Solubility of Diosgenin in Several Imidazolium-Based Ionic Liquids

Article pubs.acs.org/jced

Solubility of Diosgenin in Several Imidazolium-Based Ionic Liquids Li Ge, Liangchi Guo, Kedi Yang,* Kejia Tao, Jing Su, and Yunfei Long School of Chemistry & Chemical Engineering, Guangxi University, Nanning 530004, China ABSTRACT: The solubility of diosgenin in four pure imidazolium-based ionic liquids, including [C 4 mim]NO 3 (1-butyl-3-methylimidazolium nitrate), [C2mim]NTf2 (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), [C4mim]NTf2 (1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), and [C8mim]NTf2 (1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), were determined in the temperature range from (312.85 to 363.95) K at atmospheric pressure via a laser monitoring observation method. The solubility of diosgenin in the selected ionic liquids increased with increasing temperature. Diosgenin was especially soluble in [C8mim]NTf2, with a mole fraction of (0.287−1.630) × 10−3 at (312.85 to 332.25) K. The experimental data were successfully correlated using the dual-parameter empirical equation, Apelblat equation, and λh equation.

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INTRODUCTION Diosgenin (CAS No. 512-04-9) is an important steroidal sapogenin (Figure 1) and well-known precursor for the

commonly used imidazolium-based ILs, measured its solubility in four of them, and correlated these solubilities to temperature using the dual-parameter empirical, Apelblat and λh equations. The aim of this work was to extend the application of ILs to the extraction of diosgenin.

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EXPERIMENTAL SECTION Materials. The diosgenin (mass fraction purity greater than 0.995) used in these experiments was purchased from SigmaAldrich Corp. All of the ILs (Table 1) were purchased from Lanzhou Greenchem ILS, LICP, CAS, China. The volatile compounds and water residues in the ILs were distilled off over a period of 4 h in a rotary evaporator; the ILs were subsequently dried at 398.5 K under vacuum for 24 h. The purity of the ILs used in the current study was greater than 0.995, as determined by a Lab Alliance model 200 highperformance liquid chromatography system (Scientific System, Inc., United States). The water content in the ILs was less than 0.1 % on the basis of Karl Fischer titrations using a Metrohm 798 MPT Titrino (Metrohm Co., Switzerland). Solubility Determination. The solubility of diosgenin was determined via a laser monitoring method using purpose-made equipment, as described in our previous work.12 Diosgenin and ILs were accurately weighed on a ME204 Mettler-Toledo analytical balance with an accuracy of ± 0.1 mg (MettlerToledo Instruments (Shanghai) Co., Ltd.). The samples were placed in a glass solubilization vessel with a jacket controlled by a digital thermostatic water circulator bath with an accuracy of ± 0.1 K and a heating a rate of 0.2 K·h−1. The vessel was fitted between the laser generator and receiver to allow the laser beam to pass through it. At the beginning of the experiments, the laser power signals were low because the laser passing

Figure 1. Chemical structure of diosgenin.

semisynthesis of steroidal drugs such as progesterone and testosterone in the pharmaceutical industry.1−3 Traditionally, diosgenin is prepared via the acid hydrolysis of diosgenin glycoside from plants (fenugreek, roots of Dioscorea villosa and Solanum incanum, etc.) followed by a solid−liquid extraction using nonpolar or weakly polar organic solvents such as gasoline and petroleum ether. However, this process is a challenging and daunting task because of the volatility and flammability of conventional organic solvents. Over the past decade, ionic liquids (ILs) have received increasing interest for separation processes.4 Some examples of ILs being used for the solid−liquid and liquid−liquid extraction of natural compounds or as potential pharmaceutical solvents have been reported,5−10 thereby demonstrating that ILs can potentially be used as alternative solvents to extract pharmaceutical compounds from various plant materials. Solubility data for natural compounds in ILs is essential to understanding the extractability, design, and operation of the extraction process. Thus, far, however, only a few studies have reported solubility data for natural compounds in ILs.11 In this paper, we investigated the dissolution of diosgenin in seven © 2014 American Chemical Society

Received: May 15, 2014 Accepted: December 4, 2014 Published: December 22, 2014 11

dx.doi.org/10.1021/je5004324 | J. Chem. Eng. Data 2015, 60, 11−15

Journal of Chemical & Engineering Data

Article

Table 1. ILs Used to Dissolve Diosgenin

Table 2. Measured Values and Values Calculated from eqs 2, 3 and 4 for the Mole Fraction Solubility of Diosgenin under Atmospheric Pressurea T/K

103xexpb

c 103xcal 1

333.25 338.05 345.85 350.95 352.85 356.95 104RMSDe

0.126 0.174 0.242 0.290 0.338 0.387

0.133 0.167 0.240 0.301 0.323 0.390

342.95 350.25 355.45 363.95 104RMSD

0.168 0.220 0.266 0.317

0.175 0.219 0.254 0.323

328.95 337.95 342.05 351.55 355.55 359.45 104RMSD

0.263 0.385 0.527 0.608 0.709 0.851

0.285 0.398 0.461 0.640 0.731 0.829

312.85 315.55 323.65 325.45 328.85 332.25 104RMSD

0.287 0.419 0.772 0.992 1.322 1.630

0.320 0.407 0.821 0.955 1.266 1.667

RDd [C4mim]NO3 −5.556 4.023 0.826 −3.793 4.438 −0.775 0.087 [C2mim]NTf2 −4.167 0.455 4.511 −1.893 0.076 [C4mim]NTf2 −8.365 −3.377 12.524 −5.263 −3.103 2.585 0.341 [C8mim]NTf2 −11.498 2.864 −6.347 3.730 4.236 −2.270 0.398

103xcal 2

RD

103xcal 3

RD

0.131 0.167 0.241 0.302 0.328 0.387

−3.968 4.023 0.413 −4.138 2.959 0.000 0.073

0.133 0.167 0.240 0.301 0.327 0.390

−5.556 4.023 0.826 −3.793 3.254 −0.775 0.077

0.166 0.223 0.263 0.317

1.190 −1.364 1.128 0.000 0.023

0.176 0.218 0.254 0.323

−4.762 0.909 4.511 −1.893 0.079

0.280 0.399 0.464 0.643 0.732 0.826

−6.464 −3.636 11.954 −5.757 −3.244 2.938 0.337

0.286 0.398 0.461 0.639 0.730 0.831

−8.745 −3.377 12.524 −5.099 −2.962 2.350 0.338

0.294 0.390 0.836 0.974 1.279 1.645

−2.439 6.921 −8.290 1.815 3.253 −0.920 0.351

0.320 0.407 0.821 0.956 1.267 1.667

−11.498 2.864 −6.347 3.629 4.160 −2.270 0.394

a

cal cal Standard uncertainties u are u(T) = 0.1 K, ur(x) = 0.07. bxexp are the experimental values. cxcal 1 , x2 , and x3 are the values calculated from the duald parameter eq (2), the Apelblat eq (3) and the λh eq (4), respectively. RD is the relative average deviation, and RD = (xexp − xcal)/xexp·100 %. e RMSD = (Σi N= 1(xexp − xcal)2/N)1/2, where N is the number of experimental points for each solid−liquid system.

through the vessel was sheltered by the solid solute floating in the liquid. As the temperature was gradually increased, more

solid was dissolved and the detected laser power increased. When the solid was fully dissolved, the power signals in the 12



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Table 3. Parameters for eqs 2, 3, and 4 for Diosgenin in Four Imidazolium-Based ILs ILs dual-parameter equation

Apelblat equation

λh equation

A B R2 A B C R2 λ h R2

[C4mim]NO3

[C2min]NTf2

[C4min]NTf2

[C8min]NTf2

7.29 −5402.74 0.9927 220.09 −16175.36 −31.07 0.9930 0.01800 295999.25 0.9926

1.93 −3628.75 0.9812 1050.37 −57739.27 −152.58 0.9981 0.002664 1247215.76 0.9792

4.43 −4144.35 0.9698 116.71 −9824.75 −16.40 0.9700 0.01281 310433.10 0.9698

20.23 −8848.28 0.9930 941.57 −53016.31 −135.80 0.9944 6.3807 1387.96 0.9930

interactions and hydrogen-bonding interactions between diosgenin and the IL molecules have remarkable effects on the diosgenin solubility. Solubility Data Fitting for Diosgenin in Four Imidazolium-Based ILs. The universal relationship between solubility and temperature, which is based on thermodynamic principles, can be expressed for the solid−liquid equilibrium as16

receiver reached a maximum and remained constant, and the vessel temperature reached equilibrium. Every experimental point was measured three times, represented by the average value. The uncertainty of the mole fraction solubilities was approximately 7 %. In addition, to verify the reliability of this experimental method, the solubility of potassium chloride in water was measured at (293−343) K and compared to available solubility data;13 the average relative deviation was less than 0.12 %.

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ln(γx) =

RESULTS AND DISCUSSION Dissolving Behavior of Diosgenin in Selected Imidazolium-Based ILs. The dissolving behavior of diosgenin in seven imidazolium-based ILs was investigated. In the temperature range used during these experiments, diosgenin is almost insoluble in [C4mim]Cl, [C4mim]BF4 and [C4mim]PF6; therefore, the solubility of diosgenin in the remaining four ILs was measured. The experimental solubility data are listed in Table 2. Diosgenin is a natural, weakly polar compound that easily dissolves in organic solvents such as gasoline, petroleum ether and acetic ether. Diosgenin is less soluble in the selected ILs than in typical organic solvents;14,15 the solubility of diosgenin in methanol, ethanol and acetic ether is (0.187− 0.994)·10−3 at (291.15−331.65) K, (1.063−3.879)·10−3 at (289.15−334.15) K, and (2.402−6.726)·10−3 at (300.65− 328.95) K, respectively. However, the solubility of diosgenin in [C8mim]NTf2 was similar to that in methanol and ethanol. In addition, the experimental results illustrated that the solubility of diosgenin in the selected imidazolium-based ILs increased with increasing temperature, which is analogous to its solubility behavior in conventional organic solvents. Furthermore, the solubility of diosgenin was largely governed by the ILs’ molecular structures. As shown in Table 2, diosgenin exhibited remarkably different solubilities in ILs with the same [C4mim]+ cation and different anions (i.e., Cl−, BF4−, PF6−, NO3−, and NTf2−) and was almost insoluble in [C4mim]Cl, [C4mim]BF4, and [C4mim]PF6. The effect of the IL anion on the diosgenin dissolution decreased in the order NTf2−> NO3− > Cl− > BF4− ≈ PF6−. This phenomenon is attributed to the NTf2− anion, which contains more H acceptors to form hydrogen bonds with the −OH group in diosgenin. Additionally, the experimental solubility results indicated the imidazolium cation alkyl chain length played an important role in the dissolution of diosgenin. Among the ILs containing the NTf2− anion, [C8mim]NTf2 exhibited the best diosgenin dissolution, followed by [C4mim]NTf2 and [C2mim]NTf2; the order of this sequence is attributed to the hydrophobic interactions between diosgenin molecules and the IL cation. Therefore, the hydrophobic

ΔfusH Δc P (1 − Tt /T ) − ln(1 − Tt /T ) RTt R Δc p − ln Tt /T R

(1)

where γ, ΔfusH, Tt, and Δcp are the activity coefficient, the molar enthalpy of fusion, the triple-point temperature of the solute, and the difference in heat capacities between the solid and liquid forms of the solute at the melting temperature, respectively; x is the solute solubility expressed as a mole fraction; T is the equilibrium temperature (K); and R is the universal gas constant. Equation 1 is frequently simplified by neglecting the last two terms under the hypothesis that Δcp is small compared to ΔfusH. If the solution is assumed to be an ideal solution (γ = 1), eq 1 can be simplified as a dualparameter equation (eq 2), where A and B are empirical parameters fitted by experimental data: ln x = A + B /T

(2)

The relationship between the mole fraction of the solute and the temperature is also widely described using the Apelblat equation (eq 3), which can be deduced from the Clausius− Clapeyron equation:17 ln x = A + B /T + C ln T

(3)

where x is the mole fraction of the solute at system temperature T and A, B, and C are empirical parameters obtained via a nonlinear least-squares fit according to experimental solubility data. The Buchowski−Ksiazczak λh equation (eq 4) is also generally employed to describe the solution behavior of solid−liquid systems without considering the solute activity coefficient:18 ⎛1 ⎡ λ(1 − x) ⎤ 1 ⎞ ln⎢1 + ⎟ ⎥ = λh⎜ − ⎣ ⎦ x Tm ⎠ ⎝T

(4)

where x is the solubility expressed as a mole fraction, λ and h are empirical parameters obtained by fitting to experimental data, T is the absolute temperature, and Tm is the solute melting temperature. 13



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The parameters for eqs 2, 3, and 4 were fit according to our data; the results are listed in Table 3. The diosgenin solubility calculated using eqs 3, 4, and 5 are listed in Table 2 and displayed in Figure 2. These results indicate that the calculated

deviation (SD) are listed in Table 4. Because of the electrostatic interactions of cations and anions in the IL, the interactions Table 4. Dissolution Enthalpy and Entropy for Diosgenin in the Four Imidazolium-Based ILs

a

ILs

[C4mim] NO3

[C2mim] NTf2

[C4mim] NTf2

[C8mim] NTf2

ΔHd (kJ·mol−1) ΔSd (J·mol−1·K−1) SDa

45.79 63.06 0.697

31.75 20.53 1.006

35.75 40.56 1.100

76.62 177.59 1.188

SD is the standard deviation.

between diosgenin and the IL molecules were insufficient to destroy the original association between the IL molecules; the dissolution of diosgenin in the ILs is an endothermic process with increasing entropy (ΔHd > 0, ΔSd > 0). Thus, the dissolution of diosgenin is an entropy-driven process potentially caused by the reduced degree of order in the IL and diosgenin system as a consequence of the disruption of the IL molecular alignment upon dissolution of diosgenin.

Figure 2. Solubility of diosgenin in [C2mim]NTf2 (◊), [C4mim]NO3 (□), [C4mim]NTf2 (△), and [C8mim]NTf2 (○). The dotted lines were fit using eq 2, the dashed lines were fit using eq 3, and the solid lines were fit using the λh eq 4.

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CONCLUSIONS Experimental solubility data for diosgenin in [C4mim]NO3, [C2min]NTf2, [C4min]NTf2 and [C8min]NTf2 were measured and presented in this work. The diosgenin solubility in the four imidazolium-based ILs decreased in the order [C8min]NTf2 > [C4min]NTf2 > [C4mim]NO3 > [C2min]NTf2. According to the dissolution behavior in ILs (Table 1), the hydrophobic and hydrogen-bonding interactions between diosgenin and IL molecules have a marked effect on the solubility of diosgenin. The diosgenin solubility increased with increasing temperature. Notably, the solubility increased more quickly in [C8min]NTf2 with increasing temperature; hence, [C8min]NTf2 can be used to recrystallize diosgenin. Moreover, the solubility data for the four ILs agree well with the dual-parameter equation, Apelblat equation, and λh equation, which can be used to correlate the diosgenin solubility data for the ILs investigated in this work.

values agree well with the experimental solubility data for [C4mim]NO3, [C2min]NTf2, [C4min]NTf2, and [C8min]NTf2 according to the RD, RMSD, and R2 values; they also indicate that eqs 2, 3, and 4 can successfully fit the diosgenin solubility for the four imidazolium-based ILs. To better understand the dissolution behavior of diosgenin in the selected ILs for a real solution, the dissolution enthalpy (ΔHd) and entropy (ΔSd) were calculated using the van’t Hoff equation (eq 5):16 ΔHd ΔSd + (5) RT R where x is the mole fraction solubility. The van’t Hoff plots (ln x vs 1/T) were obtained from a linear fit of the experimental solubility data for diosgenin at different temperatures; the results are shown in Figure 3. The ΔHd, ΔSd, and standard ln x = −

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AUTHOR INFORMATION

Corresponding Author

* E-mail: [email protected]. Tel.: 0086-771-3233718. Fax: 0086-771-3233718. Funding

This research work was financially supported by the National Natural Science Foundation of China (No. 21166002) and Guangxi Natural Science Foundation (2014GXNSFAA118037). Notes

The authors declare no competing financial interest.

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REFERENCES

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Figure 3. Van’t Hoff plots of ln x vs 1/T for [C2mim]NTf2(○), [C4mim]NO3(▽), [C4mim]NTf2 (◊), and [C8mim]NTf2 (△). 14



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Solubility of Diosgenin in Several Imidazolium-Based Ionic Liquids

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