Article pubs.acs.org/jced
Solubility of Ethyl p‑Aminobenzoate in Six Alcohols within (283.15 to 327.15) K Hongjie Xu, Zuoxiang Zeng, Weilan Xue,* and Kun Li Institute of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China S Supporting Information *
ABSTRACT: The solubility of ethyl p-aminobenzoate (EPAB) was measured in six different alcohols (methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, isoamyl alcohol) within (283.15 to 327.15) K by the last solid disappearance method. The solubility increases with increasing temperature. The decreasing order satisfies the following sequence: methanol > ethanol > npropanol > n-butanol > isoamyl alcohol > isobutyl alcohol. Four models, including modified Apelblat equation, λh model, NRTL model, and Wilson model, were used to correlate the experimental data of EPAB. It is found that the modified Apelblat equation, NRTL model, and Wilson model were suitable to correlate the solubility of EPAB in the selected solvents with an overall RAD less than 2%. In addition, the changes of thermodynamic properties of solution [standard molar enthalpy (ΔdisHo), standard molar entropy (ΔdisSo), and standard molar Gibbs energy (ΔdisGo)] were obtained. The results indicate that the dissolution process of EPAB in these alcohols is endothermic and an entropy-driven process.
■
INTRODUCTION Ethyl p-aminobenzoate (EPAB, C9H11O2N, CAS Registry No. 94-09-7) is a white crystal without smell and widely used in chemical and pharmaceutical industry. As an important local anesthetic, it is extremely effective in relieving pain caused by traumatic injury, skin ulcers, and burn.1−3 EPAB also acts as an additive in cosmetics to absorb ultraviolet light, and it plays an increasingly vital role in commercial fish farms.4 In addition, EPAB can be applied in the synthesis of biological activity compounds, such as a series of new 5-substituted aryl/aralkyl1,3,4-oxadiazol-2-yl 4-(morpholin-4-ylsulfonyl) benzyl sulfides,5 cN-(4-ethoxycarbonylphenyl)-5,6,8,9-tetrahydro-7-phenyldibenzo[c,h]acridinium perchlorate,6 and 2-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)thiomethyl)-1-benzyl benzimidazole.7 All these synthesis reactions involve alcohol solvents. On the other hand, EPAB is prepared from esterification of paminobenzoic acid and ethanol with concentrated sulfuric acid as catalyst, followed by extraction and recrystallization to obtain the pure product. Therefore, it is essential to determine the solubility of EPAB in alcohols. Solubility data of EPAB in several solvents have been published previously. Schwartz et al. determined the solubility of EPAB in methanol, ethanol, and n-propanol at 25, 33, and 40 °C.8 Á vila measured the solubility of EPAB in octanol at 25, 30, 35, and 40 °C.9 Unfortunately, no systematic experimental solubility data of EPAB in alcohols were reported in the literature, so further research is needed. In this paper, the solubility data of EPAB in methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, and isoamyl alcohol were systematically measured within (283.15 to 327.15) © XXXX American Chemical Society
K by dynamic method and were correlated by modified Apelblat equation, λh model, NRTL model, and Wilson model. Moreover, the standard molar enthalpy (ΔdisHo), standard molar entropy (ΔdisSo) and standard molar Gibbs energy (ΔdisGo) for the dissolving process of EPAB in different solvents were calculated from the solubility data.
■
EXPERIMENTAL SECTION Materials. The EPAB with mass fraction purity above 0.995, determined by high-performance liquid chromatography (HPLC), was purchased from Aladdin Industrial Corporation (Shanghai, China). The solvents, including methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, and isoamyl alcohol (supplied from Meryer Co., Ltd., Shanghai, China) used in the experiments were analytical reagent grade with mass fraction above 0.995 without further purification. The detail of materials is summarized in Table 1. Melting Properties Measurements. The melting temperature (Tm) and fusion enthalpy (ΔfusHom) of EPAB were measured by differential scanning calorimeter [DSC (214 Polyma, Netzsch Instrument Inc.)]. A known mass sample (about 5 mg) was placed on the sample cell and scanned under the condition of high purity nitrogen from (283.15 to 433.15) K with the heating rate of 5 K/min. The ΔfusHom was calculated from the melting endotherm. To obtain the standard uncertainties of the determination for Tm and ΔfusHom, benzoic Received: January 13, 2016 Accepted: April 4, 2016
A
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
with a stirrer, a condenser, and mercury thermometer (standard uncertainty of 0.05 K). The temperature in the experiment remained stable in the control of a cylindrical glass thermostatic water bath. A known mass of EPAB was added to the flask at the constant temperature; the mass of sample was determined using the electronic balance (standard uncertainty of 0.0001 g). Another known mass of solute was added into the flask again if the solid previously introduced completely disappeared. The ending of the experimental process described above was that the last added solid was less than 0.01 g, and it remained partially undissolved during 3 h. Each program was performed at least three times to reduce experimental accidental error, and the mean value was applied to calculate the molar solubility. Under the conditions of changing temperature, the repeated process was conducted to obtain solubility at different temperature. The molar fraction solubility was calculated by using the following equation
Table 1. Sources and Mass Fraction Purities of Materials Used chemical name
source
ethyl paminobenzoate (EPAB) methanol
Aladdin Industrial Co., Shanghai, China Meryer Co., Ltd., Shanghai, China Meryer Co., Ltd., Shanghai, China Meryer Co., Ltd., Shanghai, China Meryer Co., Ltd., Shanghai, China Meryer Co., Ltd., Shanghai, China Meryer Co., Ltd., Shanghai, China
ethanol n-propanol n-butanol isobutyl alcohol isoamyl alcohol
mass fraction purity
analysis method
purification method
> 0.995
HPLCa
none
> 0.995
GCb
none
> 0.995
GCb
none
> 0.995
GCb
none
> 0.995
GCb
none
> 0.995
GCb
none
> 0.995
GCb
none
a
High-performance liquid chromatography. bGas−liquid chromatography.
x1 =
m1/M1 m1/M1 + m2 /M 2
(1)
where x1 is the saturated molar fraction of EPAB, m1 and M1 represent the mass and molecular mass of solute, respectively, and m2 and M2 represent the mass and molecular mass of solvent, respectively. The uncertainty of the solubility, which was caused by the measurement of weight and purity of solute and solvent, and the uncertainty of the temperature determination, is less than 2%.
acid was chosen as reference material for the determination, and the standard uncertainties of the determination for Tm and ΔfusHom of fusion were u(Tm) = 0.5 K and ur(ΔfusHom) = 2%, respectively. The DSC of EPAB was shown in Figure 1.
■
RESULT AND DISCUSSION The solubility of EPAB was determined in the pure alcohols (methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, and isoamyl alcohol) from (283.15 to 327.15) K. To have a better knowledge of the relationship between the solubility of EPAB and the temperature (T), and enlarge the application scope of solubility data, four solubility models, including modified Apelblat equation, λh model, NRTL model, and Wilson model, were applied to correlate the solubility data obtained in the experiment. Modified Apelblat Equation. The modified Apelblat equation22,23 is widely used to correlate the solubility with the temperature due to its simplicity, and it can be expressed as follows
Figure 1. DSC scan of EPAB.
From Figure 1, the values of Tm and ΔfusHom of EPAB are 363.2 K and 21.904 kJ/mol, respectively. Compared with the data reported in the literature8,10−14 (Supporting Information Table S1), the value of Tm in this work is in agreement with the published data (relative deviation is less than 0.40%) except the data by Curran et al.14 (relative deviation = 5.54%). However, the value of ΔfusHom in previous literature is different from each other, and the value of ΔfusHom in this paper is very close to that reported in literature11,12 with relative deviation of −0.33% and −1.64%, respectively. Apparatus and Procedure. The determination of solubility of the solute in the solvent is generally achieved by the gravimetric or dynamic method.15−17 In this study, the last solid disappearance method, as a member of dynamic methods, was applied to measure the solubility of EPAB in six pure alcohols. The detailed apparatus and procedure to measure the solubility of EPAB in our laboratory were described in our previous reported literatures.18−21 A belief summary was presented as follows: A known mass of solvent (about 40g ± 0.001g) was added into a three-necked flask that is equipped
ln x1 = A +
B + C ln(T ) T
(2)
where A, B, and C are the model parameters and can be obtained by multivariate regression analysis. A and B are the indication of the nonidealities of the real solution; and C reflects the relationship between the fusion enthalpy and temperature. λh Model. The λh model,24,25 including two-model variables λ and h, originates from the equation proposed by Buchowski et al.26 λ and h correspondingly represent the nonideal prosperity of the system and the excess mixing enthalpy of solution. ⎛1 ⎛ 1 − x1 ⎞ 1 ⎞ ln⎜1 + λ ⎟ ⎟ = λh⎜ − x1 ⎠ Tm ⎠ ⎝T ⎝
(3)
To express the relationship between solubility and temperature more intuitively, eq 3 can transform to the following form B
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
cal Table 2. Experimental (xexp 1 ) and Correlated (x1 ) Molar Fraction Solubility of EPAB in Pure Alcohols from (283.15 to 327.15) a K at Pressure p = 0.1 MPa
xcal 1
T
RD
K
xexp 1
Apelblat
λh
NRTL
Wilson
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15 RAD
0.0528 0.0629 0.0750 0.0863 0.1033 0.1202 0.1415 0.1675 0.1997 0.2271 0.2594 0.2956 0.3347
0.0538 0.0629 0.0738 0.0867 0.1021 0.1205 0.1424 0.1686 0.1999 0.2274 0.2588 0.2947 0.3358
0.0466 0.0572 0.0698 0.0848 0.1023 0.1227 0.1464 0.1738 0.2051 0.2314 0.2604 0.2921 0.3267
0.0543 0.0635 0.0745 0.0868 0.1024 0.1200 0.1414 0.1674 0.1993 0.2270 0.2592 0.2955 0.3355
Methanol 0.0546 0.0637 0.0746 0.0867 0.1022 0.1198 0.1412 0.1673 0.1992 0.2270 0.2592 0.2956 0.3357
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15 RAD
0.0522 0.0611 0.0712 0.0831 0.0982 0.1149 0.1349 0.1599 0.1910 0.2208 0.2512 0.2887 0.3275
0.0524 0.0608 0.0709 0.0829 0.0974 0.1149 0.1359 0.1613 0.1920 0.2192 0.2506 0.2870 0.3290
0.0438 0.0541 0.0662 0.0807 0.0976 0.1175 0.1407 0.1675 0.1983 0.2242 0.2528 0.2842 0.3186
0.0522 0.0609 0.0711 0.0831 0.0978 0.1149 0.1354 0.1605 0.1915 0.2200 0.2512 0.2881 0.3281
Ethanol 0.0522 0.0609 0.0710 0.0831 0.0977 0.1148 0.1354 0.1606 0.1916 0.2201 0.2512 0.2880 0.3278
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15 RAD
0.0441 0.0521 0.0605 0.0710 0.0850 0.1010 0.1215 0.1482 0.1794 0.2108 0.2451 0.2843 0.3259
0.0433 0.0509 0.0601 0.0714 0.0853 0.1023 0.1231 0.1488 0.1805 0.2092 0.2427 0.2822 0.3286
0.0337 0.0429 0.0542 0.0679 0.0844 0.1042 0.1278 0.1555 0.1878 0.2154 0.2460 0.2797 0.3167
0.0440 0.0518 0.0607 0.0716 0.0852 0.1014 0.1218 0.1478 0.1795 0.2099 0.2444 0.2840 0.3272
n-Propanol 0.0433 0.0511 0.0602 0.0712 0.0850 0.1015 0.1222 0.1485 0.1803 0.2106 0.2447 0.2836 0.3260
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15
0.0370 0.0467 0.0562 0.0668 0.0821 0.0981 0.1181 0.1460 0.1763 0.2072 0.2408 0.2815
0.0381 0.0458 0.0553 0.0669 0.0811 0.0984 0.1197 0.1458 0.1778 0.2065 0.2401 0.2792
0.0308 0.0395 0.0504 0.0638 0.0800 0.0997 0.1232 0.1511 0.1838 0.2118 0.2430 0.2774
0.0403 0.0481 0.0571 0.0676 0.0814 0.0974 0.1175 0.1441 0.1755 0.2061 0.2406 0.2816
n-Butanol 0.0390 0.0470 0.0561 0.0670 0.0811 0.0975 0.1180 0.1451 0.1767 0.2071 0.2411 0.2812
C
Apelblat
λh
NRTL
Wilson
−0.0198 0.0005 0.0158 −0.0051 0.0113 −0.0025 −0.0065 −0.0066 −0.0010 −0.0014 0.0023 0.0030 −0.0034 0.0058
0.1184 0.0907 0.0689 0.0178 0.0098 −0.0211 −0.0349 −0.0375 −0.0271 −0.0191 −0.0038 0.0120 0.0240 0.0373
−0.0278 −0.0099 0.0062 −0.0055 0.0090 0.0020 0.0006 0.0003 0.0021 0.0005 0.0009 0.0004 −0.0024 0.0052
−0.0345 −0.0132 0.0056 −0.0051 0.0107 0.0037 0.0020 0.0013 0.0026 0.0005 0.0007 −0.0001 −0.0031 0.0064
−0.0030 0.0042 0.0043 0.0018 0.0078 0.0002 −0.0075 −0.0088 −0.0053 0.0071 0.0023 0.0058 −0.0046 0.0050
0.1600 0.1152 0.0698 0.0294 0.0056 −0.0230 −0.0429 −0.0473 −0.0380 −0.0155 −0.0065 0.0155 0.0272 0.0458
0.0007 0.0033 0.0015 −0.0005 0.0044 0.0004 −0.0035 −0.0039 −0.0024 0.0036 0.0002 0.0022 −0.0018 0.0022
0.0006 0.0040 0.0025 0.0005 0.0053 0.0008 −0.0038 −0.0047 −0.0033 0.0031 −0.0002 0.0024 −0.0010 0.0025
0.0188 0.0235 0.0060 −0.0058 −0.0035 −0.0126 −0.0135 −0.0044 −0.0062 0.0077 0.0096 0.0072 −0.0084 0.0098
0.2352 0.1766 0.1049 0.0443 0.0070 −0.0319 −0.0515 −0.0491 −0.0470 −0.0219 −0.0036 0.0161 0.0281 0.0629
0.0022 0.0062 −0.0039 −0.0082 −0.0018 −0.0039 −0.0022 0.0027 −0.0004 0.0041 0.0028 0.0011 −0.0039 0.0034
0.0192 0.0193 0.0055 −0.0026 0.0001 −0.0051 −0.0059 −0.0021 −0.0051 0.0009 0.0016 0.0025 −0.0003 0.0054
−0.0290 0.0185 0.0157 −0.0015 0.0124 −0.0035 −0.0137 0.0012 −0.0087 0.0032 0.0028 0.0081
0.1689 0.1537 0.1033 0.0456 0.0252 −0.0161 −0.0432 −0.0348 −0.0426 −0.0222 −0.0090 0.0146
−0.0891 −0.0307 −0.0154 −0.0124 0.0086 0.0068 0.0053 0.0129 0.0044 0.0054 0.0008 −0.0003
−0.0551 −0.0071 0.0009 −0.0023 0.0121 0.0057 0.0005 0.0064 −0.0022 0.0007 −0.0013 0.0012
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 2. continued xcal 1
T xexp 1
K
a
λh
Apelblat
RD NRTL
Wilson n-Butanol 0.3240
327.15 RAD
0.3233
0.3249
0.3152
0.3255
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15 RAD
0.0281 0.0328 0.0392 0.0480 0.0583 0.0710 0.0879 0.1111 0.1404 0.1681 0.2045 0.2496 0.3035
0.0285 0.0333 0.0394 0.0473 0.0575 0.0708 0.0881 0.1107 0.1405 0.1692 0.2046 0.2487 0.3036
0.0163 0.0223 0.0302 0.0404 0.0537 0.0705 0.0916 0.1179 0.1500 0.1784 0.2108 0.2474 0.2882
Isobutyl 0.0289 0.0341 0.0405 0.0486 0.0586 0.0711 0.0875 0.1098 0.1391 0.1675 0.2044 0.2502 0.3043
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15 RAD
0.0335 0.0371 0.0439 0.0529 0.0632 0.0757 0.0917 0.1151 0.1446 0.1721 0.2062 0.2516 0.3054
0.0334 0.0381 0.0441 0.0519 0.0620 0.0751 0.0921 0.1145 0.1439 0.1720 0.2069 0.2503 0.3044
0.0193 0.0259 0.0343 0.0452 0.0589 0.0760 0.0973 0.1233 0.1548 0.1824 0.2137 0.2488 0.2880
0.0321 0.0374 0.0442 0.0528 0.0632 0.0760 0.0922 0.1147 0.1441 0.1721 0.2069 0.2519 0.3048
Alcohol 0.0272 0.0324 0.0390 0.0474 0.0578 0.0709 0.0880 0.1112 0.1411 0.1695 0.2058 0.2498 0.3011
Isoamyl Alcohol 0.0308 0.0360 0.0431 0.0519 0.0627 0.0759 0.0928 0.1160 0.1458 0.1738 0.2080 0.2514 0.3019
λh
Apelblat
NRTL
Wilson
−0.0051 0.0095
0.0250 0.0542
−0.0068 0.0153
−0.0021 0.0075
−0.0142 −0.0148 −0.0059 0.0138 0.0129 0.0029 −0.0019 0.0034 −0.0010 −0.0065 −0.0007 0.0035 −0.0005 0.0063
0.4186 0.3196 0.2298 0.1574 0.0797 0.0075 −0.0423 −0.0609 −0.0684 −0.0613 −0.0308 0.0090 0.0503 0.1181
−0.0299 −0.0395 −0.0330 −0.0134 −0.0050 −0.0010 0.0049 0.0120 0.0091 0.0035 0.0004 −0.0023 −0.0025 0.0120
0.0306 0.0113 0.0057 0.0118 0.0083 0.0017 −0.0014 −0.0006 −0.0051 −0.0086 −0.0061 −0.0006 0.0079 0.0077
0.0017 −0.0281 −0.0056 0.0195 0.0184 0.0075 −0.0046 0.0048 0.0046 0.0005 −0.0036 0.0050 0.0032 0.0076
0.4234 0.3027 0.2178 0.1462 0.0686 −0.0043 −0.0609 −0.0714 −0.0706 −0.0599 −0.0363 0.0110 0.0570 0.1177
0.0411 −0.0070 −0.0077 0.0012 0.0002 −0.0035 −0.0059 0.0030 0.0035 0.0002 −0.0034 −0.0012 0.0018 0.0061
0.0810 0.0291 0.0192 0.0180 0.0084 −0.0031 −0.0121 −0.0080 −0.0085 −0.0097 −0.0088 0.0007 0.0114 0.0168
Standard uncertainties u are u(T) = 0.05 K, ur(P) = 0.05, ur(x1) = 0.02.
x1 =
2 ⎡ ⎤ τ21G21 τ12G12 ⎥ ln γ1 = x 22⎢ + (x 2 + x1G12)2 ⎦ ⎣ (x1 + x 2G21)2
λ e
λh(1/ T − 1/ Tm)
(4)
−1+λ
Activity Coefficient Model. Considering the nonrandomness in the mixing process caused by local composition, an activity coefficient model was proposed to correlate solubility,27 and the standard form of this model can be given as follow ln γ1x1 =
ΔfusHm ⎛ 1 1⎞ 1 − ⎟− ⎜ R ⎝ Tm T ⎠ RT 1 + R
∫T
T
m
ΔCP dT T
∫T
(6)
with G12 = exp( −α12τ12)
(7)
G21 = exp( −α21τ21)
(8)
T
ΔCP dT
τ12 =
m
(5)
τ21 =
where R is the universal gas constant. ΔCP is the difference of molar heat capacity between the melting and solid state of solute, and the value of ΔCP of EPAB is 49.37 (J·mol−1·K−1).28 γ1 is the activity coefficient of solute. The NRTL model and Wilson model were used to calculate the activity coefficient in this paper. NRTL Model. As one of the most important activity coefficient models, the NRTL model was introduced by Renon and Prausnitz29 and given as follows
g12 − g22 RT
g21 − g11 RT
=
Δg12
=
Δg21
RT
RT
(9)
(10)
where Δg12, Δg21, and α12(= α21) are the NRTL model parameters. α12 reflects the nonrandomness of the mixture, and its value ranges from 0.2 to 0.47.27,30 The NRTL model has two parameters (Δg12, Δg21) when α12 is regarded as a constant. In this paper, parameter α12 = 0.3 was used in the calculations. Wilson Model. The Wilson model, proposed by Wilson in 1964 with the introduction of the local composition concept in the first time,31 can also be used to correlate the solid−liquid equilibrium and shown as follows D
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Figure 2. Plot of molar fraction solubility x1 of EPAB in different alcohols: ●, methanol; ■, n-butanol; ▼, isobutyl alcohol; −, correlation model. (a) Modified Apelblat equation; (b) λh model; (c) NRTL model; (d) Wilson model.
Table 3. Parameters of Four Models for Solubility of EPAB in the Selected Alcohols λh
Apelblat methanol ethanol n-propanol n-butanol isobutyl alcohol isoamyl alcohol
NRTL
Wilson
A
B
C
λ
h
Δg12
Δg21
Δλ12
Δλ21
−226.782 −291.003 −335.073 −250.449 −633.555 −695.175
6890.09 9787.01 11434.4 7392.57 24323.5 27397.2
35.3394 44.8975 51.6385 39.1557 96.3684 105.388
1.26603 1.25447 1.62499 1.75484 2.42978 2.10172
3341.83 3425.36 3053.11 2950.97 2639.69 2860.38
−760.954 −707.132 −1037.85 −1112.70 −1185.81 −1100.63
3867.39 3907.18 4785.85 5043.34 5945.11 5631.13
−436.532 643.866 2070.58 2929.13 3842.74 4006.79
3445.19 2507.22 1628.60 1013.95 1073.17 660.243
⎞ ⎛ Λ12 Λ 21 ln γ1 = −ln(x1 + Λ12x 2) + x 2⎜ − ⎟ x 2 + Λ 21x1 ⎠ ⎝ x1 + Λ12x 2
applicability of these four models to the experiment values. The values of RD and RAD, listed in Table 2, were calculated on the basis of the following formulas
(11)
⎛ Δλ ⎞ ⎛ λ − λ11 ⎞ V2 V ⎟= Λ12 = 2 exp⎜ − 12 exp⎜ − 12 ⎟ ⎝ ⎝ RT ⎠ V1 RT ⎠ V1 ⎛ λ − λ 22 ⎞ ⎛ Δλ ⎞ V V ⎟ = 1 exp⎜ − 21 ⎟ Λ 21 = 1 exp⎜ − 21 ⎝ ⎝ RT ⎠ V2 RT ⎠ V2
RD = (12)
x1exp − x1cal x1exp
RAD = (13)
where Δλ12 and Δλ21, as the adjustable parameters of Wilson model, represent the cross interaction energy respectively, V1, V2 are the molar volumes of solute and solvent. The experimental and fitting solubility values of EPAB were displayed in Table 2 and plotted in Figure 2. The regression parameters of four models, listed in Table 3, were obtained by the usage of Matlab sof tware R2014b (MathWorks Inc.). Especially for the Wilson model and NRTL model, the cal 2 objective function was f = ∑i N= 1(xexp 1,i − x1,i ) , and the function f minsearch was used for the minimization of the objective function. The relative deviation (RD) and the relative average deviation (RAD) were used to assess the fitting degree and
1 N
N
∑ i=1
(14)
cal x1,exp i − x1, i
x1,exp i
(15)
cal where xexp 1,i is experiment solubility and x1,i is the solubility of solute calculated from the different solubility correlation models, and N is the number of experimental points. From the data in Table 2 and Figure 2, it is found that the solubility of EPAB in different solvents increases with the increase of temperature and satisfies the order of isobutyl alcohol < isoamyl alcohol < n-butanol < n-propanol < ethanol < methanol, which is consistent with the order of the polarity of the selected solvents in this work [methanol (76.2) > ethanol (65.4) > n-propanol (61.7) > n-butanol (60.2) > isoamyl alcohol (56.5) > isobutyl alcohol (55.2)].32 It indicates that the polarity is the main factor for the solubility of EPAB in these alcohols.
E
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
The solubility data of EPAB in methanol, ethanol, and npropanol at 25, 33, and 40 °C were predicted by modified Apelblat equation and compared with the literature ones in Figure 3. From Figure 3, the predicted solubility data of EPAB are in agreement with the literature values, except for the ones in n-propanol at 33 and 40 °C. Meanwhile, we can see that the solubility difference between 25 and 33 °C (or 40 °C) reported in the literature8 is too small to be reasonable, which leads to the larger deviation of solubility at 33 and 40 °C. To verify the above view, multiple measurements were conducted for npropanol in this work, and the results show that there are obvious differences in the solubility between 25 and 33 °C (or 40 °C). Thermodynamic Properties of Solution. Generally, all the dissolution processes are accompanied by the changes of thermodynamic functions, including enthalpy, entropy, and Gibbs free energy. Therefore, it is necessary to calculate the thermodynamic parameters in order to have a deeper understanding of the dissolution process of EPAB in these selected solvents. Thereafter, ΔdisHo, ΔdisSo, and ΔdisGo of the dissolution process of EPAB can be calculated based on the following hypothetic process and eqs 16 to 1833 fusion
mixing
solutesolid(T) ⎯⎯⎯⎯⎯→ solute liquid(T) ⎯⎯⎯⎯⎯⎯→ solution(T) solvent
Table 4. Thermodynamic Properties of Fusion Process for EPAB K 283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
ΔfusHo
ΔfusSo
ΔdisS o = ΔfusS o + Δmix S o
(17)
ΔdisGo = ΔfusGo + Δmix Go
(18)
ΔfusGo
−1
J·K ·mol
J·mol−1
17951.9 18149.4 18346.9 18544.4 18741.9 18939.3 19136.8 19334.3 19531.8 19679.9 19828.0 19976.1 20124.2
48.0164 48.7089 49.3919 50.0656 50.7302 51.3859 52.0331 52.6719 53.3025 53.7703 54.2336 54.6927 55.1475
4356.09 4162.64 3966.43 3767.52 3565.92 3361.69 3154.85 2945.43 2733.48 2572.87 2410.86 2247.47 2082.71
J·mol
−1
(16)
where ΔfusHo, ΔfusSo, and ΔfusGo are the changes of enthalpy, entropy, and Gibbs energy in fusion process, and ΔmixHo, ΔmixSo, and ΔmixGo are the changes of enthalpy, entropy, and Gibbs energy in mixing process, respectively. A cycle process was designed as follow, and the values of ΔfusHo, ΔfusSo, and ΔfusGo at different temperature can be calculated from eqs 19 to 21
Figure 3. Comparison of experiment values with literature values of solubility of EPAB in different solvents at 25, 33, and 44 °C: ●, experiment value; ○, literature value;8 −, calculated from modified Apelblat equation. (a) methanol; (b) ethanol; (c) n-propanol.
T
ΔdisH o = ΔfusH o + Δmix H o
−1
ΔfusH o = Cp,solid(Tm − T ) + ΔfusHmo + Cp,liquid(T − Tm) = ΔfusHmo + ΔCp(T − Tm) Tm T + ΔfusSmo + Cp,liquid ln T Tm T = ΔfusSmo + ΔCp ln Tm
(19)
ΔfusS o = Cp,solid ln
In addition, from Table 2, the overall RAD values of these four models are 0.75% (modified Apelblat equation), 7.26% (λh model), 0.74% (NRTL model), 0.76% (Wilson model), respectively. The overall RADs of the Wilson model, modified Apelblat model, and NRTL model are less than 2% in these four models, indicating that these three models can provide accurate correlation between the solubility of EPAB and temperature in the experimental solvents, which can also be seen from Figure 2.
ΔfusGo = ΔfusH o − T ΔfusS o
(20) (21)
where Cp,solid and Cp,liquid is heat capacity of solute in solid state and liquid state, respectively. ΔfusSom is fusion entropy of solute, and the value of ΔfusSom can be calculated as follows ΔfusSmo = F
ΔfusHmo Tm
(22) DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 5. Dissolution Thermodynamic Properties of EPAB in the Selected Alcohols T
ΔdisHo
ΔdisSo
ΔdisGo
K
J·mol−1
J·K−1·mol−1
J·mol−1
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18087.3 18304.8 18524.7 18744.9 18970.2 19198.1 19421.4 19645.1 19883.9 20048.4 20214.5 20375.7 20530.8
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18089.7 18309.0 18525.6 18749.8 18973.5 19195.9 19430.1 19658.3 19887.2 20064.9 20227.3 20391.3 20548.3
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18080.6 18297.4 18517.5 18738.0 18959.4 19186.9 19420.4 19648.8 19883.2 20046.5 20209.7 20365.7 20513.4
Methanol 49.6992 4014.96 50.6098 3772.19 51.5343 3520.50 52.4277 3270.87 53.3835 3000.52 54.3201 2730.91 55.2594 2448.47 56.2116 2154.86 57.2255 1849.33 57.9348 1616.46 58.6536 1377.88 59.3479 1138.09 60.0028 900.855 Ethanol 49.6809 4022.55 50.5788 3785.28 51.4645 3541.68 52.3793 3290.01 53.3083 3026.37 54.2256 2757.41 55.1890 2478.75 56.1489 2187.55 57.1256 1884.11 57.8951 1645.57 58.5922 1410.37 59.3049 1167.65 59.9668 930.107 n-Propanol 49.4620 4075.47 50.3385 3842.70 51.2141 3606.49 52.1001 3360.61 53.0109 3101.21 53.9404 2834.88 54.9095 2554.97 55.8879 2259.31 56.8862 1955.48 57.6269 1712.53 58.3568 1468.44 59.0611 1221.06 59.7168 977.023
%ζH
%ζS
id
E
o
id
E
Δmix H = Δmix H + H Δmix G = Δmix G + G o
id
Δmix S = Δmix S + S
E
ΔdisSo
ΔdisGo
K
J·mol−1
J·K−1·mol−1
J·mol−1
43.76 44.26 44.75 45.22 45.71 46.17 46.64 47.10 47.56 47.90 48.24 48.56 48.88
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18066.5 18288.7 18510.5 18733.3 18961.8 19184.9 19419.0 19653.3 19873.3 20043.4 20204.8 20358.6 20503.6
56.25 55.76 55.28 54.81 54.33 53.87 53.41 52.95 52.49 52.14 51.81 51.47 51.16
43.75 44.24 44.72 45.19 45.67 46.13 46.59 47.05 47.51 47.86 48.19 48.53 48.84
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18059.3 18273.0 18490.1 18714.4 18941.2 19167.5 19400.3 19641.7 19882.2 20055.5 20220.9 20376.0 20513.5
56.35 55.87 55.39 54.93 54.45 53.99 53.52 53.05 52.59 52.23 51.88 51.55 51.22
43.65 44.13 44.61 45.07 45.55 46.01 46.48 46.95 47.41 47.77 48.12 48.45 48.78
283.15 287.15 291.15 295.15 299.15 303.15 307.15 311.15 315.15 318.15 321.15 324.15 327.15
18073.8 18281.5 18500.6 18723.0 18946.5 19173.2 19405.7 19644.2 19881.0 20064.9 20228.3 20388.2 20531.5
(23)
Δmix H = 0
(26)
Δmix Gid = RT (x1 ln x1 + x 2 ln x 2)
(27)
%ζH
%ζS
56.42 55.92 55.44 54.97 54.48 54.02 53.55 53.08 52.62 52.26 51.92 51.57 51.25
43.58 44.08 44.56 45.03 45.52 45.98 46.45 46.92 47.38 47.74 48.08 48.43 48.75
56.53 56.07 55.61 55.14 54.69 54.23 53.78 53.31 52.85 52.49 52.13 51.77 51.40
43.47 43.93 44.39 44.86 45.31 45.77 46.22 46.69 47.15 47.51 47.87 48.23 48.60
56.48 56.03 55.56 55.10 54.64 54.19 53.74 53.27 52.81 52.46 52.10 51.74 51.38
43.52 43.97 44.44 44.90 45.36 45.81 46.26 46.73 47.19 47.54 47.90 48.26 48.62
(28)
⎡ ∂(GE /T ) ⎤ H E = − T 2⎢ ⎥ ⎣ ∂T ⎦
(29)
G E = RT (x1 ln γ1 + x 2 ln γ2)
(30)
SE =
(25)
n-Butanol 49.2835 4111.93 50.2087 3871.23 51.1075 3630.53 52.0039 3384.37 52.9537 3120.74 53.8673 2854.97 54.8327 2577.12 55.8397 2278.75 56.7846 1977.63 57.5441 1735.78 58.2662 1492.65 58.9757 1241.68 59.6281 996.299 Isobutyl Alcohol 49.0370 4174.45 49.8570 3956.57 50.6977 3729.41 51.5779 3491.18 52.4652 3246.27 53.3572 2992.24 54.2915 2724.64 55.2853 2439.70 56.2945 2140.96 57.0490 1905.38 57.8142 1653.90 58.5699 1390.58 59.2802 1120.04 Isoamyl Alcohol 49.1887 4146.07 49.9691 3932.83 50.8211 3704.08 51.6954 3465.12 52.5703 3220.09 53.4611 2966.45 54.3856 2701.13 55.3727 2414.94 56.3727 2115.16 57.1585 1879.90 57.9008 1633.44 58.6709 1370.06 59.3927 1101.17
Δmix S id = −R(x1 ln x1 + x 2 ln x 2)
(24)
HE − GE T
(31)
The values of γ1 and γ2 were calculated from NRTL model. The thermodynamic properties of EPAB in different solvents were calculated and presented in Table 5. In addition, the relative contributions by enthalpy and entropy to the Gibbs free energy in the dissolution process, can be evaluated by the
Here, id
ΔdisHo
56.24 55.74 55.25 54.78 54.29 53.83 53.36 52.90 52.44 52.10 51.76 51.44 51.12
The values of ΔfusHo, ΔfusSo, and ΔfusGo of EPAB are listed in Table 4. For nonideal solution, the thermodynamic function in a mixing process can be obtained by using the following expression21,34,35 o
T
G
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
injection in teeth with irreversible pulpitis-A double blinded clinical trial. J. Clin. Diagn. Res. 2015, 9, 95−97. (3) Bauer, M.; Schwameis, R.; Scherzer, T.; Lang-Zwosta, I.; Nishino, K.; Zeitlinger, M. A double-blind, randomized clinical study to determine the efficacy of benzocaine 10% on histamine-induced pruritus and UVB-light induced slight sunburn pain. J. Dermatol. Treat. 2015, 26, 367−372. (4) Laird, L. M.; Ò swald, R. L. A note on the use of benzocaine (ethyl p - aminobenzoate) as a fish anaesthetic. Aquacult. Res. 1975, 6, 92−94. (5) Rehman, A.; Gul, S.; Abbasi, M. A.; Nafeesa, K.; Akhtar, M. N.; Ahmad, I.; Afzal, S. Synthesis, structural analysis, and screening of some novel 5-substituted aryl/aralkyl-1,3,4-oxadiazol-2-yl 4 - (morpholin-4 - ylsulfonyl) benzyl sulfides as potential antibacterial agents. Phosphorus, Sulfur Silicon Relat. Elem. 2015, 190, 1045−1055. (6) Aliaga, C.; Celis, F.; Lühr, S.; Oñate, R. TEMPO-attached prefluorescent probes based on pyridinium fluorophores. J. Fluoresc. 2015, 25, 979−983. (7) Mochona, B.; Mazzio, E.; Gangapurum, M.; Mateeva, N.; Redda, K. K. Synthesis of some benzimidazole derivatives bearing 1,3,4oxadiazole moiety as anticancer agents. Chem. Sci. Trans. 2015, 4, 534−540. (8) Schwartz, P. A.; Paruta, A. N. Solution thermodynamics of alkyl p-aminobenzoates. J. Pharm. Sci. 1976, 65, 252−257. (9) Á vila, C.; Martínez, F. Thermodynamic study of the solubility of benzocaine in some organic and aqueous solvents. J. Solution Chem. 2002, 31, 975−985. (10) Yalkowsky, S. H.; Flynn, G. L.; Slunick, T. G. Importance of chain length on physicochemical and crystalline properties of organic homologs. J. Pharm. Sci. 1972, 61, 852−857. (11) Grady, L. T.; Hays, S. E.; King, R. H.; Klein, H. R.; Mader, W. J.; Wyatt, D. K.; Zimmere, R. O. Drug purity profiles. J. Pharm. Sci. 1973, 62, 456−464. (12) Neau, S. H.; Flynn, G. L.; Yalkowsky, S. H. The influence of heat capacity assumptions on the estimation of solubility parameters from solubility data. Int. J. Pharm. 1989, 49, 223−229. (13) Manzo, R. H.; Ahumada, A. A. Effect of solvent medium on solubility. V: Enthalpic and Entropic contributions to the free energy changes of di-substituted benzene derivatives in ethanol: water and ethanol: cyclohexane mixture. J. Pharm. Sci. 1990, 79, 1109−1115. (14) Curran, B. C.; Estok, G. K. The stabilization of highly polar resonance structures by hydrogen bonding I. electric moments. J. Am. Chem. Soc. 1950, 72, 4575−4578. (15) Black, S.; Dang, L. P.; Liu, C. J.; Wei, H. Y. On the measurement of solubility. Org. Process Res. Dev. 2013, 17, 486−492. (16) Gandhi, P. J.; Murthy, Z. V. P. Solubility and crystal size of sirolimus in different organic solvents. J. Chem. Eng. Data 2010, 55, 5050−5054. (17) Zhu, L.; Wang, L. Y.; Li, X.C.; Sha, Z. L.; Wang, Y. F.; Yang, L. B. Experimental determination and correlation of the solubility of 4hydroxy- 2,5-dimethyl −3(2H) -furanone (DMHF) in six different solvents. J. Chem. Thermodyn. 2015, 91, 369−377. (18) Chen, J.; Zeng, Z. X.; Xue, W. L.; Wang, D.; Huang, Y. Determination and correlation of solubility of decahydropyrazino [2,3b]pyrazine in methanol, ethanol, and 2-propanol. Ind. Eng. Chem. Res. 2011, 50, 11755−11762. (19) Yang, Z. H.; Zeng, Z. X.; Sun, L.; Xue, W. L.; Chen, N. Determination and correlation of solubilities of lauric acid in eight alcohols. J. Chem. Eng. Data 2014, 59, 2725−2731. (20) Yu, C.; Zeng, Z. X.; Xue, W. L. Measurement and correlation of the solubility of hexaquonickel(II) bis(p-toluenesulfonate) in water + ethanol solvents within 288.15 - 333.15 K. Ind. Eng. Chem. Res. 2015, 54, 3961−3967. (21) Gao, X.; Xue, W. L.; Zeng, Z. X.; Fan, X. R. Determination and correlation of solubility of N-tert-butylacrylamide in seven different solvents at temperatures between (279.15 and 353.15) K. J. Chem. Eng. Data 2015, 60, 2273−2279.
parameters %ζH and %ζS, and the definitions of them were shown below %ζH =
|ΔdisH o| × 100 |ΔdisH o| + |T ΔdisS o|
(32)
%ζS =
|T ΔdisS o| × 100 |ΔdisH o| + |T ΔdisS o|
(33)
The values of %ζH and %ζS were also listed in Table 5. According to Table 5, all values of ΔdisHo and ΔdisSo are positive, indicating that the dissolution processes of EPAB in the selected solvents are endothermic and entropy-driven. Moreover, the value of ΔdisGo is lower at the higher temperature, and the order of ΔdisGo is methanol < ethanol < n-propanol < n-butanol < isoamyl alcohol < isobutyl alcohol at a given temperature, which is contrary to the order of polarity of selected alcohols. This may be because the larger the polarity of solvent, the stronger the interaction between alcohol and EPAB molecules, and then results in smaller value of ΔdisGo. For these selected systems, the main contributor to ΔdisGo is enthalpy, because all values of %ζH in this work are greater than 50%.
■
CONCLUSIONS The solubility of EPAB was measurement in methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, and isoamyl alcohol within (283.15 to 327.15) K, and it increases with increasing temperature and satisfies the following order: methanol > ethanol > n-propanol > n-butanol > isoamyl alcohol > isobutyl alcohol, which is consist with the order of the polarity of alcohol. Four models, including modified Apelblat Equation, λh model, NRTL model, and Wilson model, were used to correlate the solubility of EPAB, and the overall RAD values of these four models were 0.75% (modified Apelblat equation), 7.26% (λh model), 0.74% (NRTL model), and 0.76% (Wilson model), respectively. In addition, thermodynamic properties of solution, including ΔdisHo, ΔdisSo, and ΔdisGo, were obtained, and the results show that the dissolution process of EPAB in these selected solvents is endothermic and entropy-driven.
■
ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.6b00037. Comparison between literature value and determined value for melting properties of ethyl p-aminobenzoate (PDF)
■
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
■
REFERENCES
(1) Di Croce, D.; Trinks, P. W.; Grifo, M. B.; Takara, D.; Sánchez, G. A. Drug action of benzocaine on the sarcoplasmic reticulum CaATPase from fast-twitch skeletal muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 2015, 388, 1163−1170. (2) Raju, S. G. S.; Abarajithan, M.; Sathish, E. S.; Suryakumari, N. B. P.; Ealla, K. K. R.; Gade, W. Anaesthetic efficacy of topical benzocaine gel combined with hyaluronidase for supplemental intrapulpal H
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
(22) Shakeel, F.; Shazly, G. A.; Haq, N. Solubility of metoclopramide hydrochloride in six green solvents at (298.15 to 338.15) K. J. Chem. Eng. Data 2014, 59, 1700−1703. (23) Shakeel, F.; Bhat, M. A.; Haq, N. Solubility of N-(4chlorophenyl) −2-(pyridin-4- ylcarbonyl) hydrazinecarbothioamide (isoniazid analogue) in five pure solvents at (298.15 to 338.15) K. J. Chem. Eng. Data 2014, 59, 2660−2664. (24) Hong, M. H.; Wu, S. W.; Qi, M. H.; Ren, G. B. Solubility correlation and thermodynamic analysis of two forms of metaxalone in different pure solvents. Fluid Phase Equilib. 2016, 409, 1−6. (25) Noubigh, A.; Aydi, A.; Abderrabba, M. Experimental measurement and correlation of solubility data and thermodynamic properties of protocatechuic acid in four organic solvents. J. Chem. Eng. Data 2015, 60, 514−518. (26) 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. (27) Yu, G. M.; Wang, L. S.; Sun, J.; Jiang, L. K. Solubility of three phosphorus flame retardants in selected organic solvents. J. Chem. Eng. Data 2015, 60, 1803−1813. (28) Neau, S. H.; Flynn, G. L. Solid and liquid heat capacities of nalkyl para-aminobenzoates near the melting point. Pharm. Res. 1990, 7, 1157−1162. (29) Renon, H.; Prausnitz, J. M. Local compositions in thermodynamic excess functions for liquid mixtures. AIChE J. 1968, 14, 135−144. (30) Wei, D. W.; Pei, Y. H. Measurement and correlation of solubility of diphenyl carbonate in alkanols. Ind. Eng. Chem. Res. 2008, 47, 8953−8956. (31) 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. (32) Smallwood, I. M. Handbook of Organic Solvent Properties; Arnold: London, 1996. (33) Wang, C.; Wang, Y. L.; Yin, Q. X.; Xu, Z.; Bao, Y.; Hou, B. H.; Liu, W.; Hao, H. X. Solubility of 3-chlorophthalic anhydride and 4chlorophthalic anhydride in different pure solvents. J. Chem. Eng. Data 2015, 60, 3053−3061. (34) Zhou, G. Q.; Du, C. B.; Han, S.; Meng, L.; Wang, J.; Li, R. R.; Zhao, H. K. Solubility measurement and modeling of 1,8dinitroaphthalene in nine organic solvents from T = (273.15 to 308.15) K and mixing properties of solutions. J. Chem. Thermodyn. 2015, 90, 259−269. (35) Smith, J. M.; Ness, H. C. V.; Abbott, M. M. Introduction to Chemical Engineering Thermodynamics; McGraw-Hill: New York, 2001.
I
DOI: 10.1021/acs.jced.6b00037 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
