin

solvents

ωi =

1,4-dioxane

Here, RSS is the residual sum of squares; xe and xc are the experimental and calculated solubility data of 2-chloro-5nitroaniline. N is the number of observations. Table 6 shows the results of AIC for these four models. From this table, we can find that, in 2-chloro-5-nitroaniline + solvents, the result of Apelblat equation is obviously lower than that of the other three models. In other words, it indicates that Apelblat equation is more suitable to correlate the results. Meanwhile, Akaike weights, ωi, are employed to determine the best model with highest Akaike weights as well, which is expressed as

−1055.45 −1107.72 −1164.02 −1225.36 −1282.32 −1346.22

ethyl acetate

(20)

i=1

T/K

∑ (xie − xic)2

−923.49 −993.45 −1066.09 −1134.17 −1199.01 −1260.37 −1320.34 −1375.03 −1431.97

N

RSS =

−1083.58 −1146 −1212.07 −1276.5 −1338.83 −1398.56 −1454.67 −1512.66 −1570.86

with

−804.4 −853.13 −904.24 −949.25 −994.51 −1036.94 −1084.04 −1125.46 −1160.93

(19)

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15

AIC = N ln(RSS/N ) + 2k

acetonitrile

In the special case of least-squares estimation with normal distributed errors, apart from an additive constant, AIC can be simplified to

−235.26 −283.2 −337.06 −393.25 −454.87 −515.4 −578.62 −643.47 −710.13

Article



Article

Figure 4. Calculated mixing Gibbs energy at measured solubility points based on Wilson model: (A) ■, methanol; ●, ethanol; ▲, n-propanol; ▼, isopropanol; ◆, 1-butanol; ★, toluene; (B) ◇, 1,4-dioxane; ○, acetone; ▽, ethyl acetate; □, acetonitrile; ☆, NMP; Δ,2-butanon. (5) Wei, H. Y.; Xu, C. H.; Zhou, P. H. Method for synthesizing intermediate of Bendamustine hydrochloride. CN Patent 108,358,848, Aug. 3, 2018. (6) Chen, J.; Przyuski, K.; Roemmele, R. C. Processes for the Preparation of Bendamustine. U.S. Patent 8,420,829, Apr. 16, 2013. (7) Du, Y. G.; Zong, Z. W.; Chen, L.; Yang, J. N. Method for preparing high-purity bendamustine hydrochloride. CN Patent 101,948,436, Jan. 19, 2011. (8) Liu, S. S.; Liu, X.; Yu, L.; Liu, Y. M.; He, H. Y.; Cao, Y. Gold supported on titania for specific monohydrogenation of dinitroaromatics in the liquid phase. Green Chem. 2014, 16, 4162−4169. (9) Guillen, E.; Rico, R.; Lopez-Romero, J. M.; Bedia, J.; Rosas, J. M.; Rodriguez-Mirasol, J.; Cordero, T. Pd-activated carbon catalysts for hydrogenation and Suzuki reactions. Appl. Catal. Appl. Catal., A 2009, 368, 113−120. (10) Orlov, V. Y.; Begunov, R. S.; Demidova, N. Y.; Rusakov, A. I. Effect of the electronic structure of the radical anions of 4-substituted 1, 2-and 1, 3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups. Russ. J. Gen. Chem. 2006, 76, 76−81. (11) Yuan, M.; Long, Y.; Yang, J.; Hu, X. W.; Xu, D.; Zhu, Y. Y.; Dong, Z. P. Biomass Sucrose Derived Cobalt@ Nitrogen Doped Carbon for Catalytic Transfer Hydrogenation of Nitroarenes with Formic Acid. ChemSusChem 2018, 11, 4156−4165. (12) Ramana, M. M. V.; Malik, S. S.; Parihar, J. A. Guanidinium nitrate: a novel reagent for aryl nitrations. Tetrahedron Lett. 2004, 45, 8681−8683. (13) Yao, G. B.; Li, Z. H.; Xia, Z. X.; Yao, Q. C. Solubility of Nphenylanthranilic acid in nine organic solvents from T = (283.15 to 318.15) K: Determination and modeling. J. Chem. Thermodyn. 2016, 103, 218−227. (14) Yao, G. B.; Yao, Q. C.; Xia, X. Z.; Li, Z. H. Solubility determination and correlation for o -phenylenediamine in (methanol, ethanol, acetonitrile and water) and their binary solvents from T = (283.15−318.15) K. J. Chem. Thermodyn. 2017, 105, 179−186. (15) Xu, R. J.; Han, T. Influence of different solvent properties and composition for the solubility of Iopromide. J. Chem. Eng. Data 2018, 63, 4032−4038. (16) Smallwood, I. M. Handbook of Organic Solvent Properties; Elsevier: London, 1996. (17) Buchowski, H.; Ksiazczak, A.; Pietrzyk, S. Solvent activity along a saturation line and solubility of hydrogen-bonding solids. J. Phys. Chem. 1980, 84, 975−979. (18) 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. (19) Apelblat, A.; Manzurola, E. Solubilities of L-glutamic acid, 3nitrobenzoic acid, p-toluic acid, calcium-L-lactate, calcium gluconate, magnesium-DL-aspartate, and magnesium-L-lactate in water. J. Chem. Thermodyn. 2002, 34, 1127−1136.

5. CONCLUSIONS In this work, the results of solubility data for 2-chloro-5nitroaniline in 12 solvents were determined experimentally. It increased with increasing temperature. At a given temperature, it ranked as NMP > acetone > 2-butanone > 1,4-dioxane > ethyl acetate > acetonitrile > toluene > ethanol > n-propanol > methanol > 1-butanol > isopropanol. The achieved solubility values were correlated by the modified Apelblat equation, λh equation, Wilson model, and NRTL model. The maximum values of RMSD and RAD were 17.31 × 10−4 and 2.55%, respectively. According to the results of AIC, Apelblat equation is more suitable to correlate the solubility data. Moreover, the mixing Gibbs energy in solution was computed and the dissolution process was spontaneous and favorable.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.8b00931. Representative chromatogram with the retention time of 2-chloro-5-nitroaniline; Dscan of raw and excessive solids in 12 solvents (PDF)

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AUTHOR INFORMATION

Corresponding Author

*[email protected] (Jian Wang). ORCID

Renjie Xu: 0000-0001-5541-1622 Jian Wang: 0000-0001-5882-3470 Notes

The authors declare no competing financial interest.

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REFERENCES

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Solubility Measurement and Thermodynamic Model Correlation and

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