Measurement, Correlation, and Thermodynamics Parameters of

Article pubs.acs.org/jced

Measurement, Correlation, and Thermodynamics Parameters of Biological Active Pyrimidine Derivatives in Organic Solvents at Different Temperatures Kapil Bhesaniya and Shipra Baluja* Physical Chemistry Laboratory, Department of Chemistry, Saurashtra University, Rajkot-360005, Gujarat, India ABSTRACT: The present work describes the synthesis, characterization, and solubility studies of some biologically active pyrimidine derivatives. The characterization of these synthesized compounds was done by mass, IR, and 1H NMR spectral techniques. Further, the solubility of these compounds has been studied in methanol, N,N-dimethylformamide (DMF), and carbon tetrachloride (CCl4) by gravimetrical method from (298.15 to 328.15) K under atmospheric pressure, and the solubility data were correlated against temperature. The solubility is found to increase with temperature and order of solubility is found to be DMF > methanol > CCl4. The modified Apelblat and Buchowski−Ksiazczak λh equations were used to correlate the experimental solubility data. Further, some thermodynamic parameters such as dissolution enthalpy (ΔHsol), Gibb’s free energy (ΔGsol), and entropy (ΔSsol) of mixing have also been calculated. The positive values of enthalpy and Gibbs energy of solution suggest that the dissolution process to be endothermic and is spontaneous.

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INTRODUCTION Heterocyclic nucleus imparts an important role in medicinal chemistry and serves as a key template for the development of various therapeutic agents. Various pyrimidine derivatives having heterocyclic nucleus are known for their therapeutic applications1 such as antimicrobial,2,3 antitumor,4 anticancer,5,6 and antifungal activities.7 Further, many pyrimidine derivatives have a long distinguished history extending from the days of their discovery as important constituents of nucleic acids to their current use in the chemotherapy. In the pharmaceutical field, the determination of solubility and dissolution rate plays a prominent role to discovery and development of drug.8 Further, solubility provides necessary information to select wide range of solvents for the optimization of crystallization processes,9−12 preparation of liquid dosage and semisolid forms of drugs,13,14 bioavailability and absorption in the organism,15,16 in vitro assays,17 extraction,18 synthesis,19 and analytical methodology.20 The wide therapeutic spectrum of pyrimidine derivatives prompted us to synthesize some new pyrimidine derivatives. The solubility of these synthesized derivatives has been studied in methanol, N,N-dimethylformamide, and carbon tetrachloride at different temperatures [(298.15 to 328.15) K] under atmospheric pressure by the gravimetric method. The experimental data were correlated with the modified Apelblat21,22 and Buchowski−Ksiazczak λh equations.23,24 From the solubility data, some thermodynamic parameters like enthalpy, Gibb’s energy, and entropy of solution have also been evaluated.

synthesis were purchased from Sigma-Aldrich. Potassium carbonate (K2CO3) (CAS No.: 584-08-7) was purchased from Sisco Chem. Pvt. Ltd. (Mumbai, India). The solvents: methanol, DMF, and CCl4 used in the present work were of AR grade and were supplied by Spectrochem Pvt. Ltd. (Mumbai, India). These solvents were purified according to the standard procedure25 and were kept over molecular sieves. The purity of solvents were checked by GC-MS (Shimadzu model no. QP-2010) and found to be greater than 99.7 %. Synthesis. A mixture of 2,4-dichloropyrimidine (DCP) (0.1 mmol), 1-naphthol (NTL) (0.1 mmol), and potassium carbonate (K2CO3) (0.15 mmol) in DMF was refluxed for 4 h. The completion of reaction was confirmed by analytical thin layer chromatography (TLC) using (7:3 hexane−ethyl acetate) as the mobile phase. After completion of reaction, the reaction mass was cooled, and the resulting solid was filtered, washed with cold water, and dried under vacuo to give a crude product. This resulting product (0.1 mmol) was refluxed for 4−5 h with ethanolic solution of different aromatic amines (0.12 mmol) using hydrochloric acid as a catalyst. The completion of reaction was confirmed by TLC using a (7.5:2.5 hexane−ethyl acetate) mobile phase. After completion of reaction, the reaction mass was cooled, and the resulting solid was filtered, washed with cold ethanol, and dried under vacuo to give crude product. The obtained crude product was purified by tituration with diethyl ether and purity of all of these synthesized compounds was ascertained by TLC (performed on aluminum coated plates gel 60 F254 (E. Merck)). The reaction scheme is given in Figure 1.

EXPERIMENTAL SECTION Materials. 2,4-Dichloropyrimidine (DCP) (CAS No.: 393420-1) and 1-naphthol (NTL) (CAS No.: 90-15-3) used in the

Received: April 19, 2014 Accepted: September 3, 2014 Published: September 16, 2014

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© 2014 American Chemical Society

3380

dx.doi.org/10.1021/je5003626 | J. Chem. Eng. Data 2014, 59, 3380−3388

Journal of Chemical & Engineering Data

Article

Figure 1. Synthesis scheme of pyrimidine derivatives.

Analytical Study. Spectroscopic study of all of the synthesized compounds was done by IR, 1H NMR, and mass spectroscopy. IR spectra were recorded on KBr disc, using FT-IR model no.-8400 (Shimadzu) spectrophotometer. 1H NMR spectra were taken on a Bruker Avance II 400. In all cases, NMR spectra were obtained in DMSO-d6 using TMS as an internal standard, and NMR signals are reported in δ ppm. Mass spectra were determined using direct inlet probe on a GCMS-QP-2010 mass spectrometer. Melting points were measured by differential scanning calorimeter (DSC) (model Shimadzu DSC-60) with an uncertainty of ± 1 °C. Solubility Measurement. The solubility of synthesized compounds was determined in different selected solvents. The gravimetric method was chosen for the investigation.26 For each measurement, an excess mass of compound was added to a known mass of solvent. The equilibrium cell was heated to a constant temperature with continuous stirring for about 5 h (the temperature of the water bath approached a constant value, and then the actual value of the temperature was recorded). After 5 h, stirring was stopped, and the solution was kept for 2 h to approach equilibrium. The equilibrium time of 2 h is optimized by checking the concentration of solution at different intervals of time. After 2 h, the change in concentration was less than 1 %, so saturated solution was assumed to be equilibrium. A portion of this solution was filtered by a membrane (0.22 μm), and 2 mL of this clear solution was taken to preweighed vial (m0). The vial with solution was quickly weighed (m1) to determine the mass of the sample (m1 − m0). It was then placed in vacuum oven at 323.15 K so that solvent is completely evaporated. After complete dryness of vial mass, the vial was reweighed (m2). When the mass of the residue reached to a constant value, the final mass was recorded (m2 − m0). All of the weights were taken by electronic balance (Mettler Toledo AB204-S, Switzerland) with an uncertainty of ± 0.0001 g. At each temperature, the measurement was conducted three times, and an average value was used to determine the mole fraction solubility. The mole fraction solubility (x) of compounds in each solvent can be calculated by using eq 1. x=

(m2 − m0)/M1 (m2 − m0)/M1 + (m1 − m2)/M 2

Table 1. Physical Property of Synthesized Compounds compound code KDB-1 KDB-2 KDB-3 KDB-4 KDB-5

R 4-Cl 4-CH3 4-F 3-CF3 3-Cl, 4-F

MF

mol wt (g·mol−1)

melting point (°C)

C20H14ClN3O C21H17N3O C20H14FN3O C21H14F3N3O C20H13ClFN3O

347.80 327.38 331.11 381.35 365.79

158.04 294.60 292.18 249.24 147.27

Figures 2, 3, and 4, respectively. The melting point of KDB-1 is found to be 158.04 °C. IR Spectra. The IR spectrum of KDB-1 is depicted in Figure 2. The IR data of KDB-1 clearly shows a −NH (secondary) stretching band at 3255.95 cm−1. The IR stretching bands at (3171.08 to 3055) cm−1 and (1581 to 1492.95) cm−1 confirms the presence of aromatic C−H and CC in the basic skeleton. The absorption bands at 777.34 cm−1 and (1155 to 1082) cm−1 indicate the presence of C−Cl and ether linkage respectively in synthesized compounds. The bending vibration of pyrimidine ring C−H was observed at (667.39 to 607.6) cm−1. All of the IR group frequencies suggest that the pyrimidine derivative is prepared successfully. 1 H-NMR Spectra. The proton NMR spectrum of KDB-1 is depicted in Figure 3. The peak at 3.47 δppm is due to residual DMSO. It can be seen from the chemical structure of compound KDB-1 that proton of the phenyl ring attached to the carbons, appears as an appropriate multiplicity in the aromatic region at (6.664 to 8.437) δ ppm, whereas a singlet at 9.709 δppm is due to characteristic −NH group. All of the 1H NMR splitting of peaks suggests that the pyrimidine derivative KDB-1 is prepared successfully. Spectral Data. KDB-1: IR (cm−1, KBr): 3255.95 (−NH(sec.) str.), 3171.08 (aryl ether C−H str.), 3055 (Ar−H str.), 1581.16−1492.95 (CC str. phenyl nucleus), 1388−1325 (C−H in plane bending), 1284−1219 (diarylethers str.), 1155−1082 (C−O−C sym. str.), 1016−879 (pyrimidine ring breathing), 977.94 (C−H oop phenyl ring), 777.34 (C−Cl str.), 667.39−607.6 (in plane pyrimidine ring bending). 1H NMR (DMSO-d6) δ (ppm): 6.644−6.658 (d, 1H, J = 5.6), 6.939−6.958 (d, 2H, J = 7.6), 7.236 (s, 2H), 7.431−7.449 (d, 1H, J = 7.2), 7.523−7.654 (m, 3H), 7.796−7.816 (d, 1H, J = 12), 7.961−7.981 (d, 1H, J = 8), 8.077−8.097 (d, 1H, J = 8), 8.423−8.437 (d, 1H, J = 5.6), 9.709 (s, 1H); MS: (m/z) = 347.08. KDB-2: IR (cm−1, KBr): 3267.52 (−NH(sec.) str.), 3188.44 (aryl ether C−H str.), 3057.27 (Ar−H str.), 2872 (Ar−CH3 str.) 1585.54−1454.38 (CC str. phenyl nucleus), 1421−1327 (C−H in plane bending), 1255−1217 (diarylethers str.), 1153.47− 1076 (C−O−C sym. str.), 981 (pyrimidine ring breathing), 808

(1)

where M1 and M2 are the molar masses of compounds and solvent, respectively.

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RESULTS AND DISCUSSION The physical properties of all of the synthesized compounds (KDB-1 to KDB-5) are given in Table 1. For compound KDB-1, IR, 1H NMR spectrum, and DSC thermogram are shown in 3381



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Figure 2. IR spectrum of compound KDB-1.

Figure 3. 1H NMR spectrum of compound KDB-1.

8.429−8.443 (d, 1H, J = 5.6), 9.71 (s, 1H); MS: (m/z) = 327.38. KDB-3: IR (cm−1, KBr): 3262 (−NH (sec.) str.), 3084.28, 3061.13 (Ar−H str.), 1656.91−1664.02 (CC str. phenyl nucleus), 1398.44 (C−H in plane bending), 1244.13−1103.32

(C−H in plane bending), 628.81−723.33 (C−C out of plane bending). 1H NMR (DMSO-d6) δ (ppm): 2.325 (s, 3H), 6.639− 6.653 (d, 1H, J = 5.6), 6.941−6.960 (d, 2H, J = 7.6), 7.284 (s, 2H), 7.475−7.493 (d, 1H, J = 7.2), 7.529−7.655 (m, 3H),7.81−7.828 (m, 1H) 7.968−7.988 (d, 1H, J = 8), 8.062−8.082 (d, 1H, J = 8), 3382



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where xaci is the calculated mole fraction solubility of compounds, T is the absolute temperature, and A, B, and C are parameters determined by least-square method and values of these parameters are listed in Table 4. The calculated solubilities (xaci) are also reported in Table 2. The Buchowski−Ksiazczak λh equation23,24 describes the solid−liquid equilibrium behavior by only two adjustable parameters, λ and h. ⎛ ⎡ 1 λ(1 − xcbi) ⎞ 1 ⎤ ⎟⎟ = λh⎢ − ln⎜⎜1 + ⎥ b (Tm/K) ⎦ ⎣ (T /K) xci ⎝ ⎠

where xbci is calculated mole fraction solubility by eq 3, and T and Tm represent the experimental and melting temperatures of compounds in K. λ and h are the model adjustable parameters, which are given in Table 5. Further, relative deviations (RD) between the experimental and the calculated value are also evaluated by eq 4 and are listed in Table 2.

Figure 4. DSC thermogram of compound KDB-1.

(diarylethers str.), 1035(C−F str.), 831 (C−H in plane bending), 794.7−619.17 (C−C out of plane bending).1H NMR (DMSO-d6) δ (ppm): 6.610−6.624(d, 1H, J = 5.6), 6.762 (s, 2H), 7.613−7.631 (m, 5H), 7.946−7.967 (d, 1H, J = 8.4), 8.069−8.089(d, 1H, J = 8), 8.168−8.183 (d, 1H, J = 6), 8.400−8.414 (d, 1H, J = 5.6), 10.711 (s, 1H); MS: (m/z) = 331.11. KDB-4: IR (cm−1, KBr): 3269 (−NH(sec.) str.), 3112−3101 (Ar−H str.), 1643−1415 (CC str. phenyl nucleus), 1280.78−1241 (diarylethers str.), 1236−1150 (C−H in plane bending, phenyl ring), 1124.54−1074 (C−F str.), 927−895.93 (C−H oop phenyl ring), 804.34−613.38 (C−C out of plane bending). 1H NMR (DMSO-d6) δ (ppm): 6.705−6.719 (d, 1H, J = 5.6), 7148 (s, 2H), 7.446−7.570 (m, 5H), 7.807−7.828 (d, 2H, J = 8.4), 7.948−7.992 (d, 1H, J = 17.6), 8.049−8.069 (d, 1H, J = 8), 8.481−8.495(d, 1H, J = 5.6), 10.007 (s, 1H); MS: (m/z) = 381.35. KDB-5: IR (cm−1, KBr): 3255.95 (−NH(sec.) str.), 3171.08 (aryl ether C−H str.), 3055, 2891 (Ar−H str.), 1581.68− 1429.30 (CC str. phenyl nucleus), 1388.78−1325.14 (C−H in plane bending), 1284.63−1219.05 (diarylethers str.), 1155− 1082(C−F str.), 1016−879.57 (pyrimidine ring breathing), 977.94 (C−H oop phenyl ring), 777.34 (C−Cl str.), 667.39− 607.6 (in plane pyrimidine ring bending). 1H NMR (DMSO-d6) δ(ppm): 6.673−6.687 (d, 1H, J = 5.6), 6.687−7.292 (m, 2H), 7.519−7.640 (m, 5H), 7.794−7.814 (d, 1H, J = 8.0), 7.814− 7.830 (d, 1H, J = 6.4), 8.047−8.066 (d, 1H, J = 7.6), 8.460− 8.477 (d, 1H, J = 5.6), 9.778 (s, 1H); MS: (m/z) = 365.79. Solubility Data Correlation and Correlation Models. The mole fraction solubilities xi of compounds in the selected solvents are listed in Table 2 at different temperatures [(298.15 to 328.15) K] and more visually given in Figure 5. For each solvent, it is observed that the solubility of compounds increases nonlinearly with temperature. It is observed that, for all the compounds, the solubility is found to increase with temperature and the order of solubility is DMF > methanol > CCl4. The solubility results are correlated with the dielectric constant and dipole moment of solvents, which are given in Table 3. It is observed from Table 3 that both the dielectric constant and the dipole moment are higher for DMF and lower for CCl4. This is in accordance with the solubility trend in the three solvents. Thus, in the present study the dielectric constant and dipole moment affect the solubility. The temperature dependence of solubility of compounds in solvents is described by the modified Apelblat equation.21,22 ln x ai = A + B /T + C ln(T )

(3)

RD = (xi − xci)/xi

(4)

where xi is the experimental solubility and xci is the calculated solubility by eqs 2 and 3. The root-mean-square deviations (RMSD), together with relative average deviations (ARD), are also calculated for modified Apelblat and λh equations using eqs 5 and 6 and are listed in Tables 4 and 5. N

RMSD = [∑ (xci − xi)2 /N − 1]1/2 i=1

ARD =

1 N

(5)

N

∑ (xi − xci)/xi i

(6)

where N is the number of experimental points. It is seen from Table 2 that the calculated solubilities by the modified Apelblat and Buchowski−Ksiazczak (λh) equations are in good agreement with the experimental solubility values. It is realized from Tables 4 and 5 that RMSD values for most of the compounds are comparatively less with the Apelblat equation. So, the modified Apelblat equation is more accurately applicable for the dissolution of studied compounds in selected solvents. Thus, the experimental data and the correlation equations in this work can be used for the optimization of the crystallization process. Thermodynamic Parameters of Solution. The dissolution of compounds in a solvent is associated with changes in thermodynamic functions such as enthalpy (ΔHsol), Gibb’s energy (ΔGsol), and entropy of solution (ΔSsol). These functions have also been evaluated from experimental solubility data. The changes that occur in the solute during dissolution process can be explained by these thermodynamic functions. The enthalpies of solution (ΔHsol) was calculated by the modified Van’t Hoff equation27 i.e., from the slope of the plot of ln x versus (1/T − 1/Thm). ∂ ln xi /∂(1/T − 1/Thm)p = −ΔHsol /R

(7)

where T is the experimental temperature and R is the universal gas constant (8.314 J·mol−1·K−1). Thm is the mean harmonic temperature28 and is calculated by eq 8.

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Table 2. Measured Mole Fraction Solubilities (xi), Calculated Mole Fraction Solubilities (xci), and Relative Deviation (RD) of Studied Compounds in Selected Solvents at Different Temperatures at 0.1 MPaa T/K

xid·103

xcib,e·103

298.15 303.15 308.15 313.15 318.15 323.15 328.15

1.13 1.30 1.44 1.60 1.75 1.90 2.07

± ± ± ± ± ± ±

0.03 0.06 0.07 0.09 0.05 0.10 0.02

1.17 1.33 1.49 1.65 1.81 1.98 2.13

± ± ± ± ± ± ±

0.05 0.08 0.04 0.09 0.03 0.01 0.05

298.15 303.15 308.15 313.15 318.15 323.15 328.15

5.31 5.60 5.89 6.20 6.66 6.90 7.18

± ± ± ± ± ± ±

0.08 0.06 0.06 0.01 0.04 0.07 0.01

5.32 5.62 5.93 6.24 6.56 6.89 7.22

± ± ± ± ± ± ±

0.07 0.09 0.06 0.01 0.04 0.09 0.05

298.15 303.15 308.15 313.15 318.15 323.15 328.15

2.34 2.50 2.61 2.80 2.97 3.20 3.35

± ± ± ± ± ± ±

0.03 0.06 0.08 0.10 0.09 0.12 0.10

2.33 2.49 2.65 2.82 2.99 3.17 3.35

± ± ± ± ± ± ±

0.09 0.08 0.07 0.05 0.07 0.07 0.09

298.15 303.15 308.15 313.15 318.15 323.15 328.15

2.33 2.50 2.62 2.80 2.98 3.20 3.43

± ± ± ± ± ± ±

0.06 0.09 0.07 0.08 0.02 0.11 0.05

2.35 2.48 2.64 2.81 3.00 3.20 3.44

± ± ± ± ± ± ±

0.05 0.09 0.05 0.04 0.07 0.03 0.01

298.15 303.15 308.15 313.15 318.15 323.15 328.15

2.12 2.30 2.38 2.60 2.74 2.90 3.05

± ± ± ± ± ± ±

0.07 0.02 0.02 0.04 0.09 0.04 0.05

2.13 2.28 2.43 2.58 2.74 2.90 3.07

± ± ± ± ± ± ±

0.05 0.01 0.11 0.05 0.06 0.09 0.03

298.15 303.15 308.15 313.15 318.15 323.15 328.15

2.21 2.40 2.60 3.00 3.30 3.60 3.80

± ± ± ± ± ± ±

0.04 0.03 0.05 0.09 0.01 0.07 0.06

2.19 2.43 2.68 2.95 3.25 3.56 3.88

± ± ± ± ± ± ±

0.01 0.03 0.08 0.09 0.10 0.11 0.05

298.15 303.15 308.15 313.15 318.15 323.15 328.15

5.15 5.60 6.02 6.60 7.07 7.40 7.82

± ± ± ± ± ± ±

0.05 0.09 0.07 0.08 0.04 0.06 0.01

5.09 5.57 6.05 6.51 6.96 7.38 7.77

± ± ± ± ± ± ±

0.05 0.06 0.07 0.09 0.07 0.04 0.05

102 RDb,f Methanol KDB-1 −3.99 −2.23 −3.64 −3.16 −3.72 −3.97 −2.88 KDB-2 −0.07 −0.32 −0.54 −0.66 −0.06 0.15 −0.53 KDB-3 0.51 0.57 −1.47 −0.58 −0.65 1.03 0.00 KDB-4 −0.69 0.66 −0.63 −0.24 −0.53 −0.15 −0.17 KDB-5 −0.59 1.01 −1.93 0.79 0.08 −0.02 −0.58 DMF KDB-1 0.96 −1.12 −3.07 1.50 1.70 1.23 −2.22 KDB-2 1.14 0.49 −0.45 1.36 1.62 0.30 0.59

3384

xcic,e·103

102 RDc,f

1.16 1.29 1.44 1.59 1.75 1.92 2.11

± ± ± ± ± ± ±

0.02 0.06 0.08 0.07 0.12 0.02 0.03

−2.87 0.48 0.02 0.75 −0.13 −1.30 −1.70

5.32 5.62 5.93 6.24 6.56 6.89 7.22

± ± ± ± ± ± ±

0.04 0.01 0.08 0.09 0.13 0.07 0.01

−0.07 −0.34 −0.57 −0.69 −0.08 0.14 −0.53

2.34 2.50 2.66 2.83 3.00 3.18 3.36

± ± ± ± ± ± ±

0.05 0.06 0.01 0.08 0.07 0.07 0.12

0.12 0.17 −1.89 −0.99 −1.05 0.65 −0.36

2.32 2.49 2.66 2.83 3.02 3.20 3.40

± ± ± ± ± ± ±

0.02 0.03 0.09 0.06 0.04 0.02 0.07

0.39 0.55 −1.43 −1.22 −1.23 −0.15 0.92

2.14 2.29 2.44 2.59 2.75 2.91 3.08

± ± ± ± ± ± ±

0.03 0.09 0.11 0.18 0.04 0.02 0.04

−1.08 0.52 −2.43 0.30 −0.40 −0.49 −1.03

2.19 2.43 2.69 2.96 3.25 3.56 3.89

± ± ± ± ± ± ±

0.05 0.02 0.03 0.09 0.11 0.07 0.01

0.78 −1.33 −3.31 1.28 1.48 1.03 −2.41

5.21 5.63 6.06 6.51 6.97 7.46 7.96

± ± ± ± ± ± ±

0.01 0.02 0.03 0.15 0.13 0.18 0.05

−1.21 −0.46 −0.62 1.42 1.38 −0.76 −1.76



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Table 2. continued T/K

xid·103

xcib,e·103

298.15 303.15 308.15 313.15 318.15 323.15 328.15

5.15 5.80 6.38 7.00 7.70 8.30 8.89

± ± ± ± ± ± ±

0.08 0.06 0.09 0.01 0.07 0.13 0.04

5.14 5.75 6.38 7.01 7.64 8.27 8.88

± ± ± ± ± ± ±

0.06 0.01 0.02 0.09 0.12 0.04 0.01

298.15 303.15 308.15 313.15 318.15 323.15 328.15

6.40 6.70 6.93 7.20 7.47 7.80 8.20

± ± ± ± ± ± ±

0.05 0.02 0.09 0.11 0.11 0.09 0.08

6.39 6.67 6.95 7.24 7.53 7.82 8.12

± ± ± ± ± ± ±

0.06 0.08 0.04 0.08 0.12 0.01 0.06

298.15 303.15 308.15 313.15 318.15 323.15 328.15

3.53 4.10 4.62 5.60 6.48 7.20 8.00

± ± ± ± ± ± ±

0.06 0.07 0.09 0.01 0.03 0.07 0.07

3.48 4.10 4.78 5.52 6.32 7.17 8.08

± ± ± ± ± ± ±

0.07 0.05 0.01 0.06 0.08 0.04 0.03

298.15 303.15 308.15 313.15 318.15 323.15 328.15

0.34 0.50 0.69 0.90 1.12 1.60 2.04

± ± ± ± ± ± ±

0.09 0.08 0.01 0.06 0.04 0.04 0.03

0.35 0.48 0.66 0.90 1.19 1.56 2.01

± ± ± ± ± ± ±

0.03 0.01 0.05 0.08 0.09 0.07 0.04

298.15 303.15 308.15 313.15 318.15 323.15 328.15

0.42 0.60 0.86 1.10 1.44 1.80 2.10

± ± ± ± ± ± ±

0.01 0.09 0.05 0.06 0.03 0.04 0.02

0.44 0.63 0.88 1.17 1.50 1.85 2.21

± ± ± ± ± ± ±

0.01 0.06 0.08 0.09 0.04 0.04 0.06

298.15 303.15 308.15 313.15 318.15 323.15 328.15

0.77 0.90 1.11 1.30 1.48 1.80 2.00

± ± ± ± ± ± ±

0.01 0.06 0.04 0.09 0.05 0.08 0.08

0.77 0.92 1.09 1.29 1.52 1.78 2.08

± ± ± ± ± ± ±

0.05 0.09 0.04 0.02 0.06 0.07 0.11

298.15 303.15 308.15 313.15 318.15 323.15 328.15

1.26 1.40 1.60 1.80 1.80 2.10 2.31

± ± ± ± ± ± ±

0.08 0.09 0.01 0.04 0.07 0.02 0.02

1.27 1.42 1.57 1.73 1.91 2.09 2.29

± ± ± ± ± ± ±

0.05 0.03 0.07 0.09 0.07 0.01 0.09

298.15 303.15 308.15

1.37 ± 0.03 1.60 ± 0.05 1.77 ± 0.06

102 RDb,f KDB-3 0.15 0.79 0.01 −0.16 0.74 0.41 0.17 KDB-4 0.22 0.48 −0.33 −0.57 −0.82 −0.31 0.98 KDB-5 1.28 −0.06 −3.50 1.40 2.47 0.37 −0.96 CCl4 KDB-1 −2.09 3.16 3.79 0.51 −6.17 2.74 1.55 KDB-2 −3.78 −5.42 −2.11 −6.33 −4.03 −2.74 −5.00 KDB-3 0.47 −1.90 1.50 0.64 −2.78 0.97 0.03 KDB-4 −1.02 −1.08 1.99 3.76 −5.98 0.25 0.69 KDB-5 −0.20 0.45 −3.55

1.37 ± 0.09 1.59 ± 0.08 1.83 ± 0.07 3385

xcic,e·103

102 RDc,f

5.24 5.78 6.36 6.98 7.63 8.32 9.05

± ± ± ± ± ± ±

0.09 0.04 0.14 0.06 0.03 0.02 0.07

−1.79 0.27 0.27 0.32 0.92 −0.23 −1.77

6.37 6.66 6.94 7.23 7.52 7.81 8.11

± ± ± ± ± ± ±

0.05 0.06 0.09 0.04 0.01 0.01 0.13

0.42 0.66 −0.16 −0.40 −0.66 −0.15 1.15

3.53 4.11 4.76 5.49 6.30 7.20 8.19

± ± ± ± ± ± ±

0.05 0.01 0.04 0.09 0.14 0.18 0.07

−0.08 −0.28 −3.06 2.00 2.82 0.06 −2.36

0.36 0.49 0.66 0.89 1.19 1.57 2.06

± ± ± ± ± ± ±

0.02 0.06 0.90 0.08 0.02 0.09 0.01

−4.54 2.43 3.94 0.92 −6.11 1.87 −0.81

0.45 0.61 0.80 1.06 1.38 1.78 2.29

± ± ± ± ± ± ±

0.13 0.14 0.07 0.09 0.02 0.03 0.06

−7.58 −0.88 6.60 3.97 4.36 1.06 −8.81

0.77 ± 0.06 0.92 ± 0.08 1.09 ± 0.04 1.29 ± 0.09 1.5 ± 0.02 1.79 ± 0.11 2.08 ± 0.09

0.36 −2.06 1.32 0.45 −2.96 0.83 −0.06

± ± ± ± ± ± ±

0.01 0.02 0.06 0.08 0.09 0.04 0.02

−1.01 −1.10 1.96 3.74 −6.01 0.24 0.71

1.38 ± 0.03 1.59 ± 0.09 1.82 ± 0.11

−0.78 0.74 −2.75

1.27 1.42 1.57 1.73 1.91 2.09 2.29



Article

Table 2. continued xid·103

T/K 313.15 318.15 323.15 328.15

2.10 2.37 2.70 2.93

± ± ± ±

0.09 0.04 0.02 0.03

xcib,e·103 2.09 2.37 2.67 2.98

± ± ± ±

102 RDb,f KDB-5 0.35 −0.07 1.15 −1.82

0.03 0.04 0.06 0.04

xcic,e·103

102 RDc,f

± ± ± ±

1.26 0.66 1.37 −2.41

2.07 2.35 2.66 3.00

0.13 0.6 0.9 0.3

Standard uncertainty ur(T) = ± 0.1 K, ur(P) = ± 0.05, and ur(x) = ± 0.02. bValue calculated by the modified Apelblat equation. cValue calculated by the Buchowski−Ksiazczak equation. dxi = measured mole fraction solubility. exci = calculated mole fraction solubility. fRD = relative deviation. a

Figure 5. Variation of mole fraction solubilities (xi) with temperature for studied compounds, [A] in methanol, [B] in DMF, and [C] in CCl4.

All of these thermodynamic parameters are summarized in Table 6. It is evident from Table 6, that for all the compounds, ΔHsol and ΔGsol values are positive. Further, ΔSsol values are found to be positive as well as negative for some compounds in DMF and CCl4, whereas it is negative for all the compounds in methanol. The positive ΔGsol values suggest spontaneity of dissolution process,31 whereas positive enthalpy of dissolution (ΔHsol) indicates an endothermic effect in the dissolution process of compounds. This may be due to the powerful interaction between compounds and solvent molecules than those between the solvent−solvent and compound−compound molecules. Thus, the newly formed bond energy between compound and solvent molecule is not powerful enough to compensate the energy needed for breaking the original association bond in various solvents.32 Further, positive entropy of dissolution suggests that the entropy of solubilization is more favorable,33 whereas negative entropy is due to more order in solutions.34 As compounds contain different groups (−Cl, −F, −CH3, −CF3) of a different nature, it may involve various forces such as the electrostatic force, hydrogen bond, hydrophobic interaction, and stereoscopic effect in the dissolving process.35 Due

Table 3. Dielectric Constant and Dipole Moment of Studied Solvents sr. no.

solvent

dielectric constant

dipole moment

1 2 3

methanol DMF CCl4

32.70 36.71 2.238

1.7 3.86 0.0

n

Thm = n/∑ (1/T ) i=1

(8)

where n is the number of experimental temperatures studied.29 The Thm value calculated by this equation is found to be 312.83 K. From the intercepts of plots of ln x versus (1/T − 1/Thm), the Gibbs energy change (ΔGsol) for the solubility process was evaluated using the following equation.28 ΔGsol = −R ·Thm·Intercept

(9)

Using these evaluated ΔHsol and ΔGsol values, the entropies of solutions (ΔSsol) were obtained by the following equation28,30 ΔSsol = (ΔHsol − ΔGsol)/Thm

(10) 3386



Article

to the different type and magnitude of interactions, thermodynamic parameters vary for dissolution of compounds in studied solvents.

Table 4. Parameters of Modified Apelblat Equation for Studied Compounds in Studied Solvents

■

methanol parameters

KDB-1

A B C 105 RMSDa 100 ARDa

161.09 −9424.12 −23.91 5.56 −3.37

−3.333 −932.49 0.2146 2.57 −0.29


−2.552 −1745.96 0.4006 5.59 −0.15

140.95 −7943.33 −20.9894 6.41 0.72


175.06 −13318.8 −24.28 3.53 0.50

819.62 −42811.66 −120.01 5.77 −4.20

a

KDB-2

KDB-3

KDB-4

KDB-5

−3.6385 −1114.83 0.2306 2.25 −0.09 DMF 142.23 −8339.64 −20.979 3.14 0.30 CCl4 −1.571 −3009.3 0.7879 1.94 −0.15

−122.81 4360.29 17.9285 1.28 −0.25

−3.422 −1128.08 0.1850 2.25 −0.18

−3.6764 −725.69 0.1853 4.51 −0.05

120.45 −8160.68 −17.33 9.75 0.14

−2.733 −1805.07 0.372 5.05 −0.20

89.74 −6603.35 −13.02 3.36 −0.53

CONCLUSIONS The solubility of studied compounds in selected solvents is a function of temperature. The solubility is found to increase with temperature, and the solubility is maximum in DMF and minimum in CCl4. The modified Apelblat and λh equations are used to correlate the solubility data of synthesized compounds, and the Apelblat equation is found to be more accurately applicable for the selected compounds. The positive enthalpy and Gibbs energy indicate the dissolution process to be endothermic and spontaneous. Further, a positive entropy of dissolution suggests that the entropy of solubilization is favorable to the process, whereas negative entropy change suggests more ordered structure in solution.

■

*E-mail: shipra_baluja@rediffmail.com. Notes

Value calculated by the modified Apelblat equation.

The authors declare no competing financial interest.

■

Table 5. Parameters of the Buchowski Equation for Studied Compounds in Studied Solvents

a

solvents

λ

KDB-1 KDB-2 KDB-3 KDB-4 KDB-5

0.009 0.026 0.015 0.014 0.0068


0.0157 0.0469 0.0880 0.1970 0.0512


0.1472 2.048 0.1334 0.0202 0.0163

h

102 ARDa

Methanol −0.68 −0.31 −0.48 −0.31 −0.66 DMF 119309.89 −0.35 29415.80 −0.29 20230.18 −0.29 39698.30 0.13 53525.17 −0.13 CCl4 38887.40 −0.33 2581.52 −0.18 24406.00 −0.30 95025.27 −0.21 155441.21 −0.27 217006.3 38357.2 77620.6 89528.9 174835.0

AUTHOR INFORMATION

Corresponding Author

105 RMSDa 2.10 2.65 2.61 2.72 2.77 5.64 8.14 7.52 4.64 12.0 3.17 8.00 1.98 5.05 3.8

NOMENCLATURE m = weight M1 = molar mass of solute M2 = molar mass of solvent xi = experimental mole fraction solubility xci = calculated mole fraction solubility A, B, and C = parameters λ = Buchowski−Ksiazczak equation parameter h = Buchowski−Ksiazczak equation parameter T/K = absolute temperature in Kelvin Tm = melting temperature RD = relative deviation ARD = Average relative deviation RMSD = root-mean square deviation R = universal gas constant (8.314 J·mol−1·K−1) Thm = harmonic mean of the experimental temperatures ΔGsol = standard Gibb’s energy (kJ·mol−1) ΔHsol = standard enthalpy (kJ·mol−1) ΔSsol = standard entropy (J·mol−1·K−1)

Abbreviation

KDB-1 to KDB-5 = compound code DCP = 2,4-dichloropyrimidine

Value calculated by the Buchowski−Ksiazczak equation.

Table 6. Thermodynamic Parameters of the Dissolution of Compounds in Studied Solvents methanol parameters

KDB-1

KDB-2

KDB-3

KDB-4

KDB-5

ΔGsol/kJ·mol ΔHsol/kJ·mol−1 ΔSsol/J·mol−1·K−1

16.80 16.18 −1.97

13.22 8.31 −15.68

15.28 10.34 −15.76

15.51 9.85 −18.10

ΔGsol/kJ·mol−1 ΔHsol/kJ·mol−1 ΔSsol/J·mol−1·K−1

15.16 15.55 1.25

13.11 11.47 −5.24

12.83 6.51 −20.17

13.56 22.80 29.52

ΔGsol/kJ·mol−1 ΔHsol/kJ·mol−1 ΔSsol/J·mol−1·K−1

18.32 47.61 93.62

17.87 43.96 83.39

15.28 9.86 −17.33 DMF 12.93 14.80 5.96 CCl4 17.33 27.06 31.11

16.56 15.97 −1.87

16.09 21.05 15.84

−1

3387



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NTL = 1-naphthol DMF = dimethylformamide CCl4 = carbon tetrachloride DSC = differential scanning calorimeter RD = relative deviations ARD = relative average deviations RMSD = root-mean-square deviations Superscript

a = value calculated by modified Apelblat equation b = value calculated by Buchowski−Ksiazczak equation

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Measurement, Correlation, and Thermodynamics Parameters of

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